19-[(1'S,4'R)-4'-Hydroxy-1'-methoxy-2'-oxopentyl]geldanamycin, a natural geldanamycin analogue from Streptomyces hygroscopicus 17997

  • J Nat Prod. 2013 May 24;76(5):969-73. doi: 10.1021/np4000679.
Shufen Li  1 ,  Siyang Ni ,  Linzhuan Wu ,  Li Li ,  Bingya Jiang ,  Hongyuan Wang ,  Guizhi Sun ,  Maoluo Gan ,  Jingyan Li ,  Weiqing He ,  Ling Lin ,  Yiguang Wang ,  Shuoke Bai ,  Shuyi Si
Affiliations
  • 1. Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
PMID: 23656556 DOI: 10.1021/np4000679
Abstract

A novel natural geldanamycin analogue was discovered in Streptomyces hygroscopicus 17997. Its 4,5-dihydro form was also identified in the gdmP gene disruption mutant of Streptomyces hygroscopicus 17997. The structures of the two compounds were determined to be 19-[(1'S,4'R)-4'-hydroxy-1'-methoxy-2'-oxopentyl]geldanamycin (1) and 19-[(1'S,4'R)-4'-hydroxy-1'-methoxy-2'-oxopentyl]-4,5-dihydrogeldanamycin (2), respectively, by extensive spectroscopic data analysis, including 2D NMR, modified Mosher's method, and electronic circular dichroism. Compared to geldanamycin, 1 and 2 showed increased water solubility and decreased cytotoxicity against HepG2 cells.