organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

(±)-Asarinin

aDepartment of Chemistry, HNB Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India, bGraduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan, cInstitut für Organische Chemie, Technische Universität Braunschweig, Postfach 3329, 38023 Braunschweig, Germany, and dInstitut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Postfach 3329, 38023 Braunschweig, Germany
*Correspondence e-mail: p.jones@tu-bs.de

(Received 30 November 2012; accepted 3 December 2012; online 13 December 2012)

Asarinin, C20H18O6, was isolated as a racemate from the shrub Zanthoxylum alatum. Both forms of the enantio­merically pure substance, (+)- and (−)-asarinin, have been the subject of a total of five previous structure determinations that are essentially identical except for the absolute stereochemistry. However, there seems to be some confusion in the literature concerning these structure determinations of asarinin and also those of its stereoisomer sesamin. The mol­ecular structure of racemic asarinin differs from that of the pure enantio­mers in the orientation of one ring system. In the packing of the racemate, mol­ecules are linked by C—H⋯O inter­actions to form ribbons parallel to [101].

Comment

Zanthoxylum alatum (Rutaceae) is an evergreen shrub growing at up to 2000 m above sea level in the hot valleys of the Himalayan region. It has a variety of applications in traditional medicine, including anthelmintic and painkilling activities. Extracts of leaves are also used as disinfectants and against scabies and house flies. The chemical constituents of the plant's stem wood (Ishii, Hosoya, Ishikawa & Haginiwa, 1974[Ishii, H., Hosoya, K., Ishikawa, T. & Haginiwa, J. (1974). Yakugaku Zasshi, 94, 309-321.]), root wood (Ishii, Hosoya, Ishikawa, Hueda & Haginiwa 1974[Ishii, H., Hosoya, K., Ishikawa, T., Hueda, E. & Haginiwa, J. (1974). Yakugaku Zasshi, 94, 322-331.]), and stem and root bark (Ishii et al., 1977[Ishii, H., Ishikawa, T. & Haginiwa, J. (1977). Yakugaku Zasshi, 97, 890-900.]), have been reported, and include coumarins, furoquinoline alkaloids, benzo[c]phenanthridines, lignans, steroids and terpenoids. However, studies of the bioactivity of these compounds from Z. alatum have not been reported to date.

A chloro­form extract of the leaves of Z. alatum showed anti­feedant activity against the larvae of Spodoptera litoralis, and also antiproliferative activity against multiresistant cell lines. Asarinin was identified as one of the major constituents of the chloro­form extract. The asarinin sample obtained from the plant crystallized as a racemic compound, although a positive [α]D20 of 43° was observed. Pure (+)-asarinin has an [α]D20 of about 120° (Takahashi & Nakagawa, 1966[Takahashi, K. & Nakagawa, T. (1966). Chem. Pharm. Bull. 14, 641-647.]). The observed [α]D20 implies that the two enantio­mers occur in the plant in different proportions and that racemic asarinin crystallizes first. To the best of our knowledge, the structure of racemic asarinin, the title compound, (I)[link], has not been reported previously, so we present it here.

[Scheme 1]

