Efficient synthesis of differentially protected (S,S)-2,7-diaminooctanedioic acid, the dicarba analogue of cystine

摘要

Convenient preparative syntheses of differentially protected forms of (S,S)-2,7-diaminooctanedioic acid (2), suitable for application in peptide chemistry, are described. The key compound, the di-Cbz-protected phenacyl monoester 7a (Cbz = [(benzyloxy)carbonyl]), was obtained by means of Schollkopf bis-lactim ether methodology and optimized monoesterification procedures. Selective amino deprotection at the non-esterified amino-acid function of 7a by dichloromethyl-methyl-ether-induced 'N-carboxyanhydride' formation, and hydrolysis permitted access to the Boc/Cbz- and Fmoc/Cbz-protected monophenacyl eaters 11a and 11b, as well as to the fully orthogonally protected Fmoc/Boc monophenacyl ester 12 (Boc = (teri-butoxy)carbonyl, Fmoc = (9H-fluoren-9-ylmethoxy)carbonyl). [References: 28]