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
Publication statusPublished - 2005 Jan

Fingerprint

Amino Acids
Stereoisomerism
Transferases
Biological Products
Serine
Nitrogen
Carbon
sulfamisterin
trichloroacetamide
tartaric acid
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Sato, H., Maeba, T., Yanase, R., Yamaji-Hasegawa, A., Kobayashi, T., & Chida, N. (2005). Total synthesis and biological activities of (+)-sulfamisterin (AB5366) and its analogues. Journal of Antibiotics, 58(1), 37-49.

Total synthesis and biological activities of (+)-sulfamisterin (AB5366) and its analogues. / Sato, Hideyuki; Maeba, Takaki; Yanase, Ryota; Yamaji-Hasegawa, Akiko; Kobayashi, Toshihide; Chida, Noritaka.

In: Journal of Antibiotics, Vol. 58, No. 1, 01.2005, p. 37-49.

Research output: Contribution to journalArticle

Sato, H, Maeba, T, Yanase, R, Yamaji-Hasegawa, A, Kobayashi, T & Chida, N 2005, 'Total synthesis and biological activities of (+)-sulfamisterin (AB5366) and its analogues', Journal of Antibiotics, vol. 58, no. 1, pp. 37-49.
Sato H, Maeba T, Yanase R, Yamaji-Hasegawa A, Kobayashi T, Chida N. Total synthesis and biological activities of (+)-sulfamisterin (AB5366) and its analogues. Journal of Antibiotics. 2005 Jan;58(1):37-49.
Sato, Hideyuki ; Maeba, Takaki ; Yanase, Ryota ; Yamaji-Hasegawa, Akiko ; Kobayashi, Toshihide ; Chida, Noritaka. / Total synthesis and biological activities of (+)-sulfamisterin (AB5366) and its analogues. In: Journal of Antibiotics. 2005 ; Vol. 58, No. 1. pp. 37-49.
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