A novel and efficient synthesis of the key intermediate of 1β-methylcarbapenem antibiotics employing [ 2+2 ]-cycloaddition reaction of diketene with a chiral imine

Takeo Kawabata, Yoshikazu Kimura, Yoshio Ito, Shiro Terashima, Akira Sasaki, Makoto Sunagawa

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The key intermediate (2) of 1β-methylcarbapenems was efficiently synthesized from (S)-methyl 3-hydroxy-2-methyl-propionate ((S)-5) in ten steps and 30 % overall yield. Thus, (S)-3-benzyloxy-2-methylpropanal readily obtainable from (S)-5, was condensed with di-p-anisylmethylamine to afford the chiral imine. The [2+2]-cycloaddition reaction of diketene with the imine was found to proceed in a highly diastereoselective manner, giving the desired 3,4-trans-3-acetyl-β-lactam (max. diastereoselectivity 11-15:1). This was readily elaborated to 2 by five sequential operations.

Original languageEnglish
Pages (from-to)2149-2165
Number of pages17
JournalTetrahedron
Volume44
Issue number8
DOIs
Publication statusPublished - Jan 1 1988
Externally publishedYes

Fingerprint

Imines
Cycloaddition
Cycloaddition Reaction
Anti-Bacterial Agents
Lactams
Propionates
diketene
1 beta-methylcarbapenem
isobutyraldehyde
In Ten-S composite resin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

A novel and efficient synthesis of the key intermediate of 1β-methylcarbapenem antibiotics employing [ 2+2 ]-cycloaddition reaction of diketene with a chiral imine. / Kawabata, Takeo; Kimura, Yoshikazu; Ito, Yoshio; Terashima, Shiro; Sasaki, Akira; Sunagawa, Makoto.

In: Tetrahedron, Vol. 44, No. 8, 01.01.1988, p. 2149-2165.

Research output: Contribution to journalArticle

Kawabata, Takeo ; Kimura, Yoshikazu ; Ito, Yoshio ; Terashima, Shiro ; Sasaki, Akira ; Sunagawa, Makoto. / A novel and efficient synthesis of the key intermediate of 1β-methylcarbapenem antibiotics employing [ 2+2 ]-cycloaddition reaction of diketene with a chiral imine. In: Tetrahedron. 1988 ; Vol. 44, No. 8. pp. 2149-2165.
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