ja5b07154_si_004.cif (4.49 kB)
Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C–H Borylation
dataset
posted on 2015-08-19, 00:00 authored by Yu Feng, Dane Holte, Jochen Zoller, Shigenobu Umemiya, Leah R. Simke, Phil S. BaranVerruculogen and fumitremorgin
A are bioactive alkaloids
that contain a unique eight-membered endoperoxide. Although
related natural products such as fumitremorgins B and C have
been previously synthesized, we report the first synthesis of the
more complex, endoperoxide-containing members of this family.
A concise route to verruculogen and fumitremorgin A relied
not only on a hydroperoxide/indole hemiaminal cyclization, but also
on the ability to access the seemingly simple starting material, 6-methoxytryptophan.
An iridium-catalyzed C–H borylation/Chan–Lam procedure
guided by an N-TIPS group enabled the conversion
of a tryptophan derivative into a 6-methoxytryptophan derivative,
proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing
natural products and pharmaceuticals.