Glycal‐1‐ylmethylphosphonates – precursors of glycosyltransferase inhibitors

Direct lithiation of 2‐phenylsulfinyl‐ and 2‐phenylsulfonylsubstituted 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. Treatment with trimethyl phosphite furnished phosphonates 8 and 10 ; by treatment with sodium in liquid ammonia and subsequent reaction with acetic anhydride in pyridine both compounds were converted into monomethyl galactal‐1‐ylmethylphosphonate ( 11 ) which could not be completely demethylated without structural change. O ‐Acetyl‐protected mesylate 18 , obtained from galactosyl cyanide in a few steps, was transformed into bromide 19 which on treatment with P(OSiMe 3 ) 3 gave bis(trimethylsilyl) 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 obtained.