Synthesis of Novel Steroidal Hydroxy Cyclohexenone

Prajakta S. Sarang; Arun A. Yadav; Girish K. Trivedi; Manikrao M. Salunkhe

doi:10.1055/s-2007-984898

LETTER

Synthesis of Novel Steroidal Hydroxy Cyclohexenone

Prajakta S. Sarang^a, Arun A. Yadav^a, Girish K. Trivedi*^a, Manikrao M. Salunkhe*^b
^a Department of Chemistry, The Institute of Science, 15, Madam Cama Road, Mumbai 400 032, India
e-Mail: snehgkt@yahoo.com;
^b Shivaji University, Vidyanagar Kolhapur 416 004, India
Fax: +91(231)2691533; e-Mail: mmsalunkhe@hotmail.com;

Abstract

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Abstract

A novel steroidal hydroxy cyclohexenone with five new well-defined stereocenters has been successfully synthesized by Diels-Alder reaction. Chemoselectivity observed during sodium borohydride reduction may be attributed to the rigid geometry of the cycloadduct.

Key words

steroid - Diels-Alder reaction - p-benzoquinone - chemoselectivity - borohydride reduction

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References

References and Notes

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Procedure of Diels-Alder Reaction for the Synthesis of Cycloadduct 5
p-Benzoquinone (1 mmol) and steroidal diene 3 (1 mmol) in hexane (40 mL) were refluxed for 8 h and allowed to cool to r.t. The solvent was removed in vacuo to give 5, which was used in the next step without purification.
Procedure for Sodium Borohydride Reduction of Cycloadduct 5
Sodium borohydride (3.83 mmol) was added in small portions to a solution of 5 (1 mmol) and CeCl₃ (1.79 mmol) in MeOH-CH₂Cl₂ (9 mL + 3 mL) at 0 °C. After the addition was complete, the mixture was stirred at 0 °C for 2 h and then at r.t. for 1 h. Solvent was removed in vacuo and residue was diluted with H₂O and extracted thrice with CH₂Cl₂. The combined organic layer was washed with brine, dried over Na₂SO₄, and concentrated in vacuo. To this compound in CH₂Cl₂ was added 0.5 mL HCl. The resulting solution was then stirred at r.t. for 2 h. The solution was washed with sat. bicarbonate solution twice and then with H₂O and brine solution, dried over Na₂SO₄, and concentrated in vacuo to give 2 which was purified by column chromatography (EtOAc-hexane, 1:4).
Spectroscopic Data for 2
Colorless solid (13%,overall yield); mp >200 °C. IR (KBr): 3446, 2965, 1713, 1674, 1258, 1057, 1032 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.7 (1 H, d, J = 10.2 Hz), 6.0 (1 H, dd, J = 2.5, 10.2 Hz), 5.3 (1 H, d), 4.9 (1 H, s), 4.5 (1 H, m), 2.9 (2 H, m), 2.3-2.1 (8 H, m), 2.1 (3 H, s), 1.9-1.1 (14 H, m), 1.0 (3 H, s), 0.9 (3 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 209.0, 199.1, 170.6, 149.7, 139.7, 129.9, 122.4, 73.9, 68.9, 62.0, 54.3, 50.0, 47.6, 47.5, 43.9, 40.8, 38.9, 38.1, 36.9, 36.8, 36.6, 31.4, 31.0, 27.7, 27.1, 21.4, 20.2, 19.3, 12.3. HRMS: m/z calcd for C₂₉H₃₈O₅Na [M + Na]⁺: 489.2617; found: 489.2610.

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Crystallographic data for the structure in this paper has been deposited with the Cambridge Crystallographic data centre as supplementary publication number CCDC 650192. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB 21 EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk]. Some selected crystallographic data: empirical formula C₂₉H₃₈O₅, crystal system, space group: monoclinic, P21; some of the important bond lengths: O(1)-C(2), 1.330 (5); O(1)-C(3), 1.452 (4); O(2)-C(2), 1.213 (5); O(3)-C(22), 1.220 (5); O(4)-C(26), 1.223 (5); O(5)-C(29), 1.438 (5); O(5)-H(5), 0.8200; C(1)-C(2), 1.498 (6).