Pregna-1,4,20-trien-3-one, a cytotoxic marine steroid from the marine soft coral Nephthea sp.

The title compound, C(21)H(28)O, was isolated from the cytotoxic lipid extract of the Fidjian soft coral Nephthea sp. The steroid showed inhibitory activity to human colon adenocarcinoma SW480 cells (IC(50) = 2.5 µg ml(-1)). The mol-ecular structure indicates that the A ring is almost planar (r.m.s. deviation = 0.032 Å), the B and C rings adopt chair conformations and the five-membered D ring is a half-chair. The B/C and C/D ring junctions are trans-fused.

Related literature

For chemical background to soft corals, see: Coll (1992 ▶); Sarma et al. (2009 ▶). For the initial isolation of the title compound, see: Kingston et al. (1977 ▶); Higgs & Faulkner (1977 ▶). For further isolations of the title compound from other organisms, see: Maia et al. (1998 ▶); Ciavatta et al. (2004 ▶); Zhang et al. (2003 ▶, 2005 ▶). Huang et al. (2006 ▶, 2009 ▶); Yan et al. (2004 ▶, 2007 ▶). For steroid ring conformations, see: Kingston et al. (1979 ▶). For further information on the cytotoxicity studies, see: Grever et al. (1992 ▶); Ullrich et al. (2009 ▶). For a related structure, see: Thompson et al. (1999 ▶).

Experimental

Crystal data

C21H28O

M = 296.43

Orthorhombic,

a = 6.967 (5) Å

b = 11.470 (9) Å

c = 20.891 (16) Å

V = 1669 (2) Å3

Z = 4

Mo Kα radiation

μ = 0.07 mm−1

T = 100 K

0.32 × 0.16 × 0.06 mm

Data collection

Bruker X8 Kappa APEXII diffractometer

7256 measured reflections

2267 independent reflections

1144 reflections with I > 2σ(I)

R int = 0.142

Refinement

R[F 2 > 2σ(F 2)] = 0.063

wR(F 2) = 0.142

S = 0.97

2267 reflections

202 parameters

H-atom parameters constrained

Δρmax = 0.25 e Å−3

Δρmin = −0.26 e Å−3

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 1999 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810027352/hb5516sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810027352/hb5516Isup2.hkl

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

C21H28O	F(000) = 648
Mr = 296.43	Dx = 1.179 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 688 reflections
a = 6.967 (5) Å	θ = 2.6–24.9°
b = 11.470 (9) Å	µ = 0.07 mm−1
c = 20.891 (16) Å	T = 100 K
V = 1669 (2) Å3	Plate, colourless
Z = 4	0.32 × 0.16 × 0.06 mm

Bruker X8 Kappa APEXII diffractometer	1144 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.142
graphite	θmax = 28.0°, θmin = 2.6°
fine slicing φ and ω scans	h = −8→9
7256 measured reflections	k = −10→15
2267 independent reflections	l = −24→26

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.063	H-atom parameters constrained
wR(F2) = 0.142	w = 1/[σ2(Fo2) + (0.0414P)2] where P = (Fo2 + 2Fc2)/3
S = 0.97	(Δ/σ)max < 0.001
2267 reflections	Δρmax = 0.25 e Å−3
202 parameters	Δρmin = −0.26 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.009 (2)

Experimental. During data collection the crystal was in cold N2 gas of a Kryoflex cooler (Bruker AXS).

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.

