A novel glycoside lactone derivative with a 2-C-unsaturated diester substituent

The title 4,6-O-benzyl­idene-α-D-gluco­pyran­oside (systematic name: methyl 4-methoxy-2-oxo-8-phenyl-1,2,5a,6,9a,9b-hexa­hydro-4H,8H-7,9-dioxa­cyclo­penta­[c]­chromene-3-carboxyl­ate), C₁₈H₁₈O₈, has been synthesized from the reaction of methyl 4,6-O-benzyl­idene-α-D-2-ketogluco­pyran­oside with diethyl or di­methyl malonate. The compound adopts a chair–chair conformation. The newly formed five-membered ring is fused to the gluco­pyran­oside ring along the C₂—C₃ bond and is planar with an r.m.s. deviation of 0.0091 Å.

S1. Comment

C-Branched monosaccharides are important chiral synthons in both organic chemistry and in biological substances, and some have been found as components of living cells (Adinolfi et al., 1995, 1996). The stereoselective addition of a nucleophile to a glycosidulose is an efficient route to the synthesis of C-branched sugars (Sato et al., 1994; Adinolfi et al., 2000). In these previous syntheses, the hydroxyl groups of the glycosiduloses have been fully protected, since unprotected and partially protected glycosiduloses have proven to be difficult to synthesize selectively, are unstable in basic medium and usually exist in different forms (Liu & Tsuda, 1993, 1996a). Thus, very little is known about the syntheses and structures of C-branched glucopyranosides made from partially protected 2-ketoglucosides. We report here the X-ray structure of (II), which was synthesized from the partially protected 2-ketoglucoside (I) by reaction with diethyl or dimethyl malonate in strong basic solution.

Compound (II) adopts a chair–chair conformation. Atoms C11 and C5 are displaced by -0.6769 (2) and 0.7023 (6) Å from the least-squares plane defined by atoms O4, O6, C4 and C6 (r.m.s. deviation 0.0022 Å), giving a flattened chair conformation. Atoms C2 and C5 deviate by -0.5444 (3) and 0.7216 (3) Å, respectively, from the plane defined by atoms C3, C4, C1 and O5 (r.m.s. deviation 0.0055 Å), resulting in a chair which is more distorted from a perfect chair conformation than the former, as can be expected from the different substitution pattern. The associated non-bonding distances are 2.786 (5) Å for C11,,,C5 and 2.763 (4) Å for C5,,,C2. The five-membered ring (C2, C3, C8, C18 and O3) is fused to the glucopyranoside ring along the C3—C2 bond in the equatorial position at C3. The short C2—C8 distance of 1.328 (5) Å is typical for a double bond having two carbonyl groups as neighbours, and the five-membered ring is consequently very planar, with an r.m.s. deviation of 0.0091 Å among the five atoms. Atom C3 exhibits the largest out-of-plane displacement of 0.0124 (2) Å, and C18 is closest to the mean plane [0.0028 (2) Å]. In addition, the phenyl ring is approximately parallel to the least-squares C6/C4/O4/O6 and C5/O5/C2/C3 planes, forming interplanar angles of 9.7 (2) and 5.3 (3)°, respectively. Similarly, the five-membered C2/C3/C8/C18/O3 ring is inclined at angles of 34.98 (9), 25.89 (8) and 29.82 (8)° to the C12–C17, C4/C6/O4/O6 and C2/C3/C5/O5 planes, respectively. The absolute structure was deduced based on compound (I), which is known to be an α-D-2-ketoglucopyranoside. As shown in the packing diagram (Fig. 2), the molecules stack along the b direction in an efficient manner.

Related literature

For related literature, see: Adinolfi et al. (1995, 1996, 2000); Liu & Tsuda (1993, 1996a, 1996b); Sato et al. (1994).

S2. Experimental

The title compound was synthesized by the aldol condensation of compound (I) (400 mg, 1.43 mmol; Liu & Tsuda, 1996b) in CHCl₃ with diethyl or dimethyl malonate (5.62 mmol) in the presence of sodium methoxide (516 mg, 9.56 mmol). The product (350 mg) was obtained as colourless crystals melting at 443–445 K after recrystallization from methanol/acetone.

S3. Refinement

All H atoms were fixed at ideal positions with a common isotropic displacement parameter (U_iso = 0.08 Ų).

