(7aR)-1-[(2R,5S,E)-6-Hy­droxy-5,6-dimethyl­hept-3-en-2-yl]-7a-methyl­hexa­hydro-1H-inden-4(2H)-one

Marcos L Rivadulla; Massene Sene; María González; Berta Covelo

doi:10.1107/S1600536812051343

. 2013 Jan 12;69(Pt 2):o218. doi: 10.1107/S1600536812051343

(7aR)-1-[(2R,5S,E)-6-Hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one

Marcos L Rivadulla ^a,^*, Massene Sene ^a, María González ^a, Berta Covelo ^b

PMCID: PMC3569753 PMID: 23424499

Abstract

The chiral title compound, C₁₉H₃₂O₂, contains a [4.3.0]-bicyclic moiety in which the shared C—C bond presents a trans configuration and a side chain in which the C=C double bond shows an E conformation. The conformations of five- and six-membered rings are envelope (with the bridgehead atom bearing the methyl substituent as the flap) and chair, respectively, with a dihedral angle of 4.08 (17)° between the idealized planes of the rings. In the crystal, the molecules are self-assembled via classical O—H⋯O hydrogen bonds, forming chains along [112]; these chains are linked by weak non-classical C—H⋯O hydrogen bonds, giving a two-dimensional supramolecular structure parallel to (010). The absolute configuration was established according to the configuration of the starting material.

Related literature

The title compound is a precursor of the hormonally active form of vitamin D3. For general background to vitamin D3, see: Heaney (2008 ▶); Henry (2011 ▶). For related structures, see: Maehr & Uskokovic (2004 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₉H₃₂O₂
M _r = 292.45
Monoclinic,
a = 20.057 (4) Å
b = 7.3816 (15) Å
c = 13.700 (3) Å
β = 112.324 (4)°
V = 1876.3 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 293 K
0.45 × 0.36 × 0.18 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.602, T _max = 0.745
4958 measured reflections
3254 independent reflections
2389 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.152
S = 1.02
3254 reflections
196 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.11 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1998 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Click here for additional data file.^{(27.8KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812051343/pv2614sup1.cif

e-69-0o218-sup1.cif^{(27.8KB, cif)}

Click here for additional data file.^{(159.6KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812051343/pv2614Isup2.hkl

e-69-0o218-Isup2.hkl^{(159.6KB, hkl)}

Click here for additional data file.^{(7.4KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812051343/pv2614Isup3.cml

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
O7′—H7′⋯O4ⁱ	0.82	2.08	2.876 (3)	164
C3A—H3A1⋯O7′ⁱⁱ	0.98	2.56	3.523 (3)	166

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This work was supported financially by the Spanish Ministry of Foreign Affairs and Cooperation (PCIA/030052/10) and the Xunta de Galicia (INCITE845B, INCITE08PXIB314255PR).

supplementary crystallographic information

Comment

The title compound is a precursor of 1α,25-dihydroxyvitamin D3 (calcitriol) analogue which is the hormonally active form of vitamin D3. Besides regulating calcium homeostasis, this form is also involved in other cellular processes such as cell differentiation; immune system regulation and gene transcription (Henry, 2011). Nevertheless, the clinical utility of this hormone for treatment of cancers and skin disorders is limited by its hypercalcemic effects (Heaney, 2008), for this purpose the design and synthesis of more selective biological-effect analogues is of paramount importance. In the title compound (Figure 1), the C3A—C7A shared bond of the bicyclic moiety presents a trans configuration. Besides, the 5-membered ring adopts an envelope conformation with puckering parameters Q = 0.462 (3) Å and φ = 136.5 (4)° and with the bridgehead C7A atom bearing the methyl substituent as the flap (Cremer & Pople, 1975) and the 6-membered ring presents a chair conformation with puckering parameters Q = 0.556 (3) Å, θ = 169.5 (3)° and φ = 133.4 (18)° (Cremer & Pople, 1975). The value for the dihedral angle between the idealized planes of the rings is 4.08 (17)°. All bond lengths and bond angles are normal comparable to those observed in similar crystal structures (Maehr & Uskokovic, 2004). In the crystal structure, the molecules are self-assembled via classical O—H···O hydrogen bonds to form a chain along [112], the resulting chains are connected by weak non-classical C—H···O hydrogen bonds to create a two-dimensional supramolecular structure (Table 1, Figure 2).

Experimental

Over a stirring solution of inhoffen-lythgoe diol (2.1 g; 7.2 mmol) in CH₂Cl₂ (10 ml), PDC S-methyl-3-hydroxy-2-methylpropionate (5.4 g; 14.4 mmol) was added. The mixture was stirred at room temperature for 16 h then it was quenched with ethylic ether (20 ml) and stirred one more hour. The solid precipitated was filtered over celite, the organic layer was concentrated and the residue was purified by flash column chromatography on silica gel (10% ethyl acetate/hexane) to afford the title compound (1.8 g; 80%). The crystals were obtained by slow evaporation in a closed camera of a solution of the compound in a mixture of ethyl acetate/hexane (7:3).