Unified Total Synthesis of (−)-Enigmazole A and (−)-15-O-Methylenigmazole A

Keisuke Sakurai; Keita Sakamoto; Makoto Sasaki; Haruhiko Fuwa

doi:10.1002/asia.202001015

Unified Total Synthesis of (−)-Enigmazole A and (−)-15-O-Methylenigmazole A

Keisuke Sakurai, Keita Sakamoto, Makoto Sasaki, Haruhiko Fuwa

LIF - Molecular and Chemical Life Science

Research output: Contribution to journal › Article › peer-review

Abstract

The total synthesis of cytotoxic marine phosphomacrolides, (−)-enigmazole A and (−)-15-O-methylenigmazole A, is described in detail. The 2,6-cis-substituted tetrahydropyran ring was efficiently elaborated by using a tandem olefin cross-metathesis/intramolecular oxa-Michael addition reaction. The 18-membered macrolactone skeleton was forged via a Au-catalyzed propargylic benzoate rearrangement/macrocyclic ring-closing metathesis sequence. Late-stage diversification of a common intermediate enabled unified total synthesis of (−)-enigmazole A and (−)-15-O-methylenigmazole A.

Original language	English
Pages (from-to)	3494-3502
Number of pages	9
Journal	Chemistry - An Asian Journal
Volume	15
Issue number	21
DOIs	https://doi.org/10.1002/asia.202001015
Publication status	Published - 2020 Nov 2

Keywords

gold-catalyzed reaction
macrocycles
natural products
tandem reaction
tetrahydropyrans

ASJC Scopus subject areas

Biochemistry
Organic Chemistry

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@article{087c83df1f0d44709bbb9d4fd22a74fc,

title = "Unified Total Synthesis of (−)-Enigmazole A and (−)-15-O-Methylenigmazole A",

abstract = "The total synthesis of cytotoxic marine phosphomacrolides, (−)-enigmazole A and (−)-15-O-methylenigmazole A, is described in detail. The 2,6-cis-substituted tetrahydropyran ring was efficiently elaborated by using a tandem olefin cross-metathesis/intramolecular oxa-Michael addition reaction. The 18-membered macrolactone skeleton was forged via a Au-catalyzed propargylic benzoate rearrangement/macrocyclic ring-closing metathesis sequence. Late-stage diversification of a common intermediate enabled unified total synthesis of (−)-enigmazole A and (−)-15-O-methylenigmazole A.",

keywords = "gold-catalyzed reaction, macrocycles, natural products, tandem reaction, tetrahydropyrans",

author = "Keisuke Sakurai and Keita Sakamoto and Makoto Sasaki and Haruhiko Fuwa",

note = "Funding Information: We thank Professor Kentaro Takada (Kitasato University) for his technical advice. Kaneka Corporation is gratefully acknowledged for a generous gift of (R)‐Roche ester. This work was financially supported by The Asahi Glass Foundation. ",

year = "2020",

month = nov,

day = "2",

doi = "10.1002/asia.202001015",

language = "English",

volume = "15",

pages = "3494--3502",

journal = "Chemistry - An Asian Journal",

issn = "1861-4728",

publisher = "John Wiley and Sons Ltd",

number = "21",

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TY - JOUR

T1 - Unified Total Synthesis of (−)-Enigmazole A and (−)-15-O-Methylenigmazole A

AU - Sakurai, Keisuke

AU - Sakamoto, Keita

AU - Sasaki, Makoto

AU - Fuwa, Haruhiko

N1 - Funding Information: We thank Professor Kentaro Takada (Kitasato University) for his technical advice. Kaneka Corporation is gratefully acknowledged for a generous gift of (R)‐Roche ester. This work was financially supported by The Asahi Glass Foundation.

PY - 2020/11/2

Y1 - 2020/11/2

N2 - The total synthesis of cytotoxic marine phosphomacrolides, (−)-enigmazole A and (−)-15-O-methylenigmazole A, is described in detail. The 2,6-cis-substituted tetrahydropyran ring was efficiently elaborated by using a tandem olefin cross-metathesis/intramolecular oxa-Michael addition reaction. The 18-membered macrolactone skeleton was forged via a Au-catalyzed propargylic benzoate rearrangement/macrocyclic ring-closing metathesis sequence. Late-stage diversification of a common intermediate enabled unified total synthesis of (−)-enigmazole A and (−)-15-O-methylenigmazole A.

AB - The total synthesis of cytotoxic marine phosphomacrolides, (−)-enigmazole A and (−)-15-O-methylenigmazole A, is described in detail. The 2,6-cis-substituted tetrahydropyran ring was efficiently elaborated by using a tandem olefin cross-metathesis/intramolecular oxa-Michael addition reaction. The 18-membered macrolactone skeleton was forged via a Au-catalyzed propargylic benzoate rearrangement/macrocyclic ring-closing metathesis sequence. Late-stage diversification of a common intermediate enabled unified total synthesis of (−)-enigmazole A and (−)-15-O-methylenigmazole A.

KW - gold-catalyzed reaction

KW - macrocycles

KW - natural products

KW - tandem reaction

KW - tetrahydropyrans

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