Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C-H Borylation.
Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C-H Borylation.
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DOI：
10.1021/jacs.5b07154
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发表时间：
2015-08-19
影响因子：
15
通讯作者：
Baran PS
中科院分区：
文献类型：
--
作者：
Feng Y;Holte D;Zoller J;Umemiya S;Simke LR;Baran PS
疣孢原和烟曲霉素A是含有独特的八元内过氧化物的生物活性生物碱。虽然相关的天然产物，如烟曲霉素B和C以前已经合成，我们报告的第一个合成的更复杂的，内过氧化物含有这个家庭的成员。一个简洁的路线，疣和烟曲霉素A不仅依赖于氢过氧化物/吲哚半缩醛胺环化，但也对能力，以获得看似简单的起始材料，6-甲氧基色氨酸。铱催化的C-H硼基化/Chan-Lam程序由N-TIPS基团引导，使色氨酸衍生物转化为6-甲氧基色氨酸衍生物，证明是一种通用的方法来官能化的N，C3-二取代吲哚的C6位用于合成含吲哚的天然产物和药物。
Verruculogen an 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.