	x	y	z	Uiso*/Ueq
C1	0.0756 (6)	0.8569 (4)	0.1960 (2)	0.0264 (11)
H1	−0.0301	0.9090	0.1935	0.032*
C2	0.0531 (6)	0.7591 (4)	0.2299 (2)	0.0279 (12)
H2	−0.0662	0.7446	0.2505	0.033*
C3	0.2060 (6)	0.6750 (4)	0.2361 (2)	0.0285 (11)
C4	0.3822 (6)	0.6981 (4)	0.1998 (2)	0.0255 (11)
H4	0.4818	0.6415	0.2005	0.031*
C5	0.4080 (6)	0.7956 (3)	0.1657 (2)	0.0237 (11)
C6	0.5879 (6)	0.8167 (4)	0.1284 (2)	0.0272 (11)
H6A	0.6749	0.7490	0.1329	0.033*
H6B	0.6545	0.8864	0.1454	0.033*
C7	0.5388 (6)	0.8353 (4)	0.0578 (2)	0.0269 (11)
H7A	0.6577	0.8528	0.0336	0.032*
H7B	0.4827	0.7629	0.0400	0.032*
C8	0.3973 (6)	0.9350 (4)	0.0493 (2)	0.0250 (11)
H8	0.4591	1.0085	0.0648	0.030*
C9	0.2129 (6)	0.9137 (4)	0.0890 (2)	0.0233 (11)
H9	0.1545	0.8404	0.0719	0.028*
C10	0.2575 (6)	0.8901 (3)	0.1614 (2)	0.0229 (11)
C11	0.0639 (6)	1.0103 (4)	0.0783 (2)	0.0255 (11)
H11A	0.1130	1.0840	0.0967	0.031*
H11B	−0.0557	0.9897	0.1013	0.031*
C12	0.0181 (6)	1.0290 (3)	0.0069 (2)	0.0254 (11)
H12A	−0.0463	0.9588	−0.0103	0.031*
H12B	−0.0710	1.0958	0.0023	0.031*
C13	0.2001 (6)	1.0527 (3)	−0.0312 (2)	0.0233 (11)
C14	0.3411 (6)	0.9511 (3)	−0.0204 (2)	0.0247 (11)
H14	0.2701	0.8788	−0.0328	0.030*
C15	0.4951 (6)	0.9686 (4)	−0.0717 (2)	0.0310 (12)
H15A	0.5552	0.8934	−0.0836	0.037*
H15B	0.5961	1.0227	−0.0567	0.037*
C16	0.3837 (6)	1.0211 (4)	−0.1290 (2)	0.0336 (12)
H16A	0.3808	0.9654	−0.1651	0.040*
H16B	0.4457	1.0941	−0.1436	0.040*
C17	0.1756 (6)	1.0464 (4)	−0.1046 (2)	0.0265 (11)
H17	0.0957	0.9762	−0.1143	0.032*
C18	0.2877 (6)	1.1710 (3)	−0.0131 (2)	0.0294 (11)
H18A	0.1916	1.2325	−0.0190	0.044*
H18B	0.3988	1.1868	−0.0405	0.044*
H18C	0.3286	1.1693	0.0318	0.044*
C19	0.3332 (6)	1.0012 (4)	0.1957 (2)	0.0280 (11)
H19A	0.3791	0.9805	0.2386	0.042*
H19B	0.2294	1.0584	0.1993	0.042*
H19C	0.4391	1.0347	0.1709	0.042*
C20	0.0811 (7)	1.1483 (4)	−0.1348 (2)	0.0325 (12)
H20	0.1523	1.2189	−0.1366	0.039*
C21	−0.0940 (7)	1.1494 (4)	−0.1594 (2)	0.0394 (13)
H21A	−0.1702	1.0807	−0.1585	0.047*
H21B	−0.1435	1.2188	−0.1779	0.047*
O	0.1903 (4)	0.5870 (3)	0.27010 (17)	0.0409 (9)

	U11	U22	U33	U12	U13	U23
C1	0.027 (2)	0.027 (2)	0.025 (3)	0.004 (2)	−0.004 (2)	−0.007 (2)
C2	0.036 (3)	0.031 (2)	0.016 (3)	−0.009 (2)	0.004 (2)	−0.003 (2)
C3	0.037 (3)	0.029 (2)	0.020 (3)	−0.001 (2)	−0.001 (2)	−0.004 (2)
C4	0.031 (2)	0.024 (2)	0.022 (3)	0.005 (2)	0.001 (2)	−0.001 (2)
C5	0.029 (2)	0.023 (2)	0.019 (3)	−0.001 (2)	0.000 (2)	−0.004 (2)
C6	0.027 (2)	0.029 (2)	0.026 (3)	0.003 (2)	−0.001 (2)	0.002 (2)
C7	0.030 (3)	0.032 (2)	0.018 (3)	0.004 (2)	−0.001 (2)	0.004 (2)
C8	0.030 (2)	0.025 (2)	0.020 (3)	−0.001 (2)	−0.001 (2)	0.002 (2)
C9	0.027 (2)	0.021 (2)	0.022 (3)	−0.0005 (19)	0.006 (2)	0.0003 (19)
C10	0.026 (2)	0.029 (2)	0.014 (3)	−0.0060 (19)	−0.001 (2)	−0.0012 (19)
C11	0.030 (2)	0.034 (2)	0.013 (3)	−0.003 (2)	0.004 (2)	−0.001 (2)
C12	0.026 (2)	0.021 (2)	0.029 (3)	0.0010 (19)	−0.001 (2)	0.001 (2)
C13	0.027 (2)	0.024 (2)	0.019 (3)	−0.002 (2)	−0.001 (2)	0.001 (2)
C14	0.032 (3)	0.028 (2)	0.015 (3)	0.0025 (19)	0.003 (2)	−0.002 (2)
C15	0.035 (2)	0.041 (3)	0.017 (3)	0.004 (2)	0.005 (2)	0.004 (2)
C16	0.037 (3)	0.044 (3)	0.020 (3)	0.008 (2)	0.000 (2)	0.005 (2)
C17	0.026 (2)	0.030 (2)	0.023 (3)	−0.001 (2)	−0.001 (2)	−0.004 (2)
C18	0.032 (2)	0.034 (2)	0.023 (3)	−0.003 (2)	−0.007 (2)	0.002 (2)
C19	0.036 (2)	0.032 (2)	0.015 (3)	−0.003 (2)	−0.005 (2)	0.000 (2)
C20	0.038 (3)	0.039 (3)	0.020 (3)	0.002 (2)	0.000 (2)	0.002 (2)
C21	0.046 (3)	0.046 (3)	0.026 (3)	0.009 (3)	−0.003 (3)	0.007 (2)
O	0.047 (2)	0.0356 (18)	0.040 (3)	−0.0040 (17)	0.0076 (19)	0.0089 (18)

