1,1,3,3-Tetramethyldisiloxane (TMDS) has been developed as an excellent dual-purpose reductant for the highly regioselective ring cleavage of various hexopyranosyl 4,6-O-acetals with Cu(OTf)₂ or AlCl₃ to afford the corresponding primary and secondary ethers. Its application to the concise synthesis of carbohydrate-based surfactants is highlighted.

4,6-O-Benzylidene and alkylidene acetals of protected or unprotected glycosides can be reduced at either the O4 or O6 position regioselectively by using 1,1,3,3-tetramethyldisiloxane (TMDS) as a reductant. This methodology was also successfully applied to the straightforward preparation of carbohydrate long alkyl chain ethers.

A series of dyes bearing polymethine chromophore units in boron dipyrromethene (BODIPY) α-positions were prepared by condensation of 3,5-dimethyl boron dipyrromethene with various hemicyanines. One or two methyl groups of the starting material can react, yielding the corresponding mono- and disubstituted derivatives. The deeply coloured monosubstituted dyes belong to the family of merocyanine dyes and exhibit spectral properties and chemical behaviour similar to those of meso-analogues. On the other hand, disubstituted dyes show more complex absorption spectra compared to their monosubstituted counterparts, and their absorption maxima are redshifted (up to 970 nm, the most redshifted absorption known among borondipyrromethene derivatives). Spectral methods and quantum-chemical calculations suggest evolution of the long-wavelength electronic transition from dipyrromethene type into polymethine on changing the character of the peripheral chromophore system. The nature of highest electronic transitions has been analyzed.

A series of dyes bearing polymethine chromophore units in BODIPY α-positions were prepared by condensation of 3,5-dimethyl borondipyrromethene with various hemicyanines. One or two methyl groups of the 3,5-dimethyl borondipyrromethene can react yielding the corresponding mono- and disubstituted derivatives.

A simple and efficient method for the synthesis of 1,3-disubstituted ureas and carbamates from amides by using iodosylbenzene as the oxidant is described. Symmetric and asymmetric ureas and carbamates can be prepared by this procedure in up to 98 % yield. Ureidopeptides can also be prepared in good yield by this method.

A simple and efficient method for the synthesis of 1,3-disubstituted ureas and carbamates from amides by using iodosylbenzene as the oxidant is described. By using this method, heterocyclic products can be easily obtained in excellent yield. Ureidopeptides can also be prepared in good yield by this procedure.

An efficient synthetic procedure for the synthesis of functionalized tetrahydrospiro[indoline-3,2′-quinoline] derivatives was successfully developed and involves the four-component reaction of arylamines, dimethyl acetylenedicarboxylate, isatins, and a cyclohexane-1,3-dione in acetic acid. The advantages of this reaction include the use of common starting materials and mild reaction conditions and it is operationally simple.

An efficient synthetic procedure for the synthesis of functionalized tetrahydrospiro[indoline-3,2′-quinoline] derivatives was successfully developed and involves the four-component reaction of arylamines, dimethyl acetylenedicarboxylate, isatins, and a cyclohexane-1,3-dione in acetic acid.

A Cu-catalyzed cross-coupling reaction of diaryl disulfides or aryl thiols with pentafluorobenzene using CuBr as the catalyst, tBuOLi or tBuOK as the base in DMSO at 60 °C under an O₂ atmosphere was investigated. The corresponding bisarylthiolation products were obtained in moderate to good yields by C–H bond and C–F bond activation. When 1,10-phenanthroline·H₂O and DDQ were added to the above system, monoarylthiolation products, with/without bisarylthiolation products, could be isolated in moderate yields. A plausible mechanism for these transformations was given. Thus, it represents a method for the synthesis of polyfluorinated diaryl sulfides and polyfluorinated triarylbisulfides throughC–H bond and C–F bond activation.

The Cu-catalyzed cross-coupling of diaryl disulfides/thiols with pentafluorobenzene in the presence of CuBr and tBuOLi or tBuOK in DMSO at 60 °C under an O₂ atmosphere was investigated. The corresponding bisarylthiolation products wereobtained by C–H bond and C–F bond activation. When 1,10-phenanthroline·H₂O and DDQ were added to the above system, monoarylthiolation products could be isolated.

A new synthetic route to ring-fused imidazo[5,4-f]benzimidazoles is reported that can be used to access symmetrical and unsymmetrical quinone anticancer agents. Oxone in formic acid allows cyclisation of o-tert-aminoacetanilides to give ring-fused benzimidazoles and imidazobenzimidazoles in superior yields. A mechanism for these oxidative cyclisations is proposed that proceeds through a hydrogen-bonded amine N-oxide intermediate. The amine N-oxide is shown to act as an oxidant in the aromatisation to the imidazole ring. X-ray crystal structures of the dimorpholine N-oxide intermediate and bis[1,4]oxazinoimidazo[5,4-f]benzimidazolequinone bis(trifluoroacetate) adduct are included. Two unsymmetrical quinones are shown to have greater cytotoxicity than the previously reported imidazobenzimidazolequinones.

Double oxidative cyclisations of o-tert-aminoacetanilides give [1,4-oxazino]- and alicyclic ring-fused imidazo[5,4-f]benzimidazoles. The hydrogen-bonded orientation of the amine N-oxide intermediate is used to propose a mechanism. Unsymmetrical quinone derivatives are more potent than previously reported imidazobenzimidazolequinones.

Cyclocondensation reactions between a variety of 2-acyl-3-indoleacetic acid derivatives and (R)-phenylglycinol were studied. Successful results were obtained from N-alkyl keto acid derivatives. The resulting tetracyclic lactams provide straightforward access to enantiopure 1-substituted tetrahydro-β-carboline alkaloids.

A short synthetic route to enantiopure 1-substituted tetrahydro-β-carbolines is reported. The key step in each case is a stereoselective cyclocondensation reaction between an N-alkyl-2-acyl-3-indoleacetic acidand (R)-phenylglycinol. Subsequent reductive processes and debenzylation of the indole nitrogen provide access to N_a-unsubstituted alkaloids such as tetrahydroharman and komaroidine.

A tandem intermolecular–intramolecular 1,3-dipolar cycloaddition sequence with the bis-azomethine imine derived from a para-aryl-substituted bis-verdazyl radical has been used to form a series of [n]-paraheteraphanes, which form exclusively by a [1+1] double cycloaddition reaction, with no evidence for the formation of the [2+2] quadruple cycloadduct products. ¹H NMR spectroscopic studies show that rotation of the phenyl ring of these compounds is affected by the size and structure of the [n]-paraheteraphane cavity.

Using the azomethine imine/1,3-dipolar cycloaddition (1,3-DC) system, a series of [n]-paraheteraphanes were made through a tandem intermolecular–intramolecular 1,3-DC reaction. These phanes only resulted through the [1+1] double cycloaddition reaction with their structural features and conformational biases highlighted through variable-temperature ¹H NMR spectroscopy and X-ray crystallographic studies.

Changes in the concentration of reagents (0.009–0.2 M) have been shown to dramatically effect the yield and stereoselectivity of glycosylation with a sialic acid based glycosyl donor in a complex nonlinear manner that correlates with changes in the structures of the supramers of the reagents. The yield of disaccharide gradually increases with concentration and levels off at concentrations of glycosyl donor higher than 69 mM. The ratio of anomers is very high at some concentrations (α/β ≈ 20:1), moderate (α/β ≈ 8:1) or very low (α/β ≈ 4:1) at others. The formation of mixed supramers of glycosyl donor and glycosyl acceptor at concentrations exceeding 69 mM was detected by polarimetry and laser light scattering.

Depending on the concentration, the reagents can form different supramers with distinct chemical properties. The changes in supramer structure (indicated by the red vertical arrows) correlate with the glycosylation yield (1) and stereoselectivity (2) and can be detected by physical methods.

A new ethylidene menthane-based chiral π-allylpalladium complex catalyzes the asymmetric allylation of various imines with allyltributylstannane and 1 equiv. of water to give chiral homoallylamines in good yields and enantioselectivities. The reaction was carried out essentially under neutral conditions and displayed a good transfer of chiral information from the menthane skeleton through the formation of a bis(π-allylpalladium) species. This is the first example of menthane-based chiral bis(π-allylpalladium) catalysis.

A menthane-based chiral π-allylpalladium-catalyzed asymmetric allylation of various imines has been developed giving chiral homoallylamines in good yields and enantioselectivities. The reaction displays a good transfer of chiral information from the menthane skeleton through the formation of a bis(π-allylpalladium) complex.

A highly stereoselective synthesis of the C1–C14 macrolactone core of the cytotoxic macrolide (–)-callipeltoside A has been achieved by utilizing an anti-selective aldol reaction and Wittig olefination to introduce an (E)-trisubstituted alkene, chemoselective diisobutylaluminum hydride (DIBAL-H) reduction of the 2,3-epoxy tosylate to install the C13 stereocenter, and intramolecular trapping of the acyl-ketene intermediate by the C13 hydroxy group as key steps.

A highly convergent and stereoselective synthesis of the C1–C14 macrolactone core of (–)-callipeltoside A has been achieved by utilizing an anti-selective aldol reaction and Wittig olefination to introduce an (E)-trisubstituted alkene, chemoselective reduction of the 2,3-epoxy tosylate to install the C13 stereocenter, and intramolecular trapping of an acyl-ketene intermediate by the C13 hydroxy group.

A sequential copper-catalyzed, one-pot, click reaction–intramolecular direct arylation, which involves two mechanistically distinct reactions (atom-economical click reaction and direct arylation of 1,2,3-triazole), to generate [6,6]-, [6,7]-, [6,8]-, and [6,9]ring-fused triazoles is reported. Furthermore, a unique divergence of reactivity between the fused triazoles prepared from 2-bromobenzyl azide and 2-bromophenylazide that leads to a fused pentacyclic heterocycle for the former and a C–C-coupled, biphenyl-fused, tricyclic product for the latter is observed under Pd catalysis. All of the key products have been characterized by single-crystal X-ray crystallography.

The sequential copper-catalyzed synthesis of heterocycles with [6,6], [6,7], [6,8], and [6,9]ring-fused triazoles and the palladium-catalyzed synthesis of pentacyclic derivatives are explored.

5,14-α-Diketopentacene, a structural isomer of 6,13-α-diketopentacene, was prepared from pentacene in three steps. In addition to the typical n–π* absorption of the diketone moiety at around 468 nm and the anthracene-like absorption at 333, 349, and 367 nm, a broad absorption was observed at around 386 nm, which could be assigned to an intramolecular charge-transfer absorption from anthracene to the diketone moiety. 5,14-α-Diketopentacene could be converted into pentacene quantitatively by photoirradiation at 405 and 468 nm in toluene with quantum yields of 2.3 and 2.4 %, respectively, and these values are higher than the quantum yield of 1.4 % obtained for 6,13-α-diketopentacene irradiated at 468 nm. The quantum yields in acetonitrile were lowered to 0.33 and 0.28 % with irradiation at 405 and 468 nm. The crystal structure of 5,14-α-diketopentacene showed a CH–π interaction and π–π stacking between neighbouring anthracene and benzene moieties. The lower solubility of 5,14-α-diketopentacene compared with the 6,13-isomer could be explained by this crystal structure.

