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The stereochemistry of the title compound, C20H28O8, a key step in the preparation of analogues of mannostatins, potent inhibitors of α-mannosidase, has been established. The carboxyl­ic acid group at C1 unexpectedly eclipses the C1—C2 bond. The cyclo­propane ring makes a dihedral angle of 109.4 (2)° with the cyclo­pentene ring.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270199015309/gs1062sup1.cif
Contains datablocks I, bicyclohex

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270199015309/gs1062Isup2.hkl
Contains datablock I

CCDC reference: 143258

Comment top

Polyhydroxylated aminocyclopentanes, exemplified by mannostatins A and B, isolated from the culture broth of Streptoverticillium verticillus, exhibit potent inhibiting activity towards α-mannosidase (Aoyagi et al., 1989; Aoyagi et al., 1990). Consequently, they display interesting biological activities, such as antiviral, antimetastasic and immunomodulator (Jacob et al., 1995 and references cited therein; Breton et al., 1991). To contribute to the investigation of structure-activity relationships, we prepared the conformationally restricted bicyclo[3.1.0]hexane analogue, (I) (Cachet et al. unpublished). A novel synthetic approach was developped, starting from the natural iridoid aucubin (II) as source of chiral cyclopentane. The key step was the reaction of iodolactones derived from (II) with sodium triethylsilanolate (TMSONa) to create the cyclopropane ring. In the course of the synthesis, compound (III) was obtained. The stereochemistry at C1, C5, C6 and consequently, the mechanism of the TMSONa rearrangement were confirmed by this X-ray diffraction analysis. \sch

The carboxylic acid at C1 eclipses unexpectedly the C1—C2 bond (torsional angle: C2—C1—C7—O9 = 0.9 (3)°). This is probably to be ascribed to the hydrogen bond which links the carboxylic acid O8—H to the O13 carbonyl of symmetry-related molecule (-x, -1/2 + y, 1 - z). (O8···O13 = 2.702 (2), H···O13 1.93 Å, angle O8—H···O13 156.5°). The cyclopentene ring is practically planar: C4 being at 0.067 Å of the mean plane of the four other atoms. The cyclopropane ring makes a dihedral angle of 109.4° with the mean plane of the cyclopentene ring.

Refinement top

1626 Friedel pairs were measured. Absolute configuration was not established by anomalous dispersion effects. The enantiomer has been assigned by reference to an unchanging chiral centre in the synthetic procedure.

Computing details top

Data collection: CAD-4 Software (Enraf-Nonius, 1987); cell refinement: CAD-4 Software; data reduction: NONIUS (Riche, 1989); program(s) used to solve structure: SHELXS86 (Sheldrick, 1985); program(s) used to refine structure: SHELXL93 (Sheldrick, 1993); molecular graphics: R3M (Riche, 1983) and ORTEP (Johnson, 1963).

