Quinine-mediated parallel kinetic resolution of racemic cyclic anhydride: stereoselective synthesis, relative and absolute configuration of novel alicyclic β-amino acids

Four endo-isomers of (1R,2S)-2-amino-4-methylenecyclopentanecarboxylic acid (+)-1 (Icofungipen) have been prepared in enantiomerically pure form. Three endo-isomers were obtained by quinine-mediated kinetic resolution of a racemic anhydride, followed by Curtius rearrangement. The fourth isomer was obtained by an exo–endo isomerization of (+)-1. The assignment of the absolute configuration is based either on the Cotton effect in the CD spectra or in correlation to already known structures.

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(1R,5S)-5-Amino-3-methyl-cyclopent-2-enecarboxylic acidC7H11NO2Ee = 96%[α]D25=-115 (c 1, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,5S)

(1S,5S)-5-Amino-3-methyl-cyclopent-2-enecarboxylic acidC7H11NO2Ee = 96%[α]D25=+216 (c 0.8, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,5S)

(1R,2R)-2-Amino-4-methyl-cyclopent-3-enecarboxylic acidC7H11NO2Ee = 99%[α]D25=-180 (c 0.6, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

(1R,2S)-2-Amino-4-methyl-cyclopent-3-enecarboxylic acidC7H11NO2Ee = 99%[α]D25=+65 (c 0.8, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(1R,2R)-4-Methyl-2-(3-phenyl-allyloxycarbonylamino)-cyclopent-3-enecarboxylic acid 3-phenyl-allyl esterC26H27NO4Ee = 99%[α]D25=-101 (c 1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

(1R,5S)-3-Methyl-5-(3-phenyl-allyloxycarbonylamino)-cyclopent-2-enecarboxylic acid 3-phenyl-allyl esterC26H27NO4Ee = 96%[α]D25=-129 (c 1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,5S)

(1S,5S)-3-Methyl-5-(3-phenyl-allyloxycarbonylamino)-cyclopent-2-enecarboxylic acidC17H19NO4Ee = 96%[α]D25=+46 (c 1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,5S)

(1R,2S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-4-methyl-cyclopent-3-enecarboxylic acidC22H21NO4Ee = 99%[α]D25=+78 (c 1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(1R,5S)-5-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-methyl-cyclopent-2-enecarboxylic acidC22H21NO4Ee = 99%[α]D25=-91 (c 1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,5S)