title: Practical access to the proline analogs (S,S,S)- and (R,R,R)-2-methyloctahydroindole-2-carboxylic acids by HPLC enantioseparation.
abstract: An efficient methodology for the preparation of the α-tetrasubstituted proline analog (S,S,S)-2-methyloctahydroindole-2-carboxylic acid, (S,S,S)-(αMe)Oic, and its enantiomer, (R,R,R)-(αMe)Oic, has been developed. Starting from easily available substrates and through simple transformations, a racemic precursor has been synthesized in excellent yield and further subjected to HPLC resolution using a cellulose-derived chiral stationary phase. Specifically, a semipreparative (250 mm × 20 mm ID) Chiralpak® IC column has allowed the efficient resolution of more than 4 g of racemate using a mixture of n-hexane/tert-butyl methyl ether/2-propanol as the eluent. Multigram quantities of the target amino acids have been isolated in enantiomerically pure form and suitably protected for incorporation into peptides.
authors.affiliation: Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Sayago
authors.forename: María J
authors.initials: MJ
authors.lastname: Pueyo
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Calaza
authors.forename: Ana I
authors.initials: AI
authors.lastname: Jiménez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification*; D011392:Proline / Q000031:analogs & derivatives*; D013237:Stereoisomerism
chemical_list: D002264:Carboxylic Acids; D007211:Indoles; D011392:Proline