21α-Fluoro-7-norvouacapane-17β,21α-lactone

The crystal structure of 21α-fluoro-7-norvouacapane-17β,21α-lactone, C₂₀H₂₅FO₃, a new synthetic derivative of the diterpenoid 6α,7β-di­hydroxy­vouacapan-17β-oic acid isolated from Pterodon polygalaeflorus Benth fruits, is described.

S1. Comment

As part of our investigation of the structural requirements for the biological activities presented by derivatives of the diterpenoid 6α,7β-dihydroxyvouacapan-17β-oic acid, (I), isolated from Pterodon polygalaeflorus Benth (Rubinger et al., 1991), we have described recently an attempt to substitute the hydroxyl groups of compounds (I) and 6α-hydroxyvouacapane-7β,17β-lactone, (II), with fluorine atoms (Demuner et al., 1998). In both cases the fluorine derivative 21α-fluoro-7-norvouacapane-17β,21α-lactone, (III), has been obtained. The introduction of fluorine atoms into new molecules is a common strategy for the development of new drugs (Wilkinson, 1992). Our purpose in this case was to produce more lipophilic analogues of compounds (I) and (II) that would still be able to make hydrogen bonds at position eight and would be less sterically hindered at that position. \sch

The structure of compound (III) was proposed based on spectroscopic data. The EIMS showed a M⁺ ion peak at m/z 332.1784, corresponding to the molecular formula C₂₀H₂₅O₃F. In the infrared spectrum, no absorption around 3300 cm⁻¹ was observed, indicating that no hydroxyl group was present in the molecule. Further evidence for the presence of fluorine in this molecule comes from the ¹⁹F-NMR spectrum that showed only one double doublet (J_F,H21 = 54 Hz and J_F,H6 = 33 Hz) at δ −128.1. We now present the X-ray study that confirms the proposed structure of this rearranged diterpenoid. This was important as the product obtained has resulted from an unexpected rearrangment. An ORTEPIII (Burnett & Johnson, 1996) drawing of the title compound is shown in Figure 1.

A conformation analysis (Cremer & Pople, 1975; Iulek & Zukerman-Schpector, 1997), of (III) shows that the A [q₂ = 0.040 (3) Å, q₃ = 0.556 (3) Å, Q = 0.557 (3) Å, θ = 4.1 (3)°, ϕ = 340 (4)°] and C [q₂ = 0.418 (3) Å, q₃ = 0.365 (3) Å, Q = 0.555 (3) Å, θ = 48.8 (3)°, ϕ = 15.7 (4)°] rings, respectively, adopt chair and distorted half chair conformations, like its precursors (I) (Ruggiero et al., 1997) and (II) (Abrahão-Junior et al., 1997). The B [q₂ = 0.501 (3) Å, ϕ = 323.6 (3)°] and D [q₂ = 0.685 (3) Å, q₃ = −0.049 (3) Å, Q = 0.687 (3) Å, θ = 94.1 (2)°, ϕ = 301.2 (2)°] rings have envelope and boat conformations, respectively.

The junctions of the rings AB, BC and CD are trans and the junction BD is cis. Some bond distances and angles of the norvouacapan fused rings are shown in Table 1. In the crystal packing there is a short contact: F···C1ⁱ = 3.525 (3) Å, F···H11ⁱ = 2.808, F···H11ⁱ—C1ⁱ = 131° (i = 2 − x, 1/2 + y, 1 − z).

S2. Experimental

The title compound has been prepared from both compounds (I) and (II) under the same conditions. Its synthesis and spectroscopic characterization has been reported recently (Demuner et al., 1998). Suitable single crystals of the title compound were obtained by slow evaporation of a THF/ethanol (1:10) solution. The absolute structure could not be determined.

S3. Refinement

H atoms were positioned geometrically and a riding model was used during the refinement process, with U_iso set to 1.5 (for methyl-H atoms) or 1.2 (for the remaining) times the value of U_eq of the atom to which they are attached.

