TOTAL SYNTHESIS OF NATURAL PRODUCTS

吡咯里西丁生物碱引起了相当大的关注，因为 与某些成员相关的抗肿瘤活性，因为 可归因于消费以下物质的牲畜死亡人数增加 含有吡咯里西丁生物碱的植物。如果提出的化学 涉及二烯-硝烯合成当量是成功的 发展起来，那么我们就可以准备各种各样的蜜源基地 为吡咯里西定生物碱所共有。方法论涉圆环 2-叠氮烷基-2-环烯酮的展开一般应提供 合成吲哚里西定、吡咯里西定和喹诺里西丁环的有效途径 系统。这些亚结构广泛存在于医学上 有用的生物碱；我们将尝试合成石蒜碱来确定是否 通过我们的策略可以构建出相当复杂的生物碱。这些 同样的扩环工艺应适用于该化合物的合成 重要的抗生素类，β-内酰胺类。我们将从开发 青霉素G的一种新的全合成方法及其合成策略 改良型青霉素、头孢菌素与新一代自行车 甲氧西林等β-内酰胺类抗生素。聚奎烷研究的新方向 构建应提供总合成的细胞毒性 倍半萜五内酯。我们的目标是发展通用的和 多喹烷合成的对映选择性方法。最后， 分子内环加成概念的探索性研究 光化学产生的两性离子可以提供一种全新的概念 构建复杂环系的策略。

Pyrrolizidine alkaloids have attracted considerable attention because of antitumor activity associated with certain members and because of the increasing number of deaths to livestock attributable to consumption of plants containing pyrrolizidine alkaloids. If the proposed chemistry involving the diene-nitrene synthetic equivalence is successfully developed, then we would be able to prepare a wide variety of necine bases common to the pyrrolizidine alkaloids. Methods involving the ring expansions of 2-azidoalkyl-2-cycloalkenones should provide generally useful routes to indolizidine, pyrrolizidine and quinolizidine ring systems. These substructures are present in a wide range of medicinally useful alkaloids; we will attempt to synthesize lycopodine to determine if reasonably complex alkaloids can be constructed by our strategy. These same ring expansion processes should be applicable to synthesis of the important antibiotic group, the Beta-lactams. We will begin by developing a novel total synthesis of penicillin G and work towards a strategy for modified penicillins, cephalosperins and the new generation bicyclid Beta-lactam antibiotics such as thienamycin. New directions in polyquinane construction should provide a total synthesis of the cytotoxic sesquiterpene pentalenolactone. Our goal is to develop general and enantioselective methods for the synthesis of polyquinanes. Finally, exploratory research on the concept of intramolecular cycloadditions to photochemically generated zwitterions could provide a conceptually new strategy for the construction of complex ring systems.