Epoxidation and Reduction of DHEA, 1,4,6-Androstatrien-3-one and 4,6-Androstadien-3β,17β-diol.docVIP

Molecules 2005, 10, 572-582 molecules ISSN 1420-3049 Epoxidation and Reduction of DHEA, 1,4,6-Androstatrien-3-one and 4,6-Androstadien-3β,17β-diol Eunsook Ma* and Eunjeong Kim College of Pharmacy, Catholic University of Daegu, Hayang, 712-702, Korea. Tel. 82-053-850-3621, Fax. 82-053-850-3602. * Author to whom correspondence should be addressed; E-mail:masook@cu.ac.kr Received: 1 July 2004; in revised form: 26 February 2005 / Accepted: 1 March 2005 / Published: 25 May 2005 Abstract: Dehydroepiandrosterone (DHEA) reacted with m-chloroperoxybenzoic acid (m-CPBA) to form 3β-hydroxy-5α,6α-epoxyandrostan-17-one (1), but it did not react with 30% H2O2. 1,4,6-Androstatrien-3,17-dione (2) was obtained from DHEA and 2,3- dichloro-5,6-dicyano-1,4-benzoquinone in dioxane. Compound 2 was reacted with 30% H2O2 and 5% NaOH in methanol to give 1α,2α-epoxy-4,6-androstadien-3,17-dione (3), which was stereoselectively reduced with NaBH4 to form 1α,2α-epoxy-4,6-androstadien- 3β,17β-diol (7) and reacted with Li metal in absolute ethanol-tetrahydrofuran mixture to give 2-ethoxy-1,4,6-androstatrien-3,17-dione (8). Compound 2 was also epoxidized with m-CPBA in dichloromethane to afford 6α,7α-epoxy-1,4-androstadien-3,17-dione (4), which was reacted with NaBH4 to synthesize 6α,7α-epoxy-4-androsten-3β,17β-diol (9). Compound 4 was reduced with Li metal in absolute ethanol-tetrahydrofuran mixture to form 7β-ethoxy-6α-hydroxy-1,4-androstadien-3,17-dione (10). Compound 2 was reduced with NaBH4 in absolute ethanol to form 4,6-androstadien-3β,17β-diol (5), which was reacted with 30% H2O2 to give the original compound, but which reacted with m-CPBA to give 4β,5β-epoxy-6-androsten-3β,17β-diol (6). Keywords: Dehydroepiandrosterone; position selective and reagent selective epoxidation and reduction; H2O2; m-chloroperoxybenzoic acid; sodium borohydride, lithium  Molecules 2005, 10 573 Introduction Dehydroepiandrosterone (3β-hydro