Cladinose analogues of sixteen-membered macrolide antibiotics - VI. Synthesis of metabolically programmed, highly potent analogues of sixteen-membered macrolide antibiotics

摘要

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. [References: 17]