Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr, Germany.
Chemistry. 2013 Apr 2;19(14):4532-7. doi: 10.1002/chem.201204551. Epub 2013 Feb 18.
A concise and largely catalysis-based approach to the potent algal toxin polycavernoside A (1) is described that intercepts a late-stage intermediate of a previous total synthesis; from there on, this challenging target can be reached in a small number of steps. Key to success was a sequence of a molybdenum-catalyzed ring-closing alkyne metathesis (RCAM) reaction to forge the macrocyclic frame, followed by a gold-catalyzed and strictly regioselective transannular hydroalkoxylation of the resulting cycloalkyne that allows the intricate oxygenation pattern of the macrolactone ring of 1 to be properly set. The required cyclization precursor 5 was assembled by the arguably most advanced fragment coupling process based on an Evans-Tishchenko redox esterification known to date, which was optimized to the extent that the precious coupling partners could be used in an almost equimolar ratio (6/7 1:1.3). The preparation of these building blocks features, inter alia, the power of the Sc(OTf)(3)-catalyzed Leighton crotylation as well as the superb selectivities of alkene cross metathesis, asymmetric keto-ester hydrogenation, and the Jacobsen epoxidation/epoxide resolution technologies.
描述了一种简洁且主要基于催化的方法，用于合成强效藻类毒素多卡瓦诺昔 A（1），该方法截获了先前全合成的晚期中间体；从那里开始，可以通过少数步骤到达这个具有挑战性的目标。成功的关键是一系列钼催化的环 closing 炔烃复分解（RCAM）反应来形成大环框架，随后是金催化的、严格区域选择性的反环烷烃羟烷基化反应，使 1 的大环内酯环的复杂氧化模式得以正确设定。所需的环化前体 5 通过基于迄今为止已知的 Evans-Tishchenko 氧化还原酯化的最先进的片段偶联过程组装，该过程经过优化，以至于珍贵的偶联试剂可以以几乎等摩尔的比例（6/7 1:1.3）使用。这些构建块的制备特别体现了 Sc(OTf)(3)催化的 Leighton 烯丙基化的强大功能，以及烯烃交叉复分解、不对称酮酯加氢、Jacobsen 环氧化/环氧化物拆分技术的出色选择性。
