Abstract
A practical one-pot synthesis of bi- and triantennated australine analogues from a pivotal sp(2)-iminosugar-type reducing castanospermine precursor is reported. The transformation involves a gem-diamine intermediate that undergoes the indolizidine → pyrrolizidine Amadori-type rearrangement and proceeds under strict control of the generalized anomeric effect to afford a single diastereomer. The final compounds behave as selective competitive inhibitors of β-glucosidase and are promising candidates as pharmacological chaperones for Gaucher disease.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Biochemical Phenomena
-
Diamines / chemistry*
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology
-
Gaucher Disease / drug therapy*
-
Humans
-
Indolizidines / chemistry
-
Indolizidines / pharmacology*
-
Indolizines / chemistry*
-
Molecular Chaperones / chemical synthesis
-
Molecular Chaperones / chemistry*
-
Molecular Chaperones / pharmacology*
-
Molecular Structure
-
Pyrrolizidine Alkaloids / chemical synthesis*
-
Pyrrolizidine Alkaloids / chemistry
-
beta-Glucosidase / antagonists & inhibitors*
-
beta-Glucosidase / chemistry*
Substances
-
Diamines
-
Enzyme Inhibitors
-
Indolizidines
-
Indolizines
-
Molecular Chaperones
-
Pyrrolizidine Alkaloids
-
australine
-
beta-Glucosidase
-
castanospermine