Depsipep tides synthesis

H Kunz, H-H Bechtolsheimer. Synthesis of sterically hindered peptides and depsipep-tides by an acid chloride method with 2-phosphonioethoxycarbonyl-(Peoc)-amino acids and hydroxy acids. Liebigs Ann Chem 2068, 1982. 

A number of methods for the synthesis of piperazic acid (7) and related derivatives are currently available as a result of growing interest in natural product chemistry and in their potential in medicinal chemistry. Their chemistry and conformational properties have been comprehensively reviewed. 2451 Racemic piperazic acid is obtained by condensation of penta-2,4-dienoic acid with phthalazinedione and subsequent reductive deprotection of the resulting A,A -bis(phthaloyl)-l,2,3,6-tetrahydropyridazine-3-carboxylic acid.12431 Resolution of racemic piperazic acid is achieved by fractional crystallization of the ephedrine salt of Nl-(benzyloxycarbonyl)piperazic acid from ethyl acetate. 246,2471 A typical route to enantiomerically pure (3S)-piperazic acid 56 starts from chiral 2-amino-5-hydroxyvaleric acid 55 as shown in Scheme 12.1248 Convenient stereoselective syntheses have been reported for 5-hydroxy- and 5-chloropiperazic acids as important constituents of natural cyclic peptides and depsipep-tides.1249,2521... 

However, some other depsipeptides require additional tools. Many depsipep-tides of natural origin possess complex architectures such a cyclic or a bicyclic skeleton and may include unnatural or N-methylated amino acids in their structure. In these cases, a manual synthesis combined with careful optimization of each step is required. In this regard, syntheses of callipeltin B [171] and oxathio-coraline [172] have recently been described. 

Carpino LA, Krause E, Sferdean CD, Schumaim M, Fabian H, Bienert M, Beyermann M (2004) Synthesis of difficult peptide sequences application of a depsipep-tide technique to the Jung-Redemann 10- and 26-mers and the amyloid peptide Ab(l-42). Tetrahedron Lett 45 7519-7523... 

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