Synthesis of 3-amino-2,3,6-trideoxy-2-fluoro- l-talose and - d-allose [( R)-2-fluoro- l-daunosamine and ( R)-2-fluoro- d-ristosamine

Abstract

The title compounds were synthesized (as methyl glycosides) starting from 1,3,4,6-tetra- O-acetyl-2-deoxy-2-fluoro-β- d-glycopyranose. Stereoselective methods of glycosylation gave, via the tri- O-acetylglycopyranosyl bromide, the methyl 2-deoxy-2-fluoro-α- and -β- d-glycopyranoside triacetates. Each anomer was O-deacetylated and further transformed into the corresponding, 4,6- O-benzylidenated 3-triflate, and the triflates were converted by azide displacement into the 3-azido-2,3-dideoxy-2-fluoroglycosides having the d- allo configuration. Hanessian-Hullar reaction then furnished the corresponding 6-bromo-6-deoxy-4-benzoates, which were dehydrobrominated to give the methyl 3-azido-4- O-benzoyl-2,3,6-trideoxy-2-fluoro-α- and -β- d- ribo-hex-5-enopyranosides. Debenzoylation of the α-anomer, followed by catalytic hydrogenation, led to methyl 3-amino-2,3,6-trideoxy-2-fluoro-β- l-talopyranoside [methyl ( R)-2-fluoro-β- l-daunosaminide], whereas the same sequence applied to the β-anomer afforded methyl 3-amino-2,3,6-trideoxy-2-fluoro-β- d-allopyranoside [methyl ( R)-2-fluoro-β- d-ristosaminide]. The overall yields for these 10-step sequences were 11–12 and 16%, respectively. The 1H- and 13C-n.m.r. data for the new fluoro sugar derivatives are discussed with respect to the dependence of J F,H and J F,C values on molecular geometry and substituent effects.