Zhejiang Hisun Pharmaceutical Co., Ltd.

Wei Yan

Hua Chen

Yong Yang

Ling Zhang

Dejin Fu

Weijiang Wen

Wanzeng Tong

Xiande Gu

Jianping Wang

Xiaojun Ma

Weiqiang Yang

Kaijun Wang

Hongguan Qian

A method for enzymatic preparation of fludarabine phosphate, comprising reaction of fludarabine with a high-energy phosphate compound under the action of deoxyribonucleic acid kinase. According to said method, acetate kinase and acetyl phosphate free acid or acetyl phosphate are also added. The technical problems present in the existing processes are successfully addressed by employing the enzymatic process to prepare the fludarabine phosphate. The usage of the high-energy phosphate compound is reduced by means of adding acetate kinase to recycle and regenerate a small amount of the high-energy phosphate compound, thereby reducing the generation of by-products having similar structures to the fludarabine phosphate, enhancing the operation convenience of purification steps in the industrial production of the fludarabine phosphate. The process is environment friendly, the reaction conditions are moderate, the cost is low, and the yield and the purity of the product obtained are high.

Method for enzymatic preparation of fludarabine phosphate

The present invention provides a method for preparing epirubicin and an intermediate adaptive to the method. The preparation method may include: reacting tert-Butyldimethylsilyl chloride with N-trifluoroacetyl adriamycin to obtain a compound of formula I N-trifluoroacetyl-14-O-tert-Butyldimethylsilyl adriamycin; oxidizing the compound of formula I to obtain a compound of formula II 4'-ketone-N-trifluoroacetyl-14-O-tert-Butyldimethylsilyl adriamycin; reducing the compound of formula II to obtain a compound of formula III N-trifluoroacetyl-14-O-tert-Butyldimethylsilyl epirubicin; and performing deprotection and hydrolysis reactions on the compound of formula III to obtain epirubicin. The method of the present invention needs low cost, fewer reaction steps, provides high yield and high product purity, and avoids serious pollution caused by a bromination reaction in a conventional method.

Method for preparing epirubicin and intermediate thereof

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Taizhou, China

Wei Yan