An Access to 3,4-(Aminomethano)proline in Racemic and Enantiomerically Pure Form

• Published in: Chemistry : a European journal Vol. 11; no. 22; pp. 6593 - 6600
• Main Authors: Brackmann, Farina, Schill, Heiko, de Meijere, Armin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.11.2005; WILEY‐VCH Verlag; Wiley
• Subjects: amino acids; Chemistry; Chemistry, Multidisciplinary; Crystallography, X-Ray; cyclopropanes; enantiopure compounds; Methylamines - chemical synthesis; Methylamines - chemistry; Models, Molecular; Molecular Structure; Physical Sciences; Proline - analogs & derivatives; Proline - chemical synthesis; Proline - chemistry; Science & Technology; small ring systems; Stereoisomerism; titanium; REAGENTS; FUNCTIONALIZED CHLOROENAMINES; ANALOGS; titanium; amino acids; cyclopropanes; TERT-BUTYL ESTER; AMINOCYCLOPROPANE SYNTHESIS; POTENT; enantiopure compounds; VERSATILE; small ring systems; AMINO-ACIDS; DIASTEREOMERS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200500384

Protected racemic and enantiomerically pure 3,4‐(aminomethano)prolines rac‐9 and (2S,2′R,3R,4R)‐9 have been prepared applying a titanium‐mediated reductive cyclopropanation as a key step. Thus, cyclopropanations of N,N‐dibenzylformamide with titanacyclopropanes generated in situ from racemic or enantiomerically pure tert‐butyl N‐Boc‐3,4‐dehydroprolinates rac‐8 or (S)‐8 proceed diastereoselectively, and furnish the protected racemic and enantiomerically pure diamino acid 9. The latter was incorporated into three tripeptides containing glycyl, alanyl and phenylalanyl moieties. A potential scaffold for pharmaceutically relevant compounds, protected 3,4‐(aminomethano)proline, was synthesized in diastereomerically and enantiomerically pure form (see scheme). To demonstrate the application of 3,4‐(aminomethano)proline as a proline analogue inducing a modified hairpin motif in oligopeptides, some model tripeptides were prepared.