NEW SYNTHETIC REACTIONS FOR ACTIVE PRINCIPLES

在这个项目中，我们建议研究合成和 一系列具有生物价值的天然产物的化学。 预计从这项工作中将出现新的反应 对化学合成的价值，战略分析的新模式 合成问题，以及获得值得 在几个生物学环境中进行评估。 围绕其形成目标结构的天然产品 组织的方案是：(I)紧缩素-梅维诺林和 镰刀菌源代谢物，(Ii)庚二酸，(Iii) 里什里德。(V)刺五加生物碱；(Vi) 姜黄素，(Vii)A-58365A，(Viii)藜芦碱，(Ix) 安普霉素和(X)氨基紫红。一般的化学问题 将在这些目标方面引起重大关切的是： (A)克莱森重排的乳酸烯醇型，(B) 含氮自由基环化反应 化合物，(C)2+2+2环化反应，(D)乙二胺- 二烯环缩合反应和(E)自由基取代 芳基和烯丙基硅烷和锡烷的反应。在这些人中 目标系统所表现出的各种生物活动包括： 抑制胆固醇的生物合成，降低血压反应， 甘油醛-3-磷酸脱氢酶的抑制 纤溶酶抑制剂、修剪酶失活剂、血管紧张素转换酶 抑制剂和植物血凝素反应的抑制。

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.