Nicolaou K C, Koftis Theocharis V, Vyskocil Stepan, Petrovic Goran, Tang Wenjun, Frederick Michael O, Chen David Y-K, Li Yiwei, Ling Taotao, Yamada Yoichi M A
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 Mar 8;128(9):2859-72. doi: 10.1021/ja054750q.
The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C(1)-C(20) epimer (2) and of several truncated analogues for biological investigations are described.
从贻贝中分离出的神经毒素氮杂螺旋酸-1的分子结构已通过全合成得以阐明，全合成还增加了其供应量。这种海洋生物毒素降解衍生的片段，即化合物5（EFGHI）、6（FGHI）和40（ABCD），与合成材料进行了匹配，从而确认了它们的结构同一性。基于这项探索性工作，提出并通过全合成构建了氮杂螺旋酸-1的新结构（即1）。氮杂螺旋酸-1全合成的最终策略的特点是二硫烷阴离子（C(21)-C(27)片段）与五氟苯酚酯（C(1)-C(20)片段）反应，随后是高级烯丙基乙酸酯底物（C(1)-C(27)片段）与乙烯基锡烷进行类似施蒂勒反应的结合，作为组装分子碳骨架的主要偶联过程。除了氮杂螺旋酸-1（1）的全合成外，还描述了其C(
