A novel amphiphilic acylguanidine organocatalyst using intramolecular hydrogen bonding as a key structural motif is efficient for asymmetric aldol reactions of ketones in water at neutral pH.

The synthesis of 1,4‐unsubstituted piperazin‐2‐ones by one‐pot reductive cyclization of PheΨ[CH(CN)NH]Gly pseudodipeptides is described. Studies on the reactivity of the piperazin‐2‐one ring showed a higher reactivity at the N4 position than at the N1 position. The stepwise regioselective functionalization of piperazin‐2‐one derivatives showed great potential for molecular diversity generation.

By applying a diversity oriented synthesis strategy for the search of new antagonists of the thrombin receptor PAR1, a series of peptide-based ureas and thioureas, including analogues of the PAR1 reference antagonist RWJ-58259, has been designed and synthesized. The general synthetic scheme involves reduction of basic amino acid-derived amino nitriles by hydrogen transfer from hydrazine monohydrate in the presence of Raney Ni, followed by reaction with diverse isocyanates and isothiocyanates, and protecting group removal. All new compounds have been evaluated as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN. Some protected peptide-based ureas displayed significant antagonist activity.

Dynamic combinatorial libraries (DCLs) are excellent benchmark models to study the stimuli-responsiveness of chemical networks. However, increasingly complex systems are difficult to analyze with simple data analysis methods, because many variables and connections must be considered for their full understanding. Here we propose the use of multivariate data analysis methods to bisect the evolution of a complex synthetic dynamic library of pseudopeptidic macrocycles, containing side chains with charges of different sign. Several stimuli (ionic strength, pH and the presence of a biogenic polyamine) were applied to the same dynamic chemical mixture, and the adaptation of the whole system was characterized by HPLC and analyzed with Principal Component Analysis (PCA) and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) methods. Both multivariate data analysis chemometric approaches are an excellent combination to extract both qualitative and semi-quantitative information about the adaptive process of the library upon the action of each stimulus. The resolution of the system with these chemometric tools proved to be especially useful when two inter-connected stimuli were combined in the same dynamic system. Our results demonstrate the utility of these two approaches for the analysis of complex dynamic chemical systems and open the way toward the application of these powerful tools in the emergent field of Systems Chemistry.