5,14-α-Diketopentacene, prepared from pentacene in three steps, could be converted into pentacene by photoirradiation. Irradiation at the n–π* absorption and intramolecular charge-transfer state gave pentacene in quantum yields of 2.3 and 2.4 %, respectively.

A set of novel multi-branched chromophores consisting of two groups of fluorene/oxadiazole-based analogues with generic skeletons of donor-π-acceptor (unsymmetrical) and donor-π-acceptor-π-donor (symmetrical) type has been synthesized and shown to display strong and broadly dispersed two-photon absorptivities in the near infrared (NIR) region on irradiation with femtosecond laser pulses. It is also demonstrated that structural parameters such as the number of donor units attached and the substitution pattern are closely connected to the molecular two-photon activities of these model compounds.

A model chromophore set consisting of four fluorene/oxadiazole-based analogues was synthesized, and its members were shown to display ascending two-photon absorptivities with increasing size of their π systems. The observed nanosecond excited-state lifetimes suggested that these model compounds could be potential candidates as broad-band optical power limiters for laser pulses of long duration.

Direct base-mediated amination of aryl halides with aliphatic tertiary amines via an aryne intermediate was developed under transition-metal-free conditions. This operationally simple C–N bond-coupling protocol could tolerate a variety of functionalized aryl halides as well as several aliphatic tertiary amines. Moreover, this environmentally benign process provides a new strategy for direct C–N bond formation.

Aliphatic tertiary amines can exhibit considerable nucleophilicity. The combination of aryl halides and aliphatic tertiary amines provides efficient access to biochemically important aromatic amines. It is noteworthy that this direct amination takes place in the absence of transition metal catalysts.

An environmentally benign solvent system, Solkane365/227/ethanol blend, was developed for Suzuki–Miyaura cross-coupling reactions of aryl boronic acids and aryl halides. The reaction is quite general and gives excellent yields for various aryl, heteroaryl, and fluoroaryl boronic acids or halides. Interestingly, this system also allows the synthesis of polyaryls.

The Suzuki–Miyaura cross-coupling reactions of a variety of aryl boronic acids with aryl bromides or iodides were performed in good to excellent yields in a new environmentally benign solvent system of Solkane365/227/ethanol blend at room temperature.

Highly enantioselective catalytic conjugate additions of 3-substituted benzofuran-2(3H)-ones to 1,1-bis(phenylsulfonyl)ethylene in the presence of catalysts based on Cinchona alkaloids and containing tertiary amine and thiourea groups have been developed. Good to excellent stereoselectivities (up to 99 % ee) could be achieved. An interesting effect of substituent positions on stereoselectivities was observed, and a theoretical study to explain this phenomenon was undertaken.

Highly enantioselective conjugate additions of 3-substituted benzofuran-2(3H)-ones to 1,1-bis(phenylsulfonyl)ethylene in the presence of catalysts based on Cinchona alkaloids and containing tertiary amine andthiourea groups have been developed. Good to excellent stereoselectivity (up to 99 % ee) could be achieved. Effects of substituents' positions on stereoselectivity were studied theoretically.

Three new phosphoramidites exhibiting two or three alkyne functions were prepared and introduced at the 5′ end of oligonucleotides. The resulting bis- and tris-alkyne oligonucleotides were conjugated with acetylthiohexyl, ferrocenecarboamide hexyl, or carbohydrate-propyl azides by using click chemistry (CuAAC) to afford polyconjugated oligonucleotides. Conjugations were performed either in solution or on solid support with high efficiency.

Oligonucleotide conjugates exhibiting two or three thio-linkers, ferrocene moieties, or up to four carbohydrate residues were synthesized by poly click chemistry by using new bis- or tris-alkyne phosphoramidites

A robust library-based approach to new fused quinazolinones by the development of gold(I)-catalyzed cascade reactions between 2-aminobenzohydrazides and alkynoic acids is documented. Selected compounds were administered to lung (A549) and breast cancer cells (MDA-MB-231 and MCF-7) in vitro and it was found that some successfully inhibited cell proliferation.

Gold(I)-catalyzed reactions between alkynoic acids and benzoylhydrazides efficiently produced pyridazino- or diazepino-fused quinazolinones and pyrrolo- or isoindolo-fused quinazolinones. A switch in regioselectivity was observed in the presence of aryl substituents on the benzoylhydrazides. It was found that some of the products inhibited cell proliferation in lung and breast cancer cells in vitro.

A new photochromic fused 2H-chromene that has a dehydropyran bridge between the pyran double bond and the benzene ring was prepared. Unlike standard 2H-chromenes that give rise to two coloured species (one short- and one long-lived) under UV irradiation, flash photolysis studies on this particular 2H-chromene show that the opening of the pyran ring led to the formation of a single, coloured, open species that bleaches to the uncoloured initial form in <1 ms. The design of this fused 2H-chromene avoids the formation of the undesirable long-lived, transoid–trans, coloured, open form; therefore, the colour fades very quickly, according to monoexponential kinetics, without the persistence of any residual colour commonly observed in 2H-chromenes. Acid treatment of 4-[(ethoxycarbonyl)methyl]-2H-chromenes led to the formation of lactones.

A new fused 2H-chromene that has a dehydropyran bridge between the pyran double bond and the benzene ring was prepared. Flash photolysis studies show thatthe opening of the pyran ring leads to the formation of a single, short-lived, coloured, open species that bleaches to the uncoloured initial form in a few milliseconds.

A facile carbohydrate-based route was developed for the synthesis of the tetrahydrofuran (C13–C22) fragment of amphidinolide X. Starting from L-sorbose, the key reactions followed include the stereoselective synthesis of a quaternary center at C1, Barton–McCombie deoxygenation at C2, Mitsunobu inversion at C3, and chain elongation by a Wittig reaction at C5.

Synthesis of the C13–C22 fragment of amphidinolide X was achieved followingstereoselective installation of a quaternary center at C1, Barton–McCombie deoxygenation at C2, Mitsunobu inversion at C3, and chain elongation by a Wittig reaction at C5 as key reactions starting from L-sorbose.

The new piperideine alkaloid cicindeloine (3) was isolated from the pygidial glands of the beetles Stenus cicindeloides and Stenus solutus. The structure and absolute configuration of 3 were elucidated by NMR spectroscopy and asymmetric synthesis, respectively. A very efficient gram-scale synthesis of 3 was developed using an intramolecular aza-Wittig reaction as the final step. The synthetic route is comprised of 12 steps and proceeds in 20 % total yield. Nine of the 12 steps were conducted without column chromatography.

The new alkaloid cicindeloine was isolated from the pygidial glands of the beetles Stenus cicindeloides. This is the first epoxypiperideine alkaloid from natural sources. An asymmetric synthesis for cicindeloine was achieved in 12 steps with a total yield of 20 %. Nine of the steps were conducted without column chromatography.

Two approaches to the synthesis of the title 6-substituted 2(1H)-pyridon-3-yl C-2′-deoxyribonucleosides have been pursued. A protected 6-aminopyridine C-nucleoside intermediate was converted into the N-oxide followed by Ac₂O-mediated rearrangement and final deprotection to give 6-acetylamino-2-oxo(1H)-pyridin-3-yl deoxyribonucleoside. Due to the unusually high stability of the N-acetyl group, the full deprotection was unsuccessful. In the second approach, 6-chloro-2-pyridone was converted into phosphorodiamidate, which underwent ortho-magnesiation and iodination to give the 3-iododerivative. It was then used in a Heck coupling with a sugar glycal and the resulting product deprotected to give 6-chloro-2-oxo(1H)-pyridin-3-yl deoxyribonucleoside, which was either directly or after reprotection converted into 6-methyl-, 6-amino-, and 6-unsubstituted pyridone C-nucleosides. The final nucleosides were very unstable and easily epimerized and/or oxidized, which limits (but not excludes) their further use in chemical biology.

Long wanted and difficult to make 1-deazapyrimidine C-nucleosides: 6-Substituted 2(1H)-pyridon-3-yl C-deoxyribonucleosides were prepared through a sequence consisting of ortho-magnesiation/iodination, Heck coupling with glycal, reduction, reprotection, and cross-coupling or hydrogenation of the key chloropyridine intermediate. The final compounds were relatively unstable.

The regioselective ring lithiation of BF₃-complexed 3-picoline (1a), 3,4-lutidine (1b), and 3,5-lutidine (1c) was studied. The dilithiation of 1a, 1b, and 1c was also investigated to experimentally explore the relative preference of the sites on the substituted pyridine ring for lithiation. The role of the complex-induced proximity effect (CIPE) for inducing lithiation in these moieties was investigated using both experimental and computational studies.

The complexation of BF₃ with picoline and lutidine allows regioselective ring lithiation with lithium diisopropylamide (LDA). Experimental and computational studies indicate that the role of the complex-inducedproximity effect (CIPE) is greater than that of the electrostatic effect in achieving the selective ring lithiation of methyl-substituted pyridine derivatives.

Compounds that integrate electron donor–acceptor subunits with N-methoxyisoquinolinium as acceptors and substituted (methoxy)benzenes as donors were synthesized and their luminescent and photochemical properties studied. Photolysis yielded the corresponding photomethoxylation products in a two-step process that involves N–OMe bond scission followed by C–OMe bond formation. Homolysis of the N–OMe bond restores the aromatic isoquinoline nucleus and produces a methoxy radical that can couple to the required ring carbon atom in the benzene cation radical to give the products in a regioselective process controlled by the spin density of the cation radical. This photoprocess involves two different pathways: methoxylation of the acceptor (intracomponent methoxylation) or the donor (intercomponent metoxylation). Both methoxy-transfer pathways are controlled by the donoating ability (redox potential) of the donor subunit, consistent with the emission observed upon excitation of the charge-transfer state in systems that undergo intermethoxylation.

N-Methoxy-1-benzylisoquinolinium salts can be defined as acceptor–donor electron systems. UV irradiation causes methoxylation of the donor or acceptor ring, depending on the electron-donating ability of each compound. The electronic properties of the target compounds were studied by absorption and emission spectroscopy.

Hexahydro-2-oxo-1,4-diazocin-6-carboxylic acid constitutes a conformationally rigid, crown-shaped scaffold. An orthogonally protected (Boc at N-4 and methyl ester at 6-CO₂H) representative was prepared by ring expansion of a 3-pyrrolidone-derived 1,4-diketone with MeNH₂. After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6-CO₂H function was transformed into a 6-NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N-Boc-β-alanine and glycine methyl ester. Structural features of the eight-membered heterocycle were established by single-crystal X-ray structure analysis of a 4-bromoaniline derivative.

Hexahydro-1,4-diazocines represent new scaffolds for combinatorial chemistry andcan be prepared from pyrrolidone derivatives.