Computing details

Data collection: CAD-4 Software (Enraf Nonius, 1989); cell refinement: CAD-4 Software; data reduction: SDP (Fair, 1990); program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. An ORTEPIII view (Burnett & Johnson, 1996) of the title compound showing 40% probability displacement ellipsoids.

21α-fluoro-7-norvouacapane-17β,21α-lactone

Crystal data

C20H25FO3	F(000) = 356
Mr = 332.40	Dx = 1.309 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 9.440 (1) Å	Cell parameters from 25 reflections
b = 9.366 (1) Å	θ = 10.3–18.3°
c = 9.741 (1) Å	µ = 0.09 mm^−1
β = 101.69 (1)°	T = 293 K
V = 843.4 (2) Å^3	Plate, colourless
Z = 2	0.45 × 0.40 × 0.08 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	1571 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.031
Graphite monochromator	θmax = 26.3°, θmin = 2.7°
ω/2θ scans	h = 0→11
Absorption correction: ψ scan (North et al., 1968)	k = −11→0
Tmin = 0.961, Tmax = 0.993	l = −12→11
1920 measured reflections	3 standard reflections every 120 min
1813 independent reflections	intensity decay: 1%

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)] = 0.035	H-atom parameters constrained
wR(F^2) = 0.097	Calculated w = 1/[σ^2(Fo^2) + (0.0491P)^2 + 0.1231P] where P = (Fo^2 + 2Fc^2)/3
S = 1.11	(Δ/σ)max < 0.001
1813 reflections	Δρmax = 0.14 e Å^−3
218 parameters	Δρmin = −0.19 e Å^−3
1 restraint	Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.6 (12)