Figures top
[Figure 1] Fig. 1. ORTEP (Johnson, 1965) plot of (III) with atom numbering. Ellipsoids are set at the 30% probability level
(1S,4R,5R,6R)-(6-(methoxycarbonyl)-2-(pivaloyloxymethyl)-4- (pivaloyloxy)bicyclo[3.1.0]hex-2-en-1-yl)-1-carboxylic acid top
Crystal data top
C20H28O8Dx = 1.235 Mg m3
Mr = 396.42Melting point: 128.2 _C K
Monoclinic, P21Cu Kα radiation, λ = 1.54180 Å
a = 8.869 (2) ÅCell parameters from 25 reflections
b = 9.836 (2) Åθ = 12.9–18.7°
c = 12.225 (6) ŵ = 0.80 mm1
β = 91.40 (3)°T = 293 K
V = 1066.1 (6) Å3Prism, colourless
Z = 20.50 × 0.30 × 0.30 mm
F(000) = 424
Data collection top
Nonius CAD4
diffractometer
Rint = 0.050
Radiation source: fine-focus sealed tubeθmax = 66.9°, θmin = 3.6°
Graphite monochromatorh = 1010
θ/2θ scansk = 1111
4755 measured reflectionsl = 1014
3601 independent reflections3 standard reflections every 120 min
3430 reflections with I > 2σ(I) intensity decay: 2%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.108Calculated w = 1/[σ2(Fo2) + (0.0707P)2 + 0.0992P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.018
3601 reflectionsΔρmax = 0.20 e Å3
255 parametersΔρmin = 0.20 e Å3
1 restraintExtinction correction: SHELXL93 (Sheldrick, 1993), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0211 (15)
Crystal data top
C20H28O8V = 1066.1 (6) Å3
Mr = 396.42Z = 2
Monoclinic, P21Cu Kα radiation
a = 8.869 (2) ŵ = 0.80 mm1
b = 9.836 (2) ÅT = 293 K
c = 12.225 (6) Å0.50 × 0.30 × 0.30 mm
β = 91.40 (3)°
Data collection top
Nonius CAD4
diffractometer
Rint = 0.050
4755 measured reflections3 standard reflections every 120 min
3601 independent reflections intensity decay: 2%
3430 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0401 restraint
wR(F2) = 0.108H-atom parameters constrained
S = 1.06Δρmax = 0.20 e Å3
3601 reflectionsΔρmin = 0.20 e Å3
255 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 on F2 for ALL reflections except for 0 with very negative F2 or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating _R_factor_obs 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
C10.0911 (2)0.0373 (2)0.77730 (15)0.0374 (4)
C20.0441 (2)0.1769 (2)0.8151 (2)0.0412 (4)
C30.0776 (2)0.1960 (2)0.9188 (2)0.0489 (5)
H30.0574 (2)0.2762 (2)0.9567 (2)0.059*
C40.1517 (2)0.0748 (2)0.9690 (2)0.0450 (4)
H40.0922 (2)0.0426 (2)1.0324 (2)0.054*
C50.1520 (2)0.0301 (2)0.87907 (15)0.0400 (4)
H50.2387 (2)0.0914 (2)0.87115 (15)0.048*
C60.0038 (2)0.0753 (2)0.83816 (14)0.0382 (4)
H60.0841 (2)0.0445 (2)0.88148 (14)0.046*