C1—C2	1.336 (6)	C12—C13	1.522 (6)
C1—C10	1.508 (6)	C12—H12A	0.9900
C1—H1	0.9500	C12—H12B	0.9900
C2—C3	1.443 (6)	C13—C18	1.535 (5)
C2—H2	0.9500	C13—C14	1.541 (6)
C3—O	1.239 (5)	C13—C17	1.545 (6)
C3—C4	1.466 (6)	C14—C15	1.529 (6)
C4—C5	1.338 (6)	C14—H14	1.0000
C4—H4	0.9500	C15—C16	1.548 (6)
C5—C6	1.495 (6)	C15—H15A	0.9900
C5—C10	1.511 (6)	C15—H15B	0.9900
C6—C7	1.531 (6)	C16—C17	1.564 (6)
C6—H6A	0.9900	C16—H16A	0.9900
C6—H6B	0.9900	C16—H16B	0.9900
C7—C8	1.520 (6)	C17—C20	1.483 (6)
C7—H7A	0.9900	C17—H17	1.0000
C7—H7B	0.9900	C19—H19A	0.9800
C8—C14	1.521 (6)	C19—H19B	0.9800
C8—C9	1.548 (6)	C19—H19C	0.9800
C8—H8	1.0000	C18—H18A	0.9800
C9—C11	1.535 (6)	C18—H18B	0.9800
C9—C10	1.568 (6)	C18—H18C	0.9800
C9—H9	1.0000	C20—C21	1.324 (6)
C10—C19	1.554 (5)	C20—H20	0.9500
C11—C12	1.541 (6)	C21—H21A	0.9500
C11—H11A	0.9900	C21—H21B	0.9500
C11—H11B	0.9900
C2—C1—C10	124.4 (4)	C11—C12—H12A	109.4
C2—C1—H1	117.8	C13—C12—H12B	109.4
C10—C1—H1	117.8	C11—C12—H12B	109.4
C1—C2—C3	121.5 (4)	H12A—C12—H12B	108.0
C1—C2—H2	119.3	C12—C13—C18	111.1 (4)
C3—C2—H2	119.3	C12—C13—C14	108.7 (3)
O—C3—C2	122.0 (4)	C18—C13—C14	112.3 (3)
O—C3—C4	121.2 (4)	C12—C13—C17	114.8 (4)
C2—C3—C4	116.8 (4)	C18—C13—C17	109.3 (4)
C5—C4—C3	122.6 (4)	C14—C13—C17	100.3 (3)
C5—C4—H4	118.7	C8—C14—C15	120.5 (4)
C3—C4—H4	118.7	C8—C14—C13	113.3 (4)
C4—C5—C6	121.7 (4)	C15—C14—C13	104.2 (3)
C4—C5—C10	122.6 (4)	C8—C14—H14	105.9
C6—C5—C10	115.7 (4)	C15—C14—H14	105.9
C5—C6—C7	109.8 (4)	C13—C14—H14	105.9
C5—C6—H6A	109.7	C14—C15—C16	103.9 (3)
C7—C6—H6A	109.7	C14—C15—H15A	111.0
C5—C6—H6B	109.7	C16—C15—H15A	111.0
C7—C6—H6B	109.7	C14—C15—H15B	111.0
H6A—C6—H6B	108.2	C16—C15—H15B	111.0
C8—C7—C6	111.2 (4)	H15A—C15—H15B	109.0
C8—C7—H7A	109.4	C15—C16—C17	106.6 (4)
C6—C7—H7A	109.4	C15—C16—H16A	110.4
C8—C7—H7B	109.4	C17—C16—H16A	110.4
C6—C7—H7B	109.4	C15—C16—H16B	110.4
H7A—C7—H7B	108.0	C17—C16—H16B	110.4
C7—C8—C14	111.7 (4)	H16A—C16—H16B	108.6
C7—C8—C9	110.9 (3)	C20—C17—C13	115.7 (4)
C14—C8—C9	108.6 (3)	C20—C17—C16	114.8 (4)
C7—C8—H8	108.5	C13—C17—C16	103.3 (4)
C14—C8—H8	108.5	C20—C17—H17	107.5
C9—C8—H8	108.5	C13—C17—H17	107.5
C11—C9—C8	111.7 (3)	C16—C17—H17	107.5
C11—C9—C10	113.5 (4)	C10—C19—H19A	109.5