Computing details

Data collection: R-AXIS Software (Rigaku, 1997); cell refinement: R-AXIS Software; data reduction: R-AXIS Software; program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: TEXSAN (Molecular Structure Corporation, 1992); software used to prepare material for publication: TEXSAN.

Figures

	Fig. 1. The molecular structure of (II) drawn with 50% probability displacement ellipsoids.
	Fig. 2. Packing diagram viewed down the b axis.

(I)

Crystal data

C18H18O8	Dx = 1.397 Mg m^−3
Mr = 362.32	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 188 reflections
a = 22.469 (5) Å	θ = 2.8–26.0°
b = 4.6467 (9) Å	µ = 0.11 mm^−1
c = 16.501 (3) Å	T = 291 K
V = 1722.8 (6) Å^3	Prism, colorless
Z = 4	0.30 × 0.30 × 0.20 mm
F(000) = 760

Data collection

Rigaku R-AXIS-IV IP diffractometer	2244 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.045
Graphite monochromator	θmax = 27.5°, θmin = 1.5°
Detector resolution: 100 pixels mm^-1	h = 0→29
Oscillation frames scans	k = −6→6
2635 measured reflections	l = 0→20
2608 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.054	H-atom parameters not refined
wR(F^2) = 0.103	w = 1/[σ^2(Fo^2) + (0.0456P)^2 + 0.0022P] where P = (Fo^2 + 2Fc^2)/3
S = 1.13	(Δ/σ)max = 0.006
2608 reflections	Δρmax = 0.17 e Å^−3
236 parameters	Δρmin = −0.14 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0112 (11)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.15952 (6)	0.4688 (3)	0.32087 (6)	0.0498 (4)
O2	0.31517 (7)	0.0894 (5)	0.07470 (8)	0.0791 (6)
O3	0.23100 (5)	0.3476 (4)	0.07963 (7)	0.0557 (4)
O4	0.10271 (5)	0.5107 (3)	0.04932 (5)	0.0393 (3)
O5	0.10115 (5)	0.1443 (3)	0.24604 (6)	0.0410 (3)
O6	0.00484 (5)	0.4733 (3)	0.09490 (6)	0.0436 (3)
O7	0.31436 (7)	−0.3078 (4)	0.22505 (8)	0.0711 (5)
O8	0.27567 (6)	−0.0519 (4)	0.32712 (7)	0.0607 (4)
C1	0.15797 (8)	0.2072 (4)	0.27957 (9)	0.0389 (5)
H1A	0.1699	0.0516	0.3162	0.047*
C2	0.20214 (8)	0.2292 (4)	0.21037 (8)	0.0391 (5)
C3	0.18521 (8)	0.4054 (5)	0.13776 (9)	0.0420 (5)
H3A	0.1858	0.6101	0.1521	0.050*
C4	0.12355 (7)	0.3216 (4)	0.11118 (8)	0.0366 (4)
H4A	0.1237	0.1230	0.0911	0.044*
C5	0.08295 (8)	0.3454 (4)	0.18538 (9)	0.0371 (4)
H5A	0.0850	0.5411	0.2073	0.044*
C6	0.01979 (8)	0.2799 (5)	0.15934 (9)	0.0440 (5)
H6A	0.0168	0.0822	0.1409	0.053*
H6B	−0.0073	0.3061	0.2045	0.053*
C7	0.13260 (11)	0.4512 (6)	0.39997 (10)	0.0705 (8)
H7A	0.1373	0.6317	0.4275	0.106*
H7B	0.1515	0.3016	0.4307	0.106*
H7C	0.0910	0.4087	0.3944	0.106*
C8	0.25321 (8)	0.0942 (4)	0.19680 (9)	0.0425 (5)
C9	0.28524 (8)	−0.1123 (5)	0.24944 (10)	0.0456 (5)
C10	0.29887 (11)	−0.2571 (6)	0.38519 (13)	0.0804 (8)
H10A	0.2909	−0.1904	0.4392	0.121*
