| 第 48 卷第 2 期 |  | Vol. 48 No. 2 | | 2018 年 4 月 | Apr 2018 |
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所屬欄目：醫藥及中間體
泰利霉素關(guān)鍵中間體3-OH-6-O-甲基紅霉素的合成研究 |
| 王金龍，向 普，王宗利，侯仲軻*
（浙江國邦藥業(yè)有限公司，浙江 上虞 312369） |
| 摘 要：對泰利霉素關(guān)鍵中間體3-羥基-6-O-甲基紅霉素（4）的合成進(jìn)行了研究，以克拉霉素前體2′，4″- O-二（三甲基硅基）- 6-O-甲基紅霉素A9-O-（1-乙氧基異丙叉基）肟（1）為原料，通過(guò)對一步法工藝優(yōu)化得到產(chǎn)品4，通過(guò)使用緩沖體系和兩邊同時(shí)滴加鹽酸和NaNO2的方式來(lái)控制脫肟過(guò)程的pH，該方法顯著(zhù)提高了產(chǎn)品純度，縮短了反應時(shí)間，可有效抑制半縮酮副產(chǎn)物的生成，制得高純度目標產(chǎn)物4，可與克拉霉素聯(lián)產(chǎn)，大大簡(jiǎn)化了合成工藝，具有工業(yè)化前景。 |
| 關(guān)鍵詞：2′，4″- O-二（三甲基硅基）-6-O-甲基紅霉素A9-O-（1-乙氧基異丙叉基）肟；3-OH-6-O-甲基紅霉素；一步法合成；克拉霉素 |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：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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作者簡(jiǎn)介：王金龍（1987-），男，河南三門(mén)峽人，主要從事藥物合成及工藝開(kāi)發(fā)研究（E-mail：xiaolong10724@qq.com）
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收稿日期：1009-9212（
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