Synthesis and Biological Activities of Analogs of a Lipid A Biosynthetic Precursor : 1-O-Phosphono-oxyethyl-4'-O-phosphono-disaccharides with (R)-3-Hydroxytetradecanoyl or Tetradecanoyl Groups at Positions 2, 3, 2' and 3'

Abstract

Two novel analogs of a biosynthetic precursor of lipid A (2) were synthesized. The one analog (3) has acyl groups identical to those of 2, and the other (4) has tetradecanoyl groups in place of the (R)-3-hydroxytetradecanoyl groups of 2. Both 3 and 4 possess an α-glycosidically-bound phosphonooxyethyl group in place of the α-glycosyl phosphate group of 2.Compounds 3 and 4 exhibited definite antitumor activity against Meth A fibrosarcoma and low toxicity in rabbits, as the original compound 2 does. The replacement of the hydroxytetradecanoyl groups with tetradecanoyl groups barely affected the antitumor activity, but slightly enhanced the toxicity in rabbits.