Chemoenzymatic Distal C–H Hydroxylation
Remote C‒H Hydroxylation by an α-Ketoglutarate-Dependent Dioxygenase Enables Efficient Chemoenzymatic Synthesis of Manzacidin C and Proline Analogs.
J. Am. Chem. Soc. 2018;
15 March 2018 (online)
Zwick and Renata report the chemoenzymatic hydroxylation of the δ-position of aliphatic amino acids. By using an α-ketoglutarate-dependent dioxygenase, the desired products could usually be obtained in high yield and with high selectivity. This novel methodology was applied to the formal total synthesis of manzacidin C and proline analogues.
C–H bond functionalization of distal bonds within amino acids represents a major challenge in organic synthesis. Transition-metal-catalyzed systems are typically limited to functionalization of the β-position whereas the δ-position can be functionalized by Hofmann–Löffler–Freytag-type reactions.