Studies in the synthesis of azasteroids.

Abstract

This project involved the synthesis of azasteroids with potential GABA (gamma-aminobutyric acid) -mimetic activity. Several methods leading to the formation of azasteroids were employed. The Diels-Alder reaction of isoquinoline-derived dienes with suitable dienophiles furnished several adducts, some of which were tested for biological activity. An unusual double Diels-Alder reaction was observed for some cases i.e. one equivalent of the diene reacted with two equivalents of dieno-phile to give a "di-adduct". A possible mechanism for this reaction is discussed in Chapter Five. Many diaza-steroid intermediates were prepared from quinazoline derivatives. These, together with their mechanistic features are discussed in Chapter Six. The condensation reaction of hydroxy-naphthaldehydes with guanidine afforded benzoquinazolines. Reaction of a benzo[f]quinazoline with chloroacetyl chloride, followed by cyclization resulted in the formation of a tri-azasteroid. These reactions are discussed in Chapter Seven. The experimental details of the syntheses of 'aza-steroids' and their intermediates, from isoquinoline-, quinazoline-, and naphthalene-derivatives are given in Chapters Nine, Ten and Eleven, respectively. Results obtained for the biological activity tests of some 'aza-steroids', are discussed in Chapter Eight. Potential future studies are also mentioned in Chapter Eight. Concise reviews of gamma-aminobutyric acid, azasteroids, isoquinolines and quinazolines, pertinent to this project together with background material are given in Part One of the thesis, Chapters One, Two, Three and Four, respectively.

Date of Award	1982
Original language	English
Awarding Institution	University of Bath