Cladinose analogues of sixteen-membered macrolide antibiotics. VI. Synthesis of metabolically programmed, highly potent analogues of sixteen-membered macrolide antibiotics.
Five novel 3-hydroxyl derivatives of sixteen-membered macrolide possessing 4-O-acyl-alpha-L-cladinose as a neutral sugar moiety were synthesized by using a combination of structurally stable silyl acetal protection and selective hydrogenolysis of a 3"-methylthiomethyl ether to a 3"-OMe group. Several derivatives having n-butyryl, i-butyryl and n-valeryl substituent at the 4"-OH group exhibited significant antibacterial activity in vitro. One of them, 4"-O-n-butyryl-3"-O-methylleucomycin V, showed improved therapeutic effect in mice.
Pharmaceutical Research Center, Meiji Seika Kaisha, LTD., Yokohama, Japan.
K I
KI
Kurihara
K
K
Ajito
S
S
Shibahara
O
O
Hara
M
M
Araake
S
S
Omoto
S
S
Inouye
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006601:Hexoses / Q000737:chemistry / Q000494:pharmacology*; D018942:Macrolides; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006601:Hexoses; D018942:Macrolides; C013889:cladinose