One-pot reaction of amines, useful for preparing e.g. cyclic secondary amines or alcohols, useful as pharmaceutical intermediates, by oxidation with lysine oxidase then reduction

摘要

One-pot reaction of amines (I) to cyclic amines (II) or alcohols (III) by reaction in presence of lysine oxidase (LO) and reduction. One-pot reaction of amines (I) to cyclic amines (II) or alcohols (III) by reaction in presence of lysine oxidase (LO) and reduction. The process comprises: (1) oxidation of at least one C-NH2 group to carbonyl; (2) optionally reaction of second amino (where A = A1) with the carbonyl group to form an enamine or imine; and (3) reduction of the carbonyl to convert it to hydroxymethyl (or of the product of step (2) to form (II)). A = NH2-CHR2-R1- (A1), NH2CH2-R3- or R4-; B = HOCH2-R3- or R4-; R1 = NR5 or 2-6C linear divalent hydrocarbyl (optionally substituted by carboxy, COOR6, OH, mercapto and/or NR52 and/or including non-adjacent O, S and/or N atoms); R5 = H or linear 1-6C alkyl; R6 = linear or branched 1-6C alkyl or 6-10C aryl; R2 = H, carboxy, COOR6 or cyano; R3 = bivalent 0-1 or 5-18C hydrocarbyl (optionally substituted by 1-6C linear or branched alkyl, 6-10C aryl, 4-10C heteroaryl, and/or COOR6 and/or including non-adjacent O, S and/or N atoms); R4 = linear 1-20C hydrocarbyl, optionally substituted with functional groups such as carboxy or COOR6 and/or including non-adjacent O, S and/or N atoms.