Total synthesis and biological activities of (+)-sulfamisterin (AB5366) and its analogues

Hideyuki Sato, Takaki Maeba, Ryota Yanase, Akiko Yamaji-Hasegawa, Toshihide Kobayashi, Noritaka Chida

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The first total synthesis of (+)-sulfamisterin (AB5366), a naturally occurring α-substituted α-amino acid derivative possessing a sulfonated hydroxy function, is described. Overman rearrangement of an allylic trichloroacetimidate derived from D-tartrate effectively generated the tetrasubstituted carbon containing a nitrogen substituent. Construction of the amino acid moiety and sulfonation of the hydroxy group, followed by deprotection completed the total synthesis, which fully confirmed the proposed absolute structure of the natural product. The possible stereoisomers of (+)-sulfamisterin and their desulfonated derivatives were also synthesized. Biological assessment of all synthetic compounds revealed that natural (+)-sulfamisterin and its 3-epimer as well as their desulfonated derivatives possessing 2S-configuration strongly inhibit the serine palmitoyl transferase both in vitro and in vivo, whereas compounds with 2R-configuration were found to show much weaker inhibitory activity.

Original languageEnglish
Pages (from-to)37-49
Number of pages13
JournalJournal of Antibiotics
Volume58
Issue number1
DOIs
Publication statusPublished - 2005 Jan

Keywords

  • AB5366
  • SPT inhibitory activity
  • Sulfamisterin
  • Sulfamisterin analogues
  • Total synthesis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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