| 第 48 卷第 2 期 |  | Vol. 48 No. 2 | | 2018 年 4 月 | Apr 2018 |
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所属栏目：医药及中间体
泰利霉素关键中间体3-OH-6-O-甲基红霉素的合成研究 |
| 王金龙，向 普，王宗利，侯仲轲*
（浙江国邦药业有限公司，浙江 上虞 312369） |
| 摘 要：对泰利霉素关键中间体3-羟基-6-O-甲基红霉素（4）的合成进行了研究，以克拉霉素前体2′，4″- O-二（三甲基硅基）- 6-O-甲基红霉素A9-O-（1-乙氧基异丙叉基）肟（1）为原料，通过对一步法工艺优化得到产品4，通过使用缓冲体系和两边同时滴加盐酸和NaNO2的方式来控制脱肟过程的pH，该方法显著提高了产品纯度，缩短了反应时间，可有效抑制半缩酮副产物的生成，制得高纯度目标产物4，可与克拉霉素联产，大大简化了合成工艺，具有工业化前景。 |
| 关键词：2′，4″- O-二（三甲基硅基）-6-O-甲基红霉素A9-O-（1-乙氧基异丙叉基）肟；3-OH-6-O-甲基红霉素；一步法合成；克拉霉素 |
| 中图分类号：R914 文献标识码：A 文章编号：1009-9212（2018）02-0050-05 |
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| Synthesis of Telithromycin Key Intermediate 3-OH-6-O-Methylerythromycin |
| WANG Jin-long, XIANG Pu, WANG Zong-li, HOU Zhong-ke*
(Zhe Jiang Guo Bang Pharmaceutical Co.,Ltd., Shangyu 312369,China) |
| Abstract：The synthesis of 3-hydroxy-6-O-methylerythromycin (4), a key intermediate of telithromycin, was studied. Clarithromycin precursor 2′,4″-O-bis (trimethylsilyl)-6-O-methylerythromycin A 9-O-(1-ethoxypropylidene) oxime (1) was used as raw material to obtain product 4 through an one-step process. The pH of the deodorization process was controlled by the use of a buffer system and simultaneous addition of hydrochloric acid and NaNO2 on both sides. This method could significantly increased the purity of the product and shorten the reaction time. It could effectively inhibit the formation of hemiketal by-products and produce high-purity target product 4, which could be co-produced with clarithromycin. It greatly simplified the synthetic process and had the prospect of industrialization. |
| Key words：2′,4′′-O-bis-(trimethylsilyl)-6-O-methylerythromycin A9-O-(1-ethoxyisopropylidenel)oxime; 3-OH-6-O-methylerythromycin; one-step synthesis; Clarithromycin |
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作者简介：王金龙（1987-），男，河南三门峡人，主要从事药物合成及工艺开发研究（E-mail：xiaolong10724@qq.com）
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收稿日期：1009-9212（
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