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

• Published in: Carbohydrate research 2001-08, Vol.334 (3), p.195-205
• Main Authors: Poirot, Emmanuel, Chang, Alex H.C, Horton, Derek, Kováč, Pavol
• Format: Article
• Language: English
• Subjects: 3-Deoxy-3-fluoro- d-mannose; Diethylamines - chemistry; Fluorination with DAST; Fluorine - chemistry; Indicators and Reagents - chemistry; Magnetic Resonance Spectroscopy; Mannose - analogs & derivatives; Mannose - chemistry; Methyl 4-azido-3-fluoro-3,4,6-trideoxy-α- d-mannopyranoside; Molecular Structure; Nucleophilic displacement; O Antigens - chemistry; Vibrio cholerae - chemistry; Vibrio cholerae O:1
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(01)00188-4

Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideoxy-3-fluoro-α- d-mannopyranoside ( 18) was attempted via fluorination of methyl 4-azido-2- O-benzyl-4,6-dideoxy-α- d-altropyranoside with diethylaminosulfur trifluoride (DAST). Contrary to expectations, the reaction took place with retention of configuration at the site of the fluorination yielding methyl 4-azido-2- O-benzyl-3,4,6-trideoxy-3-fluoro-α- d-altropyranoside. Treatment with DAST of methyl 4-azido-2- O-benzyl-4,6-dideoxy-α- d-allopyranoside ( 8), or its 2-( p-methoxybenzyl) analog 9 resulted in fluorination with inversion of configuration at position 3, to give the corresponding 3-deoxy-3-fluoro glucopyranosides 10 and 11, respectively. Accordingly, compound 18 was prepared from 11, by de- p-methoxybenzylation at O-2, followed by inversion of configuration at C-2 in the resulting methyl 4-azido-3,4,6-trideoxy-3-fluoro-α- d-glucopyranoside. The 2- O-methyl analog of 18 ( 19) was prepared by methylation of 18. Compounds 18 and 19 were converted, conventionally, into the 3-fluoro analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1, serotype Inaba and Ogawa, respectively. Graphic