%0 Journal Article
%T (R)-¦Á-Aminoadipic Acid: A Versatile Precursor for the Synthesis of D-Amino Acids
%A Amina Sadiq
%A Norbert Sewald
%J Journal of Amino Acids
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/252813
%X The ready accessibility of (R)-¦Á-aminoadipic acid by enzymatic cleavage of cephalosporin C (CephC) in the production of 7-aminocephalosporanic acid (7-ACA) on a large scale makes it a favorable chiral pool building block for the synthesis of unusual amino acids. A route for the synthesis of C-5-alkenyl and C-6-alkylidene derivatives of (R)-pipecolic acid is described which utilizes (R)-¦Á-aminoadipic acid as the enantiomerically pure starting material. Moreover, the synthesis of azido and triazolyl derivatives of (R)-¦Á-aminoadipic acid is reported. 1. Introduction -Amino acids, one of the important classes of natural products, play fundamental roles in chemistry and biology. In addition to their vital roles as building block of proteins and as intermediates in metabolism, they also constitute a broad array of chiral pool building blocks and organocatalysts [1¨C3]. Their ready availability, low cost, and high enantiomeric purity make them valuable starting materials for the synthesis of unusual amino acids. D-Amino acids are far less abundant in nature in contrast to L-configured counterparts. In addition, D-amino acids display interesting conformational features; for example, they stabilize turn conformations in peptides [4]. -Aminoadipic acid is a six-carbon analog of aspartic and glutamic acid which is found in plants and microorganisms. It is a metabolite in the principal biochemical pathway of lysine [5]. During the past decades, -aminoadipic acid has received attention from chemists active in the areas of peptide chemistry, organic synthesis, biosynthesis, and neuroscience. (R)- -Aminoadipic acid exhibits a selective antagonistic activity at the N-methyl-D-aspartate subtype of glutamate receptors [6, 7]. It has also been used in the synthesis of carbocyclic nucleoside precursors [8]. (R)- -Aminoadipic acid 1 is a constituent of cephalosporin C and penicillin N. In the pharmaceutical semisynthesis of cephalosporin derivatives, the central intermediate 7-aminocephalosporanic acid (7-ACA) is obtained by enzymatic cleavage of the fermentation product cephalosporin C (CephC) [9]. As the enantiomerically pure (R)- -aminoadipic acid is available from this process on a large scale, we embarked on a project to explore the application of this chiral pool building block for the synthesis of (R)-pipecolic acid and its derivatives [10, 11]. Pipecolic acid, also known as homoproline or piperidine-2-carboxylic acid, a six-carbon natural nonproteinogenic ¦Á-amino acid, is an intermediate of lysine metabolism in various organisms including bacteria, yeast, fungi, and
%U http://www.hindawi.com/journals/jaa/2013/252813/