A regio- and stereoselective ω-transaminase/monoamine oxidase cascade for the synthesis of chiral 2,5-disubstituted pyrrolidines.
Biocatalytic approaches to the synthesis of optically pure chiral amines, starting from simple achiral building blocks, are highly desirable because such motifs are present in a wide variety of important natural products and pharmaceutical compounds. Herein, a novel one-pot ω-transaminase (TA)/monoamine oxidase (MAO-N) cascade process for the synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The reactions proceeded with excellent enantio- and diastereoselectivity (>94 % ee; >98 % de) and can be performed on a preparative scale. This methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the transaminase is not affected by the monoamine oxidase, and highlights the potential of this multienzyme cascade for the efficient synthesis of chiral building blocks.
School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester, M1 7DN (UK).
Elaine
E
O'Reilly
Cesar
C
Iglesias
Diego
D
Ghislieri
Jennifer
J
Hopwood
James L
JL
Galman
Richard C
RC
Lloyd
Nicholas J
NJ
Turner
D001234:Aspergillus niger / Q000201:enzymology*; D055162:Biocatalysis; D008995:Monoamine Oxidase / Q000378:metabolism*; D009346:Neisseriaceae / Q000201:enzymology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D000637:Transaminases / Q000378:metabolism*
D011759:Pyrrolidines; D008995:Monoamine Oxidase; D000637:Transaminases
biocatalysis; cascade reactions; monoamine oxidase; pyrrolidines; transaminase