New Synthetic Methodology in Sesquiterpene Chemistry

与碳环化学优雅的多环程序相比，在合成含有呋喃环的天然产物时，很少有人尝试将类似的策略纳入其中。雅各比博士开创了这些材料的新的高度紧凑的合成方法，这些材料在某些药物化合物中非常重要。有机化学和高分子化学计划中的这项拨款将进一步发展双杂环化的概念，在这种概念中，稠环呋喃很容易制备，并具有完全的区域化学控制。这种方法的关键要素涉及恶唑和乙炔之间的分子内Diels-Alder反应。它目前被用于合成愈创木倍半萜间歇素和丁烯内酯生物碱去甲肾上腺素。此外，还描述了苯醇或烯酮通过串联S型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械意义，可用于合成各种材料，如橡胶烷、亚甲氧霉素抗生素、多糖和各种天然酚类。以亚甲基霉素B和亚甲基A、抗肿瘤药物肌霉素、乌头酮、毛状菌素和结节醇的合成为代表进行了研究。

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.