Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2010 Aug 18;132(32):11350-63. doi: 10.1021/ja1048994.
The total synthesis of the structurally unique secondary metabolite sporolide B (1b) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37 and 75) that underwent exquisite intramolecular [4+2] cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b. The requisite indene o-quinone precursor 75 was synthesized through a ruthenium-catalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol and a chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed [2+2+2] cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus.
本文描述了结构独特的次级代谢产物 sporolide B（1b）的全合成。1b 的全合成是基于初步研究发展起来的，该研究揭示了适当的邻醌作为二烯体系对许多茚衍生物作为亲二烯体的反应性，首先是在分子间，然后是分子内。因此，设计了底物（37 和 75），它们在热条件下经历精妙的分子内[4+2]环加成反应，提供原始的 sporolide 型结构，随后进一步发展到 sporolide 模型系统、9-epi-sporolide B 和 1b。所需的茚醌前体 75 通过钌催化的[2+2+2]环加成反应在丙炔醇和氯乙酰基环戊烯炔之间合成，然后对得到的氯茚衍生物进行修饰和银促进氧化。除了 1b 的全合成外，这项工作首次展示了分子内杂[4+2]环加成反应在复杂分子全合成中的强大功能，以及钌催化的[2+2+2]环加成反应在具有芳香核上氯原子的高度取代茚系统中的应用。
