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Glycal‐1‐ylmethylphosphonates – precursors of glycosyltransferase inhibitors
Author(s) -
Frische Klaus,
Schmidt Richard R.
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199419940312
Subject(s) - chemistry , glycal , acetic anhydride , phosphonate , trimethyl phosphite , mesylate , hydroxymethyl , pyridine , bromide , cyanide , medicinal chemistry , organic chemistry , catalysis , stereoselectivity
Abstract 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.