Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors.

Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia A and B inhibitor patients. A library of compounds was synthesized with different tripeptide sequences, N-terminals and d-amino acids in the P3 position.

DFT investigation of the palladium-catalyzed ene-yne coupling.

The mechanism of the recently developed palladium-catalyzed ene-yne coupling has been evaluated by DFT methods. The calculations validate the previously proposed reaction mechanism and explain the stereoselectivity of the reaction (exclusive formation of the E isomer of the disubstituted alkene). Concerning chemoselectivity, the calculations also clarify why the ene-yne coupling is able to dominate over plausible alternative reaction pathways such as alkene homocoupling and alkyne polymerization.

Combined experimental and theoretical study of the mechanism and enantioselectivity of palladium- catalyzed intermolecular Heck coupling.

The asymmetric Heck reaction using P,N-ligands has been studied by a combination of theoretical and experimental methods. The reaction follows Halpern-style selectivity; that is, the major isomer is produced from the least favored form of the pre-insertion intermediate. The initially formed Ph-Pd(P,N) species prefers a geometry with the phenyl trans to N.