P-60 Studies on the Structure-activity Relationship of Salacinol, a Potent Naturally Occurring α-Glucosidase Inhibitor

• Muraoka Osamu

  School of Pharmaceutical Sciences, Kinki University

• Yoshikai Kazuya

  School of Pharmaceutical Sciences, Kinki University

• Hatanaka Takanori

  School of Pharmaceutical Sciences, Kinki University

• Minematsu Toshie

  School of Pharmaceutical Sciences, Kinki University

• Shao Ying

  School of Pharmaceutical Sciences, Kinki University

• Tanabe Genzoh

  School of Pharmaceutical Sciences, Kinki University

• Yoshikawa Masayuki

  Kyoto Pharmaceutical University

• Matsuda Hisashi

  Kyoto Pharmaceutical University

• Morikawa Toshio

  Kyoto Pharmaceutical University

• Wang Tao

  Kyoto Pharmaceutical University

Bibliographic Information

Other Title

• P-60 α-Glucosidase阻害剤,Salacinol類縁体の合成と構造活性相関(ポスター発表の部)

Abstract

Salacinol (1a) is a new class of potent natural glycosidase inhibitor isolated by presenters from Ayruvedic medicine Salacia reticulata, having the unique spirobicyclic-like configuration comprised of 1-deoxy-4-thio-D-arabinofranosyl cation and 1-deoxy-L-erythrosyl-3-sulfate anion. The characteristic feature of 1a represented as sulfonium cation and the side-chain bearing sulfate anion have been supposed to be the origin of its α-glucosidase inhibitory activity. In this study, aza analogue (1b), its enantiomer (4b) and diastereomer (5b) were synthesized by applying the ring-opening method of cyclic sulfate (2a and 2b) with D- and L-azasugars (D- and L-3b) in order to explore the effect of heteroatom substitution in the 5-membered sugar ring on the α-glucosidase inhibitory activity. Three sulfonium analogs (6, 7, 8) lacking hydroxyl and/or hydroxymethyl groups of the side chain of 1a and two O-desulfonated sulfoniums (9a, 9b) with CH_3OSO_3^- or Cl^- as a counter anion were also synthesized and their inhibitory activities were examined and compared with those of 1a. Upon substitution of sulfur atom with nitrogen, 1b sustained the modest inhibitory activity, however, the inhibitory activities of 4b and 5b were reduced considerably. Three deoxy analogs (6, 7, 8) also showed less inhibitory activity compared to 1a, and proved the importance of cooperative role of the polar substituents to exhibit the α-glucosidase inhibitory activity. Interestingly, O-desulfonated analogs 9a and 9b sustained the potent α-glucosidase inhibitory activity equal to that of 1a irrespective of the counter anions, thus the sulfate anion moiety of 1a was found to be not essential for the inhibitory activity.

Journal

• Symposium on the Chemistry of Natural Products, symposium papers

  Symposium on the Chemistry of Natural Products, symposium papers 47 (0), 619-624, 2005

  Symposium on the Chemistry of Natural Products Steering Committee

Details

• CRID: 1390001206077526656
• NII Article ID: 110006682616
• DOI: 10.24496/tennenyuki.47.0_619
• ISSN: 24331856
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed