SYNTHESIS OF THE NOVEL MANNOSIDASE INHIBITORS (3R)-3-(HYDROXYMETHYL)SWAINSONINE AND (3S)-3-(HYDROXYMETHYL)SWAINSONINE

Swainsonine (9) is an important mannosidase inhibitor that has been ex amined clinically as an anticancer drug. The preparation of analogs of swainsonine bearing a hydroxymethyl group at C(3), i.e., (3R)-3-(hydr oxymethyl)swainsonine [(10), (3R)-HMS] and (3S)-3-(hydroxymethyl)swain sonine [(11), (3S)-HMS] is described. The synthesis of each analog beg ins with D-ribose, and involves a Claisen rearrangement, a Sharpless o smylation, and a reductive double-cyclization of either an azido mesyl ate bearing a lactone (i.e. 24 double right arrow 11) or an azido epox ide bearing a lactone (i.e. 27 double right arrow 10). Both (3R)-HMS a nd (3S)-HMS were found to be effective inhibitors of a-mannosidase fro m jack bean. (C) 1997 Elsevier Science Ltd.