Skip to main content
Open Access Publications from the University of California


UCLA Previously Published Works bannerUCLA

Synthesis of Diverse 11- and 12-Membered Macrolactones from a Common Linear Substrate Using a Single Biocatalyst.

  • Author(s): Gilbert, Michael M
  • DeMars, Matthew D
  • Yang, Song
  • Grandner, Jessica M
  • Wang, Shoulei
  • Wang, Hengbin
  • Narayan, Alison RH
  • Sherman, David H
  • Houk, KN
  • Montgomery, John
  • et al.

The diversification of late stage synthetic intermediates provides significant advantages in efficiency in comparison to conventional linear approaches. Despite these advantages, accessing varying ring scaffolds and functional group patterns from a common intermediate poses considerable challenges using existing methods. The combination of regiodivergent nickel-catalyzed C-C couplings and site-selective biocatalytic C-H oxidations using the cytochrome P450 enzyme PikC addresses this problem by enabling a single late-stage linear intermediate to be converted to macrolactones of differing ring size and with diverse patterns of oxidation. The approach is made possible by a novel strategy for site-selective biocatalytic oxidation using a single biocatalyst, with site selectivity being governed by a temporarily installed directing group. Site selectivities of C-H oxidation by this directed approach can overcome positional bias due to C-H bond strength, acidity, inductive influences, steric accessibility, or immediate proximity to the directing group, thus providing complementarity to existing approaches.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View