Enantioselective Preparation of β2-Amino Acid Derivatives for β-Peptide Synthesis


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Date

2009-01

Publication Type

Review Article

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Abstract

β-Amino acids with a single side chain in the α-position (β²-amino acids or H-β²hXaa(PG)-OH; i.e., homo-amino acids with proteinogenic side chains) have turned out to be important components in β-peptides. They contribute to unique secondary structures, they are required for mimicking the structure and the activity of β-turn-forming α-peptides, and they can be used for protecting α-peptides against attack by aminopeptidases. In contrast to β³-homo-amino acids, the β²-isomers cannot be obtained simply by enantiospecific homologation of the (natural) α-amino acids, but have to be prepared by enantioselective reactions or sequences of transformations, which are presented herein. The various preparative methods are ordered according to the bond at the stereogenic center, which is formed in the stereoselective step, with the four strategic bonds being the C(2)-C(3) backbone bond, the C(2)-side-chain bond, the C(2)-H bond, and the C(1)-C(2) bond between the carboxylate and the α-carbon. In the most frequently employed methods, a chiral auxiliary group is attached at the carboxyl C(1) atom or at the nitrogen in the 3-position, but there are also a number of enantioselective catalytic processes, including the hydrogenation of suitable acrylates. The alternative of stereoselective synthesis, namely resolution of racemic mixtures (for instance by biocatalysis), is also discussed. A critical comparison of the various methods and strategies is presented. For the peptide chemist, a list is included with the Cbz-, Boc-, and Fmoc-protected β²-amino acid building blocks, ready for peptide coupling. In addition, the search strategy for nonracemic β²-amino acids and their precursors from the databases is described in detail.

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published

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Volume

2009 (1)

Pages / Article No.

1 - 32

Publisher

Thieme

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Subject

Beta(2)-amino acids; Beta-peptide; Retrosynthetic analysis; Overall enantioselective synthesis; Chiral auxiliaries; Enantioselective catalysis; Database literature search strategies

Organisational unit

03492 - Hilvert, Donald (emeritus) / Hilvert, Donald (emeritus) check_circle

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