The stereoselective total synthesis of (+)-aspicilin is described. The pivotal step in this approach is the generation of an enyne intermediate by the coupling of an alkyne with vinyl iodide, which constructed the C6–C7 bond. Conversion of the enyne to the desired macrolide was achieved through Sharpless asymmetric dihydroxylation and Yamaguchi macrolactonization as the key steps. Additionally, the biological activity of (+)-aspicilin was evaluated on A549, HeLa, and MCF7 cancer cell lines.

The total synthesis of (+)-aspicilin has been achieved in 12 steps using an alkyne-based approach. The key steps used were an alkyne-zipper reaction, Sonogashira coupling, Sharpless asymmetric dihydroxylation, and Yamaguchi macrolactonization. The biological activity of (+)-aspicilin has also been evaluated.

Modified phenylalanine-based di- and tripeptides have been efficiently assembled by cross enyne metathesis and a Diels–Alder reaction as key steps under mild conditions. In all cases, peptide integrity was preserved, no racemisation was observed, and good yields of modified peptides were obtained.

The design of a simple, highly efficient and versatile method to synthesise modified phenylalanine-based peptides by usingcross enyne metathesis and a Diels–Alder reaction is described.

Tandem reactions of nitriles with 2-aminoethanethiol hydrochloride or amino alcohols in the presence of a catalytic amount of cupric methacrylate (Cu^II₂L₄, L = methacrylate) were employed to prepare 2-thiazolines and 2-oxazolines under mild reaction conditions. The synthetic procedure showed high selectivity for the synthesis of mono- and bis-thiazolines and oxazolines, and a variety of 2-thiazolines and 2-oxazolines was obtained in good to excellent yields.

Tandem reactions of nitriles with 2-aminoethanethiol hydrochloride or amino alcohols in the presence of a catalytic amount of cupric methacrylate were employed to prepare 2-thiazolines and 2-oxazolines under solvent-free conditions.

A mild method for the allylation of carbonyl compounds is presented. This methodology allows the allylation of a broad range of carbonyl compounds starting with allyl carbonates as pronucleophiles. Noteworthy is that ketones, infrequent substrates in other related protocols, are suitable substrates under these reaction conditions. Moreover, the reaction proceeds at room temperature with the use of catalytic amounts of both Ni and Ti catalysts. The success of this strategy is based on the perfect match between the late transition metal (nickel) and the radical reagent (titanium). The use of Ni instead of Pd widens the scope of this transformation and makes this method more economical.

A method that uses a mixture of Ni and Ti metal catalysts was shown to be an excellent protocol for the efficient allylation of carbonyl compounds, including less reactive ketones. This method benefits from the compatibility of transition metal and free radical chemistries.

The structural elucidation of the compounds isolated from the endophytic Phomopsis sp. revealed phomopsinones A–D (1–4), four new α-pyrone derivatives. Three known compounds were also isolated, namely two phomosines, phomosine A (5) and phomosine C (6), and ergosterol (7). The structures of these compounds were determined by spectroscopic analysis (¹H, ¹³C, ¹H–¹H COSY, HMQC, HMBC, and ROESY NMR, and mass spectrometry), supported by molecular modeling. The absolute configurations of the new compounds 1–4 were determined by circular dichroism spectroscopy and TDDFT calculations. Preliminary studies indicated that compounds 1 and 4 show strong and good antifungal activity, respectively. Similarly, compounds 2 and 3 showed good antifungal and moderate antibacterial activities as well as antialgal activities.

Four new pyrenocines (α-pyrones), phomopsinones A–D (1–4), have been isolated from an endophytic fungus, Phomopsis sp., and their absolute structures elucidated byNMR, molecular modeling, and CD spectroscopy. All compounds showed good or strong antifungal activity, and 2 and 3 also showed antibacterial and antialgal activity.

A new original strategy for the synthesis of axially and helically chiral bidentate diphosphane ligands featuring a rigid triangulanyl backbone has been elaborated and executed for several representative enantiomerically pure ligands. Thus,(1R,3S,4S)-1,4-bis[(diphenylphosphanyl)methyl]spiro[2.2]pentane [(1R,3S,4S)-24·(BH₃)₂], [(1R,3R,4S)-4-(diphenylphosphanyl)methylspiro[2.2]pentan-1-yl]diphenylphosphane [(1R,3R,4S)-27·(BH₃)₂], [(1R,3R,4S,5R)-5-(diphenylphosphanyl)methyldispiro[2.0.2.1]heptan-1-yl]diphenylphosphane [(1R,3R,4S,5R)-30·(BH₃)₂], (1S,3S,4S)-1,4-bis(diphenylphosphanyl)spiropentane [(1R,3S,4S)-35·(BH₃)₂], (1S,3S,4S)-1,4-bis(diphenylphosphanyl)spiropentane [(1S,3S,4S)-35·(BH₃)₂], (1S,3S,4S)-1,4-bis(diphenylphosphanyl)spiropentane [(1R,3R,4S)-35·(BH₃)₂], and (1R,3R,4R,5R)-1,5-bis(diphenylphosphanyl)dispiro[2.0.2.1]heptane [(1R,3R,4R,5R)-36·(BH₃)₂] with a spiropentyl and a dispiro[2.0.2.1]heptyl moiety, respectively, have been prepared as bishydroborane complexes applying repetitively the same set of standard synthetic operations, starting from [(1S,3R)-4-methylenespiropent-1-yl]methyl acetate [(1S,3R)-7], (4,4-dibromospiropent-1-yl)methanols [(1S,3R)-8 and (1R,3S)-8] and (dibromodispiro[2.0.2.1]heptyl)methanols (1R,3S,4R)-9, (1S,3R,4S)-9 and (1S,3R,4R)-9 in 4–7 steps. The relative configurations of all important intermediates as well as the absolute configurations of the key intermediates and most final products were established by X-ray crystal structure analyses.

Novel bidentate diphosphane ligands featuring a rigid triangulanyl backbone with axial and helical chirality have been synthesized employing a new original strategy, and a preliminary evaluation of their efficiency in enantioselective allylations of 1,3-dicarbonyl compounds has been performed.

Ketoreductases from Klebsiella pneumoniae (NBRC 3319) selectively reduce several 2-substituted ethyl 3-oxobutyrates to yield the corresponding syn-β-hydroxy esters with remarkable stereocontrol (de > 99 %, ee > 99 %). The enantiopure hydroxy oxo esters were synthetically manipulated to access new small-ring carbocycles.

Synthetically useful chiral intermediates containing a syn-β-hydroxy ester functional group have been accessed by a biocatalytic reduction of 2-substituted ethyl 3-oxobutyrates in an efficient way. The synthesized chiral hydroxy esters serve as precursors for novel small-ring carbocyclic derivatives.

Suzuki–Miyaura reactions of the bis(triflate) of 5,7- and 7,8-dihydroxyflavone proceed with very good site selectivity in favor of position 7 and allow the synthesis of various arylated flavones. The reaction of 5,7-dihydroxyflavone with one equivalent of triflic anhydride also proceeds with very good site selectivity in favor of position 7. The subsequent Suzuki–Miyaura reaction of the product allows the synthesis of 7-aryl-5-hydroxyflavones. The regioselectivity is discussed based on DFT calculations.

Various arylated flavones have been prepared by Suzuki–Miyaura reactions of the bis(triflate) of 5,7- and 7,8-dihydroxyflavone. These reactions proceed with verygood site selectivity in favor of ring position 7 for electronic and steric reasons. DFT calculations have also been used to investigate the regioselectivity.

A series of axially chiral 4-substituted-1-silyl-2,3-butadienes [(allenylmethyl)silanes] were synthesized from 3-bromo-5-silylpenta-1,3-dienes by a Pd-catalyzed asymmetric reaction with a soft nucleophile. The optically active (allenylmethyl)silanes react with an acetal in the presence of TiCl₄ to give the enantiomerically enriched 1,3-diene derivatives through an S_E2′ pathway. Effects of the silyl groups on the enantioselectivity of the asymmetric allene synthesis and the subsequent S_E2′ chirality transfer reaction were studied. It was found that as the steric bulk of the silyl groups in the 3-bromo-5-silylpenta-1,3-dienes was increased from -SiMe₃ to -SiiPr₃, the enantioselectivity of the two enantioselective processes also improved.

The substituent effects of the silyl groups were studied in the palladium-catalyzed asymmetric synthesis of (allenylmethyl)silanes and their S_E2′ chirality transfer reactions with an acetal. As the steric bulk ofthe silyl groups in the 3-bromo-5-silylpenta-1,3-dienes was increased, the enantioselectivity of the two enantioselective processes also improved.

A simple method has been developed for functionalizing glycine derivatives by iron-catalysed cross-dehydrogenative coupling (CDC) reactions. In particular, N-arylglycine derivatives reacted with alkynes by oxidative C–H/C–H coupling reactions to provide a series of substituted quinolines starting from commercially inexpensive materials. Moreover, N-arylglycine esters can be oxidatively coupled to ketones by using FeCl₃ in the presence of DDQ.

A simple method has been developed for functionalizing glycine derivatives by iron-catalysed cross-dehydrogenative coupling reactions. N-Arylglycine derivatives react with alkynes to provide a series of substituted quinolines starting from commercially inexpensive materials. Moreover, N-arylglycine esters can be oxidatively coupled to ketones by using FeCl₃ with DDQ.

The oxy-Cope rearrangement of aldol products has been studied both experimentally and theoretically to gain insight into the aspects that are responsible for the exceptional rate and diastereoselectivity of this process. Kinetic studies as well as DFT calculations convincingly show that the activation barrier of this process is mainly dependent on the electronic nature of the oxy-substituent, with electron-withdrawing O-substituents raising this barrier. The diastereoselectivity, however, remains uniformly high for all derivatives investigated and steric factors are proposed to account for the selectivity to a large extent. The poor diastereoselectivity in the case of the anti-aldols was also found in our calculations and it appears to result from unfavorable gauche interactions between the oxy and carboximide groups in the transition state.

Kinetic measurements and DFT calculations on the Cope rearrangement of 3-oxy-1,5-dienes with a syn-aldol structure reveal a close correlation between the activation barrier and the electronic nature of the oxy-substituent, which reflects the exceptional rate and diastereoselectivity of the [3,3]-sigmatropic rearrangement. Steric factors are proposed to account for the diastereoselectivity.

Depending on their structures, imines are able to undergo either olefination or vicinal difunctionalization with various α-(benzothiazol-2-ylsulfonyl) carbonyl compounds in the absence of external bases. The olefination reaction of aromatic imines with α-(benzothiazol-2-ylsulfonyl) carbonyl compounds proceeds smoothly in tetrahydrofuran at 70 °C to give structurally diverse α,β-unsaturated esters, amides, and ketones in good to excellent yields and with extremely high (E) selectivity. In contrast, the carbon–nitrogen double bonds of cyclic imines and the carbon–carbon double bonds of α,β-unsaturated imines are subjected to regiospecific vicinal difunctionalization with α-(benzothiazol-2-ylsulfonyl) carbonyl compounds under the same reaction conditions to give a variety of benzothiazole derivatives in good to excellent yields. It is noteworthy that the benzothiazole moiety is present in a number of antitumor agents and bioluminescent molecules. In addition, plausible reaction pathways have been proposed to account for these transformations, and these are substantially supported by ESI-MS analysis of the reaction mixtures.