The furofuran asarinin, (I)[link], has four asymmetric centres (labelled C1, C2, C5 and C6 in this study, with relative configurations 1R, 2R, 5R and 6S). The (−)-enantio­mer of asarinin seems to be the prevalent form in nature (as judged from citations in Chemical Abstracts, but we have not counted these exactly). The naturally occurring stereoisomers epiasarinin (inverted at C6) and sesamin (inverted at C5) are also known; for a brief overview, see Aldous et al. (2006[Aldous, D. J., Batsanov, A. S., Yufit, D. S., Dalençon, A. J., Dutton, W. M. & Steel, P. G. (2006). Org. Biomol. Chem. 4, 2912-2927.]). A search of the Cambridge Structural Database (CSD, Version 5.33; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]; see also Table 1[link]) reveals that several crystal structures have been reported, but in some cases confusion may have arisen. For epiasarinin, the structure of the synthetic racemate was determined by Aldous et al. (2006[Aldous, D. J., Batsanov, A. S., Yufit, D. S., Dalençon, A. J., Dutton, W. M. & Steel, P. G. (2006). Org. Biomol. Chem. 4, 2912-2927.]; we adopt an analogous atom-numering scheme for the racemate of asarinin), but no enantio­merically pure structure has yet been determined. Three closely similar structures of sesamin have been reported, by Baures et al. (1992[Baures, P. W., Miski, M. & Eggleston, D. S. (1992). Acta Cryst. C48, 574-576.]), Hsieh et al. (2005[Hsieh, T.-J., Lu, L.-H. & Su, C.-C. (2005). Biophys. Chem. 114, 13-20.]) and Li et al. (2005[Li, C.-Y., Chow, T. J. & Wu, T.-S. (2005). J. Nat. Prod. 68, 1622-1624.]). However, the sign of the optical rotation is given as (+) by Hsieh et al. (2005[Hsieh, T.-J., Lu, L.-H. & Su, C.-C. (2005). Biophys. Chem. 114, 13-20.]), as (−) by Li et al. (2005[Li, C.-Y., Chow, T. J. & Wu, T.-S. (2005). J. Nat. Prod. 68, 1622-1624.]) and is not quoted by Baures et al. (1992[Baures, P. W., Miski, M. & Eggleston, D. S. (1992). Acta Cryst. C48, 574-576.]). In no case could the absolute configuration be determined crystallographically because the anomalous dispersion effects were insignificant. For asarinin, there are no fewer than five reported structures in the CSD, but they are given three different families of refcodes. Again, the unit cells are closely similar. The references are: Li et al. (2005[Li, C.-Y., Chow, T. J. & Wu, T.-S. (2005). J. Nat. Prod. 68, 1622-1624.]), optical rotation (−) (the space group is reported as P1 with two independent mol­ecules, but the cell constants are close to those of the other determinations, and inspection of the structure suggests that the true space group is indeed P21); Macías et al. (1992[Macías, F. A., Zubía, E., Quijano, L., Fronczek, F. R. & Fischer, N. H. (1992). Acta Cryst. C48, 2240-2244.]), (−); Parmar et al. (1998[Parmar, V. S. et al. (1998). Phytochemistry, 49, 1069-1078.]), optical rotation given as (−) in the CSD but (+) in the publication; Il'in et al. (1994[Il'in, S. G., Artyukow, A. A., Kochergina, T. Yu., Lindeman, S. V. & Struchkov, Yu. T. (1994). Chem. Nat. Compd, 30, 567-568.]), (−); and Mata et al. (1998[Mata, R., Macías, M. L., Rojas, I. S., Lotina-Hennsen, B., Toscano, R. A. & Anaya, A. L. (1998). Phytochemistry, 49, 441-449.]). For this last determination, the absolute configuration was determined crystallo­graph­i­cally by exploiting the stronger anomalous dispersion effects of copper radiation, but the optical rotation was not given, so frustratingly no correlation has been established between the absolute configuration and the optical rotation for this compound despite five determinations of its crystal structure. The determination of the absolute configuration of (+)-asarinin by the `optical shift rule' (Freudenberg & Sidhu, 1961[Freudenberg, K. & Sidhu, G. S. (1961). Chem. Ber. 94, 851-862.]) has not been universally accepted [see e.g. Gunatilaka et al. (1982[Gunatilaka, A. A. L., De Silva, A. M. Y. J., Subramaniam, S. & Tillekeratne, L. M. V. (1982). Phytochemistry, 21, 2719-2723.])].

The mol­ecule of asarinin in the racemate is shown in Fig. 1[link]. Mol­ecular dimensions may be regarded as normal. A least-squares fit to the (inverted) mol­ecule of VUKBUY gives an r.m.s. deviation of 0.08 Å for all atoms except C21–O28, since this ring is oriented differently with respect to the furofuran system [torsion angle O7—C6—C20—C21 = −2.96 (14)°, cf. −30.9° for the corresponding angle of VUKBUY].

In the packing pattern of (I)[link], four short inter­molecular H⋯O contacts might be inter­preted as `weak' hydrogen bonds (Table 2[link]). The shortest two of these link the mol­ecules via inversion centres to form mol­ecular ribbons parallel to [101] (Fig. 2[link]).

[Figure 1]
Figure 1
The mol­ecular structure of (I)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. This enantio­mer has the configurations S, S, S and R at atoms C1, C2, C5 and C6, respectively. The crystal structure, however, contains both entantiomers.
[Figure 2]
Figure 2
A packing diagram for (I)[link], viewed perpendicular to (11[\overline{1}]). Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonds have been omitted for clarity.

Experimental

The plant material was collected from Rudraprayag Uttarakhand, India (29° 43′ 19′′ North, 78° 31′ 6′′ East). The plant was identified by the Botanical Survey of India, Dehradun, and a voucher specimen has been deposited (BSD Accession No. 112749).

The shade-dried leaves of Z. alatum were extracted exhaustively with 90% ethanol at room temperature. The combined ethanolic extracts were concentrated under reduced pressure at 723 K to a dark viscous mass. Water was added (10% by weight) and the mixture was extracted with hexane (3 × 500 ml). The combined organic phases were washed with water and dried by evaporation of the solvent under reduced pressure to yield 35.4 g of solid residue. The water phase was extracted again, this time with chloro­form (3 × 500 ml), and the combined chloro­form phases were washed with water and dried with MgSO4. Evaporation of the solvent under reduced pressure yielded another 6.5 g of solid residue. The extracts were tested against the polyphagous pest Spodoptera litoralis for anti­feedant activity and against K526/Adr cells for cytotoxic activity.

The biologically active chloro­form extract was subjected to column chromatography over silica gel (60–120 mesh) using chloro­form–methanol of increasing polarity. Eluates were collected in fractions of 50 ml and each was evaporated to dryness under reduced pressure. Fractions exhibiting similar thin-layer chromatography behaviour were combined. Three fractions collected upon elution with chloro­form–methanol, viz. A (solvent ratios 39–46:100), B (50–68:100) and C (70–100:100), afforded solid material after evaporation of the solvents. Fraction B was separated again by chromatography with chloro­form–methanol (9:1 v/v) to yield asarinine (12 mg).

