DÁVILA ZAMPIERI,LARA DIAS LIMA,MARCOS CARLOS DE MATTOS,MARIA DA CONCEIÇÃO FERREIRA DE OLIVEIRA,TELMA LEDA GOMES DE LEMOS,THIAGO DE SOUSA FONSECA
申请号：
BR102017022680
公开号：
BR102017022680A2
申请日:
2017.10.20
申请国别(地区):
BR
年份:
2019
代理人:
摘要：
Development of a biocatalitical process for the production of the drug luliconazole. This invention refers to the development of a biocatalitic process for the synthesis of the luliconazol e drug, used for the treatment of tinea pedis, known popularly as athlete's foot, in addition to treatment against candidiasis and pityriasis. The drug was developed in Japan and approved for marketing in 2005 by the Japanese health organs. The main strategy in the development of this process includes enzymatic kinetic resolution, via hydrolysis reaction of the 2 -chloro -1 -(2,4 -dichlorophenyl)ethyl racacetate,An intermediate in the synthesis of luliconazole, in the presence of lipase of type B Antarctic Candide immobilized in acrylic resin (cal -b, Novozym 435). The enzymatic reaction was performed by adding to a solution phosphate buffer 0,1m (ph 7),The 2 -chloro -1 -(2,4 -dichlorophenyl)ethyl (b) and cal -b. The resulting solution remained in turmoil for 15 minutes to 45 (c. After treatment and purification of the reaction, the (r)-acetate of 2 -chloro -1 -(2,4 -dichlorophenyl)ethyl and the (s)-2 -chloro -1 -(2,4 -dichlorophenyl)ethanol were obtained, AMB With e.E.Gt.99%. In addition, the reuse study of this enzyme has been carried out, since cal -b is a fixed enzyme and allows its reuse. Conversion values near 50% were obtained over ten reactionary cycles and E.E. Values. gt；90% of (s)-2 -chloro -1 -(2,4 -dichlorophenyl)ethanol up to the fifth cycle of reuse. Afterwards,O (s)-2 -chloro -1 -(2,4 -dichlorophenyl)ethanol was subjected to a mesilation reaction in the presence of mesyl chloride, forming the (s)-2 -chloro -1 -(2,4 -dichlorophenyl)-2 -methanesulfonate. In parallel, 1 -cyanomethylamide was synthesized from imidazole. Finally, the (s)-2 -chloro -1 -(2,4 -dichlorophenyl)-2 -methanesulfonate reacted with 1 -cyanomethylamide, leading to the production of luliconazol e with e.E. This biocatalitic process is in line with the aspects of green chemistry, since it makes use
