Asymmetric Synthesis of 3-Substituted Proline Chimeras Bearing Polar Side Chains of Proteinogenic Amino Acids

Abstract

The amino-zinc-ene-enolate cyclization reaction is a straightforward route to the synthesis of 3-substituted prolines. Herein we report the application of this reaction to the syntheses of proline chimeras of lysine, glutamic acid, glutamine, arginine, and serine. All these compounds were obtained in enantiomerically pure form and suitably protected for peptide synthesis.

Enantiopure antituberculosis candidates synthesized from (−)-fenchone

“…The pure product was obtained in quantitative yield after crystallization from heptane/MTBE. The N-carbobenzyloxy (Cbz) protected guanidine derivative 37 was prepared in quantitative yield from 3 and commercially available 1,3-bis(benzyloxycarbonyl)-2-methyl-isothiourea (35) according analogous procedure described in literature [12].…”

Peptides and Peptidomimetics in Medicinal Chemistry

“…For example, -substituted-prolines such as 3-carboxyproline, 3-phenylproline, and 3-dimethylproline combine amino acid side chain functionality with proline's conformational www.intechopen.com rigidity. In these cases, replacement of the natural amino acids in peptides by proline-amino acid chimeras provided better understanding of the bioactive conformations of peptides binding to receptors (Quancard et al, 2004; and references therein).…”

Rearrangement of β‐amino alcohols and application to the synthesis of biologically active compounds

“…26 This compound was transformed to the desired prolinol 25 using a diastereo-and enantioselective amino-zinc-ene-enolate cyclization [27][28][29][30][31][32][33][34][35] /Negishi coupling, 36,37 an one-pot sequence as the key step. The synthesis of Ro 67-8867 started with N,N-alkylation of (R)-phenylethylamine under basic conditions to furnish the precursor of the amino-zinc-ene-enolate cyclization, compound 22, in two steps (62% overall yield).…”