C70.1508 (2)0.0184 (2)0.6646 (2)0.0431 (4)
O80.1896 (2)0.1086 (2)0.64240 (13)0.0600 (4)
HO80.2194 (2)0.1141 (2)0.57851 (13)0.081 (9)*
O90.1629 (3)0.1081 (2)0.59943 (14)0.0787 (6)
C100.0429 (2)0.2694 (2)0.7438 (2)0.0479 (5)
H10A0.0197 (2)0.3024 (2)0.6833 (2)0.058*
H10B0.0815 (2)0.3465 (2)0.7852 (2)0.058*
O110.1649 (2)0.18663 (15)0.70465 (12)0.0515 (4)
C120.2374 (2)0.2267 (2)0.6167 (2)0.0479 (5)
O130.2115 (2)0.3354 (2)0.57380 (14)0.0696 (5)
C140.3456 (3)0.1210 (3)0.5766 (2)0.0584 (6)
C150.4674 (4)0.1887 (5)0.5104 (3)0.1082 (13)
H15A0.5361 (4)0.1210 (5)0.4849 (3)0.162*
H15B0.5213 (4)0.2531 (5)0.5556 (3)0.162*
H15C0.4218 (4)0.2349 (5)0.4488 (3)0.162*
C160.4187 (3)0.0424 (4)0.6714 (3)0.0842 (9)
H16A0.4868 (3)0.0241 (4)0.6432 (3)0.126*
H16B0.3419 (3)0.0024 (4)0.7120 (3)0.126*
H16C0.4732 (3)0.1042 (4)0.7185 (3)0.126*
C170.2516 (4)0.0235 (4)0.5048 (3)0.1015 (11)
H17A0.3157 (4)0.0464 (4)0.4769 (3)0.152*
H17B0.2059 (4)0.0728 (4)0.4449 (3)0.152*
H17C0.1743 (4)0.0171 (4)0.5476 (3)0.152*
O180.3029 (2)0.1104 (2)1.00098 (12)0.0512 (4)
C190.3685 (2)0.0229 (2)1.0707 (2)0.0471 (5)
O200.3041 (2)0.0782 (2)1.1025 (2)0.0702 (5)
C210.5253 (2)0.0666 (2)1.1027 (2)0.0529 (5)
C220.5878 (4)0.0405 (4)1.1798 (4)0.1093 (14)
H22A0.5224 (4)0.0484 (4)1.2432 (4)0.164*
H22B0.5937 (4)0.1264 (4)1.1427 (4)0.164*
H22C0.6867 (4)0.0138 (4)1.2018 (4)0.164*
C230.5132 (3)0.2031 (3)1.1615 (3)0.0782 (8)
H23A0.4494 (3)0.1937 (3)1.2257 (3)0.117*
H23B0.6117 (3)0.2322 (3)1.1824 (3)0.117*
H23C0.4708 (3)0.2694 (3)1.1135 (3)0.117*
C240.6253 (3)0.0817 (5)1.0022 (3)0.0954 (11)
H24A0.7242 (3)0.1093 (5)1.0233 (3)0.143*
H24B0.6317 (3)0.0038 (5)0.9644 (3)0.143*
H24C0.5837 (3)0.1491 (5)0.9548 (3)0.143*
C250.0095 (2)0.2157 (2)0.7905 (2)0.0409 (4)
O260.0663 (2)0.3108 (2)0.81357 (14)0.0623 (4)
O270.1220 (2)0.21990 (15)0.72120 (13)0.0542 (4)
C280.1418 (3)0.3480 (3)0.6647 (2)0.0694 (7)
H28A0.2255 (3)0.3410 (3)0.6167 (2)0.104*
H28B0.0519 (3)0.3691 (3)0.6228 (2)0.104*
H28C0.1612 (3)0.4188 (3)0.7173 (2)0.104*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0353 (8)0.0411 (9)0.0359 (9)0.0014 (7)0.0038 (7)0.0029 (7)
C20.0426 (9)0.0392 (9)0.0418 (9)0.0018 (7)0.0022 (8)0.0028 (8)
C30.0555 (11)0.0464 (10)0.0450 (11)0.0060 (9)0.0065 (9)0.0111 (9)
C40.0444 (10)0.0540 (11)0.0369 (9)0.0022 (8)0.0078 (8)0.0038 (8)
C50.0377 (9)0.0451 (9)0.0376 (10)0.0028 (7)0.0059 (7)0.0031 (8)
C60.0383 (8)0.0415 (9)0.0348 (9)0.0004 (7)0.0020 (7)0.0000 (7)
C70.0411 (9)0.0497 (10)0.0385 (10)0.0012 (8)0.0014 (8)0.0036 (8)
