Efficient access to N-protected derivatives of (R,R,R)- and (S,S,S)-octahydroindole-2-carboxylic acid by HPLC resolution

The preparation of the proline analogue (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (Oic) and its enantiomer, (2R,3aR,7aR)-Oic, is described. A racemic precursor has been synthesized in good yield and subjected to HPLC resolution on a chiral column. The high efficiency of both the synthetic and chromatographic procedures has allowed the isolation of multigram quantities of each amino acid in enantiomerically pure form and suitably protected for use in peptide synthesis.

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Benzyl (2R,3aR,7aR)-N-(tert-butoxycarbonyl)octahydroindole-2-carboxylateC21H29NO4Ee >99%[α]D = +38.1 (c 0.96, CHCl3)Source of chirality: resolution by chiral HPLCAbsolute configuration: (2R,3aR,7aR)

(2R,3aR,7aR)-N-(tert-Butoxycarbonyl)octahydroindole-2-carboxylic acidC14H23NO4Ee >99%[α]D = +22.6 (c 0.50, MeOH)Source of chirality: resolution by chiral HPLCAbsolute configuration: (2R,3aR,7aR)