Three new reactions of α-(benzothiazol-2-ylsulfonyl) carbonyl compounds have been developed with aromatic, cyclic, and α,β-unsaturated imines through stereoselective olefination and regiospecific vicinal difunctionalization in the absence of external bases.

The 19-nor-clerodanes are compact, densely functionalized diterpenes based on a stereocentre-rich decalin scaffold. To date only a few examples of the 19-nor-clerodanes have been synthesized, hence new flexible strategies are required. We herein describe the stereocontrolled construction of the cis-hydroxy decalin core in a concise fashion.

A 9-step concise synthesis of the core structure of 5β-hydroxy-cis-dehydrocrotonin is presented. The key steps involve a 6π-electrocyclization, endo-peroxide formation and cleavage.

By changing the position of the homochiral alkoxy substituents of C₃-symmetric 1,3,5-trialkynylbenzenes from the center to the periphery, the macroscopic chirality of the resulting aggregates (crystals or fibers), studied by various spectroscopic and microscopic techniques, was inverted, as confirmed by single-crystal X-ray diffraction analysis.

The chirality of molecular building units has been efficiently transferred to themacroscopic level, leading to chiral bulk materials of opposite handedness.

Glaser coupling of 4-ethynyl[2.2]paracyclophane (1) led to a mixture of dimers that could not be separated by either chromatographic or chemical methods. That two diasteromers of the dimer 2 were produced in a 7:3 ratio was demonstrated by the resolving power of modern NMR spectroscopy.

Two structurally very similar cyclophane diastereomers, inseparable by chemical means, have been differentiated by modern NMR techniques.

Imination and amidation of sulfides, sulfoxides, and olefins using 4H-1,2,4-triazole-4-amine as a nitrogen source with PhI(OAc)₂ as an oxidant were achieved in moderate to high yields without the addition of a catalyst. The carbon–nitrogen and sulfur–nitrogen bond forming reactivity is consistent with a nitrene insertion mechanism in which the reactivity generally increases with decreasing N–H bond dissociation energy of the nitrogen source and increasing oxidation potential of the oxidant.

Imination and amidation of sulfides, sulfoxides, and olefins using 4H-1,2,4-triazole-4-amine as a nitrogen source with PhI(OAc)₂ as an oxidant were achieved in moderate to high yields without the addition of a catalyst. Decreasing N–H bond dissociation energy of the nitrogen source facilitated the nitrene insertion reaction.

Tripyrrolidinophosphoric acid triamide (TPPA) can replace carcinogenic HMPA as a Lewis basic additive in many reactions involving samarium ketyls. In most cases, yields and selectivities of cyclizations of (het)aryl, alkenyl, and alkynyl ketones are similar. TPPA is also a good substitute of HMPA in the O-silylation of an ester enolate and in reactions oflithiated 1,3-dithiane. All these results clearly demonstrate that in many cases the use of HMPA can be avoided.

Red or green, that is the question! Tripyrrolidinophosphoric acid triamide (TPPA) can replace carcinogenic HMPA as an additive in many reactions of γ-(het)aryl ketones involving samarium ketyls. TPPA is also a good substitute of HMPA in the O-silylation of an ester enolate and in reactions of lithiated 1,3-dithiane. These results demonstrate that in many cases the use of HMPA can be avoided.

N-Functionalized IndPHOX ligands bearing various groups have been synthesized and the effects of the N¹-substituent on the reaction rate, yield, and asymmetric induction in a palladium-catalyzed allylic substitution reaction are reported. The presence of an oxygen atom in the ligands, namely an N-MOM or N-THP group, led to enhancement of the enantioselectivity in the allylic amination reaction. In addition, a ligand with a chiral oxazoline ring at C-1 and a phosphane substituent at C-2 provided high enantioselectivity in good yield in an asymmetric allylic alkylation reaction.

Two types of IndPHOX ligands with different substituents at the C-1 have been synthesized. Their use in Pd-catalyzed asymmetric allylic amination and alkylation reactions gave good-to-excellent enantioselectivities and high yields. The presence of an oxygen atom in the 1-substituent led to enhancement of the enantioselectivity in the allylic amination reaction.

The first practical synthesis of isoxazole triflones 3 (4-trifluoromethanesulfonylisoxazoles, 4-triflylisoxazoles) has been achieved by an operationally simple procedure consisting of the reaction between readily available α-triflyl ketones 4 and imidoyl chlorides 5 in the presence of triethylamine. The present method provides the biologically attractive isoxazoles featuring a triflyl group at the 4-position with a wide substrate scope in good to high yield in all cases.

The synthesis of isoxazole triflones 3 was achieved by an operationally simple procedure consisting of the reaction between readily available α-triflyl ketones 4 and imidoyl chlorides 5 in the presence of triethylamine. The present method provides biologically attractive isoxazoles featuring a triflyl group at the 4-postion with a wide substrate scope in good to high yield in all cases.

A straightforward procedure is presented for the covalentimmobilization of ester and silyl ether derivatives of theCinchona alkaloid 10,11-dihydroquinidine within insoluble cross-linked silicone elastomeric films. These materials were effective heterogeneous organocatalysts in the asymmetric dimerization of ketenes, which provided chiral Weinreb β-ketoamides in 28–83 % yield and 79–99 % ee in the course of several recycles. A productivity/enantioselectivity protocol is also proposed to better assess the relative merits of soluble and supported asymmetric catalytic systems towards process intensification.

A series of hydroquinidine derivatives embedded into elastomeric silicone films was prepared and used as insoluble organocatalysts in the asymmetric dimerization of ketenes. A protocol was introduced to compare the productivity/enantioselectivity of the supported catalysts with those of their analogous soluble counterparts.

An efficient three-step synthetic route to α-ketoaldehydes starting from aryl aldehydes is reported. The aldehydes were treated with iPrMgCl and iodoform to obtain β-diiodoalcohols, which were then oxidized with o-iodoxybenzoic acid at room temperature to the corresponding β-diiodoketones. Subsequent reaction of the β-diiodoketone to the α-ketoaldehyde occurred under oxygen transfer from dimethyl sulfoxide. These sensitive products were in situ cyclized with o-phenylenediamine to form the stable monosubstituted quinoxalines, which could be characterized and isolated easily.

α-Ketoaldehydes are a versatile, highly reactive moiety for the synthesis of heterocyclic compounds. We investigated the transformation of aldehydes into α-ketoaldehydes via β-diiodoketone intermediates and finally applied the procedure to the synthesis of peptidic substrates.

Cyclodepsipeptides of the enniation, PF1022 and verticilide families represent a diverse class of highly interesting natural products with respect to their manifold biological activities. However, until now, no practicable solid-phase syntheses of these compounds have been accomplished, probably due to the problematic combination of N-methyl amino acids and hydroxycarboxylic acids. We report herein an efficient synthesis of the anthelmintic PF1022A and its commercial analogue emodepside on Kaiser and Wang resins. Our protocol provides the basis for the solid-phase synthesis of cyclodepsipeptide libraries with a high probability of anthelmintic, antibacterial or insecticidal activity.

The natural product PF1022A and its commercial analogue emodepside exhibit potent activity against parasitic worms. We have accomplished total syntheses of these cyclooctadepsipeptides on Kaiser and Wang resins by a segment coupling approach. Our protocol allows the preparation of cyclodepsipeptide libraries with a high probability of biological activity.

The 3-amino-6-hydroxy-2-piperidone (Ahp) containing cyclodepsipeptides are an interesting class of natural products that inhibit S1 (trypsin and chymotrypsin-like) serine protease in a reversible, noncovalent manner, turning them into potential chemical tools for protease research. Their systematic use in chemical biology is however hampered by their tedious solution-phase chemical synthesis. To overcome this limitation, we report a solid-phase approach to Ahp cyclodepsipeptides that is based on the use of a maskedglutamic aldehyde moiety as a general Ahp precursor molecule. As a proof-of-concept, we therefore recently reported the solid-phase synthesis of Symplocamide A. Here, we want to give a full account on the development and application of the masked glutamic aldehyde moiety as well as the optimization of the solid-phase synthesis, which allowed the successful synthesis of the natural product Symplocamide A.

To gain flexible access to the natural product class of 3-amino-6-hydoxy-2-piperidone (Ahp) containing cyclodepsipeptides, a solid-phase precursor based on a masked glutamic aldehyde was synthesized in solution and used as a key block for a solid-phase approach. The established methodology was subsequently demonstrated in the synthesis of the natural product Symplocamide A.

A series of difluoromethyl-containing α-acyloxycarboxamide derivatives were synthesized through a Passerini reaction of acids, aldehydes, and phenylsulfanyl-protected difluorinated isocyanide followed by meta-chloroperoxybenzoic acid mediated oxidation and the removal of the phenylsulfonyl protecting group. The unexpected formation of deacylation products from the reaction between the Passerini products and Bu₃SnH/azobis(isobutyronitrile) was also reported.

A new approach to the synthesis of difluoromethyl-containing α-acyloxycarboxamide derivatives through a Passerini reaction followed by meta-chloroperoxybenzoic acid mediated oxidation and removal of thephenylsulfonyl group was developed. The formation of deacylation products from the reaction between the Passerini products and Bu₃SnH/azobis(isobutyronitrile) was also reported.

Rapid and versatile access to (Z)-trisubstituted olefins 2 and their cyclization into 4-aryl-2H-chromenes 1 starting fromarylalkynes 3 is described. In a one-pot fashion, alkynes 3 were first hydrated, then transformed into N-tosylhydrazones, and finally coupled with ortho-substituted aryl halides under palladium catalysis to give trisubstituted olefins 2 in good yields and very high to total Z selectivity. 1,1-Diarylolefins 2 having an ortho-OMOM (methoxymethoxy) substituent underwent rapid cyclization in the presence of p-toluensulfonic acid to give a variety of 4-aryl-2H-chromenes in good to excellent yields. This methodology was also successfully applied to the preparation of 5-aryl-2,3-dihydrobenzo[b]oxepine 4 from the required arylbutynol 3b.

A one-pot three-step synthesis of (Z)-trisubstituted olefins from arylalkynols is presented. Olefins having an ortho-OMOM (methoxymethoxy) substituent were successfully transformed into 4-aryl-2H-chromenes using p-toluensulfonic acid in EtOH in good to excellent yields.

1,2,4-Oxadiazole 4-oxides display nitronic reactivity and selectivities identical to those of N-methyl-C-phenyl nitrone, which is a typical acyclic nitrone, affording comparable amounts of endo- and exo-5-alkoxyisoxazolidines. The exo stereoisomers undergo an easy rearrangement under the reaction conditions to yield oxadiazolinic esters. The structures of the adducts have been confirmed by X-ray structures and spectroscopic data. A donor p-methoxyphenyl at the nitronic carbon slows down the cycloaddition rate, while an acceptor p-nitrophenyl retards the rearrangement of the exo adduct.