H10B	0.3411	−0.2767	0.3778	0.121*
H10C	0.2801	−0.4404	0.3771	0.121*
C11	0.04338 (7)	0.4382 (4)	0.02755 (9)	0.0381 (5)
H11A	0.0420	0.2377	0.0092	0.046*
C12	0.02272 (8)	0.6318 (4)	−0.03955 (9)	0.0396 (5)
C13	−0.03775 (9)	0.6585 (6)	−0.05419 (10)	0.0552 (6)
H13A	−0.0647	0.5584	−0.0221	0.066*
C14	−0.05827 (10)	0.8321 (7)	−0.11589 (11)	0.0683 (7)
H14A	−0.0990	0.8502	−0.1249	0.082*
C15	−0.01877 (10)	0.9780 (6)	−0.16404 (10)	0.0665 (7)
H15A	−0.0328	1.0975	−0.2050	0.080*
C16	0.04172 (10)	0.9485 (6)	−0.15192 (10)	0.0578 (6)
H16A	0.0685	1.0444	−0.1854	0.069*
C17	0.06238 (9)	0.7749 (5)	−0.08959 (9)	0.0461 (5)
H17A	0.1031	0.7544	−0.0813	0.055*
C18	0.27312 (9)	0.1657 (6)	0.11221 (11)	0.0524 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0637 (8)	0.0490 (8)	0.0367 (5)	−0.0051 (8)	0.0023 (6)	−0.0055 (6)
O2	0.0533 (8)	0.1257 (16)	0.0582 (6)	0.0181 (11)	0.0180 (7)	0.0163 (10)
O3	0.0397 (7)	0.0855 (11)	0.0421 (5)	−0.0016 (9)	0.0034 (6)	0.0185 (7)
O4	0.0361 (6)	0.0450 (7)	0.0367 (5)	−0.0006 (7)	−0.0030 (5)	0.0078 (5)
O5	0.0400 (6)	0.0398 (7)	0.0432 (5)	−0.0055 (7)	0.0008 (5)	0.0077 (5)
O6	0.0387 (6)	0.0491 (8)	0.0430 (5)	0.0079 (7)	0.0036 (5)	0.0010 (5)
O7	0.0637 (9)	0.0732 (11)	0.0762 (8)	0.0200 (10)	0.0085 (8)	0.0125 (9)
O8	0.0665 (9)	0.0702 (10)	0.0456 (6)	0.0046 (9)	−0.0106 (6)	0.0135 (7)
C1	0.0405 (10)	0.0395 (11)	0.0366 (7)	−0.0002 (10)	0.0013 (7)	0.0056 (8)
C2	0.0417 (10)	0.0406 (11)	0.0351 (7)	−0.0081 (9)	−0.0060 (7)	0.0047 (7)
C3	0.0353 (9)	0.0491 (12)	0.0417 (7)	−0.0045 (10)	0.0025 (7)	0.0061 (8)
C4	0.0358 (9)	0.0365 (10)	0.0376 (7)	0.0006 (9)	0.0009 (7)	0.0028 (8)
C5	0.0414 (9)	0.0340 (9)	0.0358 (7)	−0.0012 (10)	0.0023 (7)	0.0011 (7)
C6	0.0434 (11)	0.0455 (12)	0.0432 (8)	−0.0011 (11)	0.0016 (8)	0.0072 (8)
C7	0.0855 (16)	0.0828 (19)	0.0433 (9)	−0.0026 (17)	0.0112 (10)	−0.0102 (11)
C8	0.0352 (10)	0.0525 (13)	0.0399 (8)	−0.0051 (10)	−0.0017 (7)	0.0041 (8)
C9	0.0364 (10)	0.0527 (13)	0.0478 (8)	−0.0048 (11)	−0.0023 (8)	0.0029 (9)
C10	0.0827 (16)	0.0913 (19)	0.0670 (10)	−0.0067 (18)	−0.0229 (12)	0.0327 (13)
C11	0.0359 (10)	0.0362 (11)	0.0424 (7)	−0.0013 (10)	−0.0007 (7)	−0.0046 (7)
C12	0.0454 (10)	0.0384 (11)	0.0350 (7)	0.0053 (10)	−0.0058 (7)	−0.0080 (7)
C13	0.0457 (12)	0.0695 (15)	0.0504 (9)	0.0021 (13)	−0.0055 (9)	−0.0011 (10)
C14	0.0545 (13)	0.0925 (19)	0.0579 (10)	0.0126 (15)	−0.0150 (10)	0.0034 (13)
C15	0.0786 (15)	0.0732 (16)	0.0476 (9)	0.0125 (15)	−0.0193 (10)	0.0051 (11)
C16	0.0729 (14)	0.0590 (14)	0.0414 (8)	−0.0022 (14)	−0.0065 (9)	0.0062 (9)
C17	0.0490 (11)	0.0464 (12)	0.0430 (8)	0.0026 (11)	−0.0026 (8)	−0.0033 (9)
C18	0.0383 (10)	0.0758 (15)	0.0430 (8)	−0.0019 (12)	−0.0022 (8)	0.0079 (10)

