(1R,2R,3R,4S,5S)-3-Methyl-8-oxa­bicyclo­[3.2.1]oct-6-ene-2,4-diyl diacetate

Viktor A Tafeenko; Leonid A Aslanov; Marina V Proskurnina; Sergei E Sosonyuk; Dmitrii A Khlevin

doi:10.1107/S1600536811027292

. 2011 Jul 23;67(Pt 8):o2127–o2128. doi: 10.1107/S1600536811027292

(1R,2R,3R,4S,5S)-3-Methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4-diyl diacetate

Viktor A Tafeenko ^a, Leonid A Aslanov ^a,^*, Marina V Proskurnina ^a, Sergei E Sosonyuk ^a, Dmitrii A Khlevin ^a

PMCID: PMC3213568 PMID: 22091145

Abstract

The molecule of the title compound, C₁₂H₁₆O₅, has crystallographically imposed mirror symmetry with the mirror plane passing through the endocyclic O atom and the mid-point of the double bond. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming chains running along the a axis.

Related literature

Compounds containing the 8-oxabicyclo[3.2.1]octane framework have shown broad utility as chiral building blocks for synthesis of polyketides, see: Coste & Gerber-Lemaire (2005 ▶); Meilert et al. (2003 ▶); Schwenter & Vogel (2001 ▶); Gerber-Lemaire & Vogel (2003 ▶); Gerber & Vogel (1999 ▶, 2001 ▶); Re et al. (2009 ▶); Pascual et al. (2004 ▶); Derwick (1998 ▶). For the inhibitory activity of calystegines and other tropane alkaloids against several glycosidase enzymes, see: Asano et al. (2000 ▶); Drager (2004 ▶). Several 8-oxabicyclo[3.2.1] octane derivatives possess moderate anti-HIV activity, see: Montana et al. (2009 ▶). For the syntheses of a full set of hybrid d- and l-C-glycosides and thymine polyoxin C starting with the unsaturated 8-oxabicyclo[3.2.1]octane framework, see: Gethin & Simpkins (1997 ▶); Hoffmann et al. (2001 ▶). For the synthesis of an 8-oxabicyclo[3.2.1]octane from tetrachlorocyclopropene and furan, see: Batson et al. (2004 ▶). For a synthetic approach to 8-oxabicyclo[3.2.1]octane derivatives based on the reaction of tetrachlorocyclopropene with furan, see: Law & Tobey (1968 ▶). For structures of related 8-oxabicyclo[3.2.1]octanes, see: Kreiselmeier et al. (2006 ▶); Hoffmann et al. (2001 ▶). For a report of prior research, see: Tafeenko et al. (2009 ▶).

Experimental

Crystal data

C₁₂H₁₆O₅
M _r = 240.25
Orthorhombic,
a = 6.8680 (12) Å
b = 12.295 (4) Å
c = 14.120 (3) Å
V = 1192.3 (5) Å³
Z = 4
Ag Kα radiation
λ = 0.56085 Å
μ = 0.06 mm⁻¹
T = 296 K
0.1 × 0.07 × 0.05 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
1974 measured reflections
1974 independent reflections
1085 reflections with I > 2s(I)
2 standard reflections every 120 min intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.138
S = 1.02
1974 reflections
91 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2000 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811027292/mw2015sup1.cif

e-67-o2127-sup1.cif^{(14.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811027292/mw2015Isup2.hkl

e-67-o2127-Isup2.hkl^{(95.2KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯O2ⁱ	0.93	2.55	3.482 (2)	178

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

Compounds containing the 8-oxabicyclo[3.2.1]octane framework are important precursors in the field of biologically active compounds. They have shown broad utility as chiral building blocks for synthesis of polyketides (Coste & Gerber-Lemaire, 2005; Meilert et al., 2003; Schwenter & Vogel, 2001; Gerber-Lemaire & Vogel, 2003), C-linked disaccharides (Gerber & Vogel, 1999; Gerber & Vogel, 2001), calystegines (Re et al., 2009; Pascual et al., 2004; Derwick, 1998) and other natural products. Calystegines and other tropane alkaloids show remarkable inhibitory activities against several glycosidase enzymes, in comparison with other alkaloidal glycosidase inhibitors (Asano et al., 2000; Drager, 2004). They are used medicinally, e.g., as anticholinergics, competing with acetylcholine for the muscarinic receptor site of the parasympathetic nervous system (Derwick, 1998). De novo syntheses of a full set of hybrid d- and l-C-glycosides and thymine polyoxin C starting with the unsaturated 8-oxabicyclo[3.2.1]octane framework have been reported (Hoffmann et al., 2001; Gethin & Simpkins, 1997). Moreover, recent research showed that several 8-oxabicyclo[3.2.1] octane derivatives possess moderate anti-HIV activity (Montana et al., 2009). In studies of novel biologically active homoinositol compounds, including selective glycosidase inhibitors, we have investigated a new synthetic approach to 8-oxabicyclo[3.2.1]octane derivatives based on the reaction of tetrachlorocyclopropene with furan (Law et al., 1968) for the preparation of (1R,2R,3r,4S,5S)-3-methyl-8-oxabicyclo[3.2.1]oct-6-ene- 2,4-diol (4). Several structural results in this field have been previously reported (Tafeenko et al., 2009; Batson et al., 2004; Kreiselmeier et al., 2006; Hoffmann et al. 2001).