To obtain single crystals of asarinin, the compound (1 mg) was dissolved in pentane (2 ml). The resulting solution was concentrated by evaporation in a slightly permeable screw-capped vial. Single crystals of (I)[link] in the form of colourless laths formed over a period of 96 h.

Crystal data
  • C20H18O6

  • Mr = 354.34

  • Triclinic, [P \overline 1]

  • a = 6.5002 (4) Å

  • b = 10.8931 (7) Å

  • c = 11.8005 (8) Å

  • α = 103.793 (6)°

  • β = 102.111 (6)°

  • γ = 95.836 (6)°

  • V = 783.22 (9) Å3

  • Z = 2

  • Cu Kα radiation

  • μ = 0.93 mm−1

  • T = 100 K

  • 0.25 × 0.20 × 0.10 mm

Data collection
  • Oxford Xcalibur diffractometer with Nova source and Atlas detector

  • Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.]) Tmin = 0.770, Tmax = 1.000

  • 41535 measured reflections

  • 3254 independent reflections

  • 3200 reflections with I > 2σ(I)

  • Rint = 0.027

Refinement
  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 0.086

  • S = 1.05

  • 3254 reflections

  • 235 parameters

  • H-atom parameters constrained

  • Δρmax = 0.31 e Å−3

  • Δρmin = −0.21 e Å−3

Table 1
X-ray structure determinations of asarinin and its stereoisomers from the CSD (Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.])

CompoundReferenceCSD refcodeOptical rotationSpace groupNotes
Synthetic epiasarininAldous et al. (2006[Aldous, D. J., Batsanov, A. S., Yufit, D. S., Dalençon, A. J., Dutton, W. M. & Steel, P. G. (2006). Org. Biomol. Chem. 4, 2912-2927.])CERWOM(±)P21/n 
SesaminBaures et al. (1992[Baures, P. W., Miski, M. & Eggleston, D. S. (1992). Acta Cryst. C48, 574-576.])TAPWAINot givenP21 
SesaminHsieh et al. (2005[Hsieh, T.-J., Lu, L.-H. & Su, C.-C. (2005). Biophys. Chem. 114, 13-20.])TAPWAI01(+)P21a
SesaminLi et al. (2005[Li, C.-Y., Chow, T. J. & Wu, T.-S. (2005). J. Nat. Prod. 68, 1622-1624.])TAPWAI02(−)P21a
AsarininLi et al. (2005[Li, C.-Y., Chow, T. J. & Wu, T.-S. (2005). J. Nat. Prod. 68, 1622-1624.])MAKJIT(−)P1 (probably P21)b, e
AsarininMacías et al. (1992[Macías, F. A., Zubía, E., Quijano, L., Fronczek, F. R. & Fischer, N. H. (1992). Acta Cryst. C48, 2240-2244.])VUKBUY(−)P21b
AsarininParmar et al. (1998[Parmar, V. S. et al. (1998). Phytochemistry, 49, 1069-1078.])VUKBUY03(+)P21c
AsarininIl'in et al. (1994[Il'in, S. G., Artyukow, A. A., Kochergina, T. Yu., Lindeman, S. V. & Struchkov, Yu. T. (1994). Chem. Nat. Compd, 30, 567-568.])YODLEI(−)P21b
AsarininMata et al. (1998[Mata, R., Macías, M. L., Rojas, I. S., Lotina-Hennsen, B., Toscano, R. A. & Anaya, A. L. (1998). Phytochemistry, 49, 441-449.]))YODLEI01Not givenP21d
AsarininThis work (±)P[\overline{1}] 
Notes: (a) no coordinates were deposited; (b) no H-atom coordinates were deposited; (c) given in CSD as (−) (probably erroneous); (d) absolute configuration determined by anomalous dispersion; (e) given in CSD as `unknown solvate', but may be solvent-free.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯AD—HH⋯ADAD—H⋯A
C4—H4A⋯O17i0.992.413.3501 (14)159
C15—H15⋯O26ii0.952.453.3093 (14)151
C16—H16⋯O28iii0.952.673.5503 (14)154
C18—H18B⋯O28iv0.992.603.2600 (13)124
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) -x, -y+1, -z; (iii) -x+1, -y+1, -z; (iv) x-1, y+1, z+1.

H atoms were placed in calculated positions and refined using a riding model, with aromatic C—H = 0.95 Å, methyl­ene C—H = 0.99 Å and methine C—H = 1.00 Å, and with Uiso(H) = 1.2Ueq(C).

Data collection: CrysAlis PRO (Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: XP (Siemens, 1994[Siemens (1994). XP. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

Zanthoxylum alatum (Rutaceae) is an evergreen shrub growing at up to 2000 m above sea level in the hot valleys of the Himalayan region. It has a variety of applications in traditional medicine, including anthelmintic and painkilling activities. Extracts of leaves are also used as disinfectants and against scabies and house flies. The chemical constituents of the plant's stem wood (Ishii, Hosoya, Ishikawa & Haginiwa, 1974), root wood (Ishii, Hosoya, Ishikawa, Hueda & Haginiwa 1974), and stem and root bark (Ishii et al., 1977), have been reported, and include coumarins, furoquinoline alkaloids, benzo[c]phenanthridines, lignans, steroids and terpenoids. However, studies of the bioactivity of these compounds from Z. alatum have not been reported to date.