Geometric parameters (Å, º)

O1—C1	1.394 (2)	C6—H6A	0.9700
O1—C7	1.441 (2)	C6—H6B	0.9700
O2—C18	1.184 (2)	C7—H7A	0.9600
O3—C18	1.378 (3)	C7—H7B	0.9600
O3—C3	1.432 (2)	C7—H7C	0.9600
O4—C11	1.421 (2)	C8—C9	1.481 (3)
O4—C4	1.426 (2)	C8—C18	1.503 (2)
O5—C1	1.422 (2)	C10—H10A	0.9600
O5—C5	1.429 (2)	C10—H10B	0.9600
O6—C11	1.4185 (18)	C10—H10C	0.9600
O6—C6	1.432 (2)	C11—C12	1.500 (2)
O7—C9	1.190 (3)	C11—H11A	0.9800
O8—C9	1.330 (2)	C12—C17	1.385 (3)
O8—C10	1.449 (3)	C12—C13	1.386 (3)
C1—C2	1.516 (2)	C13—C14	1.378 (3)
C1—H1A	0.9800	C13—H13A	0.9300
C2—C8	1.327 (3)	C14—C15	1.371 (3)
C2—C3	1.500 (2)	C14—H14A	0.9300
C3—C4	1.505 (2)	C15—C16	1.381 (3)
C3—H3A	0.9800	C15—H15A	0.9300
C4—C5	1.531 (2)	C16—C17	1.387 (3)
C4—H4A	0.9800	C16—H16A	0.9300
C5—C6	1.514 (2)	C17—H17A	0.9300
C5—H5A	0.9800
C1—O1—C7	112.53 (16)	O1—C7—H7C	109.5
C18—O3—C3	110.31 (13)	H7A—C7—H7C	109.5
C11—O4—C4	110.05 (13)	H7B—C7—H7C	109.5
C1—O5—C5	113.28 (13)	C2—C8—C9	128.87 (15)
C11—O6—C6	111.48 (13)	C2—C8—C18	108.03 (16)
C9—O8—C10	116.13 (18)	C9—C8—C18	122.92 (17)
O1—C1—O5	113.08 (15)	O7—C9—O8	125.19 (18)
O1—C1—C2	107.04 (15)	O7—C9—C8	124.29 (16)
O5—C1—C2	107.97 (12)	O8—C9—C8	110.50 (17)
O1—C1—H1A	109.6	O8—C10—H10A	109.5
O5—C1—H1A	109.6	O8—C10—H10B	109.5
C2—C1—H1A	109.6	H10A—C10—H10B	109.5
C8—C2—C3	110.03 (14)	O8—C10—H10C	109.5
C8—C2—C1	131.40 (16)	H10A—C10—H10C	109.5
C3—C2—C1	118.18 (16)	H10B—C10—H10C	109.5
O3—C3—C2	104.50 (15)	O6—C11—O4	110.33 (12)
O3—C3—C4	114.69 (13)	O6—C11—C12	108.68 (14)
C2—C3—C4	108.96 (15)	O4—C11—C12	109.55 (15)
O3—C3—H3A	109.5	O6—C11—H11A	109.4
C2—C3—H3A	109.5	O4—C11—H11A	109.4
C4—C3—H3A	109.5	C12—C11—H11A	109.4
O4—C4—C3	110.57 (15)	C17—C12—C13	118.94 (17)
O4—C4—C5	109.41 (14)	C17—C12—C11	121.93 (16)
C3—C4—C5	107.27 (12)	C13—C12—C11	119.07 (17)
O4—C4—H4A	109.9	C14—C13—C12	120.6 (2)
C3—C4—H4A	109.9	C14—C13—H13A	119.7
C5—C4—H4A	109.9	C12—C13—H13A	119.7
O5—C5—C6	109.61 (14)	C15—C14—C13	120.1 (2)
O5—C5—C4	110.03 (14)	C15—C14—H14A	120.0
