Zwick III CR.
Renata H.
* The Scripps Research Institute, Jupiter, USA
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;
140: 1165-1169
Key words
hydroxylation - dioxygenases - amino acids
Significance
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.
Comment
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.
