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|