GLYCAL-1-YLMETHYLPHOSPHONATES - PRECURSORS OF GLYCOSYLTRANSFERASE INHIBITORS

Direct lithiation of 2-phenylsulfinyl- and 2-phenylsulfonyl-substitute d galactal derivatives 3a-c and subsequent reaction with DMF gave 1-C- formyl derivatives 4a-c. Reduction afforded hydroxymethyl derivatives 5a-c which were transformed into mesylates 7 and 9, respectively. Trea tment with trimethyl phosphite furnished phosphonates 8 and 10; by tre atment with sodium in liquid ammonia and subsequent reaction with acet ic anhydride in pyridine both compounds were converted into monomethyl galactal-1-ylmethylphosphonate (11) which could not be completely dem ethylated without structural change. O-Acetyl-protected mesylate 18, o btained from galactosyl cyanide in a few steps, was transformed into b romide 19 which on treatment with P(OSiMe(3))(3) gave bis(trimethylsil yl) phosphonate 20. Reaction with NaOMe/MeOH afforded the unprotected disodium salt of D-galactal-1-ylmethylphosphonate 1. Similarly, from L -fucopyranosyl cyanide 22 the corresponding target molecule 2 was obta ined.-