Synthesis and biological activities of analogs of a lipid A biosynthetic precursor: 1-O-phosphonooxyethyl-4'-O-phosphono-disaccharides with (R)-3-hydroxytetradecanoyl or tetradecanoyl groups at positions 2, 3, 2' and 3'.
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 alpha-glycosidically-bound phosphonooxyethyl group in place of the alpha-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.
Kusama
T
T
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Soga
T
T
Ono
Y
Y
Kumazawa
E
E
Shioya
E
E
Osada
Y
Y
Kusumoto
S
S
Shiba
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005354:Fibrosarcoma / Q000188:drug therapy; D008050:Lipid A / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011817:Rabbits
D000970:Antineoplastic Agents; D008050:Lipid A