New Synthetic Methodology in Sesquiterpene Chemistry

与碳环化学的优雅的多环过程相比，很少有努力将类似的策略纳入合成含有呋喃环的天然产物。雅可比博士开创了新的高度紧凑的合成这些后一种材料，这在某些药物化合物中是重要的。有机和大分子化学项目的这笔拨款将进一步发展双杂环的概念，在这种概念中，融合环呋喃很容易在完全的区域化学控制下制备。这种方法的关键要素涉及到恶唑和乙炔之间的分子内Diels-Alder反应。目前正用于合成愈创木烷倍半萜皂苷和丁烯内酯生物碱去安全碱。此外，还描述了乙炔醇或烯酮通过串联异位重排直接转化为亚甲基环戊烯酮或苯酚。这些转化具有相当大的机理意义，可用于合成各种材料，如橡胶果烷、亚甲霉素、抗生素、多苏烷和各种天然存在的酚类。以亚甲菌素B和A、抗肿瘤药物沙霉素、阿柯罗酮、毛素烯和juncusol的合成为代表。

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.