Total asymmetric synthesis of complex antibiotic achieved

Abstract

Organic chemists often look to nature for synthetic targets. In the absence of the right synthetic tools, however, the kinds of molecules that can be built from simple precursors are limited. For lonomycin A, a particularly complex natural product, the synthetic tools were in place. Using them, Harvard University chemistry professor David A. Evans, graduate student Andrew M. Ratz, and postdoctoral fellows Bret E. Huff and George S. Sheppard recently completed the total asymmetric synthesis of lonomycin A [ J. Am. Chem. Soc, 117, 3448 (1995)]. Lonomycins are polyether antibiotics produced by Streptomyces ribosidificus (lonomycin A) or Streptomyces hygrospicus (lonomycins B and C). Their unique structures, which incorporate a carboxyl group and two to five other oxygen groups, allow them to complex cations effectively. Polyether antibiotics are members of a class of compounds called ionophores, which are compounds that help ions move across lipid barriers such as the cell membrane. By wrapping cations in ...