Synthetic studies of the spirocyclic cyclohexene part of versipelostatin, a novel GRP78/Bip molecular chaperone downregulator

Shu Sasaki, Suguru Samejima, Tomoki Uruga, Kai Anzai, Natsumi Nishi, Eriko Kawakita, Kenichi Takao, Kin Ichi Tadano

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The spirocyclic part consisting of an -acylated tetronic acid and a multisubstituted cyclohexene embedded in versipelostatin, a novel GRP78/Bip molecular chaperone downregulator, has been synthesized in enantiomerically pure form. The asymmetric synthesis of the targeted spiro4.5-1-oxa-7-decen-2,4-dione derivative was characterized by (1) stereoselective allylation at the -carbon of methylmalonate diester, in which one carboxylic acid was esterified with a D-glucose-derived chiral template, (2) construction of the tetrasubstituted cyclohexenone substructure by high-yielding ring-closing metathesis and (3) stereoselective construction of the spirocyclic tetronic acid part starting from the cyclohexenone obtained as the ring-closing metathesis product.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalJournal of Antibiotics
Volume66
Issue number3
DOIs
Publication statusPublished - 2013 Mar

Fingerprint

Carboxylic Acids
Carbon
Glucose
versipelostatin
tetronic acid
cyclohexene
molecular chaperone GRP78

Keywords

  • a-acyltetronic acid
  • asymmetric quaternary carbon
  • ring-closing metathesis
  • spirocyclic cyclohexene
  • versipelostatin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Synthetic studies of the spirocyclic cyclohexene part of versipelostatin, a novel GRP78/Bip molecular chaperone downregulator. / Sasaki, Shu; Samejima, Suguru; Uruga, Tomoki; Anzai, Kai; Nishi, Natsumi; Kawakita, Eriko; Takao, Kenichi; Tadano, Kin Ichi.

In: Journal of Antibiotics, Vol. 66, No. 3, 03.2013, p. 147-154.

Research output: Contribution to journalArticle

Sasaki, Shu ; Samejima, Suguru ; Uruga, Tomoki ; Anzai, Kai ; Nishi, Natsumi ; Kawakita, Eriko ; Takao, Kenichi ; Tadano, Kin Ichi. / Synthetic studies of the spirocyclic cyclohexene part of versipelostatin, a novel GRP78/Bip molecular chaperone downregulator. In: Journal of Antibiotics. 2013 ; Vol. 66, No. 3. pp. 147-154.
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