Kurihara K I, Ajito K, Shibahara S, Hara O, Araake M, Omoto S, Inouye S
Pharmaceutical Research Center, Meiji Seika Kaisha, LTD., Yokohama, Japan.
J Antibiot (Tokyo). 1998 Aug;51(8):771-85. doi: 10.7164/antibiotics.51.771.
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.
通过结合结构稳定的硅烷基缩醛保护和将3''-甲硫基甲基醚选择性氢解为3''-甲氧基，合成了五种具有4-O-酰基-α-L-克拉定糖作为中性糖部分的新型十六元大环内酯3-羟基衍生物。几种在4''-羟基处具有正丁酰基、异丁酰基和正戊酰基取代基的衍生物在体外表现出显著的抗菌活性。其中一种，4''-O-正丁酰基-3''-O-甲基柱晶白霉素V，在小鼠中显示出改善的治疗效果。
