Scheme 2. Synthesis of the Second Series of Ketoamide Tripeptide Derivatives.

Reagents and conditions: (a) vinylmagnesium bromide, CH₂Cl₂; (b) p-toluensulfonic acid, 2,2-dimethoxypropane, CH₂Cl₂; (c) NaIO₄, ruthenium(IV) oxide hydrate, acetone; (d) appropriate amines a–e, HATU, DIPEA, DMF; (e) TFA; (f) Z-Leu-Leu-OH, HATU, DIPEA, DMF; (g) 2-iodoxybenzoic acid, DMSO; 11–13a R = 4-fluorobenzyl-NH; 11–13b R = morpholin-4-yl; 11–13c R = 1-naphthyl-NH; 11–13d R = isobutyl-NH; 11–13e R = tetrahydroisoquinolin-2-yl.