Synthetic explorations towards 3-deoxy-3-fluoro derivatives of D-perosamine

Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideo xy-3-fluoro-alpha -D-mannopyranoside (18) was attempted via fluorination of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha -D-altropyranoside with diethy laminosulfur trifluoride (DAST). Contrary to expectations, the reaction too k place with retention of configuration at the site of the fluorination yie lding methyl 4-azido-2-O-benzyl-3,4,6-trideoxy-3-fluoro-alpha -D-altropyran oside. Treatment with DAST of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha - D-allopyranoside (8), or its 2-(p-methoxybenzyl) analog 9 resulted in fluor ination with inversion of configuration at position 3, to give the correspo nding 3-deoxy-3-fluoro glucopyranosides 10 and 11, respectively. Accordingl y, compound 18 was prepared from 11, by de-p-methoxybenzylation at O-2, fol lowed by inversion of configuration at C-2 in the resulting methyl 4-azido- 3,4,6-trideoxy-3-fluoro-alpha -D-glucopyranoside. The 2-O-methyl analog of 18 (19) was prepared by methylation of 18. Compounds 18 and 19 were convert ed, conventionally, into the 3-fluoro analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1, serotype Inaba and Ogawa, respectively. (C) 2001 Elsevier Science Ltd. All rights reserved.