UC Irvine

Cyclic peptides have attracted attention due to their promising metabolic stability, conformational rigidity, and potential to mimic protein−protein interactions. We describe a method to access cyclic peptides using dehydrophenylalanine as a traceless turn inducer in the total synthesis of dichotomin E. The enamide facilitates ring-closing at high concentrations, and Rh-catalyzed hydrogenation of the unsaturated cyclic peptide results in selective formation of the natural product or its epimer, depending on our choice of phosphine ligand.

In addition, we demonstrate how a simple amino acid sequence can be recognized by a Rh-catalyst in a process which initiates the sequential reduction of cyclic dehydropeptides. Molecular recognition of amino acid sequences plays a key role in enzyme-substrate specificity, the regulation of genes, and the treatment of diseases. While critical in biological processes, molecular recognition of amino acids using a transition metal catalyst also holds great promise in organic synthesis. We report experimental and theoretical evidence to support the unidirectional hydrogenation toward the synthesis of cyclic peptides.

Like their peptide counterparts, depsipeptides are valuable therapeutic drug targets. These peptides are characterized by a combination of ester and amide linkages. To this end, we report the first enantioselective, intermolecular ketone hydroacylation of α-ketoamides with simple aldehydes for the construction of α-acyloxyamides in high yields and enantioselectivities.

Carbohydrates find importance in cellular communication, structural recognition, and cancer treatment. Although many of these oligosaccharides are generated through chemical synthesis, the presence of multiple hydroxyl sites in the carbohydrate presents a synthetic challenge. Toward a solution to this challenge, we have achieved a Cu-catalyzed regioselective functionalization of monosaccharides.

Constructing stereodefined alkenes is a longstanding challenge in organic synthesis. While methods to di- and trisubstituted alkenes have been reported, general protocols toward the synthesis of tetrasubstituted alkenes are underdeveloped. We describe a method toward the synthesis of stereodefined all-carbon tetrasubstituted alkenes from readily accessible ketones, first by a stereoselective enol tosylation followed by a Pd-catalyzed Suzuki-Miyaura cross coupling.