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

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

Research output: Contribution to journalArticle

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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Biosynthetic Pathways
Cycloaddition Reaction
Epichlorohydrin
Biological Products
Stereochemistry
Biosynthesis
Substrates
Geometry
macquarimicin C

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Total synthesis of macquarimicins using an intramolecular Diels-Alder approach inspired by a biosynthetic pathway. / Munakata, Ryosuke; Katakai, Hironori; Ueki, Tatsuo; Kurosaka, Jun; Takao, Kenichi; Tadano, Kin Ichi.

In: Journal of the American Chemical Society, Vol. 126, No. 36, 15.09.2004, p. 11254-11267.

Research output: Contribution to journalArticle

Munakata, Ryosuke ; Katakai, Hironori ; Ueki, Tatsuo ; Kurosaka, Jun ; Takao, Kenichi ; Tadano, Kin Ichi. / Total synthesis of macquarimicins using an intramolecular Diels-Alder approach inspired by a biosynthetic pathway. In: Journal of the American Chemical Society. 2004 ; Vol. 126, No. 36. pp. 11254-11267.
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