Towards the elusive structure of kotalanol, a naturally occurring glucosidase inhibitor

Nat Prod Rep. 2010 Apr;27(4):481-8. doi: 10.1039/b925950c. Epub 2010 Feb 18.

Abstract

This Highlight describes the detailed approach used to determine the absolute stereochemistry of the stereogenic centers in the acyclic side chain of kotalanol, a naturally occurring glucosidase inhibitor isolated from the plant Salacia reticulata. The plant extract itself is used in Ayurvedic medicine for the treatment of Type 2 diabetes. We highlight the syntheses of proposed candidates based on structure-activity relationships, the total synthesis of kotalanol, and crystallographic studies of kotalanol and its de-O-sulfonated derivative complexed with recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the breakdown of glucose oligomers into glucose.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Products* / chemistry
  • Biological Products* / isolation & purification
  • Biological Products* / pharmacology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology
  • Glucosidases / antagonists & inhibitors*
  • Glucosidases / metabolism
  • Glycoside Hydrolase Inhibitors*
  • Humans
  • Intestines / enzymology
  • Medicine, Ayurvedic
  • Molecular Structure
  • Monosaccharides* / chemistry
  • Monosaccharides* / isolation & purification
  • Monosaccharides* / pharmacology
  • Salacia / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfates* / chemistry
  • Sulfates* / isolation & purification
  • Sulfates* / pharmacology
  • alpha-Glucosidases / metabolism

Substances

  • Biological Products
  • Glycoside Hydrolase Inhibitors
  • Kotalanol
  • Monosaccharides
  • Sulfates
  • Glucosidases
  • alpha-Glucosidases