New Synthetic Methodology in Sesquiterpene Chemistry

与碳环化学的优雅的多环化过程相反，在含有呋喃环的天然产物的合成中，很少有努力将类似的策略纳入其中。Jacobi博士开创了这些后一种材料的新型高度紧凑的合成方法，这些材料在某些药物化合物中很重要。有机和高分子化学计划的这项资助将进一步发展双杂环化的概念，其中稠环呋喃很容易在完全的区域化学控制下制备。这种方法的关键元素涉及恶唑和乙炔之间的分子内Diels-Alder反应。这是目前用于合成愈创木烷倍半萜geigerin和丁烯内酯生物碱norsecurinine。此外，还描述了炔醇或烯酮通过串联σ迁移重排直接转化为亚甲基环戊烯酮或苯酚。这些转变是相当大的机械感兴趣，并可用于合成材料的不同，如菖蒲，亚甲基霉素抗生素，hirsutanes和各种天然存在的酚。亚甲基霉素B和A、抗肿瘤剂Sarkomycin、acorone、hirsutene和juncusol的合成计划作为代表性实例。

In contrast to the elegant multiple-annulation procedures of carbocyclic chemistry, there have been few efforts to incorporate similar strategies in the synthesis of natural products containing furan rings. Dr. Jacobi has pioneered new highly compact syntheses of these latter materials which are important in certain medicinal compounds. This grant in the Organic and Macromolecular Chemistry Program will further develop the concept of bis-heteroannulation, in which fused ring furans are readily prepared with complete regiochemical control. The key element of this approach involves an intramolecular Diels-Alder reaction between an oxazole and an acetylene. This is currently being employed for the synthesis of the guaiane sesquiterpene geigerin and the butenolide-alkaloid norsecurinine. In addition are described the direct conversion of either acetylenic alcohols or enones to methylenecyclopentenones or to phenols via tandem sigmatropic rearrangements. These transformations are of considerable mechanistic interest and could be utilized in the synthesis of materials as diverse as the acoranes, methyleneomycin antibiotics, hirsutanes and various naturally occurring phenols. The syntheses of methyleneomycins B and A, the antitumor agent sarkomycin, acorone, hirsutene and juncusol are planned as representative examples.