The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations.

中文翻译：

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可编程的茂金属合成。

双环[3.3.1]壬烷结构是在1000多种天然产物中发现的特权结构基序，与神经退行性疾病，细菌和寄生虫感染以及癌症有关。尽管有不同的生物合成机制，但生物碱，萜烯和聚酮化合物生产生物均已进化出整合该碳环系统的途径。混合的聚酮化合物/萜类化合物来源的天然产物（金属萜类化合物）是生物活性双环[3.3.1]壬烷分子的特别丰富和重要的来源。在此，我们详细介绍了针对这一广泛的目标家族的全面合成策略，该策略基于非生物类环化/重排策略，可完成10步总合成Garsubellin A，胆碱乙酰基转移酶的增强剂，是多环多烯丙基化酰基间苯三酚的大家族的成员。这项工作巩固了一种在涉及最少化学转化次数的可编程组装过程中制备多种多样的异丙基苯化学型的策略。