1,2,4-Oxadiazole 4-oxides undergo 1,3-dipolar cycloaddition reactions with vinyl ethers to afford endo adducts and labile exo adducts that rearrange to oxadiazolinicesters. The structures of the isolated products were assigned on the basis of spectroscopic data and X-ray analyses.

The enantioselective α-alkylation reaction of cyclic ketones is described. Our catalyst, based on a “privileged” pyrrolidine ring bearing a chiral thioxotetrahydropyrimidinone ring, is a highly reactive catalyst for cyclic ketones. When this catalyst was coupled with in situ generated carbocations derived from alcohols, the corresponding α-alkylated adducts were obtained in moderate to quantitative yields and low to high enantioselectivities (up to 80 % ee). The catalyst loading can be efficiently reduced to 10 %, which is the lowest value reported in the literature for such an organocatalytic transformation.

The α-alkylation reaction of carbonyl compounds is a daunting challenge in modern asymmetric synthesis. The combination of a “privileged” pyrrolidine ring bearing athioxotetrahydropyrimidinone moiety is an excellent catalyst for the α-alkylation ofketones.

First isolated in the late 1960s from microalgae of theOchromonas species, the chlorosulfolipids were largely considered as intractable synthetic challenges until recently. Indeed, only in the last few years has this class of natural products received intense attention from the synthetic community, motivated by the many interdisciplinary questions these entities raise. As a consequence, the numerous synthetic and spectroscopic studies that have appeared have contributed to a better understanding of the chemistry of chlorosulfolipids. More than forty years after their discovery, their mysteries are being revealed through the implementation of synthetic tactics and strategies. This microreview summarizes the progress in the synthesis and study of these fascinating natural products.

Chlorosulfolipids, natural products that are produced by sea- and freshwater microalgae, were first discovered in the late 1960s. Uncertainties concerning their biological function and their toxicology sparked off an enormous interest in the last years. The results of these efforts, leading to the successful total synthesis and biological evaluation of several chlorosulfolipids, are summarized in this microreview.

A palladium catalyst that mediates the one-pot sequential Sonogashira and decarboxylative coupling of propiolic acid with two different aryl bromides has been developed. Selective coupling of the first aryl bromide was achieved in the presence of a copper-free, monometallic catalyst generated in situ from allylpalladium chloride dimer and SPhos with tetra-n-butylammonium fluoride as the base in an N-methyl-2-pyrrolidone/water solvent mixture. Upon addition of another aryl bromide and raising the temperature from 50 to 80 °C, the intermediate arylpropiolic acid underwent decarboxylative coupling to give the corresponding diarylacetylene. Thus, the new system permits a one-pot three-component synthesis of unsymmetrical diarylacetylenes from widely available aryl bromides, rather than expensive aryl iodides, and propiolic acid, rather than (trimethylsilyl)acetylene, as an inexpensive and easy-to-handle acetylene synthon. The process is highly selective, modular, and gives access to a wide range of unsymmetrical diarylacetylenes in good yields.

A palladium-catalyzed three component synthesis of diaryl acetylenes has been optimized. Several disubstituted alkynes have been prepared from two different aryl bromides and propiolic acid in good yields.

Di- and trinuclear complexes of copper(I) bearing bis- or tris-N-heterocyclic carbene ligands have been prepared and evaluated as catalysts in nitrene transfer reactions from PhI=NTs to unsaturated and saturated substrates (olefin aziridination and C–H bond amidation) and carbene transfer reactions from diazo compounds to olefins. The complexes exhibited moderate-to-high catalytic activity in both processes. The tosylamidation of C–H bonds, previously unreported with a NHC-containing copper catalyst, was promoted by the dinuclear complexes.

Polynuclear oligo-NHC–copper complexes catalyse the transfer of carbene or nitrene fragments to unsaturated and saturated substrates. The first example of the tosylamidation of C–H bonds with a catalyst containing the NHCCu core is described.

Oxacalix[4]aromatics comprised of terphenylene units have been synthesized by cyclooligomerization of 5′-tert-butyl-1,1′:3′,1″-terphenyl-4,4″-diol (1) and electron-deficient meta-dihalogenated benzene and heterocycles. Single-crystal X-ray analysis revealed that oxacalix[2]terphenylene[2]pyrazine 13 adopts a chair conformation, forming a molecular cavity to trap an ethyl acetate guest molecule in the solid state. 1,3-Alternate conformations are adopted by other oxacalix[2]terphenylene[2]aromatics (11, 12 and 15), which form a narrow tweezer-like molecular cavity that is incapable of encapsulating any guest molecules.

Oxacalix[4]aromatics comprised of terphenylene units have been synthesized, andtheir structures and conformations have been elucidated.

Oxadisilole-fused benzisoxazoles or naphthisoxazoles were obtained through 1,3-dipolar cycloaddition of arynes with nitrile oxides in good yields at room temperature. Key to the procedure is the simultaneous in situ generation of reactive nitrile oxides from arenecarbohydroximoyl chlorides and aryne reactants from benzobis(oxadisilole) or 2,3-naphthoxadisilole. One oxadisilole-fused benzisoxazole is a new precursor of a benzyne formed by a phenyliodination/fluoride-induced elimination protocol. By using this benzyne, cycloadducts were synthesized in good yields. The de-oxadisilole reaction of some of the oxadisilole-fused benzisoxazoles could be easily conducted with a 1.0 M solution of tetrabutylammonium fluoride in THF at room temperature.

Oxadisilole-fused benzisoxazoles or naphthisoxazoles were obtained through 1,3-dipolar cycloaddition of arynes with nitrile oxides in good yields at room temperature. Oxadisilole-fused benzisoxazole is a new precursor of benzyne. The de-oxadisilole reaction of the oxadisilole-fused benzisoxazoles could be easily conducted with tetrabutylammonium fluoride/THF at room temperature.

A new receptor 1 has been designed and synthesized for the selective recognition of anions, which employs hydrogen bonding and electrostatic interactions. Receptor 1 selectively recognizes H₂PO₄^– to exhibit a ratiometric emission response and formed a stable gel in CHCl₃ that contained 10 % CH₃CN, which is useful to visually sense H₂PO₄^–. In comparison, receptor 2 did not form a gel with H₂PO₄^– under similar conditions. Upon interaction with H₂PO₄^–, the intensity of the monomer and excimer emission peaks of 2 increased markedly. Moreover, F^– ions induced quenching of monomer emission in both 1 and 2 in a nonratiometric manner, which distinguished it from the other anions examined.

A new anthracene-labeled 1,2,3-triazole-linked bispyridinium amide molecular receptor has been synthesized. Its ratiometric response in fluorescence and gel formation in the presence of H₂PO₄^– are discussed. Interaction studies were performed by ¹H NMR, fluorescence, and UV/Vis spectroscopy.

The study of the structure and dynamics of the nucleic acids and their complexes with other biomolecules is the basis for understanding their functions. Electron paramagnetic resonance (EPR) spectroscopy is a biophysical technique that in recent years has been increasingly used to investigate nucleic acids. EPR studies require paramagnetic centre(s), usually nitroxide spin-label(s) that are incorporated at specific sites in the nucleic acid by site-directed spin labelling (SDSL). In the last few years, spin labels with improved spectroscopic properties have emerged and new SDSL techniques have been developed. This microreview describes SDSL of nucleic acids in the context of the three spin labelling strategies: post-synthetic spin labelling, labelling during oligonucleotide synthesis and noncovalent labelling.

The application of EPR spectroscopy to study of the structures and dynamics of nucleic acids requires site-specific incorporation of stable free radicals (spin labels), known as site-directed spin labelling (SDSL). This review recapitulates the three main strategies used for SDSL of nucleic acids: spin labelling during oligonucleotide synthesis, post-synthetic labelling and noncovalent labelling.

Jadomycins are unique angucycline polyketides produced by Streptomyces venezuelae soil bacteria under specific nutrient and environmental conditions. Their unique structural complexity and biological activities have engendered extensive study of the jadomycin class of natural compounds in terms of biological activity, biosynthesis, and synthesis. This review outlines recent developments in the study of the synthesis and biosynthesis of jadomycins.

Jadomycins are angucycline polyketides produced by Streptomyces venezuelae under specific nutrient and environmental conditions. Their structural complexity and biological activities have resulted in extensive study of these natural compounds in terms of biological activity, biosynthesis, and synthesis. This review focuses on developments in biosynthetic and total synthetic studies on jadomycins.

The first synthetic approach to the entire carbon skeleton of the sesquiterpenes dunniane and cumacrene has been developed. The sequence features a [2+2] photochemical reaction of a chiral 2(5H)-furanone with ethylene to form the cyclobutane, a Meyer–Schuster-type rearrangement of an α-acetylenic alcohol to an α,β-unsaturated aldehyde, and a microwave-assisted Diels–Alder reaction of an elaborated dienamine with methyl acrylate to construct the six-membered ring with the desired 1,4-substitution pattern.

A synthetic route to the entire carbon skeleton of the sesquiterpenes dunniane and cumacrene is described. Key advances in the synthetic sequence include a [2+2] photochemical reaction and a microwave-assisted Diels–Alder reaction.

Four new 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine (BTBP) ligands, which contain either additional alkyl groups on the pyridine rings or seven-membered aliphatic rings attached to the triazine rings, have been synthesized, and the effects of the additional alkyl substitution in the 4- and 4′-positions of the pyridine rings on their extraction properties with Ln^III and An^III cations in simulated nuclear waste solutions have been studied. The speciation of ligand 13 with some trivalent lanthanide nitrates was elucidated by ¹H NMR spectroscopic titrations and ESI-MS. Although 13 formed both 1:1 and 1:2 complexes with La^III and Y^III, only 1:2 complexes were observed with Eu^III and Ce^III. Quite unexpectedly, both alkyl-substituted ligands 12 and 13 showed lower solubilities in certain diluents than the unsubstituted ligand CyMe₄-BTBP. Compared to CyMe₄-BTBP, alkyl-substitution was found to decrease the rates of metal-ion extraction of the ligands in both 1-octanol and cyclohexanone. A highly efficient (D_Am > 10) and selective (SF_Am/Eu > 90) extraction was observed for 12 and 13 in cyclohexanone and for 13 in 1-octanol in the presence of a phase-transfer agent. The implications of these results for the design of improved extractants for radioactive waste treatment are discussed.

Four lipophilic alkyl-substituted 6,6′-bis(1,2,4-triazin-3-yl)-2,2′-bipyridine (BTBP) ligands have been synthesized and the effects of the additional alkyl substitution on their extraction properties in nuclear waste treatment have been studied by Am^III/Eu^III solvent extraction experiments and lanthanide NMR spectroscopic titrations.

The introduction of a perfluoroalkyl group, with emphasis on the trifluoromethyl moiety, is a challenging topic. Of the synthetic methods available in the repertoire of chemists, electrophilic introduction was until recently the least developed. In five years, however, a renaissance of this chemistry has happened. This renewal has been made possible thanks to reports both of numerous new reagents (stable, easy tohandle and to prepare) and of easier preparation of older reagents. Their availability rapidly inspired highly original works involving their use, in particular with the help of catalysis. This virtuous spiral, as well as all these exciting new developments, is described in this microreview.

