Engineering d-amino acid containing novel protease inhibitors using catalytic site architecture.

The mechanism of proteolysis by serine proteases is a reasonably well-understood process. Typically, a histidine residue acting as a general base deprotonates the catalytic serine residue and the hydrolytic water molecule. We disclose here, the use of an unnatural d-amino acid as a strategic residue in P1 position, designed de novo based on the architecture of the protease catalytic site to impede the catalytic histidine residue at the stage of acyl-enzyme intermediate.

The Willgerodt-Kindler reaction on lupenone: unusual oxidative dimerization.

In continuation of our interest in chemical modification of triterpenoids, the Willgerodt-Kindler reaction of a lupane type triterpenoid lupenone provided a novel dimerized product 2. Formation of 2 is associated with an unusual oxidative dimerization of lupenone under Willgerodt-Kindler reaction conditions. The structure 2 was confirmed by extensive analysis of spectroscopic data including ES-MS and 2D-NMR.