Synthesis of Carbocyclic and Heterocyclic Compounds (Chemistry)

这项研究将导致新的合成反应和途径的发展，以获得一些重要的生物活性生物碱类。此外，它还将为重要的β -内酰胺提供新的途径。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物领域的选定目标。光化学介导的β -酮酯烯醇酯环化将扩展到一个系统，该系统设计用于测试该反应在九元环中的可行性，其中环化将提供腺苷酸环化酶抑制剂forskolin的三环前体。氯化锡介导的烯烃-酮酯环化也将用于不对称诱导，其中酯是由手性醇衍生的。展望了该技术在合成甾烷、甾烷和苯环烷类二萜中的应用。最后，β -酮酯在醋酸锰存在下的环化将作为一种精心设计新型桥接框架的手段进行研究。一条通往二萜类紫杉烷家族的路线，特别是红豆杉素，已经围绕这个结构进行了规划。在杂环方面，新合成了β。内酰胺类的研究将取决于n -氨基吡唑啉酮的亚砜胺中氮的挤压，同时伴有环收缩。该方法将纳入青霉素和其他β -内酰胺类抗生素的手性合成。在Ghosez最初进行的工作的扩展中，将在Diels-Adler反应中使用α， β -不饱和醛的腙作为制备过氢异喹啉的装置进行研究。手性进入明胶类生物碱，特别是koumine，将通过这种方式进行探索。

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.