Isolation and SAR studies of bicyclic iminosugars from Castanospermum australe as glycosidase inhibitors

Phytochemistry. 2015 Mar:111:124-31. doi: 10.1016/j.phytochem.2014.12.011. Epub 2015 Jan 9.

Abstract

We report the isolation and structural determination of fourteen iminosugars, containing five pyrrolizidines and five indolizidines, from Castanospermum australe. The structure of a new alkaloid was elucidated by spectroscopic methods as 6,8-diepi-castanospermine (13). Our side-by-side comparison between bicyclic and corresponding monocyclic iminosugars revealed that inhibition potency and spectrum against each enzyme are clearly changed by their core structures. Castanospermine (10) and 1-deoxynojirimycin (DNJ) have a common d-gluco configuration, and they showed the expected similar inhibition potency and spectrum. In sharp contrast, 6-epi-castanospermine (12) and 1-deoxymannojirimycin (manno-DNJ) both have the d-manno configuration but the α-mannosidase inhibition of 6-epi-castanospermine (12) was much better than that of manno-DNJ. 6,8-Diepi-castanospermine (13) could be regarded as a bicyclic derivative of talo-DNJ, but it showed a complete loss of α-galactosidase A inhibition. This behavior against α-galactosidase A is similar to that observed for 1-epi-australine (6) and altro-DMDP.

Keywords: Australine; Castanospermine; Castanospermum australe; Glycosidase inhibitor; Iminosugar; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives
  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / pharmacology
  • Alkaloids / chemistry
  • Alkaloids / isolation & purification*
  • Alkaloids / pharmacology*
  • Castanospermum / chemistry*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology*
  • Glucosamine / analogs & derivatives
  • Glucosamine / chemistry
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Imino Sugars / chemistry
  • Imino Sugars / isolation & purification*
  • Imino Sugars / pharmacology*
  • Indolizines / chemistry
  • Indolizines / isolation & purification*
  • Indolizines / pharmacology*
  • Piperidines / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 1-deoxy-nojirimycin
  • Alkaloids
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Imino Sugars
  • Indolizines
  • Piperidines
  • miglitol
  • 1-Deoxynojirimycin
  • Glycoside Hydrolases
  • Glucosamine
  • castanospermine