O80.0753 (10)0.0555 (9)0.0483 (8)0.0044 (8)0.0158 (7)0.0104 (7)
O90.117 (2)0.0672 (10)0.0506 (9)0.0123 (11)0.0280 (10)0.0097 (9)
C100.0507 (10)0.0422 (10)0.0514 (11)0.0031 (9)0.0081 (9)0.0003 (9)
O110.0498 (7)0.0501 (7)0.0551 (8)0.0027 (6)0.0131 (6)0.0135 (7)
C120.0482 (10)0.0547 (11)0.0409 (10)0.0048 (9)0.0036 (9)0.0094 (9)
O130.0930 (12)0.0599 (9)0.0567 (9)0.0122 (9)0.0173 (9)0.0224 (8)
C140.0467 (11)0.0698 (14)0.0593 (13)0.0076 (10)0.0146 (10)0.0169 (11)
C150.071 (2)0.135 (3)0.120 (3)0.025 (2)0.047 (2)0.057 (3)
C160.068 (2)0.100 (2)0.085 (2)0.028 (2)0.0116 (14)0.032 (2)
C170.097 (2)0.107 (2)0.100 (2)0.031 (2)0.003 (2)0.040 (2)
O180.0525 (8)0.0549 (8)0.0469 (8)0.0101 (6)0.0170 (6)0.0025 (6)
C190.0481 (10)0.0538 (11)0.0397 (10)0.0046 (9)0.0076 (8)0.0018 (8)
O200.0585 (9)0.0678 (10)0.0848 (12)0.0141 (9)0.0148 (8)0.0243 (10)
C210.0484 (11)0.0612 (12)0.0497 (11)0.0058 (9)0.0136 (9)0.0025 (10)
C220.087 (2)0.093 (2)0.150 (3)0.016 (2)0.067 (2)0.034 (2)
C230.0684 (15)0.079 (2)0.088 (2)0.0189 (14)0.0143 (14)0.023 (2)
C240.0542 (14)0.149 (3)0.083 (2)0.018 (2)0.0076 (13)0.030 (2)
C250.0419 (9)0.0436 (10)0.0373 (9)0.0018 (8)0.0022 (8)0.0004 (8)
O260.0705 (10)0.0454 (8)0.0718 (10)0.0101 (7)0.0190 (8)0.0018 (7)
O270.0510 (8)0.0507 (8)0.0617 (9)0.0008 (6)0.0189 (7)0.0122 (7)
C280.0683 (14)0.066 (2)0.074 (2)0.0077 (12)0.0148 (13)0.0267 (13)
Geometric parameters (Å, º) top
C1—C71.476 (3)C12—O131.210 (3)
C1—C21.504 (3)C12—C141.505 (3)
C1—C51.520 (3)C14—C151.519 (4)
C1—C61.533 (3)C14—C161.525 (4)
C2—C31.323 (3)C14—C171.533 (5)
C2—C101.488 (3)O18—C191.353 (3)
C3—C41.499 (3)C19—O201.206 (3)
C4—O181.450 (2)C19—C211.516 (3)
C4—C51.507 (3)C21—C241.505 (4)
C5—C61.486 (3)C21—C221.526 (4)
C6—C251.505 (3)C21—C231.526 (4)
C7—O91.192 (3)C25—O261.190 (2)
C7—O81.323 (3)C25—O271.325 (2)
C10—O111.445 (2)O27—C281.449 (3)
O11—C121.326 (3)
C7—C1—C2119.5 (2)O13—C12—O11121.5 (2)
C7—C1—C5125.6 (2)O13—C12—C14125.8 (2)
C2—C1—C5104.36 (15)O11—C12—C14112.6 (2)
C7—C1—C6121.8 (2)C12—C14—C15109.8 (2)
C2—C1—C6112.19 (14)C12—C14—C16111.4 (2)
C5—C1—C658.23 (12)C15—C14—C16109.4 (2)
C3—C2—C10127.3 (2)C12—C14—C17106.1 (2)
C3—C2—C1110.9 (2)C15—C14—C17110.7 (3)
C10—C2—C1121.5 (2)C16—C14—C17109.4 (3)
C2—C3—C4113.0 (2)C19—O18—C4115.5 (2)
O18—C4—C3109.6 (2)O20—C19—O18121.4 (2)
O18—C4—C5112.1 (2)O20—C19—C21125.5 (2)
C3—C4—C5103.8 (2)O18—C19—C21113.1 (2)
C6—C5—C4117.7 (2)C24—C21—C19110.1 (2)
C6—C5—C161.32 (12)C24—C21—C22110.9 (3)
C4—C5—C1107.7 (2)C19—C21—C22108.2 (2)