A chloroform extract of the leaves of Z. alatum showed antifeedant activity against the larvae of Spodoptera litoralis, and also anti-proliferative activity against multi-resistant cell lines. Asarinin was identified as one of the major constituents of the chloroform extract. The asarinin sample obtained from the plant crystallized as a racemic compound, although a positive [α]D20 of 43° was observed. Pure (+)-asarinin has an [α]D20 of about 120° (Takahashi & Nakagawa, 1966).The (-)-enantiomer of asarinin seems to be the prevalent form in nature (as judged from citations in Chemical Abstracts [Reference?], but we have not counted these exactly). The observed [α]D20 implies that the two enantiomers occur in the plant in different proportions and that racemic asarinin crystallizes first. To the best of our knowledge, the structure of racemic asarinin, the title compound, (I), has never been reported, so we present it here.

The furofuran asarinin, (I), has four asymmetric centres (numbered C1, C2, C5 and C6 in this study, with relative configurations 1R, 2R, 5R and 6S). The naturally occurring stereoisomers epiasarinin (inverted at C6) and sesamin (inverted at C5) are also known; for a brief overview, see Aldous et al. (2006). A search of the Cambridge Structural Database (CSD, Version?; Allen, 2002; see also Table 2) reveals that several crystal structures have been reported, but in some cases confusion may have arisen. For epiasarinin, the structure of the synthetic racemate was determined by Aldous et al. (2006; we adopt an analogous atom-numering scheme for the racemate of asarinin), but no enantiomerically pure structure has yet been determined. Three closely similar structures of sesamin have been reported, by Baures et al. (1992), Hsieh et al. (2005) and Li et al. (2005). However, the sign of the optical rotation is given as (+) by Hsieh et al. (2005), as (-) by Li et al. (2005) and is not quoted by Baures et al. (1992). In no case could the absolute configuration be determined crystallographically because the anomalous dispersion effects were insignificant. For asarinin, there are no fewer than five reported structures in the CSD, but they are given three different families of refcodes. Again, the cells are closely similar. The references are: Li et al. (2005), optical rotation (-) [the space group is reported as P1 with two independent molecules, but the cell constants are close to those of the other determinations, and inspection of the structure suggests that the true space group is indeed P21]; Macías et al. [1992, (-)]; Parmar et al. [1998; optical rotation given as (-) in the database but (+) in the publication]; Il'in et al. [1994, (-)]; and Mata et al. (1998). For this last determination, the absolute configuration was determined crystallographically by exploiting the stronger anomalous dispersion effects of copper radiation, but the optical rotation was not given, so frustratingly no correlation has been established between the absolute configuration and the optical rotation for this compound despite five determinations of its crystal structure. The determination of the absolute configuration of (+)-asarinin by the `optical shift rule' (Freudenberg & Sidhu, 1961) has not been universally accepted [see e.g. Gunatilaka et al. (1982)].

The molecule of asarinin in the racemate is shown in Fig. 1. Molecular dimensions may be regarded as normal. A least-squares fit to the (inverted) molecule of VUKBUY gives an r.m.s. deviation of 0.08 Å for all atoms except C21–O28, since this ring is differently oriented with respect to the furofuran system [torsion angle O7—C6—C20—C21 = -3.0 (1)°, cf. -30.9° for the corresponding angle of VUKBUY].

In the packing pattern of (I), four short intramolecular H···O contacts might be interpreted as `weak' hydrogen bonds (Table 1). The two shortest of these link the molecules via inversion centres to form molecular ribbons parallel to [101] (Fig. 2).

Related literature top

For related literature, see: Aldous et al. (2006); Allen (2002); Baures et al. (1992); Freudenberg & Sidhu (1961); Gunatilaka et al. (1982); Hsieh et al. (2005); Ishii et al. (1977); Ishii, Hosoya, Ishikawa & Haginiwa (1974); Ishii, Hosoya, Ishikawa, Hueda & Haginiwa (1974); Li et al. (2005); Mata et al. (1998); Takahashi & Nakagawa (1966).

Experimental top

The plant material was collected from Rudraprayag Uttarakhand, India (290 43' 19'' North, 780 31' 6'' East). The plant was identified by the Botanical Survey of India, Dehradun, and a voucher specimen has been deposited (BSD Accession No. 112749).

The shade-dried leaves of Z. alatum were exhaustively extracted with 90% ethanol at room temperature. The combined ethanolic extracts were concentrated under reduced pressure at 723 K to a dark viscous mass. Water was added (10% by weight) and the mixture was extracted with hexane (3 × 500 ml). The combined organic phases were washed with water and dried by evaporation of the solvent under reduced pressure to yield 35.4 g of solid residue. The water phase was again extracted, this time with chloroform (3 × 500 ml), and the combined chloroform phases were washed with water and dried with MgSO4. Evaporation of the solvent under reduced pressure yielded another 6.5 g of solid residue. The extracts were tested against the polyphagous pest Spodoptera litoralis for antifeedant activity and against K526/Adr cells for cytotoxic activity.

