Details

Autor(en) / Beteiligte

• Hammer, Stephan C.
• Kubik, Grzegorz
• Watkins, Ella
• Huang, Shan
• Minges, Hannah
• Arnold, Frances H.

Titel

Anti-Markovnikov alkene oxidation by metal-oxo–mediated enzyme catalysis

Ist Teil von

• Science (American Association for the Advancement of Science), 2017-10, Vol.358 (6360), p.215-218

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2017

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering of a cytochrome P450 enzyme by directed evolution to catalyze metal-oxo–mediated anti-Markovnikov oxidation of styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant and achieves selectivity for anti-Markovnikov oxidation over the kinetically favored alkene epoxidation by trapping high-energy intermediates and catalyzing an oxo transfer, including an enantioselective 1,2-hydride migration. The anti-Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic pathways to access a variety of challenging anti-Markovnikov functionalization reactions.