BioChem - DOS

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

ACS central science

Gilbert, Michael M.; DeMars II, Matthew D.; Yang, Song; Grandner, Jessica M.; Wang, Shoulei; Wang, Hengbin; Narayan, Alison R. H.; Sherman, David H.; Houk, K. N.; Montgomery, John

<▼1><P/><P>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&#x2013;C couplings and site-selective biocatalytic C&#x2013;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&#x2013;H oxidation by this directed approach can overcome positional bias due to C&#x2013;H bond strength, acidity, inductive influences, steric accessibility, or immediate proximity to the directing group, thus providing complementarity to existing approaches.</P></▼1><▼2><P>A new strategy for tuning site selectivity in biocatalytic oxidations is paired with catalytic regiodivergent macrocyclizations to provide a versatile approach for structural diversification.</P></▼2>

2017

American Chemical Society

publisher-specific-oa

2374-7943

2374-7951

3

12

pp.1304-1310

10.1021/acscentsci.7b00450

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART79358388

https://pubs.acs.org/doi/pdf/10.1021/acscentsci.7b00450