A novel acid-catalyzed isomerization of Aib-containing thiodipeptides

The use of amino thioacids in the 'azirine/oxazolone method' led to complet ely epimerized Aib-containing endothiodipeptides (Aib = 2-aminoisobutyric a cid). It could be established that the epimerization occurred during the ac idic hydrolysis of the primarily formed dipeptide thioanilides in which the thiocarbonyl group was shifted from the last to the penultimate amino-acid residue. Several conditions for the hydrolysis were tested, and, in some o f them. the degree of epimerization could be reduced. By treatment of the A ib-containing dipeptide thioanilides 21 with ZnCl2 in AcOH followed by HCl in AcOH, the isomeric endothiodipeptide anilides 25 were formed. i.e., the thiocarbonyl group was again shifted from the last to the penultimate amino acid residue. Under optimized reaction conditions, this novel isomerizatio n proceeded in high yields and without any epimerization. Two conceivable m echanisms are proposed in Scheme IZ, X-Ray diffraction analyses were perfor med for Z - Gly - Aib-Psi(CS) - N(Me)Ph (21f) and the isomeric Z - Gly-Psi( CS) - Aib - N(Me)Ph (25f).