Work

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

Year: 2017

Type: article

Abstract: 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.

Source: ACS Central Science

DOI: 10.1021/acscentsci.7b00450