NEW SYNTHETIC REACTIONS FOR ACTIVE PRINCIPLES

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In this program we propose to investigate the synthesis and chemistry of a series of natural products of biological interest. It is expected that from this work will emerge new reactions of value to chemical synthesis, new modes of strategic analysis of synthetic problems, and new access to compounds worthy of evaluation in several biological settings. The natural products which form the goal structures around which the program is organized are: (i) compactin-mevinolin and a Fusarium derived metabolite, (ii) heptelidic acid, (iii) rishirilide. (iv) aflavinine, (v) erythrina alkaloids, (vi) zincophorin, (vii) A-58365A, (viii) castanospermine, (ix) apramycin, and (x) amauromine. The general chemical issues which will be of significant concern with respect to these targets are: (a) the lactonic enolate version of the Claisen rearrangement, (b) free radical cyclization reactions of nitrogen containing compounds, (c) the 2+2+2 cyclization reaction, (d) the aldimine- diene cyclocondensation reaction, and (e) radical substitution reactions of aryl and allylic silanes and stannanes. Among the sorts of biological activities manifested by the goal systems are: inhibition of cholesterol biosynthesis, hypotensive responses, inhibition of glyceraldehyde-3-phosphate dehydrogenase, inhibition of plasmin inhibitors, trimming enzyme inactivators, ACE inhibitors, and inhibition of phytohemeagglutinin response.