Gotoh Y, Saitoh H, Miyake T
Institute of Bioorganic Chemistry, Kawasaki, Japan.
Carbohydr Res. 1998 Jun;309(1):45-55. doi: 10.1016/s0008-6215(98)00126-8.
This paper describes the chemical transformation of the basic 16-membered macrolides, tylosin derivatives, into neutral macrolides having a 3'-methoxyl group. 2',4'-Di-O-acetyl-3,23-bis(O-tert-butyldimethylsilyl)mycaminosyltylon olide 9,20-bis(ethylene acetal) N-oxide (1b) was treated with Ac2O-pyridine in CH2Cl2 to afford the 3'-ketone 1c and the 3'-N-acetyl-3'-N-demethyl derivative 1d in 67 and 5% yield; respectively. Reduction of 1c with Zn(BH4)2 gave the 3'-alcohol 1e in 84% yield stereoselectively. O-Methylation of 1e with MeOTf and 2,6-di-tert-butylpyridine gave the 3'-methyl ether 1f in 49% yield in spite of the presence of the adjacent acetoxyl groups. Deprotection of 1f provided the desired neutral macrolide 1g. Similar synthetic routes were also used for transformation of the suitably protected 4'-deoxymycaminosyltylonolide 2b and desmycosin 3c into neutral macrolides having a 3'-methoxyl group. It was found that the mycinose moiety of a neutral macrolide plays an important role in its antimicrobial activity.
本文描述了碱性16元大环内酯类泰乐菌素衍生物向具有3'-甲氧基的中性大环内酯类的化学转化。2',4'-二-O-乙酰基-3,23-双（O-叔丁基二甲基甲硅烷基）麦考胺基泰洛内酯9,20-双（亚乙基缩醛）N-氧化物（1b）在二氯甲烷中用乙酸酐-吡啶处理，分别以67%和5%的产率得到3'-酮1c和3'-N-乙酰基-3'-N-去甲基衍生物1d。用Zn(BH4)2还原1c，以84%的产率立体选择性地得到3'-醇1e。尽管存在相邻的乙酰氧基，1e用三氟甲磺酸甲酯和2,6-二叔丁基吡啶进行O-甲基化，仍以49%的产率得到3'-甲基醚1f。1f脱保护得到所需的中性大环内酯1g。类似的合成路线也用于将适当保护的4'-脱氧麦考胺基泰洛内酯2b和去霉胺3c转化为具有3'-甲氧基的中性大环内酯。发现中性大环内酯的霉糖部分在其抗菌活性中起重要作用。
