European Journal of Organic Chemistry

The cover picture shows the coincidence of our entry into genetic chemistry and the genetic chemistry laboratory at CSIR-IICT. In this article, we have achieved the first total synthesis and structure confirmation of Cryptocaryol A, a new structural class of programmed cell death 4 (Pdcd4) stablizing natural product, by combining Maruoka asymmetric allylation, Reetz chelation-controlled 1,3-induced allylation, Bartlett–Smith iterative iodocyclization and ring-closing metathesis reactions. Details are discussed in the article by D. S. Reddy and D. K. Mohapatra on page p. 1051 ff.

The direct addition of O–H bonds to C=C bonds is an attractive way to synthesise alcohols, ethers and esters. This microreview addresses the use of group 11 metals in promoting these transformations. The involvement of Brønsted acid catalysis in some of these reactions is highlighted.

The first synthesis of BINOL-fused maleimides has been achieved. This type of new chiral scaffold can be easily obtained from various BINOL analogues and 2,3-dihalomaleimide derivatives under basic conditions and can be easily functionalized on the BINOL moiety. BINOL-fused maleimides are promising new classes of chiral organocatalysts and ligands.

The results of catalyst-free, decarboxylative Mannich reactions of enolizable imines are described. When the reaction is performed with imines obtained from chiral aldehydes, access to optically pure Mannich products is possible.

Maruoka asymmetric allylation, chelation-controlled 1,3-induced allylation, iterative iodocyclization and ring-closing metathesis reactions were used sequentially to achieve the first total synthesis and structure confirmation of cryptocaryol A.

Diphosphonylated diazaheterocyclic compounds are synthesized in a one-step reaction from naphthyridines and phenanthrolines by using dimethyl trimethylsilyl phosphite (DMPTMS). The substrate has a profound influence on the product yields for the tandem 1,4–1,2-addition. The product yields are theoretically rationalized by evaluating proton affinities, aromaticities and free energies of activation.

Inhibitors of the kinase E. coli IspE, an enzyme involved in the synthesis of isoprenoids and a model for IspE from P. falciparum, were developed. Decorated imidazole- and benzimidazole-based scaffolds address the cytidine-binding pocket, the hydrophobic sub-pocket, and the phosphate-binding region in the active site. In vitro activities in the micromolar IC₅₀-range were measured.

Both binding sites of the ditopic molecular tweezers bind arginine–glycine–aspartate (RGD) loops (K_d ≈ 20 μM in buffer), but not by inclusion inside the cavity of the tweezers.

δ,δ-Dimethylproline derivatives have been efficiently synthesized by employing a β-amino acid as the starting material. The methodology is amenable to the preparation of other δ,δ-disubstituted prolines.

Racemic total syntheses of the four title spirocyclic oxindole alkaloids are reported starting from 4-hydroxytryptamine. The key steps were a base-mediated Mannich spirocyclisation to form the C-ring, and a Pd-catalysed cyclisation of a keto ester enolate onto an allylic carbonate to form the D-ring. Thus, convenient syntheses of the alkaloids were achieved, for three of them for the first time.

Microwave-assisted direct arylation reactions were successfully employed in the synthesis of azafluoranthene alkaloids for the first time. Rufescine and triclisine were efficiently prepared using this method. The method has broader applicability in the synthesis of structurally similar tetracyclic isoquinoline alkaloids.

The preparation of four new analogues of the natural pyrone pironetin, known to bind to α-tubulin, is described. The C₉ side-chain of pironetin has been replaced in one analogue by a 4-phenylbutyl chain and in the other three analogues by C₁₃ or C₁₆ aliphatic chains, all of them bearing two stereogenic centres. Their cytotoxic activities and interactions with tubulin have been investigated.

Two strategies have been considered for the stereoselective synthesis of nhatrangins A and B. A sequence involving diastereoselective alkylation and aldolization employing ephedrine derivatives as chiral auxiliaries was the most efficient approach to deliver a key aldehyde framework.

The superacidic generation of vinyl cations from aryl(trifluoromethyl)acetylenes was effectively performed using triflic and fluorosulfonic acids under mild conditions. These vinyl cations underwent a subsequent reaction with various arenes to give the corresponding alkenes and alcohols in high yields. The formation of these trifluoroethylated carbocations was confirmed by NMR spectroscopy.

Typical hexadecavalent glyco-POSS prepared by thiol-yne coupling. A measured IC₅₀ of 2 nM was found by ELLA with tetrameric wheat germ agglutinin (WGA).

The oxidative coupling of substituted phenyl carbamates and acetates with alkenes in the presence of [RuCl₂(p-cymene)]₂, AgSbF₆, and Cu(OAc)₂·H₂O provided substituted alkene derivatives in a highly regio- and stereoselective manner. In the presence of either LiOH·H₂O or K₂CO₃, ortho-alkenylated phenyl carbamates and acetates were converted into the corresponding phenols.

C8-NAc-Arylamine adducts of 2′-deoxyguanosine with various aromatic amines were synthesized by using cross-coupling reactions and converted into 3′-phosphoramidites. Site-specific damaged NarI-, EcoRI- and 20mer-oligonucleotides were prepared by automated DNA-synthesis. Biophysical properties, restriction endonuclease studies and DNA-polymerase assays were performed.