New reagents! Easier access to former ones! Great choice of number of atoms of fluorine to be introduced! Catalytic methodologies improving the use of these compounds! Electrophilic perfluoroalkylation is in rapid expansion and full of promise.

Bimacrocyclic concave annelated terpyridines were generated from a U-shaped nonmacrocyclic tetraalkene precursor by ring closing metathesis followed by hydrogenation. The U-shaped precursor was synthesized by condensing two aryl-tetrahydroquinolones with Eschenmoser's salt. The quinolones themselves were accessible by coupling a 2-chloroquinolone with a bis-alkenyloxy-substituted boronic acid. The concave terpyridine was tested for reactivity and stereoselectivity in a copper(I)-catalyzed cyclopropanation.

A bimacrocyclic annelated terpyridine was synthesized from a tetraalkene precursor by ring closing metathesis. The U-shaped starting material was obtained from first connecting a chloroquinolone with a bis-alkenyloxy-substituted boronic acid followed by dimerization using Eschenmoser's salt.

The concise and efficient total syntheses of alkannin (1) and shikonin (2), based on the resolution of a key acid intermediate, are achieved with excellent enantiomeric excesses and high overall yields (99 % ee, 15.6 % for 1 and 99.8 % ee, 11.9 % for 2). The key steps of the synthetic strategy involve the convenient synthesis and separation of a pair of amide diastereoisomers and the mild hydrolysis of the amide to remove the amine chiral auxiliary, together with an efficient deprotection sequence of the methyl protecting groups.

The concise and efficient syntheses of alkannin and shikonin remained elusive until recently. We have developed a new method of resolution for achieving the syntheses of alkannin (1) and shikonin (2) in excellentenantiomeric excesses (≥ 99 % ee for 1 and ≥ 99.8 % ee for 2) and high yields (27.5 %) with low cost, which is practical for use in large-scale preparation.

The photoinversion of sulfoxides has been exploited to generate a photodynamic combinatorial library (PDCL) of tetrasulfinylcalix[4]arenes. Irrespective of the starting isomer, the same product distribution is obtained at the photostationary state upon irradiation at a given wavelength. The order of appearance of the different isomers in the reaction mixture plays a key role in the disclosure of the identity of all the isomers of the PDCL.

The photoinversion of sulfoxides has been exploited to generate a photodynamic combinatorial library (PDCL) of tetrasulfinylcalix[4]arenes. The order of appearance ofthe different isomers in the reaction mixture makes a major contribution to the disclosure of the identity of all the isomers of the PDCL.

An efficient copper-catalyzed cascade reaction of 4-iodopyrazolecarbaldehydes and 4-iodopyrazolecarboxamides with substituted amidines for the preparation of substituted pyrazolo[4,3-d]pyrimidines and pyrazolo[4,3-d]pyrimidin-7(6H)-ones, respectively, is described.

A copper-mediated, one-step synthesis of substituted pyrazolo[4,3-d]pyrimidines and pyrazolo[4,3-d]pyrimidin-7(6H)-ones by reaction between 4-iodopyrazole derivatives and substituted amidines is reported.

Three new anthracene derivatives, which include tetrahydroanthraquinone 1 and two tetrahydroanthraquinone heterodimers 2 and 3, were isolated from Stemphylium globuliferum, together with four known metabolites 4–7. Detailed analysis of the spectroscopic data allowed the unambiguous determination of the structures of 1 and 2 and a revision of the structure of alterporriol C and its atropisomer. Furthermore, alterporriol G, previously obtained as part of a mixture, was isolated in its pure form for the first time and its structure was also revised. The absolute configurations of 1, 2 and 3 were assigned by calculation of their CD spectra, which also allowed the configurational assignment of altersolanol A and the determination of the axial chirality of alterporriols D and E. All isolated compounds were analysed for their antimicrobial and cytotoxic activities. Compound 5 inhibited the growth of most pathogenic microorganisms tested, whereas 2, 6 and 7 showed selective inhibition of bacteria but were inactive against fungi.

Three new anthracene derivatives and four known metabolites were isolated from the extract of the endophytic Stemphylium globuliferum. The structures were determined by comprehensive NMR spectroscopy and MS, and the absolute configurations by TDDFT and ZINDO methods. All isolated compounds were tested for their cytotoxic and antimicrobial activities.

N-Mesyloxylactams can undergo ring contraction either by C-3 (usually observed) or C-5 migration. C-5 migration can occur when the C-3 migration product possesses ring strain, but it does not usually compete with C-3 migration. The greater preference for C-3 migration is due to the carbonyl oxygen atom, which greatly stabilizes the intermediate.

Studies of the photochemical rearrangement of N-mesyloxylactams showed that the lone pair of the carbonyl oxygen atom, and not the degree of the substitution atthe migrating carbon atoms, is the governing factor in the regioselectivity of the reaction.

[¹¹C]Methyl iodide is the most widely used reagent for labeling radiotracers with carbon-11 (t_1/2 = 20.4 min) for molecular imaging with positron emission tomography. However, some substrates for labeling, especially primary arylamines and pyrroles, are sluggishly reactive towards [¹¹C]methyl iodide. We found that insoluble inorganic bases, especially Li₃N or Li₂O, effectively promote rapid reactions (≤ 10 min) of such substrates with no-carrier-added [¹¹C]methyl iodide in N,N-dimethylformamide (DMF) at room temperature to give ¹¹C-methylated products in useful radiochemical yields. In particular, we discovered that some primary arylamines in Li₃N/DMF were converted into their corresponding formanilides, and that these were readily N-methylated with [¹¹C]methyl iodide, which preceded easy basic hydrolysis to the desired [¹¹C]N-methyl secondary arylamines. The use of a solid base permitted selective reaction at an arylamino group and, in some cases, avoided undesirable side reactions, such as ester group hydrolysis. An ultrasound device proved useful to provide remote and constant agitation of the radioactive heterogeneous reaction mixtures but imparted no ultrasound-specific chemical effect.

Solid inorganic-bases in DMF promote rapid ¹¹C-N-methylation of primary arylamines at room temperature when agitated with ultrasound, often through reactive N-formyl intermediates.

Original new fluorescent and electroactive compounds have been prepared, which feature two different fluorescent groups linked through an oxygen atom spacer. We describe here the synthesis, photophysical and electrochemical properties and their interplay, and our theoretical calculations. These molecules are composed of two fluorophores, an electron-rich triphenylamine unit and an electron-poor tetrazine unit. Although the bichromophores are not fluorescent in the neutral state due to a photoinduced electron transfer from the triphenylamine unit to the tetrazine unit, one can restore the fluorescence by oxydation of the triphenylamine moiety. Thus, a redox-fluorescent switch has been realized.

Tetrazine–triphenylamine bichromophores linked by an oxygen atom were designed and synthesized. Their photophysical and electrochemical properties were investigated. These dyads are nonfluorescent compounds in their neutral state because of phoinduced electron transfer. However, tetrazine fluorescence was restored by chemical oxidation (cation radical formation).

The asymmetric catalytic synthesis of naturally occurring and biologically active spiro compounds is a challenge for modern chemical methodology. Here we report the construction of spiro compounds through cascade [5+1] double Michael reactions between divinyl ketones and N-unprotectedoxindoles or N-phenyl-protected pyrazolones catalyzed by a combination of the easily available 9-amino-9-deoxy-epi-quinine with N-Boc-D-phenylglycine. The desired multistereogenic spiro[cyclohexanone-oxindoles and -pyrazolones] were obtained with high yields (up to 98 %) andstereoselectivities (up to >20:1 dr, 99 % ee).

An efficient approach to spiro compounds through cascade [5+1] double Michael reactions between divinyl ketones and oxindoles or N-protected pyrazolones in the presence of 9-amino-9-deoxy-epi-quinine and N-Boc-D-phenylglycine is reported. Multistereogenic spiro[cyclohexanone-oxindoles and -pyrazolones] are obtained with high yields (up to 98 %) and stereoselectivities (up to >20:1 dr, 99 % ee).

In this study, we report on in vitro incorporation experiments of several labelled fatty acids in the ladybird alkaloids coccinelline (Coccinella 7-punctata), adaline (Adalia 2-punctata), and harmonine (Harmonia axyridis). The obtained results clearly indicate that stearic acid is the precursor of coccinelline and harmonine, whereas myristic acid is at the origin of the carbon skeleton of adaline. Possible pathways for the biosynthesis of these alkaloids are presented.

In vitro incorporation experiments of labelled fatty acids in the ladybird alkaloids coccinelline (Coccinella 7-punctata), adaline (Adalia 2-punctata) and harmonine (Harmonia axyridis) indicate that stearic acid is the best precursor for the biosynthesis of coccinelline and harmonine, whereas myristic acid is more efficient for the formation of the carbon skeleton of adaline.

The formation of β-amyloid plaques is considered a histopathological hallmark of Alzheimer's disease (AD), a neurodegenerative disorder that affects millions of people worldwide. For effective treatment of AD, diagnosis at an earlier stage of the degenerative process is essential. Therefore, in the last few years significant efforts to find probes for in vitro and/or in vivo imaging of β-amyloid deposits have been made. This work presents an overview of different small molecules explored as fluorescent or radioactive probes for targeting β-amyloid deposits. It focuses mainly on the different synthetic approaches used for their synthesis or radiosynthesis but their biological behaviour is also briefly discussed when appropriate.

Different classes of aromatic and heteroaromatic compounds designed as nuclear and optical probes for detection of Aβ aggregates are reviewed with special focus on the synthetic strategies explored.

This microreview highlights the synthetically versatile N-acylpyrrole functional group. The preparation, electronic properties and unique reactivity of these amide systems are highlighted. Capable of functioning as acid, ester, amide, aldehyde and ketone equivalents, of serving as acylating agents, of enhancing the reactivities of α,β-unsaturated systems and of undergoing a wide range of other reactions, this microreview shows N-acylpyrroles to be more than just amides.

This microreview highlights the synthesis, properties and reactions of the valuable N-acylpyrrole functional group.

Acylative kinetic resolution of racemic amines occupies a highly important place among the methods for preparation of enantio enriched or pure amines. Nonenzymatic acylative kinetic resolution is usually carried out in the presence of chiral acyl-transfer catalysts or under the action of chiral enantio- or diastereoselective resolving agents. Recently, this line of investigations has been rapidly developed and very interesting results of design and synthetic application of both new catalysts and chiral acylating agents have been obtained. This microreview summarizes the recent advances in this area.

This microreview discusses the methods of nonenzymatic acylative kinetic resolution of racemic amines and related compounds carried out in the presence of chiral acyl-transfer catalysts and under the action of chiral enantioselective or diastereoselective resolving agents.

