摘要
优化抗寄生虫新兽药莫西菌素的合成工艺。本研究在参考目前合成工艺的基础上,优化了反应路线、反应条件及后处理过程。采用β-苯基丙烯酰氯作为保护试剂对尼莫克汀中的手性羟基进行保护,再进行氧化反应、肟化反应和脱保护反应,制备莫西菌素。结果显示,尼莫克汀与苯甲酰氯反应生成5-氧(苯甲酰基)尼莫克汀,得率为92%;通过5-氧(苯甲酰基)尼莫克汀与甲苯基磷酰氯进行氧化反应,生成5-氧(苯甲酰基)-23-氧代尼莫克汀,得率为85%;将5-氧(苯甲酰基)-23-氧代尼莫克汀在哌啶作用下与甲氧胺盐酸盐反应,生成5-氧(苯甲酰基)-23-(甲基肟)尼莫克汀;通过将5-氧(苯甲酰基)-23-(甲基肟)尼莫克汀在碳酸氢钠水溶液脱保护,合成莫西菌素,得率为88%。采用1HNMR和13CNMR对目标化合物进行结构表征,NMR测得数据均与结构对应,证明合成物为莫西菌素。结果表明,该反应工艺简单易操作,反应条件温和,通过进一步改进,将会在产业化中广泛应用。
To optimize the synthesis process of a new anti-parasite veterinary medicine Moxidectin. In this study, the reaction route, reaction conditions and post-treatment process were optimized on the basis of referring to the current synthetic process. β-phenylacryloyl chloride was used as a protective reagent to protect the chiral hydroxyl groups in Nemadectin, and then the steps of oxidation, oxime and deprotection were carried out to prepare Moxidectin. The results showed that Nemadectin reacted with benzoyl chloride to produce 5-oxygen(benzoyl) Nemadectin with 92% yield under mild conditions. Through the oxidation reaction of 5-oxygen(benzoyl) Nimoxtin and methylphenyl phosphoryl chloride, under the control of reaction conditions, 5-oxygen(benzoyl)-23-oxynimoctin was obtained with the yield of 85%. Under the action of piperidine, 5-oxygen(benzoyl)-23-oxynimoctin reacted with methoxamine hydrochloride to produce 5-oxygen(benzoyl)-23-(methyl oxime) Nemadectin. Moxidectin was synthesized by deprotecting 5-oxygen(benzoyl)-23-(methyl oxime) Nemadectin in sodium bicarbonate aqueous solution with 88% yield. The structure of the target compound was characterized, and the data measured by NMR were corresponding to the structure, which proved that the synthesized compound was Moxidectin. The results show that the reaction process is simple and easy to operate, and the reaction conditions are mild. It will be widely used in industrialization through further improvement.
作者
陶蕾
孟冽
孟凡桥
梁剑平
王卫华
杨潇
TAO Lei;MENG Lie;MENG Fanqiao;LIANG Jianping;WANG Weihua;YANG Xiao(Lanzhou Vocational and Technical College,Lanzhou Gansu 730070,China;Hebei Meihe Pharmaceutical Co.,LTD.,Shijiazhuang Hebei 051530,China;Lanzhou Institute of Husbandry and Veterinary Medicine of CAAS,Lanzhou Gansu 730050,China;China Agricultural University,Beijing 100083,China)
出处
《中兽医医药杂志》
CAS
2022年第6期64-67,共4页
Journal of Traditional Chinese Veterinary Medicine
基金
甘肃省科技计划项目(重点研发计划)-国际科技合作类项目(20YE3WA009)
河南省三门峡市引进高层次人才(团队)创新创业项目(2020101)。
