Nicolaou K C, Pihko Petri M, Bernal Federico, Frederick Michael O, Qian Wenyuan, Uesaka Noriaki, Diedrichs Nicole, Hinrichs Jürgen, Koftis Theocharis V, Loizidou Eriketi, Petrovic Goran, Rodriquez Manuela, Sarlah David, Zou Ning
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Am Chem Soc. 2006 Feb 22;128(7):2244-57. doi: 10.1021/ja0547477.
Syntheses of the three key building blocks (65, 98, and 100) required for the total synthesis of the proposed structure of azaspiracid-1 (1a) are described. Key steps include a TMSOTf-induced ring-closing cascade to form the ABC rings of tetracycle 65, a neodymium-catalyzed internal aminal formation for the construction of intermediate 98, and a Nozaki-Hiyama-Kishi coupling to assemble the required carbon chain of fragment 100. The synthesized fragments, obtained stereoselectively in both their enantiomeric forms, were expected to allow for the construction of all four stereoisomers proposed as possible structures of azaspiracid-1 (1a-d), thus allowing the determination of both the relative and absolute stereochemistry of the natural product.
本文描述了全合成所提议的氮杂螺旋酸-1（1a）结构所需的三个关键结构单元（65、98和100）的合成方法。关键步骤包括：三甲基硅基三氟甲磺酸酯（TMSOTf）诱导的闭环串联反应以形成四环65的ABC环；钕催化的分子内胺形成反应以构建中间体98；以及Nozaki-Hiyama-Kishi偶联反应以组装片段100所需的碳链。所合成的片段以对映体形式立体选择性地获得，有望用于构建作为氮杂螺旋酸-1（1a-d）可能结构提出的所有四种立体异构体，从而确定天然产物的相对和绝对立体化学。
