US0091151 77B2  c12)  United States Patent  Jiao et al.  (54)  PREPARATION METHOD OF MICAFUNGIN  SODIUM  (IO)  Patent No.:  US 9,115,177 B2  (45)  Date of Patent:  Aug. 25, 2015  Ohigashi et al. (2006) "Process development ofmicafungin. a novel  lipopeptide antifungal agent."  Yuki Gosei Kagaku Kyokaishi ..  64( 12):  1294-1303.  Tomishima et al. (2008) "Novel echinocandin antifungals. Part 2:  Optimization of the side chain of the natural product FR901379.  Discovery of micafungin"  Bioorganic  &  Medicinal Chemistry Let› ters  18: 2886-2890.  * cited by examiner  Primary Examiner  - Jeffrey E Russel  (7 4)  Attorney, Agent, or Firm  - Tom Hunter; Weaver Austin  Villeneuve & Sampson LLP  The method of the preparation of micafungin sodium com› prises the step of mixing the weak base and the aqueous  solution containing micafungin acid (the structure is illus› trated by formula I) or the mixed aqueous solution containing  the compound of formula I and organic solvent in order to  obtain the sodium salt of micafungin (the structure is illus› trated by formula II).  (57)  ABSTRACT  II  (75)  Inventors:  Guangjun Jiao,  Shanghai (CN);  Shidong Liu,  Shanghai (CN);  Bingming  He,  Shanghai (CN);  Zhijun Tang,  Shanghai (CN);  Xiaoming Ji,  Shanghai  (CN)  (73)  Assignee:  Shanghai Techwell Biopharmaceutical  Co., Ltd.,  Shanghai (CN)  ( *)  Notice:  Subject to any disclaimer, the term ofthis  patent is extended or adjusted under 35  U.S.C. 154(b) by  O  days.  (21)  Appl. No.:  14/116,947  (22)  PCT Filed:  May 11, 2012  (86)  PCT No.:  PCT /CN2012/075339  § 371 (c)(l),  (2), ( 4) Date:  Jan.2,2014  (87)  PCT Pub. No.:  WO2012/152225  PCT Pub. Date:  Nov.15, 2012  (65)  Prior Publication Data  (30)  Foreign Application Priority Data  US 2014/0114049 Al  Apr. 24, 2014  May 12, 2011  (CN) .......................... 2011 1 0121705  2014/0371422 Al* 12/2014 Gunnes et al. ................ 530/329  PCT International Search Report and Written Opinion dated Aug. 23,  2012 issued in PCT/CN2012/075339 (WO/2012/152225).  17 Claims, 4 Drawing Sheets  (51)  Int. Cl.  C07K 11113  C07K 7156  C07K 1114  C07D413/12  (2006.01)  (2006.01)  (2006.01)  (2006.01)  (52)  U.S. Cl.  CPC ................  C07K 1114  (2013.01);  C07D 413112  (2013.01);  C07K 11113  (2013.01);  C07K 7156  (2013.01)  ( 58)  Field of Classification Search  None  See application file for complete search history.  (56)  References Cited  U.S. PATENT DOCUMENTS  FOREIGN PATENT DOCUMENTS  OTHER PUBLICATIONS  WO  WO 9611210  4/1996  WO  WO 2004014879  2/2004  WO  WO 2012143293 Al * 10/2012 