Patent ID: 7772159
Filing Date: 2010-08-10
Classification: C07D

Abstract:
1. A solid-phase process for preparing an optical isomer of a polypyrrolinone comprising the steps: (a) linking an optical isomer of carboxylic acid that contains a latent aldehyde to a solid support wherein the latent aldehyde is converted to an aldehyde (41); wherein: R R  is para-hydroxy benzyl alcohol resin; (b) reacting an α-amino-α-substituted-1,4-dioxo compound (41), optionally with an alkoxycarbonyl protecting group, with an optical isomer of 2-substituted-2-aminovalerolactone (7), trimethylorthoformate, optionally in the presence of a solvent, to produce imine (40) wherein: R R (c) cyclizing (40) by forming metalloimine carbanion with base, optionally in the presence of a crown ether, to form a pyrrolinone (41) (d) oxidizing the —CH (e) repeating steps (b)-(d) m times to produce polypyrrolinone (42) (f) terminating the synthesis using a substituted α amino acid ester in place of the valerolactone (7) in step (b) to yield (43) (g) Cleaving the polypyrrolinone from the resin by removing the protecting group R (h) cyclizing the imine by forming the metalloimine carbanion with base, optionally in the presence of a crown ether, to produce the (i) the polypyrrolinone having the formula (38) wherein: R is independently selected from a group consisting of a straight C 1 -C 6 alkyl, a branched C 3 -C 7 alkyl, C 3 -C 7 cycloalkyl, a straight C 1 -C 6 alkenyl, a branched C 3 -C 7 alkenyl, C 1 -C 4 hydroxyalkyl, C 1 -C 4 thioalkyl, C 1 -C 4 methylthioalkyl, —(CH 2 ) o N(R 5 ) 2 , —(CH 2 ) 0 CO 2 H, —(CH 2 ) o CON(R 5 ) 2 , heteroaryl, phenyl optionally substituted with one to three hydroxyl, C 1 -C 8 alkoxy, halo, nitro, or cyano groups, and benzyl optionally substituted with one to three hydroxyl, C 1 -C 8 alkoxy, halo, nitro or cyano groups; R R R R R n is 0 to 3; o is 1 to 4; wherein the stereochemical configuration, R or S, is preserved at each chiral center of the starting material through the ultimate product.