Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies.

Peptides have become valuable as catalysts for a variety of different reactions, but little is known about the conformational properties of peptidic catalysts. We investigated the conformation of the peptide H-dPro-Pro-Glu-NH, a highly reactive and stereoselective catalyst for conjugate addition reactions, and the corresponding enamine intermediate in solution by NMR spectroscopy and computational methods. The combination of nuclear Overhauser effects (NOEs), residual dipolar couplings (RDCs), J-couplings, and temperature coefficients revealed that the tripeptide adopts a single predominant conformation in its ground state.

A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine).

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle.

Crystal structures of peptidic catalysts of the H-dPro-Pro-Xaa type.

Crystal structures of catalytically active tripeptides of the general type H-dPro-Pro-Xaa and related N-acetylated analogs were compared. The influence of acylation at the N-terminus, the nature of the C-terminal residue, coordinating groups, and intramolecular hydrogen bonds on the conformation of the tripeptides was examined. Regardless of the presence or absence of stabilizing intramolecular H-bonds or n → π* interactions, all of the analyzed peptides share a β-turn-like conformation, which highlights the structural rigidity of the dPro-Pro motif and its value for conformational preorganization.

Peptide-Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide.

The tripeptide H-dPro-Pro-Asn-NH2 is presented as a catalyst for asymmetric conjugate addition reactions of aldehydes to maleimide. The peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields. The obtained products were readily derivatized to the corresponding pyrrolidines, lactams, lactones, and peptide-like compounds.

Synthetic strategies toward hetidine and hetisine-type diterpenoid alkaloids.

Within the diterpenoid alkaloid family of natural products, the hetidine and hetisine structural types have been the targets of a number of synthetic studies. Various strategies have been pursued to access the azacyclic moiety of these natural products as well as the characteristic [2.2.