The biologically active chloroform extract was subjected to column chromatography over silica gel (60–120 mesh) using chloroform–methanol of increasing polarity [Range of ratios?]. Eluates were collected in fractions of 50 ml and each was evaporated to dryness under reduced pressure. Fractions exhibiting similar thin-layer chromatography behaviour were combined. Three fractions collected upon elution with chloroform–methanol, Fr A (solvent ratios 39–46:100), Fr B (50–68:100) and Fr C (70–100:100), afforded solid material after evaporation of the solvents. Fraction B was again separated by chromatography with chloroform–methanol (9:1 v/v) to yield asarinine (12 mg).

To obtain single crystals of asarinin, the compound (1 mg) was dissolved in pentane (2 ml). The resulting solution was concentrated by evaporation in a slightly permeable screw-capped vial. Single crystals of (I) in the form of colourless laths [Tablet in CIF tables - please clarify] formed over a period of 96 h.

Refinement top

H atoms were placed in calculated positions and refined using a riding model, with C—Harom = 0.95, C—Hmethylene = 0.99 and C—Hmethine = 1.00 Å, and with Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP (Siemens, 1994); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
Fig. 1. The molecular structure of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. This enantiomer has the configurations S, S, S and R at C1, C2, C5 and C6, respectively.

Fig. 2. A packing diagram for (I), viewed perpendicular to (111). Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonds have been omitted for clarity.
(1RS,3aRS,4SS,6aRS)-1,4-bis(benzo[d][1,3]dioxol-5-yl)hexahydrofuro[3,4-c]furan top
Crystal data top
C20H18O6Z = 2
Mr = 354.34F(000) = 372
Triclinic, P1Dx = 1.503 Mg m3
a = 6.5002 (4) ÅCu Kα radiation, λ = 1.54184 Å
b = 10.8931 (7) ÅCell parameters from 33759 reflections
c = 11.8005 (8) Åθ = 4.0–75.7°
α = 103.793 (6)°µ = 0.93 mm1
β = 102.111 (6)°T = 100 K
γ = 95.836 (6)°Tablet, colourless
V = 783.22 (9) Å30.25 × 0.20 × 0.10 mm
Data collection top
Oxford Xcalibur
diffractometer with Nova source and Atlas detector
3254 independent reflections
Radiation source: Nova (Cu) X-ray Source3200 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.027
Detector resolution: 10.3543 pixels mm-1θmax = 75.9°, θmin = 4.0°
ω scansh = 88
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2012)
k = 1313
Tmin = 0.770, Tmax = 1.000l = 1414
41535 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.086H-atom parameters constrained
S = 1.05 w = 1/[σ2(Fo2) + (0.0399P)2 + 0.3692P]
where P = (Fo2 + 2Fc2)/3
3254 reflections(Δ/σ)max = 0.002
235 parametersΔρmax = 0.31 e Å3
0 restraintsΔρmin = 0.21 e Å3
Crystal data top
C20H18O6γ = 95.836 (6)°
Mr = 354.34V = 783.22 (9) Å3
Triclinic, P1Z = 2
a = 6.5002 (4) ÅCu Kα radiation
b = 10.8931 (7) ŵ = 0.93 mm1
c = 11.8005 (8) ÅT = 100 K
α = 103.793 (6)°0.25 × 0.20 × 0.10 mm
β = 102.111 (6)°
Data collection top
Oxford Xcalibur
diffractometer with Nova source and Atlas detector
3254 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2012)
3200 reflections with I > 2σ(I)
Tmin = 0.770, Tmax = 1.000Rint = 0.027
41535 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.086H-atom parameters constrained
S = 1.05Δρmax = 0.31 e Å3
3254 reflectionsΔρmin = 0.21 e Å3
235 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.56365 (12)0.57923 (7)0.36599 (7)0.01883 (18)
C10.35735 (17)0.57985 (10)0.17724 (9)0.0162 (2)
H10.34510.63510.12030.019*
C20.44275 (17)0.66030 (10)0.30911 (9)0.0163 (2)
H20.54290.73690.31030.020*
C40.68497 (18)0.52866 (11)0.28201 (10)0.0188 (2)
H4A0.74300.45300.30010.023*
H4B0.80470.59410.28490.023*
C50.52740 (16)0.49134 (10)0.15893 (9)0.0155 (2)
H50.59750.50550.09430.019*
C60.39849 (17)0.35556 (10)0.12489 (10)0.0182 (2)
H60.40230.32880.20060.022*
O70.18453 (13)0.36849 (8)0.07580 (8)0.0261 (2)
C80.15160 (18)0.48480 (11)0.15241 (10)0.0211 (2)
H8A0.12590.47040.22840.025*
H8B0.02780.51740.11190.025*