The formal total synthesis of the antitubercular agent erogorgiaene was achieved in 12 steps by using a protecting group free strategy. The synthesis involves an enamine-mediated 1,4-addition, an aldol condensation, dehydrogenation, Wittig olefination, intramolecular Friedel–Crafts cyclization, TEMPO-BAIB-mediated oxidation, and Evans auxiliary based diastereoselective methylation.

The formal total synthesis of the antitubercular agent erogorgiaene was achieved in 12 steps by using a protecting group free strategy. The synthesis involves an enamine-mediated 1,4-addition, an aldol condensation, dehydrogenation, Wittig olefination, intramolecular Friedel–Crafts cyclization, TEMPO-BAIB-mediated oxidation, and Evans auxiliary based diastereoselective methylation.

The cover picture shows the image of the original crystals of the Wheland–Meisenheimer complex between 2,4-dipyrrolidin-1-yl-1,3-thiazole and 4,6-dinitrobenzofuroxan (DNBF) visible under an Olympus SZX10 microscope and photographed by us. X-ray diffraction analysis of zwitterionic Wheland–Meisenheimer complexes [derived from the reaction between 2,4-dipyrrolidin-1-yl-1,3-thiazole and DNBF or 4,6-dinitrotetrazolopyridine (DNTP)] has been achieved for the first time. Details are discussed in the article by L. Forlani, C. Boga et al. on p. 1123 ff. The authors thank Dr. Anna Nasci who created the background and inserted the images of the crystals in a frame of aesthetic appeal.

Selected recent developments in ketene chemistry are described. They include examples of stereoselective reactions, ketenes and polymers, ketenes and carbenes, ketenes in synthesis, ketenes from photochemical processes, and bis-β-lactam formation.

Many fascinating new ketenes and valuable processes involving ketene chemistry have appeared recently, and selected examples of these are briefly reviewed. They include stereoselective reactions, ketenes and polymers, ketenes and carbenes, ketenes in synthesis, ketenes from photochemical processes, and bis-β-lactam formation.

Chiral, self-supported, polytopic imidazoline–pyridine ligands were designed and synthesized for use in Cu catalysis. The tripodal imidazoline–pyridine L6-Cu(BF₄)₂ complex catalyzed the asymmetric p-(tert-butyl)benzoylation of meso-hydrobenzoin to give the adduct in up to 85 % ee. After completion of the asymmetric benzoylation reaction, the self-supported tripodal imidazoline–pyridine–Cu catalyst could be easily recovered as a precipitate by adding hexane, and the recovered catalyst could be reused several times while maintaining the catalyst activity and selectivity.

Chiral tripodal imidazoline–pyridine L6-Cu(BF₄)₂ complex catalyzed the asymmetric p-(tert-butyl)benzoylation of meso-hydrobenzoin to give the adduct in up to 85 % ee. After completion of the asymmetric benzoylation reaction, the self-supported tripodal imidazoline–pyridine–Cu catalyst was easily recovered and reused several times while maintaining the catalyst activity and selectivity.

We report herein the Pd-catalyzed P–C cross-coupling reaction between enol phosphates and secondary phosphane–borane complexes or phosphane oxides. The reaction was performed under mild conditions, owing to Pd activation of the P–H bonds of the phosphane–boranes (or phosphane oxides) and to the powerful enol phosphate coupling reagents. New useful chiral and achiral α-β-alkenylphosphane derivatives bearing an amido group in the α-position to the P center were obtained in yields up to 70 %.

A useful and versatile Pd-catalyzed P–C cross-coupling reaction was applied with success to a range of secondary phosphane–borane or phosphane oxide derivatives and α-amido enol phosphate reagents. The reaction afforded new chiral or achiral tertiary α-enamido phosphane derivatives.

The absolute configurations of onchidione (1), previously reported from the marine pulmonate Onchidium sp., and the related alcohols onchidiol (2) and 4-epi-onchidiol (3), first described as methanolysis products of 1, were assigned by X-ray diffraction analysis and solid-state time-dependent density functional theory electronic circular dichroism. Alcohol 3 was incorrectly reported as the C-16 epimer of 2.

The absolute configuration of three complex marine polypropionates was established by X-ray diffraction analysis and solid-state time-dependent density functional theory electronic circular dichroism.

Palladium-catalyzed tandem reactions of β-(2-bromophenyl)-α,β-unsaturated carbonyl compounds with 2-hydroxyphenylboronic acid for the synthesis of benzo[c]chromenes are presented. This mild reaction allows formation of onecarbon–carbon bond and one carbon–oxygen bond in one pot.

A mild method for the synthesis of asymmetrical 6H-benzo[c]chromenes was developed. The process involved the palladium-catalyzed tandem reaction of β-(2-bromophenyl)-α, β-unsaturated carbonyl compounds with 2-hydroxyphenylboronic acid.

The asymmetric allylboration of aldehydes with pinacolallylboronates catalyzed by 1,1′-spirobiindane-7,7′-diol (SPINOL) based phosphoric acids is described. 6,6′-Bis(2,4,6-triisopropylphenyl)SPINOL-based phosphoric acid was found to be a general, highly enantioselective catalyst for such allylboration reactions and excellent enantioselectivities were obtained for different types of aldehydes including aromatic aldehydes, α,β-unsaturated aldehydes, propargylic aldehydes, and aliphatic aldehydes.

6,6′-Bis(2,4,6-triisopropylphenyl)SPINOL-based phosphoric acid was found to be a general, highly enantioselective catalyst for the asymmetric allylboration of pinacol allylboronates with different types of aldehydes.

A catalytic enantioselective Michael addition–cyclization reaction of nitroalkanes with o-hydroxycinnamaldehydes has been established by using a diphenylprolinol TMS ether as an organocatalyst. The reaction afforded the corresponding 4-substituted chroman-2-ols in excellent yields with high levels of enantioselectivities (95 to >99 % ee).

A catalytic enantioselective Michael addition–cyclization reaction of nitroalkanes with o-hydroxycinnamaldehydes has been established by using a diphenylprolinol TMS ether as an organocatalyst. The reaction afforded the corresponding 4-substituted chroman-2-ols in excellent yields with high levels of enantioselectivities (95 to >99 % ee).

The reactions between 2,4-dipyrrolidin-1-yl-1,3-thiazole, a supernucleophilic reagent, and 4,6-dinitrobenzofuroxan (DNBF) or 4,6-dinitrotetrazolopyridine (DNTP), two superelectrophilic reagents, afforded new covalent complexes that are contemporaneously intermediates of an S_NAr reaction (a Meisenheimer complex) and of an S_EAr reaction (a Wheland complex). These compounds belong to a new class of covalent complexes, which we have named Wheland–Meisenheimer complexes (WM). The high stability of the complexes reported herein allowed the first X-ray diffraction analyses of WM complexes. In addition, the reactions are diastereoselective, probably because of the specific approach of the two starting partners. The WM complex obtained with DNBF unexpectedly evolved to a neutral substitution product, a furazan derivative. Probably, the protons bonded to two sp³ carbon atoms are lost together with the oxygen atom of the furoxan moiety to form water. This represents a unique example of the formation of a neutral substitution compound from a C–C WM complex. Finally, exchange of the DNBF moiety in WM8 with DNTP in a solution of CD₃CN was observed; the formation of the WM9 complex provided further evidence for the reversibility of the formation of the WM complexes.

The reactions of the thiazole derivative 6 with DNBF and DNTP afforded the corresponding new Wheland–Meisenheimer complexes. Their unusually high stability allowed the first X-ray diffraction analyses of these types of complexes. The reactions are diastereoselective, and the complex derived from DNBF unexpectedly evolves to a neutral substitution product, a furazan derivative.

A new family of dipolar ionic dendrimers that consist of a cationic pyridinium core surrounded by a negatively charged shell of carboxylic acids was successfully synthesized and characterized. Both spherical architectures and examples of amphiphiles with a dipolar head group were synthesized. Studies of the aggregation behaviour in aqueous solution by determining the cmc values were performed. This new type of dipolar core–shell dendrons can be considered as molecular architectures that contain a positively charged nucleus covalently incorporated within a negatively charged shell.

Dipolar ionic dendrimers that consist of dendronized pyridinium units surrounded by a shell of carboxylic acids are a new family of dendritic architectures in which opposite charges are organized within specific areas of one macromolecule. They can be considered as molecular architectures that contain a positively charged nucleus covalently incorporated within a negatively charged shell.

A series of tetrakis(tetrathiafulvalene-tetrathiacrown ether)porphyrazine triads with long and flexible aliphatic side-chains at the periphery have been synthesized and characterized. Electrochemical investigations show two reversible four-electron oxidation waves, one reversible one-electron oxidation wave and two irreversible one-electron reduction waves, which indicates that these triads are good π-electron donors. Selected triad 4a reacted with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F₄TCNQ) to form a charge-transfer complex, which exhibits absorption bands at around 760 and 860 nm. Selected triads 4a and 5a bind silver(I) and mercury(II) ions. In the case of triad 4a, the addition of silver(I) ions led to dimerization of the triad, which fragmented to form monomeric 4:1 host–guest complexes when more than 2 equiv. of the metal ions were added. X-ray scattering at room temperature showed that triad 5c is a highly ordered oblique columnar structure in the bulk state. The crystal structures of the precursors 3b,c were also determined by X-ray diffraction analysis.

A series of tetrakis(tetrathiafulvalene-tetrathiacrown ether)porphyrazine triads with long and flexible aliphatic side-chains at the periphery have been synthesized and their electronic absorption, intermolecular charge transfer, electrochemistry, recognition of transition-metal ions, and structure in the bulk state have been investigated.

Manadomanzamine A is a complex alkaloid isolated from a marine sponge that shows promising biological activities. A biosynthetic hypothesis is proposed and is used as a guideline for biomimetic approaches to the pentacyclic indole nucleus of manadomanzamine A. The rich chemistry of reactive C₅ units such as glutaconaldehydes or aminopentadienals was exploited towards this end.

Biomimetic models towards a better understanding of the biosynthesis of manadomanzamine A were carried out and permitted the construction of the central pentacyclic core of this complex alkaloid.

A new boron–dipyrromethene (BODIPY) derivative (FS1) containing two triazole units exhibits an enhanced fluorescence in the presence of Hg²⁺ ions and a high selectivity for Hg²⁺ ions over competing metal ions in methanol: Ag⁺, Ca²⁺, Cd²⁺, Co²⁺, Cu²⁺, Fe²⁺, Fe³⁺, K⁺, Mg²⁺, Mn²⁺, Ni²⁺, Pb²⁺, and Zn²⁺ produced only minor changes in the fluorescence of FS1. The apparent dissociation constant (K_d) of FS1–Hg²⁺ was found to be 62 μM. Moreover, fluorescence microscopy experiments showed that FS1 can be used as a fluorescent probe for detecting Hg²⁺ ions in living cells.

A new BODIPY-based fluorescence chemosensor FS1 shows high selectivity for Hg²⁺ ions over other transition-metal ions. The fluorescence of FS1 was significantly enhanced in the presence of Hg²⁺, with green emission, and the addition of other metal ions barely affected the fluorescence. This FS1 chemosensor is an effectivemethod for Hg²⁺ sensing in living cellimaging.