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
F	0.90740 (17)	0.2733 (2)	0.65624 (19)	0.0620 (5)
O1	0.8964 (2)	−0.3908 (2)	0.7621 (2)	0.0574 (6)
O2	0.7468 (2)	0.0673 (3)	0.9568 (2)	0.0634 (6)
O3	0.8758 (2)	0.2340 (2)	0.8779 (2)	0.0552 (5)
C1	1.3326 (3)	−0.0233 (3)	0.5930 (3)	0.0474 (6)
H11	1.2616	−0.0167	0.5060	0.057*
H12	1.3728	−0.1190	0.5998	0.057*
C2	1.4535 (3)	0.0857 (4)	0.5916 (3)	0.0546 (7)
H21	1.5288	0.0725	0.6745	0.066*
H22	1.4956	0.0691	0.5101	0.066*
C3	1.3974 (3)	0.2385 (3)	0.5882 (3)	0.0523 (7)
H31	1.3318	0.2538	0.4990	0.063*
H32	1.4786	0.3028	0.5921	0.063*
C4	1.3186 (3)	0.2792 (3)	0.7064 (3)	0.0413 (6)
C5	1.2049 (3)	0.1618 (3)	0.7090 (2)	0.0336 (5)
H51	1.1390	0.1690	0.6175	0.040*
C6	1.1046 (3)	0.1656 (3)	0.8168 (2)	0.0350 (5)
H61	1.1649	0.1832	0.9096	0.042*
C8	1.0472 (2)	0.0123 (3)	0.8146 (2)	0.0335 (5)
H81	1.0831	−0.0300	0.9071	0.040*
C9	1.1124 (3)	−0.0711 (3)	0.7075 (2)	0.0357 (5)
H91	1.0538	−0.0493	0.6148	0.043*
C10	1.2590 (2)	0.0040 (3)	0.7170 (2)	0.0355 (5)
C11	1.0972 (3)	−0.2314 (3)	0.7314 (3)	0.0477 (6)
H111	1.1096	−0.2847	0.6493	0.057*
H112	1.1697	−0.2630	0.8110	0.057*
C12	0.9489 (3)	−0.2542 (3)	0.7589 (3)	0.0447 (6)
C13	0.8498 (3)	−0.1591 (3)	0.7835 (3)	0.0409 (6)
C14	0.8819 (2)	−0.0014 (3)	0.7811 (3)	0.0373 (5)
H141	0.8466	0.0336	0.6855	0.045*
C15	0.7268 (3)	−0.2401 (4)	0.8025 (3)	0.0485 (7)
H151	0.6405	−0.2044	0.8206	0.058*
C16	0.7606 (4)	−0.3776 (4)	0.7893 (3)	0.0565 (8)
H161	0.6998	−0.4538	0.7976	0.068*
C17	0.8255 (3)	0.0949 (3)	0.8791 (3)	0.0458 (6)
C18	1.2420 (4)	0.4220 (4)	0.6681 (4)	0.0596 (8)
H181	1.3115	0.4925	0.6541	0.089*
H182	1.1961	0.4518	0.7427	0.089*
H183	1.1703	0.4112	0.5834	0.089*
C19	1.4264 (3)	0.3014 (4)	0.8455 (3)	0.0549 (7)
H191	1.4836	0.3850	0.8390	0.082*
H192	1.4886	0.2197	0.8646	0.082*
H193	1.3745	0.3135	0.9199	0.082*
C20	1.3605 (3)	−0.0374 (3)	0.8550 (3)	0.0483 (7)
H201	1.3228	−0.0008	0.9325	0.072*
H202	1.4548	0.0022	0.8573	0.072*
H203	1.3675	−0.1395	0.8617	0.072*