C8—C9—C10	112.3 (3)	C10—C19—H19B	109.5
C11—C9—H9	106.3	H19A—C19—H19B	109.5
C8—C9—H9	106.3	C10—C19—H19C	109.5
C10—C9—H9	106.3	H19A—C19—H19C	109.5
C1—C10—C5	111.9 (3)	H19B—C19—H19C	109.5
C1—C10—C19	105.8 (4)	C13—C18—H18A	109.5
C5—C10—C19	108.9 (4)	C13—C18—H18B	109.5
C1—C10—C9	109.9 (3)	H18A—C18—H18B	109.5
C5—C10—C9	108.6 (4)	C13—C18—H18C	109.5
C19—C10—C9	111.8 (3)	H18A—C18—H18C	109.5
C9—C11—C12	112.4 (4)	H18B—C18—H18C	109.5
C9—C11—H11A	109.1	C21—C20—C17	125.5 (4)
C12—C11—H11A	109.1	C21—C20—H20	117.2
C9—C11—H11B	109.1	C17—C20—H20	117.2
C12—C11—H11B	109.1	C20—C21—H21A	120.0
H11A—C11—H11B	107.9	C20—C21—H21B	120.0
C13—C12—C11	111.0 (3)	H21A—C21—H21B	120.0
C13—C12—H12A	109.4
C10—C1—C2—C3	−0.2 (7)	C8—C9—C10—C19	69.2 (4)
C1—C2—C3—O	176.2 (4)	C8—C9—C11—C12	53.7 (5)
C1—C2—C3—C4	−4.1 (6)	C10—C9—C11—C12	−178.2 (3)
O—C3—C4—C5	−175.9 (4)	C9—C11—C12—C13	−54.9 (4)
C2—C3—C4—C5	4.4 (6)	C11—C12—C13—C18	−68.0 (4)
C3—C4—C5—C6	−179.2 (4)	C11—C12—C13—C14	56.1 (4)
C3—C4—C5—C10	−0.4 (7)	C11—C12—C13—C17	167.4 (3)
C4—C5—C6—C7	121.8 (5)	C7—C8—C14—C15	−54.7 (5)
C10—C5—C6—C7	−57.1 (5)	C9—C8—C14—C15	−177.4 (4)
C5—C6—C7—C8	56.5 (5)	C7—C8—C14—C13	−179.1 (3)
C6—C7—C8—C14	−177.7 (4)	C9—C8—C14—C13	58.3 (4)
C6—C7—C8—C9	−56.4 (5)	C12—C13—C14—C8	−60.0 (4)
C7—C8—C9—C11	−177.0 (4)	C18—C13—C14—C8	63.4 (5)
C14—C8—C9—C11	−53.9 (5)	C17—C13—C14—C8	179.3 (4)
C7—C8—C9—C10	54.2 (5)	C12—C13—C14—C15	167.2 (3)
C14—C8—C9—C10	177.3 (3)	C18—C13—C14—C15	−69.4 (5)
C2—C1—C10—C5	4.0 (6)	C17—C13—C14—C15	46.5 (4)
C2—C1—C10—C19	−114.5 (5)	C8—C14—C15—C16	−161.8 (4)
C2—C1—C10—C9	124.7 (4)	C13—C14—C15—C16	−33.3 (4)
C4—C5—C10—C1	−3.6 (6)	C14—C15—C16—C17	7.2 (5)
C6—C5—C10—C1	175.3 (4)	C12—C13—C17—C20	76.7 (5)
C4—C5—C10—C19	113.0 (5)	C18—C13—C17—C20	−48.9 (5)
C6—C5—C10—C19	−68.1 (5)	C14—C13—C17—C20	−167.1 (3)
C4—C5—C10—C9	−125.0 (5)	C12—C13—C17—C16	−157.0 (3)
C6—C5—C10—C9	53.9 (5)	C18—C13—C17—C16	77.4 (4)
C11—C9—C10—C1	58.4 (4)	C14—C13—C17—C16	−40.8 (4)
C8—C9—C10—C1	−173.7 (3)	C15—C16—C17—C20	148.1 (4)
C11—C9—C10—C5	−178.9 (3)	C15—C16—C17—C13	21.2 (4)
C8—C9—C10—C5	−51.0 (4)	C13—C17—C20—C21	−108.6 (6)
C11—C9—C10—C19	−58.7 (5)	C16—C17—C20—C21	131.2 (5)