Total Synthesis of Bafilomycin A1

Kazunobu Toshima, Takaaki Jyojima, Hiroyuki Yamaguchi, Yasunobu Noguchi, Takehito Yoshida, Hidekazu Murase, Masaya Nakata, Shuichi Matsumura

Research output: Contribution to journalArticle

Abstract

The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side- chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.

Original languageEnglish
Pages (from-to)3263-3270
Number of pages8
JournalJournal of Organic Chemistry
Volume62
Issue number10
Publication statusPublished - 1997

Fingerprint

Lactones
Vacuolar Proton-Translocating ATPases
Macrolides
Ketones
Aldehydes
Hydroxyl Radical
Anti-Bacterial Agents
Glucose
bafilomycin A1
methyl lactate
vinyl iodide
3-hydroxybutanal

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Toshima, K., Jyojima, T., Yamaguchi, H., Noguchi, Y., Yoshida, T., Murase, H., ... Matsumura, S. (1997). Total Synthesis of Bafilomycin A1 Journal of Organic Chemistry, 62(10), 3263-3270.

Total Synthesis of Bafilomycin A1 . / Toshima, Kazunobu; Jyojima, Takaaki; Yamaguchi, Hiroyuki; Noguchi, Yasunobu; Yoshida, Takehito; Murase, Hidekazu; Nakata, Masaya; Matsumura, Shuichi.

In: Journal of Organic Chemistry, Vol. 62, No. 10, 1997, p. 3263-3270.

Research output: Contribution to journalArticle

Toshima, K, Jyojima, T, Yamaguchi, H, Noguchi, Y, Yoshida, T, Murase, H, Nakata, M & Matsumura, S 1997, 'Total Synthesis of Bafilomycin A1 ', Journal of Organic Chemistry, vol. 62, no. 10, pp. 3263-3270.
Toshima K, Jyojima T, Yamaguchi H, Noguchi Y, Yoshida T, Murase H et al. Total Synthesis of Bafilomycin A1 Journal of Organic Chemistry. 1997;62(10):3263-3270.
Toshima, Kazunobu ; Jyojima, Takaaki ; Yamaguchi, Hiroyuki ; Noguchi, Yasunobu ; Yoshida, Takehito ; Murase, Hidekazu ; Nakata, Masaya ; Matsumura, Shuichi. / Total Synthesis of Bafilomycin A1 In: Journal of Organic Chemistry. 1997 ; Vol. 62, No. 10. pp. 3263-3270.
@article{224f9a34c5314a85ae2367e11b08095c,
title = "Total Synthesis of Bafilomycin A1",
abstract = "The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side- chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.",
author = "Kazunobu Toshima and Takaaki Jyojima and Hiroyuki Yamaguchi and Yasunobu Noguchi and Takehito Yoshida and Hidekazu Murase and Masaya Nakata and Shuichi Matsumura",
year = "1997",
language = "English",
volume = "62",
pages = "3263--3270",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "10",

}

TY - JOUR

T1 - Total Synthesis of Bafilomycin A1

AU - Toshima, Kazunobu

AU - Jyojima, Takaaki

AU - Yamaguchi, Hiroyuki

AU - Noguchi, Yasunobu

AU - Yoshida, Takehito

AU - Murase, Hidekazu

AU - Nakata, Masaya

AU - Matsumura, Shuichi

PY - 1997

Y1 - 1997

N2 - The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side- chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.

AB - The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side- chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.

UR - http://www.scopus.com/inward/record.url?scp=1542734979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542734979&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:1542734979

VL - 62

SP - 3263

EP - 3270

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 10

ER -