Carbenes in Their Natural Habitat

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Science  09 Aug 2013:
Vol. 341, Issue 6146, pp. 593
DOI: 10.1126/science.341.6146.593-a
CREDIT: MEYER ET AL., NAT. CHEM. BIOL. 9, 488 (2013)

Over 50 years ago, Ronald Breslow suggested that thiamin may adopt a short-lived reactive carbene structure—with a divalent carbon center stabilized by flanking sulfur and nitrogen—during the enzymatic reaction cycle of vitamin B1. In the interim time, chemists have synthesized a huge range of stabilized cyclic carbenes, most of which are derived from imidazole (with two flanking nitrogens) rather than thiazole frameworks. These N-heterocyclic carbenes, or NHCs, are frequently stable and possible to isolate and have been applied as ligands in transition-metal catalysts. They are also versatile catalysts in their own right. Nonetheless, the question of whether thiamin itself reacts as a catalytic carbene in native context has remained open. Meyer et al. present a high-resolution (1.06 Å) crystal structure of pyruvate oxidase with bound phosphate (an unreactive analog of the pyruvate substrate), and the associated thiamin molecule shows clear evidence of carbene character. The carbon center in question appears to be deprotonated while lacking the excess electron density indicative of a carbanion.

Nat. Chem. Biol. 9, 488 (2013).

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