Total Synthesis and Properties of the Crambescidin Core Zwitterionic Acid and Crambescidin 359

The total synthesis of the crambescidin core acid 9, crambescidins 359 (8) and 431 (7), and the
properties of the crambescidin core are described. A key step of the synthetic route to guanidinium
carboxylate 9 is Pd(0) catalyzed cleavage of the ester side chain of pentacyclic cinnamyl ester 15. This
ester is also employed to prepare a small library of crambescidin alkaloid analogues that differ in their C14
side chain. The zwitterionic guanidinium carboxylate 9 was shown to readily decarboxylate to form
crambescidin 359 (8). Decarboxylation of crambescidin core acid 9 was fastest under basic conditions. In
the presence of base, up to eight deuterium atoms can be incorporated into the pentacyclic crambescidin
core. Both deuterium incorporation and decarboxylation of crambescidin core acid 9 are the result of facile
ring opening of the spirocyclic ether rings of the pentacyclic guanidinium moiety.

本研究报道了克兰贝西丁（crambescidin）核心羧酸9、克兰贝西丁359（8）与431（7）的全合成，以及克兰贝西丁核心的理化性质。针对胍鎓羧酸酯（guanidinium carboxylate）9的合成路线，其关键步骤为零价钯（Pd(0)）催化裂解五环肉桂酸酯15的酯侧链。该肉桂酸酯还被用于构建一组克兰贝西丁生物碱类似物的小型文库，此类类似物的C14侧链存在差异。实验证实，两性离子（zwitterionic）型胍鎓羧酸酯9可快速发生脱羧反应，生成克兰贝西丁359（8）。克兰贝西丁核心羧酸9的脱羧反应在碱性条件下速率最快。在碱性环境中，最多可向五环克兰贝西丁核心中掺入8个氘原子。克兰贝西丁核心羧酸9的氘原子掺入与脱羧反应，均源于五环胍鎓（guanidinium）结构单元的螺环醚（spirocyclic ether）环易发生开环反应。