| 摘要 |
Preparation of enantiomerically pure alpha -phenyl alanine esters of formulae (I) and (II), by contacting a mixture of enantiomers with a lipase, protease or esterase, and the use of these pure esters in the preparation of imidazoline derivatives (F). The esters are of the following formulae (I) and (II). Alk = 1 - 6C alkyl When (I) is required, the enzyme used is preferably a protease, especially Biofeed, Prozyme, Subtilisine A, Trypsin, protease PS, P5147, or P4032. When (II) is required, the enzyme used is preferably a lipase or esterase, especially lipase A Rhizopus, lipase CE, Chirazyme E1, L1, L2, L3, L4, L5, L6, L7, or L8, lipase GC, L3001, L3126, pancreatic lipase L115P, or lipase PLE. The reaction may be effected in a homogeneous or heterogeneous phase, with the enzyme either free or immobilized on a support. The reaction medium has a pH of 5 - 10, a temperature of 4 - 70 deg C, and may include one or more aromatic solvents, especially toluene or monochlorobenzene. Independent claims cover the preparation of compounds of formula (F) from (I) or (II). R1 = phenyl; R2 = methyl; W = O, S or SO; M = O, S, or CH2, optionally halogenated; p = 0 or 1; R3 = methyl or ethyl, optionally halogenated, and, when p is 0 or (M)p is methylene, it may also be H; R4 = H, 1-6C alkyl, alkoxyalkyl, alkylthioalkyl, haloalkyl, cyanoalkyl, thiocyanatoalkyl, alkenyl, alkynyl, dialkylamino alkyl, alkoxycarbonyl alkyl, N-alkyl carbamoyl alkyl, N,N-dialkyl carbamoyl alkyl, aryl, heteroaryl, aralkyl, aryloxyalkyl, arylythioalkyl, aryl sulfonyl alkyl; R5 = H, alkyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkyl, alkylthioalkyl, acyl, alkenyl, alkynyl, haloacyl, alkoxycarbonyl, haloalkoxycarbonyl, alkoxyalkylsulfonyl, cyanoalkylsulfonyl, alkoxyalkoxy carbonyl, alkylthioalkoxy carbonyl, cyanoalkoxy carbonyl, formyl, cycloalkyl, alkoxyacyl, alkylthioacyl, cyanoacyl, alkenyl carbonyl, alkynyl carbonyl, cycloalkyl carbonyl, phenyl, arylalkyl carbonyl, aryl carbonyl, thienyl carbonyl, furyl carbonyl, pyridyl carbonyl, benzyloxy carbonyl, furfuryloxy carbonyl, tetrahydrofurfuryloxy carbonyl, thienylmethoxy carbonyl, pyridylmethoxy carbonyl, phenoxy carbonyl, phenylthio carbonyl, carbamoyl optionally mono- or di-substituted, alkylthioalkyl sulfonyl, cycloalkylsulfonyl, or R4-N-R forms pyrrolidino, piperidino, morpholino, or piperazino, optionally substituted by alkyl . |