Determination of the relative stereochemistry of compound (4) (Fig. 2) by NMR methods was ambiguous so recourse was made to X-ray crystallography for which purpose the crystalline diacetate (I) was synthesized.

Molecule (I) has crystallographically-imposed mirror symmetry with the mirror plane, m, passing through atoms C3, C8, the endocyclic oxygen O8 and the midpoint of the double bond C6/C6ⁱ (i: x,1.5 - y, z). The 6-membered ring of the molecule adopts a chair conformation, with atoms O8 and C3 displaced out of plane defined by the atoms C2/C2ⁱ/C1/C1ⁱ (plane 1) by 0.856 (2) and -0.525 (2) Å, respectively. The carbon atom of the methyl-group and atoms C6,C6ⁱ (double bond) are displaced out of plane 1 by -2.028 (2) Å and -1.326 (2) Å respectively. The molecules (I) are linked by means of weak C—H···O hydrogen bonds to form chains running along a axis.

Experimental

(1R,5S)-3-Chloro-3-methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4-dione (see Fig.2) (2).

To a solution of 0.5 g (2.9 mmol) of (1) (Law & Tobey, 1968) in acetone (10 ml) 0.83 g (5.8 mmol) K₂CO₃ and 1.38 g (8.7 mmol) MeI were added. The mixture was stirred at 298 K for 36 h, then concentrated under reduced pressure. The residue was purified via silica gel flash chromatography (10% EtOAc in CH₂Cl₂), to give a pale yellow crystalline solid; yield: 0.45 g, (83%) (compound 2), mp 370–372 K.

(1R,5S)-3-methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4-dione (see Fig.2) (3).

To a solution of 0.4 g (2.1 mmol) of diketone (2) in 4 ml of glacial acetic acid was added 0.23 g of Zn-powder. After the beginning of heating-up the mixture was stirred at 298 K for 0.5 h and 20% aqueous NaOH was added dropwise until solid formed. The solid was dissolved by addition of 1 ml 0.1 N HCl, the mixture was extracted with CH₂Cl₂ (5*20 ml), the combined organic layers were dried over Na₂SO₄ and evaporated under reduced pressure to yield 0.26 g of compound (3) as a pale yellow crystalline solid, (compound 3) mp 359–361 K.

(1R,2R,4S,5S)-3-methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4 -diol (see Fig.2) (4).

To a solution of 200 mg (1.3 mmol) of diketone (3) in 15 ml of MeOH 340 mg (8.9 mmol) of NaBH₄ was added portionwise for 3 h, during which time the reaction temperature was kept between 293–303 K. The mixture was stirred at 298 K for 2 h, then 0.4 g of crystalline NH₄Cl was added followed by 0.5 ml of 1 N HCl. The solvents were evaporated under reduced pressure, the residue was flashed by EtOAc/Me₂CO (1:1) through a silica gel column to give 0.2 g of a yellow oil. The ¹H and ¹³C NMR spectra showed that the oil contained several isomers so it was purified by column chromatography on silica gel eluting with a EtOAc/Me₂CO (5:2) mixture to afford 95 mg of the major isomer (4) as a colorless oil, yield 46%; Rf = 0.5 (Et₂O/Me₂CO = 3:1).

(1R,2R,3r,4S,5S)-3-methyl-8-oxabicyclo[3.2.1]oct-6-ene- 2,4-diyl diacetate (see Fig.2) (I).

Compound (4) (95 mg, 0.61 mmol) was dissolved in 5 ml of py and 3 ml of Ac₂O was added. The mixture was stirred for 24 h at room temperature and then concentrated under reduced pressure (1 mm Hg) to give a thick brown oil. Diacetate (I) was separated by flash chromatography on silica gel (CH₂Cl₂) as colorless crystals, yield 134 mg (92%), mp 428–430 K, Rf = 0.4 (CH₂Cl₂). Crystals suitable for diffraction analysis were obtained by slow evaporation of solvents from a dichloromethane-hexane solution.