Evolution of a Unified, Stereodivergent Approach to the Synthesis of Communesin F and Perophoramidine

Expedient synthetic approaches to
the highly functionalized polycyclic
alkaloids communesin F and perophoramidine are described using a unified
approach featuring a key decarboxylative allylic alkylation to access
a crucial and highly congested 3,3-disubstituted oxindole. Described
are two distinct, stereoselective alkylations that produce structures
in divergent diastereomeric series possessing the critical vicinal
all-carbon quaternary centers needed for each synthesis. Synthetic
studies toward these challenging core structures have revealed a number
of unanticipated modes of reactivity inherent to these complex alkaloid
scaffolds. Additionally, several novel and interesting intermediates
en route to the target natural products, such as an intriguing propellane
hexacyclic oxindole encountered in the communesin F sequence, are
disclosed. Indeed, such unanticipated structures may prove to be convenient
strategic intermediates in future syntheses.

本研究报道了针对高度官能化多环生物碱communesin F与perophoramidine的便捷合成策略，采用统一的合成路径，核心步骤为关键的脱羧烯丙基烷基化反应，以获取具有重要意义且空间位阻较大的3,3-二取代羟吲哚（oxindole）。本研究还报道了两种截然不同的立体选择性烷基化反应，它们可生成不同非对映异构系列的分子结构，这些结构带有各合成步骤所需的关键邻位全碳季碳中心。针对这些具有挑战性的核心骨架的合成研究，揭示了这类复杂生物碱支架所固有的多种未被预见的反应模式。此外，本研究还公开了数种通往目标天然产物的新颖且值得关注的合成中间体，例如在communesin F合成序列中发现的一种引人关注的螺桨烷（propellane）型六环羟吲哚。事实上，这类未被预见的结构有望在未来的合成研究中成为便捷的战略型中间体。