A mild and efficient procedure for the aza-Michael addition of amines to acrylates by using lipases as catalysts is reported. Various lipases, mono- and bifunctional amines, alkyl acrylates, and reaction parameters were studied. Under the optimal conditions, Rhizomucor miehei lipase showed high selectivity. It catalyzed the formation of the Michael monoadduct as the only product in high yield and purity. Moreover, when diamines were used as nucleophiles, the lipase catalyzed the addition of only one of the two amino groups, showing in this case high substrate specificity. This promiscuous and highly selective behavior displayed by Rhizomucor miehei lipase allowed us to obtain 22 N-substituted β-amino esters, 15 of them being new products.

A mild and efficient enzymatic method for the aza-Michael addition of mono- and bifunctional amines to acrylates was developed. The high substrate specificity showed by Rhizomucor miehei lipase as the catalyst for this reaction was a key feature for obtaining various N-substituted β-amino esters in high yield and purity.

Bromo-substituted Hunter/Vögtle-type tetralactam macrocycles (TLMs) represent key intermediates for the attachment of terpyridyl and phenanthroline metal binding sites through cross-coupling reactions. From these monovalent precursors, metal complexes can easily be obtained that present the macrocycles in a multivalent fashion. Depending on the nature of the metal ion, the properties of the complexes can be tuned with respect to valency (e.g., phen-TLM + Cu^I: divalent, phen-TLM + Fe^II: trivalent) and lability against TLM ligand exchange (e.g., Cu^I: slow, but reversible exchange, Ru^IICl₂: kinetically inert).

Hunter/Vögtle-type tetralactam macrocycles are equipped with metal coordination sites through Suzuki cross-coupling. The same bromo-substituted macrocycle can be used irrespective of the individual binding site, which provides versatile access to different complexes. The complexes represent multivalent hosts that are potentially useful for the formation of multiply interlocked molecules.

Asymmetric conjugate additions (1,4-additions) of aryl-Grignard reagents to cyclohex-2-enone, currently a more or less unsolved challenge, were investigated. For this purpose, a small library of phenol-derived chiral phosphane-phosphite ligands containing TADDOL- or BINOL-based phosphite moieties was evaluated. These ligands are easily prepared by a short modular scheme previously developed in this laboratory. Two particularly powerful ligands (4a and 4b, both TADDOL-derived and each possessing a bulky tert-butyl substituent ortho to the phosphite group) were identified. Conditions were optimized with use of the addition of (4-methoxyphenyl)magnesium bromide to cyclohexenone as a standard reaction system. Under optimized conditions [CuBr·SMe₂ (4 mol-%), ligand 4a (6 mol-%), 2-methyl-THF, –78 °C, slow addition of Grignard reagent] the 1,4-product was obtained with high enantioselectivity (up to 95 % ee) and good regioselectivity (r.r. = 90:10). The scope of the method was probed with different aryl-Grignard reagents. It was found that reagents with electron-donating substituents in meta- or para-positions performed particularly well, whereas the presence of F or CF₃ substituents led to decreased ee values. Only ortho-substituted aryl-Grignard reagents did not give rise to useful results. A series of phosphane-phosphite ligands were also tested in the Rh-catalyzed 1,4-addition of phenylboronic acid to cyclohexenone, but enantioselectivities did not exceed 70 % ee in this case.

The difficult task of employing aryl-Grignard reagents in Cu-catalyzed enantioselective 1,4 addition reactions was achieved with the assistance of readily accessible chiral modular P,P ligands. High enantioselectivities were obtained in a number of synthetically relevant cases.

The facial selectivity in the Diels–Alder reactions via endo transition states of the plane-nonsymmetric dienophiles spiro[bicyclo[2.2.2]octane-2,1′-[3]cyclopentene]-2′,5′-dione (6) and spiro[bicyclo[2.2.1]heptane-2,1′-[3]cyclopentene]-2′,5′-dione (7) has been found to be very similar to the facial selectivity of reactions of cyclopentadienes fused to bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane (4 and 5). This is strong evidence for steric control in their facial selectivities. Density functional computations involving the reactions of these compounds, as well as a series of conformationally locked model addends (26a–c and 27a–c), revealed geometrical and energetic properties that confirmed that the facial selectivity is governed by steric effects. Steric interactions appeared to be the reason for the low endo/exo selectivity of dienophiles 6, 7, 2,2-dimethylcyclopent-4-ene-1,3-dione (20), and spiro[5.4]dec-8-ene-7,10-dione (23).

Structurally similar plane-nonsymmetric dienes and dienophiles have been found to have similar facial selectivities in their Diels–Alder reactions. This indicates steric rather than electronic stereochemical control. The computed facial selectivities for these reactions are in accord with experiment and computational data for simple model compounds corroborated steric control.

The syntheses of azido-1,2,4-triazoles 1–5 were carried out from triaminoguanidine hydrochloride and a carboxylic acid (formic, acetic, 2,2,2-trifluoroacetic, 2-benzylacetic, monochloroacetic acid) by a three-step synthetic route and were analyzed by accelerating rate calorimetry (ARC). The thermal decomposition of 1–5 was studied theoretically by using CHETAH and T1 software, and experimentally by using DSC to obtain kinetic data. Numerical modelling and mass spectrometry were also performed to estimate the nature of the intrinsic molecular reactivity of 1–5 and the possible early stages of a self-heating process. Complete optimization by using HF, B3LYP and MP2(full) methods at the 6-31G* level were performed on significant tautomeric forms of the azido-triazoles to confirm the electronic structures that were obtained by EI-MS.

We have synthesized azido-1,2,4-triazoles 1–5 from triaminoguanidine hydrochloride and a carboxylic acid by a three-step route. The procedure has been optimized from a “green agreeability” point of view. The thermal decomposition of 1–5 has been investigated theoretically by using predictive software, and experimentally by using differential scanning calorimetry.

Chiral perhydrobenzoxazines derived from (–)-8-aminomenthol and containing a 1,6-enyne moiety participate in intramolecular diastereoselective Pauson–Khand reactions with diastereoselection that depends on the nature of the starting compounds. 3-Propargyl-2-vinyl-substituted perhydrobenzoxazines yielded the cyclization products with low diastereoselectivity except for compounds where the double bond was 1,2-disubstituted. Regioisomeric perhydrobenzoxazines with the acetylenic bond at C-2 and an allyl substituent at the nitrogen atom gave much better stereochemical discrimination.

Chiral perhydrobenzoxazines derived from (–)-8-aminomenthol and containing a 1,6-enyne moiety participate in intramolecular diastereoselective Pauson–Khand reactions leading to cyclization products with moderate to good diastereoselectivity. The diastereoselection depends on both the substitution pattern of the double bond and the regiochemistry of the starting perhydrobenzoxazines

Studies towards the biomimetic synthesis of mycaperoxide B (1) are described. We have established the synthesis of four diastereoisomers of mycaperoxide B methyl ester (1a) by employing a Michael addition across an α,β-unsaturated ester precursor 2 as the key step. This result strongly suggestsstereocontrol in the addition of the hydroperoxide functionality to the E double bond and discloses the importance of choosing the correct geometry of the α,β-unsaturated double bond when attempting to synthesise mycaperoxide B. Four diastereoisomeric tetrahydrofurans derived from an intramolecular rearrangement of the 1,2-dioxolane enolate 12 were also isolated and characterised.

Four diastereoisomers of mycaperoxide B methyl ester (1a) have been synthesised by employing a Michael addition across an α,β-unsaturated ester precursor 2 as the key step. The stereochemistry observed suggests stereocontrol in this step and discloses the importance of choosing the correct geometry of the α,β-unsaturated double bond when attempting to synthesise mycaperoxide B (1).

The onnamides, pederin, and psymberin have each attracted attention because of their potent biological activity and interesting structural features. A short (eight steps) and efficient stereocontrolled route to the central tetrahydropyran ring in these natural products has been developed from (S)-malic acid. The key sequence involves the conversion of a γ-lactone to a tetrahydropyran structure triggered by the addition of ammonia.

A new approach to a tetrahydropyransubunit found in pederin, psymberin, and onnamides D–F is presented. The key sequence involves a ring expansion from a γ-lactone to a tetrahydropyran ring. Conditions for achieving both the kinetic and thermodynamic cyclization reactions have been developed, and models to explain the course of each are presented.

Modular diboronic acid receptors R-1 and S-1 were synthesized and found to be selective fluorescent chemosensors for saccharides. The fluorescence intensity of R-1 and S-1 increased on addition of saccharides due to the formation of intramolecular 1:1 cyclic complexes. In general, R-1 has higher binding constants and produces a higher fluorescent response with saccharides than S-1.

The fluorescence intensity of receptors R-1 and S-1 increased on addition of saccharides due to the formation of intramolecular 1:1 cyclic complexes. In general, R-1 has higher binding constants and produces a higher fluorescent response with saccharides than S-1.

Indolylnitroethanes and their derivatives are key intermediates to many bioactive structures. Most approaches to access chiral indolylnitroethanes involve organocatalyzed or metal-catalyzed asymmetric Friedel–Crafts reaction of indoles with nitroalkenes. We have developed an efficient approach to optically pure α-aryl-3-indolylnitroethanes through rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to indolylnitroalkenes. Excellent yields (up to 99 %) and enantiomeric excesses (up to 99 % ee) of chiral indolylnitroethanes were achieved under mild conditions.

An efficient approach to optically pure α-aryl-3-indolylnitroethanes through rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to indolylnitroalkenes was developed. Excellent yields (up to 99 %) and enantiomeric excesses (up to 99 %) were achieved under mild conditions.

A variety of new glycosylglycerol derivatives have been prepared by stereoselective dihydroxylation of a range of alkenyl β-D-hexopyanosides under Donohoe's conditions. We have studied the relationship between the diastereoisomeric excess and the structural features of the precursor (sugar and alkenyl moieties). The stereochemical yields demonstrated that the presence of a hydrogen-bond donor group (OH, NHAc) at the 2-position of the sugar moiety is required to obtain high levels of stereofacial discrimination. New 1-O-acyl-3-O-β-D-glycosyl-sn-glycerol analogues were obtained by functionalisation of the primary hydroxy group with a fatty acid. Preliminary cytotoxic activity assays of both glycosylglycerol and glycoglycerolipid analogues are also presented.

An efficient asymmetric dihydroxylation reaction of alkenyl β-D-hexopyranoside derivatives is described. New glycosylglycerol and glycoglycerolipid analogues have been synthesised by this methodology. Preliminary cytotoxic activity assays are presented.

Putaminoxin E, a natural nonanolide, and its C-9 epimer were synthesized for the first time starting from pentane-1,5-diol and butyraldehyde. The synthetic sequences involve Maruoka asymmetric allylation, Sharpless kinetic resolution, and ring-closing metathesis as the key steps. The cytotoxic and antimicrobial activities of these compounds were evaluated.

Putaminoxin E, a natural nonanolide, and its C-9 epimer were synthesized for the first time starting from pentane-1,5-diol and butyraldehyde.