Ajito K, Kurihara K, Shibahara S, Hara O, Okonogi T, Kikuchi N, Araake M, Suzuki H, Omoto S, Inouye S
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
J Antibiot (Tokyo). 1997 Feb;50(2):150-61. doi: 10.7164/antibiotics.50.150.
Six derivatives of sixteen-membered macrolides possessing 4-O-acyl-alpha-L-cladinose as a neutral sugar were synthesized via 3"-methylthiomethyl ether intermediates in reasonable yield. Introduction of a methyl group on the 3"-hydroxyl group of midecamycin A1 was effective for enhancing its antibacterial activity. All these derivatives exhibited excellent therapeutic effects in mice, and some of them showed improved pharmacokinetics compared with the natural antibiotics (mycarose type) in mice. Facile synthesis of 9-O-acylated analogues are also described.
通过3″-甲硫基甲基醚中间体合成了六种具有4-O-酰基-α-L-克拉定糖作为中性糖的十六元大环内酯衍生物，产率合理。在麦迪霉素A1的3″-羟基上引入甲基可有效增强其抗菌活性。所有这些衍生物在小鼠中均表现出优异的治疗效果，其中一些与天然抗生素（鼠李糖型）相比，在小鼠中的药代动力学有所改善。还描述了9-O-酰化类似物的简便合成方法。
