Total synthesis of macquarimicins using an intramolecular Diels-Alder approach inspired by a biosynthetic pathway

Ryosuke Munakata, Hironori Katakai, Tatsuo Ueki, Jun Kurosaka, Ken Ichi Takao, Kin Ichi Tadano

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50 Citations (Scopus)

Abstract

A total synthesis of the macquarimicins A-C (1-3), novel natural products with intriguing tetra- or pentacyclic frameworks, has been achieved. The synthesis features an extensive investigation of the biosynthesis-based intramolecular Diels-Alder (IMDA) reactions of (E,Z,E)-1,6,8-nonatrienes. Considering possible biosynthetic sequences, four types of substrates were synthesized, and their IMDA reactions were examined. From one of the four substrates, the total synthesis was achieved via a transannular Diels-Alder reaction, which led to the stereoselective construction of the unique molecular framework. The convergent and efficient synthetic pathway afforded (+)-1 in 27 linear steps with 4.3% and 9.9% overall yields from readily available ethyl (2E,4S)-4,5-(isopropylidene)dioxy-2-pentenoate (22) and (R)-epichlorohydrin (30), respectively, Furthermore, efficient syntheses of 2, 3, and the 9-epi-cochleamycins A (57) and B (58) were accomplished. Additionally, the present work established the absolute stereochemistry of macquarimicins and revised the C(2)-C(3) geometry of 1.

Original languageEnglish
Pages (from-to)11254-11267
Number of pages14
JournalJournal of the American Chemical Society
Volume126
Issue number36
DOIs
Publication statusPublished - 2004 Sep 15

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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