| 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
拉氧头孢钠合成工艺的改进 |
| 何小鹏，黄伟平，李日生
（浙江东邦药业有限公司 浙江 临海 317016） |
| 摘 要：以氧头孢烯为起始原料，通过甲氧基化得到甲氧基氧头孢烯，然后在磺酰氯和三乙胺催化作用下，反应得到（6R，7R）-苯甲酰氨基-3-（1-甲基-5-四氮唑）-硫甲基-7-甲氧基-8-氧代-5-氧杂-1-氮杂二环［4.2.0］辛-2-烯-2-羧酸二苯甲酯，然后依次在五氯化磷，吡啶和氯化氢作用下去氨基，羧基保护，最后在酰化酶作用下进行氨基酰化和溶媒法成盐生成拉氧头孢钠。总收率由30%提高到49%，产物含量在92%以上，产物结构经核磁进行了表征。 整条路线步骤少，操作简单，节约成本，工艺路线绿色环保，适合工业化生产。 |
| 关键词：氧头孢烯；拉氧头孢钠；缩合 |
| 中图分类号：R914 文献标识码：A 文章编号：1009-9212（2018）02-0043-04 |
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| An Improved Process for the Synthesis of Latamoxef Disodium |
| HE Xiao-peng, HUANG Wei-ping, LI Ri-sheng
(Zhejiang Dong Bang Pharmaceutical Co., Ltd., Linhai 317016, China) |
| Abstract：In this process, methoxy oxacephem is formed by methoxylation reaction using oxacephem as the starting material. (6R,7R)-Benzamindo-3-(1-methyl-5-tetrazolium) thiomethyl-7-methoxy-8-oxo-5- oxa-1-azabicyclo[4.2.0]Oct-2-ene-2-carboxyylic acid benzhydryl ester was obtained from a series reactions including the catalytic reaction of sulfuryl chloride and trimethylamine, and deprotection of amino and carboxyl under the action of phosphorus pentachloride, pyridine and hydrogen chloride respectively. In the final, under the action of acylase, Latamoxef disodium was obtained by aminoacylation reaction and solvent salt forming reaction. The yield was increased from 30% to 49%. The purity of product was of more than 92%. And the structure of the product was characterized by 1H NMR, 13C NMR. The preparation process was of less steps and simple in operation, low cost, green and environmental friendly, and suitable for industrial production. |
| Key words：oxacephem; Latamoxef disodium; condensation |
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作者简介：何小鹏（1974-），男，浙江台州人，工程师，主要从事药物合成研究（E-mail：hexiaopeng222@sohu.com）。
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收稿日期：2018-04-03
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