C21	0.9790 (3)	0.2700 (3)	0.7957 (3)	0.0474 (6)
H211	1.0169	0.3656	0.8226	0.057*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F	0.0583 (10)	0.0536 (11)	0.0704 (10)	0.0184 (9)	0.0041 (8)	0.0180 (9)
O1	0.0713 (15)	0.0360 (12)	0.0676 (13)	−0.0094 (10)	0.0203 (11)	0.0007 (9)
O2	0.0562 (12)	0.0694 (16)	0.0733 (14)	−0.0052 (11)	0.0341 (10)	−0.0162 (12)
O3	0.0521 (11)	0.0424 (11)	0.0768 (14)	0.0061 (9)	0.0265 (10)	−0.0139 (10)
C1	0.0484 (14)	0.0462 (16)	0.0520 (15)	0.0017 (13)	0.0205 (11)	−0.0066 (13)
C2	0.0578 (17)	0.0576 (18)	0.0563 (16)	−0.0043 (15)	0.0302 (13)	−0.0097 (15)
C3	0.0607 (17)	0.0528 (18)	0.0484 (15)	−0.0126 (14)	0.0226 (13)	−0.0025 (13)
C4	0.0485 (13)	0.0370 (14)	0.0410 (12)	−0.0040 (12)	0.0150 (10)	−0.0025 (11)
C5	0.0371 (12)	0.0322 (12)	0.0309 (11)	0.0015 (10)	0.0055 (9)	−0.0008 (10)
C6	0.0386 (12)	0.0327 (12)	0.0334 (11)	0.0039 (10)	0.0063 (9)	−0.0001 (10)
C8	0.0353 (11)	0.0332 (12)	0.0313 (10)	0.0055 (10)	0.0049 (9)	0.0004 (9)
C9	0.0381 (12)	0.0313 (13)	0.0382 (12)	0.0055 (10)	0.0089 (10)	0.0008 (10)
C10	0.0394 (12)	0.0349 (13)	0.0332 (11)	0.0077 (11)	0.0100 (9)	0.0010 (10)
C11	0.0498 (14)	0.0315 (14)	0.0648 (16)	0.0057 (12)	0.0186 (12)	−0.0007 (13)
C12	0.0536 (15)	0.0293 (14)	0.0509 (15)	−0.0039 (11)	0.0102 (12)	0.0011 (11)
C13	0.0419 (13)	0.0413 (15)	0.0383 (13)	−0.0013 (11)	0.0057 (10)	−0.0019 (11)
C14	0.0361 (12)	0.0362 (14)	0.0384 (12)	0.0031 (10)	0.0048 (9)	0.0002 (11)
C15	0.0479 (14)	0.0551 (18)	0.0428 (13)	−0.0101 (13)	0.0098 (11)	−0.0010 (13)
C16	0.0637 (19)	0.056 (2)	0.0518 (15)	−0.0189 (15)	0.0167 (14)	0.0010 (14)
C17	0.0353 (12)	0.0496 (17)	0.0527 (14)	0.0060 (12)	0.0091 (11)	−0.0072 (13)
C18	0.071 (2)	0.0365 (16)	0.074 (2)	−0.0020 (15)	0.0216 (16)	0.0073 (15)
C19	0.0509 (15)	0.061 (2)	0.0534 (15)	−0.0170 (15)	0.0117 (12)	−0.0140 (14)
C20	0.0361 (12)	0.0551 (17)	0.0530 (14)	0.0100 (12)	0.0071 (10)	0.0110 (13)
C21	0.0488 (14)	0.0342 (14)	0.0605 (16)	0.0059 (13)	0.0142 (12)	−0.0015 (13)

