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Asymmetric ?-Lactam Synthesis with a Monomeric Streptavidin Artificial Metalloenzyme.


ABSTRACT: Reliable design of artificial metalloenzymes (ArMs) to access transformations not observed in nature remains a long-standing and important challenge. We report that a monomeric streptavidin (mSav) Rh(III) ArM permits asymmetric synthesis of ?,?-unsaturated-?-lactams via a tandem C-H activation and [4+2] annulation reaction. These products are readily derivatized to enantioenriched piperidines, the most common N-heterocycle found in FDA approved pharmaceuticals. Desired ?-lactams are achieved in yields as high as 99% and enantiomeric excess of 97% under aqueous conditions at room temperature. Embedding a Rh cyclopentadienyl (Cp*) catalyst in the active site of mSav results in improved stereocontrol and a 7-fold enhancement in reactivity relative to the isolated biotinylated Rh(III) cofactor. In addition, mSav-Rh outperforms its well-established tetrameric forms, displaying 11-33 times more reactivity.

SUBMITTER: Hassan IS 

PROVIDER: S-EPMC6980373 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Asymmetric δ-Lactam Synthesis with a Monomeric Streptavidin Artificial Metalloenzyme.

Hassan Isra S IS   Ta Angeline N AN   Danneman Michael W MW   Semakul Natthawat N   Burns Matthew M   Basch Corey H CH   Dippon Vanessa N VN   McNaughton Brian R BR   Rovis Tomislav T  

Journal of the American Chemical Society 20190313 12


Reliable design of artificial metalloenzymes (ArMs) to access transformations not observed in nature remains a long-standing and important challenge. We report that a monomeric streptavidin (mSav) Rh(III) ArM permits asymmetric synthesis of α,β-unsaturated-δ-lactams via a tandem C-H activation and [4+2] annulation reaction. These products are readily derivatized to enantioenriched piperidines, the most common N-heterocycle found in FDA approved pharmaceuticals. Desired δ-lactams are achieved in  ...[more]

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