TOTAL SYNTHESIS OF NATURAL PRODUCTS

吡咯里西啶生物碱已经引起了相当大的关注，因为 与某些成员相关的抗肿瘤活性， 由于消费高消费量食品而造成的牲畜死亡人数增加 含有吡咯里西啶生物碱的植物。 如果所提出的化学物质 涉及二烯-氮烯合成等价物的合成方法， 发展，那么我们将能够制备各种各样的necine基地， 常见于吡咯里西啶生物碱。 涉及环的方法 2-叠氮基烷基-2-环烯酮的膨胀通常应提供 吲哚里西啶、吡咯里西啶和喹里西啶环的有用路线 系统. 这些亚结构存在于广泛的药用植物中， 有用的生物碱;我们将尝试合成石松碱，以确定是否 通过我们的策略可以构建合理复杂的生物碱。 这些 相同的扩环方法应适用于合成 一种重要的抗生素β-内酰胺类 我们将开始开发 一种新的青霉素G的全合成方法， 改性青霉素、头孢菌素和新一代双环内酯 β-内酰胺类抗生素，如硫霉素。 聚喹烷的新方向 构建应提供细胞毒性的全合成， 倍半萜并环戊二烯内酯。 我们的目标是发展通用和 对映选择性方法合成聚醌。 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个概念上新的 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.