C110.27919 (17)0.70606 (10)0.37603 (9)0.0157 (2)
C120.22906 (17)0.65162 (10)0.46569 (9)0.0156 (2)
H120.29570.58380.48680.019*
C130.07832 (17)0.70191 (10)0.52113 (9)0.0157 (2)
C140.02119 (17)0.80026 (10)0.49173 (9)0.0164 (2)
C150.02389 (18)0.85422 (10)0.40406 (10)0.0188 (2)
H150.04540.92130.38340.023*
C160.17765 (18)0.80495 (10)0.34669 (10)0.0185 (2)
H160.21390.84010.28580.022*
O170.00734 (13)0.66835 (8)0.61359 (7)0.02143 (19)
C180.15893 (18)0.74211 (11)0.63322 (10)0.0210 (2)
H18A0.29830.68510.60880.025*
H18B0.13270.78730.71950.025*
O190.16073 (13)0.83282 (8)0.56301 (7)0.02070 (18)
C200.47343 (17)0.25291 (10)0.03896 (10)0.0171 (2)
C210.33643 (18)0.18013 (10)0.07008 (10)0.0187 (2)
H210.19380.19420.09420.022*
C220.41905 (18)0.08719 (10)0.14047 (10)0.0186 (2)
C230.62636 (18)0.06578 (10)0.10748 (10)0.0174 (2)
C240.76342 (18)0.13606 (11)0.00203 (10)0.0205 (2)
H240.90620.12160.02030.025*
C250.68222 (18)0.23060 (11)0.07133 (10)0.0205 (2)
H250.77250.28110.14550.025*
O260.31790 (14)0.00396 (9)0.25045 (8)0.0294 (2)
C270.46989 (19)0.07388 (12)0.28494 (11)0.0248 (3)
H27A0.49110.06720.36400.030*
H27B0.41770.16460.29190.030*
O280.66683 (13)0.03090 (8)0.19555 (7)0.02196 (19)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0194 (4)0.0244 (4)0.0134 (4)0.0100 (3)0.0052 (3)0.0025 (3)
C10.0169 (5)0.0192 (5)0.0137 (5)0.0061 (4)0.0058 (4)0.0037 (4)
C20.0169 (5)0.0167 (5)0.0153 (5)0.0041 (4)0.0050 (4)0.0025 (4)
C40.0171 (5)0.0227 (5)0.0155 (5)0.0075 (4)0.0052 (4)0.0002 (4)
C50.0151 (5)0.0178 (5)0.0140 (5)0.0040 (4)0.0056 (4)0.0024 (4)
C60.0165 (5)0.0189 (5)0.0186 (5)0.0029 (4)0.0071 (4)0.0016 (4)
O70.0147 (4)0.0261 (4)0.0287 (4)0.0027 (3)0.0060 (3)0.0098 (3)
C80.0163 (5)0.0229 (6)0.0206 (5)0.0047 (4)0.0059 (4)0.0031 (4)
C110.0157 (5)0.0156 (5)0.0132 (5)0.0023 (4)0.0036 (4)0.0007 (4)
C120.0160 (5)0.0153 (5)0.0143 (5)0.0047 (4)0.0026 (4)0.0014 (4)
C130.0169 (5)0.0170 (5)0.0119 (5)0.0024 (4)0.0034 (4)0.0019 (4)
C140.0156 (5)0.0164 (5)0.0157 (5)0.0047 (4)0.0049 (4)0.0005 (4)
C150.0214 (5)0.0164 (5)0.0191 (5)0.0071 (4)0.0049 (4)0.0038 (4)
C160.0224 (5)0.0176 (5)0.0165 (5)0.0040 (4)0.0071 (4)0.0042 (4)
O170.0248 (4)0.0266 (4)0.0208 (4)0.0132 (3)0.0136 (3)0.0104 (3)
C180.0220 (6)0.0259 (6)0.0193 (5)0.0107 (5)0.0103 (4)0.0064 (4)
O190.0227 (4)0.0220 (4)0.0221 (4)0.0106 (3)0.0121 (3)0.0060 (3)
C200.0189 (5)0.0155 (5)0.0180 (5)0.0025 (4)0.0087 (4)0.0029 (4)
C210.0185 (5)0.0191 (5)0.0190 (5)0.0055 (4)0.0058 (4)0.0038 (4)
C220.0214 (5)0.0180 (5)0.0147 (5)0.0033 (4)0.0035 (4)0.0021 (4)
C230.0213 (5)0.0146 (5)0.0183 (5)0.0050 (4)0.0099 (4)0.0029 (4)
C240.0164 (5)0.0216 (5)0.0224 (6)0.0044 (4)0.0064 (4)0.0020 (4)
C250.0181 (5)0.0202 (5)0.0192 (5)0.0011 (4)0.0046 (4)0.0013 (4)
O260.0282 (5)0.0312 (5)0.0198 (4)0.0147 (4)0.0018 (3)0.0074 (3)
C270.0245 (6)0.0247 (6)0.0207 (6)0.0078 (5)0.0040 (5)0.0030 (5)
O280.0232 (4)0.0214 (4)0.0186 (4)0.0082 (3)0.0055 (3)0.0022 (3)
Geometric parameters (Å, º) top
O1—C21.4319 (13)C22—C231.3816 (16)
O1—C41.4365 (12)C23—C241.3675 (16)
C1—C81.5349 (15)C23—O281.3811 (12)
C1—C21.5447 (14)C24—C251.4021 (15)
C1—C51.5543 (14)O26—C271.4266 (14)
C2—C111.5082 (14)C27—O281.4307 (14)
C4—C51.5276 (14)C1—H11.0000
C5—C61.5410 (15)C2—H21.0000
C6—O71.4250 (14)C4—H4A0.9900
C6—C201.5143 (14)C4—H4B0.9900
O7—C81.4346 (13)C5—H51.0000
C11—C161.3938 (15)C6—H61.0000
C11—C121.4078 (15)C8—H8A0.9900
C12—C131.3767 (14)C8—H8B0.9900
C13—O171.3798 (13)C12—H120.9500
C13—C141.3823 (15)C15—H150.9500
C14—C151.3725 (16)C16—H160.9500
C14—O191.3782 (12)C18—H18A0.9900
C15—C161.4019 (15)C18—H18B0.9900
O17—C181.4353 (13)C21—H210.9500
C18—O191.4322 (14)C24—H240.9500
C20—C251.3931 (16)C25—H250.9500
C20—C211.4023 (15)C27—H27A0.9900
C21—C221.3785 (15)C27—H27B0.9900
C22—O261.3777 (13)
C2—O1—C4103.72 (8)C23—O28—C27105.44 (8)
C8—C1—C2115.27 (9)C8—C1—H1111.5
C8—C1—C5103.20 (8)C2—C1—H1111.5
C2—C1—C5103.11 (8)C5—C1—H1111.5
O1—C2—C11111.03 (8)O1—C2—H2108.2
O1—C2—C1104.12 (8)C11—C2—H2108.2
C11—C2—C1116.71 (9)C1—C2—H2108.2
O1—C4—C5105.09 (8)O1—C4—H4A110.7
C4—C5—C6114.11 (9)C5—C4—H4A110.7
C4—C5—C1103.28 (8)O1—C4—H4B110.7
