Synthesis of Carbocyclic and Heterocyclic Compounds (Chemistry)

这项研究将为合成一些重要的生物活性生物碱开辟新的合成反应和途径。此外，它还将为重要的β-内酰胺类药物提供新的途径。将研究几种碳环和杂环体系的合成，目的是开发新的方法，并将其应用于天然产品领域中选定的目标。光化学介导的β-酮酯烯醇酸酯的环化反应将扩展到一个旨在测试该反应在九元环中的可行性的系统，其中环化反应将提供腺基环化酶抑制剂Forsklin的三环前体。四氯化锡介导的烯烃β-酮酯的环化反应也将被用于不对称诱导，其中的酯来自手性醇。展望了该技术在合成球茎十二烷、球茎芳烷和氨基二环己烷二萜中的应用。最后，将研究在醋酸锰存在下β-酮酯的环化反应，以此作为设计新型桥联骨架的一种手段。围绕这一结构，已经规划了一条通往紫杉烷二萜类化合物家族的路线，特别是紫杉素。在杂环领域，将寻求一种新的合成β-内酰胺类化合物，其关键是从N-氨基吡唑啉酮的亚磺胺中挤出氮，并伴随环的收缩。这种方法将被纳入青霉素和其他β-内酰胺类抗生素的手性合成中。在Ghosez最初进行的工作的扩展中，将研究在Diels-Adler反应中使用α，β-不饱和醛的肼作为制备全氢异喹啉的装置。手性进入钩吻类生物碱，特别是库明，将通过这种方法进行探索。

This research will lead to the development of new synthetic reactions and pathways to some important classes of biologically active alkaloids. It will in addition provide new routes to the important beta-lactams. The synthesis of several carbocyclic and heterocyclic ring systems will be studied with the objective of developing new methodology and applying it to selected targets in the natural product domain. A photochemically mediated cyclization of beta-ketoester enolates will be extended to a system designed to test the feasibility of this reaction in a nine-membered ring, where annulation would afford a tricyclic precursor to the adenylatecyclase inhibitor forskolin. A stannic chloride-mediated cyclization of olefinic beta-ketoesters will also be examined for asymmetric induction where the ester is derived from a chiral alcohol. Application of this technology to synthesis of diterpenes of the stemodane, stemarane, and aphidicolane group is projected. Finally, the cyclization of beta-ketoesters in the presence of manganese acetate will be investigated as a means for elaborating novel bridged frameworks. A route to the taxane family of diterpenoids, specifically taxusin, has been planned around this construct. In the heterocyclic area, a new synthesis of beta.lactams will be pursued that hinges on extrusion of nitrogen from the sulfoximine of a N-aminopyrazolinone with concomitant ring contraction. This methodology will be incorporated into a chiral synthesis of penicillins and other beta-lactam antibiotics. In an extension of work originally carried out by Ghosez, the use of hydrazones of alpha, beta-unsaturated aldehydes in the Diels-Adler reaction will be examined as a device for preparing perhydroisoquinolines. A chiral entry to the gelsemine class of alkaloids, specifically koumine, would be explored by this means.