Synthesis Of Antibiotic Drug-Surotomycin

Antibiotics are the main drug products used in the treatment of bacterial infection.This paper briefly describes the main classification and mechanism of antibiotics,emphatically studies the synthesis of novel antibiotic Surotomycin.Surotomycin is a cyclic lipopeptide antibiotic developed by American Cubist.At present,two clinical phase ? trials have been finished.Its indication is clostridium difficile-related diarrhea(CDAD).In December 2012,the drug was granted Qualified Infectious Disease Product qualification by FDA,and in October 2013,it was granted Fast Track status by FDA.Different from the method of link the mother nucleus and side chain activated ester reported by the literature,novel condensation reagent HBTU is used to link the mother nucleus and side chain.This method reduces the cost by shortening the process steps and avoiding the use of expensive dehydrating agents EDCI.During the preparation of BOC-protected Daptomycin and BOC-protected Surotomycin mother nucleus,nanofiltration technology is innovatively used to deal with liquid feed directly,instead of the methods packing material adsorption,washing,elution and concentration reported by literature,the method reduces the process procedures and material use.In addition,the scalability of the whole process was optimized based on the literature,and a suitable for industrial production process with low cost,low pollution,and easy operation was determined.Daptomycin is used as starting material,first protect the exposed ornithine amines with BOC group,then remove the n-decanoyl group with acylase to get BOC protected Surotomycin mother nucleus,then condensate with side chain obtained by multi-step reactions to get BOC-protected Surotomycin,then separate by acidizing and purify to obtain sample with the purity of 98.9%.The structures of all the critical intermediates and finished product during the synthesized process have been identified by MS,1H-NMR and 13C-NMR.