First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16-carbolactone (Diosgeninlactone).docVIP

564 Molecules 2000, 5 First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16- carbolactone (Diosgeninlactone) Andrea C. Bruttomesso and Eduardo G. Gros Departamento. de Química. Orgánica, UMYMFOR. Facultad de Ciencias Exactas y Naturales, UBA. Pabellón II, 3o P. Ciudad Universitaria. (1428). Buenos Aires, Argentina E-mail: aachiocc@quimor.qo.fcen.uba.ar Abstract: Diosgeninlactone (1), a natural product from Solanum vespertilio, was stereo- selectively synthesized in high yield from 3β-hydroxy-5-androstene. Introduction Our development of synthetic approaches to cis-20,16-γ-carbolactones originated during the course of studies on the catabolic pathway by which tomato plants degrade steroidal alkaloids into 3β- hydroxy-5α-pregn-16-en-20-ona. The isolation of some related compounds, such as (23R)-23-acetoxytomatidine and (23S)-23- acetoxysoladulcidine from Lycopersicum esculentum, suggested a probable mechanism for the degra- dation of nitrogen containing rings [1]. In addition, products containing the 20,16-cis-γ-lactone moiety have been isolated from different vegetable sources, and postulated to be metabolic products of the corresponding sapogenins. At the moment none of them have been synthesized. In 1971 Diosgeninlactone (1) was isolated from the ethanolic extract of the fruits of Solanum vespertilio [2]. In view of the highly efficient protocol developed by us, in the synthesis of tigogeninlactone [3,4] we decided to explore this synthetic strategy to obtain 1. Experimental Wittig reaction on 3β-(dimethyl-t-butylsilyloxy)-5-androsten-17-one yielded the Z-olefin stereo- selectively with the introduction of a two-carbon lateral side chain at C-17. Allylic hydroxylation on C-16 with t-butylhydroperoxide in the presence of catalytic amounts of selenium dioxide introduced the hydroxy group from the α-face of the steroid nucleus. Swern oxidation produced the conjugated ketone 3 in very