C6—C5—C1103.46 (8)C5—C4—H4B110.7
O7—C6—C20110.90 (9)H4A—C4—H4B108.8
O7—C6—C5105.39 (9)C4—C5—H5111.8
C20—C6—C5116.17 (9)C6—C5—H5111.8
C6—O7—C8104.65 (8)C1—C5—H5111.8
O7—C8—C1105.50 (8)O7—C6—H6108.0
C16—C11—C12120.37 (10)C20—C6—H6108.0
C16—C11—C2117.96 (9)C5—C6—H6108.0
C12—C11—C2121.67 (9)O7—C8—H8A110.6
C13—C12—C11116.42 (10)C1—C8—H8A110.6
C12—C13—O17127.53 (10)O7—C8—H8B110.6
C12—C13—C14122.84 (10)C1—C8—H8B110.6
O17—C13—C14109.60 (9)H8A—C8—H8B108.8
C15—C14—O19127.93 (10)C13—C12—H12121.8
C15—C14—C13121.80 (10)C11—C12—H12121.8
O19—C14—C13110.26 (9)C14—C15—H15121.8
C14—C15—C16116.39 (10)C16—C15—H15121.8
C11—C16—C15122.18 (10)C11—C16—H16118.9
C13—O17—C18105.71 (8)C15—C16—H16118.9
O19—C18—O17108.17 (8)O19—C18—H18A110.1
C14—O19—C18105.51 (8)O17—C18—H18A110.1
C25—C20—C21120.27 (10)O19—C18—H18B110.1
C25—C20—C6118.44 (10)O17—C18—H18B110.1
C21—C20—C6121.28 (10)H18A—C18—H18B108.4
C22—C21—C20116.65 (10)C22—C21—H21121.7
O26—C22—C21127.78 (10)C20—C21—H21121.7
O26—C22—C23109.60 (9)C23—C24—H24121.7
C21—C22—C23122.62 (10)C25—C24—H24121.7
C24—C23—O28127.98 (10)C20—C25—H25118.9
C24—C23—C22121.82 (10)C24—C25—H25118.9
O28—C23—C22110.19 (10)O26—C27—H27A110.0
C23—C24—C25116.50 (10)O28—C27—H27A110.0
C20—C25—C24122.14 (10)O26—C27—H27B110.0
C22—O26—C27106.08 (9)O28—C27—H27B110.0
O26—C27—O28108.60 (9)H27A—C27—H27B108.3
C4—O1—C2—C11171.12 (8)O19—C14—C15—C16178.33 (10)
C4—O1—C2—C144.73 (10)C13—C14—C15—C160.54 (16)
C8—C1—C2—O184.08 (10)C12—C11—C16—C150.10 (17)
C5—C1—C2—O127.58 (10)C2—C11—C16—C15179.82 (10)
C8—C1—C2—C1138.66 (13)C14—C15—C16—C110.35 (17)
C5—C1—C2—C11150.32 (9)C12—C13—O17—C18176.22 (11)
C2—O1—C4—C544.14 (10)C14—C13—O17—C185.66 (12)
O1—C4—C5—C686.43 (10)C13—O17—C18—O198.60 (11)
O1—C4—C5—C125.14 (11)C15—C14—O19—C18176.20 (11)
C8—C1—C5—C4118.87 (9)C13—C14—O19—C184.83 (12)
C2—C1—C5—C41.44 (10)O17—C18—O19—C148.26 (11)
C8—C1—C5—C60.34 (10)O7—C6—C20—C25177.96 (10)
C2—C1—C5—C6120.65 (9)C5—C6—C20—C2557.68 (14)
C4—C5—C6—O7135.84 (9)O7—C6—C20—C212.96 (14)
C1—C5—C6—O724.37 (10)C5—C6—C20—C21123.23 (11)
C4—C5—C6—C20100.96 (11)C25—C20—C21—C220.50 (16)
C1—C5—C6—C20147.57 (9)C6—C20—C21—C22178.56 (10)
C20—C6—O7—C8167.79 (9)C20—C21—C22—O26179.95 (11)
C5—C6—O7—C841.30 (11)C20—C21—C22—C230.47 (16)
C6—O7—C8—C141.66 (11)O26—C22—C23—C24179.59 (10)
C2—C1—C8—O7136.40 (9)C21—C22—C23—C240.03 (18)
C5—C1—C8—O724.79 (11)O26—C22—C23—O280.68 (13)
O1—C2—C11—C16167.64 (9)C21—C22—C23—O28178.88 (10)
C1—C2—C11—C1673.29 (13)O28—C23—C24—C25179.08 (10)
O1—C2—C11—C1212.29 (14)C22—C23—C24—C250.37 (17)
C1—C2—C11—C12106.79 (11)C21—C20—C25—C240.11 (17)
C16—C11—C12—C130.37 (15)C6—C20—C25—C24178.98 (10)
C2—C11—C12—C13179.56 (9)C23—C24—C25—C200.33 (17)
C11—C12—C13—O17177.70 (10)C21—C22—O26—C27179.19 (11)
C11—C12—C13—C140.19 (16)C23—C22—O26—C271.28 (13)
C12—C13—C14—C150.28 (17)C22—O26—C27—O282.71 (13)
O17—C13—C14—C15178.50 (10)C24—C23—O28—C27178.86 (11)
C12—C13—C14—O19178.77 (9)C22—C23—O28—C272.32 (12)
O17—C13—C14—O190.54 (12)O26—C27—O28—C233.08 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4A···O17i0.992.413.3501 (14)159
C15—H15···O26ii0.952.453.3093 (14)151
C16—H16···O28iii0.952.673.5503 (14)154
C18—H18B···O28iv0.992.603.2600 (13)124
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+1, z; (iii) x+1, y+1, z; (iv) x1, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC20H18O6
Mr354.34
Crystal system, space groupTriclinic, P1
Temperature (K)100
a, b, c (Å)6.5002 (4), 10.8931 (7), 11.8005 (8)
α, β, γ (°)103.793 (6), 102.111 (6), 95.836 (6)
V3)783.22 (9)
Z2
Radiation typeCu Kα
µ (mm1)0.93
Crystal size (mm)0.25 × 0.20 × 0.10
Data collection
DiffractometerOxford Xcalibur
diffractometer with Nova source and Atlas detector
Absorption correctionMulti-scan
(CrysAlis PRO; Agilent, 2012)
Tmin, Tmax0.770, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections
41535, 3254, 3200
Rint0.027
(sin θ/λ)max1)0.629
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.086, 1.05
No. of reflections3254
No. of parameters235
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.31, 0.21

