(2S,4R)-4-Allyloxycarbonylamino-1-(9-fluorenylmethyloxycarbonyl)-pyrrolidine-2-carboxylic acid

The proximity of the amine and carboxylic acid enforced by the pyrrolidine ring in cis-4-amino-proline can induce both beta and gamma turn depending on the location of the intramolecular hydrogen bond. Turns have been identified as sites for posttranslational modification of proteins. This is particularly true with respect to phosphorylation and glycosylation. Additionally, formation of gamma-turns may initiate formation of beta-sheets in protein folding. Preparing analogues of naturally occurring hexapeptide echinocandin B bearing an aminoproline residue imparts greatly improved water solubility. References: N-alpha-Benzoyl-Cis-4-Amino-L-Proline: A gamma-Turn Mimetic; Timothy P. Curran, Nicole M. Chandler, Robert J. Kennedy and Meghan T. Keaney; Tetrahedron Letters 1996; 37(12): 1933-1936. Total Synthesis and Antifungal Evaluation of Cyclic Aminohexapeptides; Larry L. Klein, Leping Li, Hui-Ju Chen, Cynthia B. Curty, David A. DeGoey, David J. Grampovnik, Christina L. Leone, Sheela A. Thomas, Clinton M. Yeung, Kenneth W. Funk, Vimal Kishore, Edwin O. Lundell, Dariusz Wodka, Jon A. Meulbroek, Je?rey D. Alder, Angela M. Nilius, Paul A. Lartey and Jacob J. Plattner; Bioorganic & Medicinal Chemistry 2000; 8: 1677-1696. The cis-4-Amino-L-proline Residue as a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues; Adriano Mollica, Francesco Pinnen, Azzurra Stefanucci, Federica Feliciani, Cristina Campestre, Luisa Mannina, Anatoly P. Sobolev, Gino Lucente, Peg Davis, Josephine Lai, Shou-Wu Ma, Frank Porreca, and Victor J. Hruby; J. Med. Chem. 2012; 55: 3027-3035. dx.doi.org/10.1021/jm201402v.