Synthetic explorations towards 3-deoxy-3-fluoro derivatives of D-perosamine.
Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideoxy-3-fluoro-alpha-D-mannopyranoside (18) was attempted via fluorination of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha-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-alpha-D-altropyranoside. 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 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-alpha-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.
Poirot
E
E
National Institutes of Health, NIDDK, LMC, Building 8, Room B1A24, Bethesda, MD 20892-0815, USA.
Chang
A H
AH
Horton
D
D
Kovác
P
P
D004048:Diethylamines / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000031:analogs & derivatives* / Q000737:chemistry*; D015394:Molecular Structure; D019081:O Antigens / Q000737:chemistry*; D014734:Vibrio cholerae / Q000737:chemistry*
D004048:Diethylamines; D007202:Indicators and Reagents; D019081:O Antigens; D005461:Fluorine; C057033:4-amino-4,6-dideoxy-D-mannose; C040394:diethylaminosulfur trifluoride; D008358:Mannose