CLADINOSE ANALOGS OF 16-MEMBERED MACROLIDE ANTIBIOTICS .4. IMPROVED THERAPEUTIC EFFECTS OF 4-O-ACYL-L-CLADINOSE ANALOGS OF 16-MEMBERED MACROLIDE ANTIBIOTICS

Six derivatives of sixteen-membered macrolides possessing 4-O-acyl-alp ha-L-cladinose as a neutral sugar were synthesized via 3 ''-methylthio methyl ether intermediates in reasonable yield. Introduction of a meth yl group on the 3 ''-hydroxyl group of midecamycin A(1) was effective for enhancing its antibacterial activity. All these derivatives exhibi ted excellent therapeutic effects in mice, and some of them showed imp roved pharmacokinetics compared with the natural antibiotics (mycarose type) in mice. Facile synthesis of 9-O-acylated analogues are also de scribed.