C5—C6—C25118.9 (2)C24—C21—C23109.3 (3)
C5—C6—C160.45 (12)C19—C21—C23108.5 (2)
C25—C6—C1121.2 (2)C22—C21—C23109.8 (2)
O9—C7—O8122.9 (2)O26—C25—O27124.5 (2)
O9—C7—C1123.8 (2)O26—C25—C6125.4 (2)
O8—C7—C1113.3 (2)O27—C25—C6110.1 (2)
O11—C10—C2104.7 (2)C25—O27—C28115.7 (2)
C12—O11—C10118.9 (2)
C7—C1—C2—C3143.5 (2)C6—C1—C7—O9148.5 (2)
C5—C1—C2—C33.2 (2)C2—C1—C7—O8179.2 (2)
C6—C1—C2—C364.3 (2)C5—C1—C7—O840.1 (3)
C7—C1—C2—C1042.6 (3)C6—C1—C7—O831.4 (3)
C5—C1—C2—C10170.8 (2)C3—C2—C10—O11124.1 (2)
C6—C1—C2—C10109.6 (2)C1—C2—C10—O1148.8 (2)
C10—C2—C3—C4173.4 (2)C2—C10—O11—C12161.4 (2)
C1—C2—C3—C40.1 (2)C10—O11—C12—O135.7 (3)
C2—C3—C4—O18117.0 (2)C10—O11—C12—C14171.7 (2)
C2—C3—C4—C53.0 (2)O13—C12—C14—C1526.1 (4)
O18—C4—C5—C6179.7 (2)O11—C12—C14—C15156.6 (2)
C3—C4—C5—C661.5 (2)O13—C12—C14—C16147.5 (3)
O18—C4—C5—C1113.4 (2)O11—C12—C14—C1635.2 (3)
C3—C4—C5—C14.8 (2)O13—C12—C14—C1793.5 (3)
C7—C1—C5—C6108.6 (2)O11—C12—C14—C1783.8 (3)
C2—C1—C5—C6107.5 (2)C3—C4—O18—C19164.3 (2)
C6—C1—C5—C60.0C5—C4—O18—C1980.9 (2)
C7—C1—C5—C4139.0 (2)C4—O18—C19—O200.6 (3)
C2—C1—C5—C44.9 (2)C4—O18—C19—C21179.1 (2)
C6—C1—C5—C4112.4 (2)O20—C19—C21—C24122.4 (3)
C4—C5—C6—C25152.4 (2)O18—C19—C21—C2457.9 (3)
C1—C5—C6—C25111.5 (2)O20—C19—C21—C221.1 (4)
C4—C5—C6—C196.0 (2)O18—C19—C21—C22179.3 (2)
C1—C5—C6—C10.0O20—C19—C21—C23118.0 (3)
C7—C1—C6—C5115.0 (2)O18—C19—C21—C2361.7 (3)
C2—C1—C6—C593.6 (2)C5—C6—C25—O2627.3 (3)
C5—C1—C6—C50.0C1—C6—C25—O2698.4 (2)
C7—C1—C6—C257.1 (3)C5—C6—C25—O27154.9 (2)
C2—C1—C6—C25158.5 (2)C1—C6—C25—O2783.8 (2)
C5—C1—C6—C25107.9 (2)O26—C25—O27—C285.4 (3)
C2—C1—C7—O90.9 (3)C6—C25—O27—C28176.7 (2)
C5—C1—C7—O9140.0 (2)

Experimental details

Crystal data
Chemical formulaC20H28O8
Mr396.42
Crystal system, space groupMonoclinic, P21
Temperature (K)293
a, b, c (Å)8.869 (2), 9.836 (2), 12.225 (6)
β (°) 91.40 (3)
V3)1066.1 (6)
Z2
Radiation typeCu Kα
µ (mm1)0.80
Crystal size (mm)0.50 × 0.30 × 0.30
Data collection
DiffractometerNonius CAD4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
4755, 3601, 3430
Rint0.050
(sin θ/λ)max1)0.597
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.108, 1.06
No. of reflections3601
No. of parameters255
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.20, 0.20

Computer programs: CAD-4 Software (Enraf-Nonius, 1987), CAD-4 Software, NONIUS (Riche, 1989), SHELXS86 (Sheldrick, 1985), SHELXL93 (Sheldrick, 1993), R3M (Riche, 1983) and ORTEP (Johnson, 1963).

 

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