Synthetic investigation in streoids and terpenes

Abstract

The thesis entitled “Synthetic Investigations in Steroids and Terpenes” consists of three chapters and a short appendix. Chapter I contains a brief review of the course of Dieckmann cyclisation of 2 alkyl and 2 alkoxycarbonyl substituted adipic esters and a study of the Dieckmann cyclisation of dimethyl 2 methyl 3 methoxycarbonyladipate (1), which could yield two possible products, namely 2,3 dimethoxycarbonyl 4 methylcyclopentanone (2) and 2,4 dimethoxycarbonyl 3 methylcyclopentanone (3). Actually, only the keto ester (2) was obtained; earlier studies also led us to expect this product to be formed at least as the major component. The structure of the product was shown to be (2) by methylation of the keto ester followed by hydrolysis and decarboxylation to obtain 2,4 dimethyl 3 hydroxycarbonylcyclopentanone (4), identical with a sample prepared by an unambiguous route. For comparison, an authentic specimen of the keto acid, viz. 2,3 dimethyl 4 hydroxycarbonylcyclopentanone (5), obtainable similarly from the keto ester (3), was also prepared. Chapter II begins with a short review of physiologically active 16 methyl and 17 and/or 18 substituted steroids, and the recent methods of total syntheses of oestrone developed by Herchel Smith and Torgov. Utilisation of the keto ester (2), whose preparation has been described in Chapter I, for the synthesis of 16 methyl analogues of oestrone and 19 nortestosterone with substituents at C 17 and C 18 by following one of the methods of Herchel Smith has been described next. Thus, we prepared:

3 methoxy 16 methyl 13,17 dimethoxycarbonyl 18 noroestra 1,3,5(10) triene 3 methoxy 16 methyl 13,17 dimethoxycarbonyl 18 nor 8 isooestra 1,3,5(10) triene 3 methoxy 16 methyl 17 hydroxymethyl 18 hydroxyoestra 1,3,5(10) triene 3 methoxy 16 methyl 17 hydroxymethyl 18 hydroxy 8 isooestra 1,3,5(10) triene 3 methoxy 16 methyl 18,20 epoxy 19,21 dinorpregna 1,3,5(10) triene 3 methoxy 16 methyl 18,20 epoxy 19,21 dinor 8 isopregna 1,3,5(10) triene 16 methyl 18,20 epoxy 19,21 dinorpregn 4 en 3 one 16 methyl 18,20 epoxy 19,21 dinor 8 isopregn 5(10) en 3 one

Chapter III contains a review of the isolation, structure, and syntheses of the monoterpene nepetalactone, followed by an account of the unsuccessful attempts to synthesise it from the keto ester (2). The appendix gives the results of the screening for physiological activity of some of the compounds described in Chapter II.