UBC Theses and Dissertations

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UBC Theses and Dissertations

Synthetic studies in salamander alkaloids Paisley, Joseph Kenneth


Part I, describes an efficient four step method to effect an unsymmetric ring cleavage between carbons 2 and 3 in the A ring of 17β-acetoxy-5β-androstan-3-one (81b). Bromination of 81b followed by treatment with sodium acetate in refluxing acetic acid gave 2β,17β-diacetoxy-5β-androstan-3-one (159) in good yield. Subjecting 159 to hydroxylamine hydrochloride-sodium acetate in refluxing methanol afforded anti 17β-acetoxy-2β-hydroxy-58-androstan-3-one oxime (187) in 75-85% crude yield. Beckmann fragmentation of 187 by employing thionyl chloride furnished 17β-acetoxy-2-oxo-2,3-seco-5β-androstane-3-nitrile (195) in over 80% purified yield. Mechanistic studies on the formation of 159 from 17β-acetoxy-4β-bromo-5β-androstan-3-one (158) indicated that neither 4β,17β-diacetoxy-5β-androstan-3-one (175a) or 43,178-diacetoxy-58-androstan-3-one (175b) can be intermediates and that the intermediate isolated by Satoh and Takahashi must be 2α-acetoxy-5 β -cholestan-3-one (174). Part II, describes attempts to elaborate 195 to the 17B-hydroxy isomer of samandarine 47b. Treatment of 195 with refluxing isopropenyl acetate in the presence of concentrated sulphuric acid yielded a mixture of cis and trans 2,17β-diacetoxy-2,3-seco-5β-androst-l-ene-3-nitrile (223a) and (223b) in 62-58% purified yield. Ozonization of this mixture followed by reduction gave 17β-acetoxy-l-oxo-2,3-seco-A-nor-5β-androstane-3-nitril (262) in 86% yield. A Wittig reaction on 262 with subsequent acetyla tion afforded 17β-acetoxy-2,3-seco-5β-androst-l-ene-3-nitrile (57a) in ca. 65% purified yield. Attempts to construct 47b from 57a proved unrewarding. However, most recently, Shimizu has converted 57a to 47b in three steps.

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