4378-19-2Relevant articles and documents
Memory of chirality of tertiary aromatic amides: A simple and efficient method for the enantioselective synthesis of quaternary α-amino acids
Branca, Mathieu,Pena, Sebastien,Guillot, Regis,Gori, Didier,Alezra, Valerie,Kouklovsky, Cyrille
scheme or table, p. 10711 - 10718 (2009/12/04)
A new methodology for the asymmetric synthesis of quaternary R-substituted amino acids using memory of chirality has been developed. The strategy utilizes the dynamic axial chirality of tertiary aromatic amides to memorize the initial chirality of an α-amino acid during an enolization step. Starting from five different L-amino acids, the corresponding oxazolidin-5-ones containing a tertiary aromatic amide group have been synthesized in one step and then alkylated with various electrophiles, with good yields and enantioselectivities (up to 96% and up to >99% after recrystallization). One-step deprotection affords enantioenriched or enantiopure quaternary α-amino acids. We describe here the optimization process, the results obtained in each series and a plausible explanation, based on NMR studies, DFT calculations and crystallographic structures. The methodology presented herein constitutes an efficient synthesis of enantiopure quaternary R-amino acids (three steps only) starting from tertiary L-amino acids, without any external source of chirality.
Enantioselective synthesis and enantiomeric amplification of amino acids under prebiotic conditions
Levine, Mindy,Kenesky, Craig Scott,Mazori, Daniel,Breslow, Ronald
supporting information; experimental part, p. 2433 - 2436 (2009/05/27)
(Chemical Equation Presented) A plausible origin of biomolecular homochirality is advanced, where α-methyl amino acids found on meteorites transfer their chirality in the synthesis of normal amino acids. This asymmetry can be amplified to nearly homochiral levels, thus providing the necessary prerequisite for life to start on this planet and elsewhere in the universe.
L-phenylalanine cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α-disubstituted (R)- and (S)-amino acids
Obrecht,Bohdal,Broger,Bur,Lehmann,Ruffieux,Schonholzer,Spiegler,Muller
, p. 563 - 580 (2007/10/02)
This work describes L-phenylalanine cyclohexylamide (5c) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure α,α-disubstituted (R)- and (S)-amino acids of type 1, such as (R)- and (S)-2-methyl-phenylalanine (1a), (R)- and (S)-2-methyl-2-phenylglycine (1b), and (R)- and (S)-2-methylvaline (1c). These amino acids were efficiently transformed into the suitably protected and activated amino-acid building blocks (R)- and (S)-12b and (R)- and (S)-12c which are ready for incorporation into peptides by solution or solid-phase techniques. Based on the crystal structures of 6b, 6c, and 7a belonging to the diastereoisomeric peptides series 6 and 7, the absolute configurations of each member of the series were determined. β-Turn geometries of type II' and I were observed for 6b and 7a, respectively, whereas 6c crystallized in an extended conformation. The impacts of side-chain variation on conformation and crystal packing of these triamides are discussed.
