Synthesis of multibranched australine derivatives from reducing castanospermine analogues through the amadori rearrangement of gem -diamine intermediates: Selective inhibitors of β-glucosidase

摘要

© 2014 American Chemical Society. A practical one-pot synthesis of bi- and triantennated australine analogues from a pivotal sp2-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.