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]

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 JF,H and JF,C values on molecular geometry and substituent effects. © 1990.