Geometric parameters (Å, º)

F—C21	1.390 (3)	C5—C10	1.560 (3)
O1—C16	1.366 (4)	C6—C21	1.518 (3)
O1—C12	1.375 (3)	C6—C8	1.533 (4)
O2—C17	1.192 (3)	C8—C9	1.528 (3)
O3—C17	1.387 (4)	C8—C14	1.533 (3)
O3—C21	1.421 (3)	C9—C11	1.531 (4)
C1—C10	1.532 (3)	C9—C10	1.539 (3)
C1—C2	1.533 (4)	C10—C20	1.535 (3)
C2—C3	1.524 (5)	C11—C12	1.493 (4)
C3—C4	1.540 (3)	C12—C13	1.347 (4)
C4—C18	1.530 (4)	C13—C15	1.430 (4)
C4—C19	1.536 (4)	C13—C14	1.509 (4)
C4—C5	1.540 (4)	C14—C17	1.488 (4)
C5—C6	1.550 (3)	C15—C16	1.338 (5)
C16—O1—C12	106.1 (2)	C1—C10—C9	115.0 (2)
C17—O3—C21	120.2 (2)	C20—C10—C9	109.3 (2)
C10—C1—C2	110.6 (2)	C1—C10—C5	108.4 (2)
C3—C2—C1	111.7 (2)	C20—C10—C5	115.0 (2)
C2—C3—C4	115.8 (2)	C9—C10—C5	98.53 (18)
C18—C4—C19	107.0 (2)	C12—C11—C9	106.7 (2)
C18—C4—C3	108.1 (2)	C13—C12—O1	110.2 (2)
C19—C4—C3	111.0 (2)	C13—C12—C11	130.3 (3)
C18—C4—C5	109.4 (2)	O1—C12—C11	119.5 (2)
C19—C4—C5	114.9 (2)	C12—C13—C15	106.4 (3)
C3—C4—C5	106.2 (2)	C12—C13—C14	119.7 (2)
C4—C5—C6	121.2 (2)	C15—C13—C14	133.8 (3)
C4—C5—C10	117.0 (2)	C17—C14—C13	119.0 (2)
C6—C5—C10	103.10 (19)	C17—C14—C8	107.1 (2)
C21—C6—C8	109.7 (2)	C13—C14—C8	106.1 (2)
C21—C6—C5	119.4 (2)	C16—C15—C13	106.4 (3)
C8—C6—C5	103.42 (19)	C15—C16—O1	110.9 (3)
C9—C8—C14	110.21 (19)	O2—C17—O3	117.9 (3)
C9—C8—C6	107.32 (19)	O2—C17—C14	128.7 (3)
C14—C8—C6	114.99 (19)	O3—C17—C14	113.3 (2)
C8—C9—C11	109.5 (2)	F—C21—O3	107.6 (2)
C8—C9—C10	101.96 (19)	F—C21—C6	111.0 (2)
C11—C9—C10	123.4 (2)	O3—C21—C6	112.1 (2)
C1—C10—C20	110.3 (2)
C10—C1—C2—C3	−56.4 (3)	C4—C5—C10—C9	−176.55 (19)
C1—C2—C3—C4	55.4 (3)	C6—C5—C10—C9	47.7 (2)
C2—C3—C4—C18	−167.6 (3)	C8—C9—C11—C12	42.3 (3)
C2—C3—C4—C19	75.3 (3)	C10—C9—C11—C12	162.1 (2)
C2—C3—C4—C5	−50.3 (3)	C16—O1—C12—C13	0.1 (3)
C18—C4—C5—C6	−64.3 (3)	C16—O1—C12—C11	179.9 (3)
C19—C4—C5—C6	56.1 (3)	C9—C11—C12—C13	−10.6 (4)
C3—C4—C5—C6	179.3 (2)	C9—C11—C12—O1	169.7 (2)
C18—C4—C5—C10	168.3 (2)	O1—C12—C13—C15	−0.4 (3)
C19—C4—C5—C10	−71.3 (3)	C11—C12—C13—C15	179.9 (3)
C3—C4—C5—C10	51.9 (3)	O1—C12—C13—C14	−178.3 (2)
C4—C5—C6—C21	75.3 (3)	C11—C12—C13—C14	2.0 (4)
C10—C5—C6—C21	−151.3 (2)	C12—C13—C14—C17	−145.5 (3)
C4—C5—C6—C8	−162.5 (2)	C15—C13—C14—C17	37.2 (4)
C10—C5—C6—C8	−29.1 (2)	C12—C13—C14—C8	−24.8 (3)
C21—C6—C8—C9	127.5 (2)	C15—C13—C14—C8	157.9 (3)
C5—C6—C8—C9	−0.9 (2)	C9—C8—C14—C17	−173.8 (2)
C21—C6—C8—C14	4.5 (3)	C6—C8—C14—C17	−52.3 (3)
C5—C6—C8—C14	−123.85 (19)	C9—C8—C14—C13	58.2 (2)
C14—C8—C9—C11	−71.1 (3)	C6—C8—C14—C13	179.6 (2)
C6—C8—C9—C11	163.0 (2)	C12—C13—C15—C16	0.5 (3)
C14—C8—C9—C10	156.75 (19)	C14—C13—C15—C16	178.0 (3)
C6—C8—C9—C10	30.9 (2)	C13—C15—C16—O1	−0.4 (3)
C2—C1—C10—C20	−71.4 (3)	C12—O1—C16—C15	0.2 (3)
C2—C1—C10—C9	164.4 (2)	C21—O3—C17—O2	174.9 (2)
C2—C1—C10—C5	55.3 (3)	C21—O3—C17—C14	−4.1 (4)
C8—C9—C10—C1	−162.5 (2)	C13—C14—C17—O2	−5.8 (4)
C11—C9—C10—C1	74.3 (3)	C8—C14—C17—O2	−125.9 (3)
C8—C9—C10—C20	72.9 (2)	C13—C14—C17—O3	173.1 (2)
C11—C9—C10—C20	−50.4 (3)	C8—C14—C17—O3	53.0 (3)
C8—C9—C10—C5	−47.5 (2)	C17—O3—C21—F	74.3 (3)
C11—C9—C10—C5	−170.8 (2)	C17—O3—C21—C6	−48.0 (3)
C4—C5—C10—C1	−56.6 (3)	C8—C6—C21—F	−75.9 (3)
C6—C5—C10—C1	167.69 (19)	C5—C6—C21—F	43.1 (3)
C4—C5—C10—C20	67.4 (3)	C8—C6—C21—O3	44.5 (3)
C6—C5—C10—C20	−68.4 (2)	C5—C6—C21—O3	163.5 (2)