Studies on synthetic drugs : Investigations on synthetic estrogens

Abstract

PART I Section A After briefly reviewing the work on synthetic estrogens, the various methods for the synthesis of 2-methyl-2-carbomethoxy-5-(p-methoxyphenyl)-cyclohexanone are detailed. This ketone has been synthesized by different methods, the details of which are given in this section. Section B This section deals with the experiments carried out towards the synthesis of estrone without the B ring, viz., 5-(p-hydroxyphenyl)-8-methyl-hydrindanone (I). The introductory portion includes a brief review of the total synthesis of estrone in chart form. Further, the syntheses of 2,5-dicarbomethoxy-3-methyl-6-(p-methoxyphenyl)-cyclohexanone, 2,3-dicyano-3-methyl-6-(p-methoxyphenyl)-cyclohexanone, and their condensations with p-chloropropionic ester, ?-bromopropionic ester, acrylonitrile, and acrylic ester have been described. Syntheses of 2-methyl-2-cyano-5-(p-methoxyphenyl)-cyclohexanecarbonitrile as well as methyl 2-methyl-2-carbomethoxy-5-(p-methoxyphenyl)-cyclohexenecarboxylate and their Michael condensations with malonic ester and cyanacetic ester have also been detailed in this part.

PART II The different procedures employed for building up the C ring with an angular methyl group in steroidal compounds have been outlined. The synthesis of 3-carbomethoxy-4,5-(3',4'-methoxybenzo)-hydrindenone (II) and the attempts to introduce the methyl group in the 8-position have been described.

PART III The subject matter of the thesis deals with a systematic study of some new synthetic approaches for building up the estrone molecule, the female sex hormone, and its analogue.

Several syntheses of estrone have been reported, out of which only one, recently achieved by Johnson, is stereospecific. This work was undertaken with a view to developing a practical method for the synthesis of this female sex hormone. The analogue will be the same as the estrone molecule without the B ring. The study of the physiological activity of this model compound will determine whether the B ring in the estrone molecule is essential for its estrogenic activity.

STATEMENT II The candidate has, with the concurrence of the University Teacher, worked on synthetic estrogens suggested by Professor Dr. D.K. Banerjee. The entire experimental work described in the thesis, except the analyses of Carbon, Hydrogen, and Nitrogen, has been carried out by the candidate. These elemental analyses were done in the micro-analytical section of the Department. Scientific journals and textbooks have been duly consulted in writing the thesis, and detailed references to these are given in the reference section.