Enantiospecific Total Synthesis of the Hapalindoles, Fischerindoles, and Welwitindolinones via a Redox Economic Approach

Full details are provided for the total synthesis of several members of the hapalindole family of natural products, including hapalindole Q, 12-epi-hapalindole D, 12-epi-fischerindole U, 12-epi-fischerindole G, 12-epi-fischerindole I, and welwitindolinone A. Use of the recently developed direct indole coupling enabled an efficient, practical, scalable, and protecting-group-free synthesis of each of these natural products. The original biosynthetic proposal is reviewed, and a revised biosynthetic hypothesis is suggested, validated by the above syntheses. The syntheses are also characterized by an adherence to the concept of “redox economy”. Analogous to “atom economy” or “step economy”, “redox economy” minimizes the superfluous redox manipulations within a synthesis; rather, the oxidation state of intermediates linearly and steadily increases throughout the course of the synthesis.

本描述详尽地提供了天然产物哈帕林多家族数个成员的总体合成细节，包括哈帕林多Q、12-表哈帕林多D、12-表费舍尔林多U、12-表费舍尔林多G、12-表费舍尔林多I以及威尔维托林酮A。通过应用最近开发的直接吲哚偶联技术，实现了这些天然产物的有效、实用、可扩展且无保护基团的合成。对原始的生物合成假设进行了回顾，并提出了修订后的生物合成假说，该假说经上述合成得到验证。这些合成过程亦体现了对“氧化还原经济”理念的坚持。与‘原子经济’或‘步骤经济’相似，‘氧化还原经济’旨在最小化合成过程中不必要的氧化还原操作；相反，中间体的氧化态在整个合成过程中线性且稳步上升。