C6—C5—C4	108.49 (13)	C13—C14—H14A	120.0
O5—C5—H5A	109.6	C14—C15—C16	120.3 (2)
C6—C5—H5A	109.6	C14—C15—H15A	119.9
C4—C5—H5A	109.6	C16—C15—H15A	119.9
O6—C6—C5	107.72 (15)	C15—C16—C17	119.6 (2)
O6—C6—H6A	110.2	C15—C16—H16A	120.2
C5—C6—H6A	110.2	C17—C16—H16A	120.2
O6—C6—H6B	110.2	C12—C17—C16	120.40 (19)
C5—C6—H6B	110.2	C12—C17—H17A	119.8
H6A—C6—H6B	108.5	C16—C17—H17A	119.8
O1—C7—H7A	109.5	O2—C18—O3	121.86 (17)
O1—C7—H7B	109.5	O2—C18—C8	131.1 (2)
H7A—C7—H7B	109.5	O3—C18—C8	107.07 (16)
C7—O1—C1—O5	77.34 (18)	C3—C2—C8—C18	−1.6 (2)
C7—O1—C1—C2	−163.89 (15)	C1—C2—C8—C18	170.92 (19)
C5—O5—C1—O1	63.63 (16)	C10—O8—C9—O7	−5.4 (3)
C5—O5—C1—C2	−54.60 (19)	C10—O8—C9—C8	173.15 (17)
O1—C1—C2—C8	112.9 (2)	C2—C8—C9—O7	147.1 (2)
O5—C1—C2—C8	−125.0 (2)	C18—C8—C9—O7	−27.5 (3)
O1—C1—C2—C3	−75.05 (19)	C2—C8—C9—O8	−31.4 (3)
O5—C1—C2—C3	47.0 (2)	C18—C8—C9—O8	153.94 (19)
C18—O3—C3—C2	−2.0 (2)	C6—O6—C11—O4	−63.75 (19)
C18—O3—C3—C4	−121.27 (18)	C6—O6—C11—C12	176.13 (15)
C8—C2—C3—O3	2.3 (2)	C4—O4—C11—O6	62.38 (18)
C1—C2—C3—O3	−171.37 (16)	C4—O4—C11—C12	−178.03 (13)
C8—C2—C3—C4	125.29 (17)	O6—C11—C12—C17	142.21 (17)
C1—C2—C3—C4	−48.3 (2)	O4—C11—C12—C17	21.6 (2)
C11—O4—C4—C3	−177.14 (14)	O6—C11—C12—C13	−40.7 (2)
C11—O4—C4—C5	−59.21 (18)	O4—C11—C12—C13	−161.28 (17)
O3—C3—C4—O4	−71.2 (2)	C17—C12—C13—C14	−2.1 (3)
C2—C3—C4—O4	172.14 (14)	C11—C12—C13—C14	−179.31 (19)
O3—C3—C4—C5	169.61 (16)	C12—C13—C14—C15	0.7 (4)
C2—C3—C4—C5	52.9 (2)	C13—C14—C15—C16	1.1 (4)
C1—O5—C5—C6	−174.29 (14)	C14—C15—C16—C17	−1.4 (4)
C1—O5—C5—C4	66.49 (17)	C13—C12—C17—C16	1.8 (3)
O4—C4—C5—O5	176.50 (13)	C11—C12—C17—C16	178.91 (18)
C3—C4—C5—O5	−63.5 (2)	C15—C16—C17—C12	−0.1 (3)
O4—C4—C5—C6	56.6 (2)	C3—O3—C18—O2	−179.9 (2)
C3—C4—C5—C6	176.58 (16)	C3—O3—C18—C8	1.2 (2)
C11—O6—C6—C5	60.36 (18)	C2—C8—C18—O2	−178.5 (3)
O5—C5—C6—O6	−176.17 (13)	C9—C8—C18—O2	−2.9 (4)
C4—C5—C6—O6	−56.01 (19)	C2—C8—C18—O3	0.3 (2)
C3—C2—C8—C9	−176.85 (19)	C9—C8—C18—O3	175.91 (17)
C1—C2—C8—C9	−4.3 (3)