Computer programs: CrysAlis PRO (Agilent, 2012), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP (Siemens, 1994).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4A···O17i0.992.413.3501 (14)158.5
C15—H15···O26ii0.952.453.3093 (14)150.6
C16—H16···O28iii0.952.673.5503 (14)154.4
C18—H18B···O28iv0.992.603.2600 (13)124.3
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+1, z; (iii) x+1, y+1, z; (iv) x1, y+1, z+1.
X-ray structure determinations of asarinin and its stereoisomers from the Cambridge Structural Database (CSD; Allen, 2002) top
CompoundReferenceRefcodeOptical rotationSpace groupComments
Synthetic epiasarininAldous et al. (2006)CERWOM(±)P21/n
SesaminBaures et al. (1992)TAPWAINot givenP21
SesaminHsieh et al. (2005)TAPWAI01(+)P21a
SesaminLi et al. (2005)TAPWAI02(-)P21a
AsarininLi et al. (2005)MAKJIT(-)P1 (probably P21)b, e
AsarininMacías et al. (1992)VUKBUY(-)P21b
AsarininParmar et al. (1998)VUKBUY03(+)P21c
AsarininIl'in et al. (1994)YODLEI(-)P21b
AsarininMata et al. (1998))YODLEI01Not givenP21d
AsarininThis work(±)P1
(a) No coordinates were deposited. (b) No H coordinates were deposited. (c) Given in CSD as (-) (probably erroneous). (d) Absolute configuration determined by anomalous dispersion. (e) Given in CSD as `unknown solvate', but may be solvent-free.
 

Acknowledgements

The authors are grateful to Dr K. Chandrasekhar, NBRI, Lucknow, for anti­feedant activity testing, and to HNB Garhwal University, UGC, CSIR, INSA, New Delhi, and the Deutsche Forschungsgemeinschaft for financial support.

References

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