The diverser eactivity of N-heterocyclic carbenes (NHCs) in organocatalysis is due to the possibility of different modeso fa ction. Although NHC-bounde nolates and dienolates are known, the related NHC-bound cross-conjugated aza-trienolates remain elusive. Herein,w ed emonstrate the NHC-catalyzed formal [6+ +2] annulation of nitrogen-containing heterocyclic aldehydes with a,a,a-trifluoroacetophenones leadingt ot he formation of versatile pyrrolooxazolones (29 examples). The catalytically generated cross-conjugated aza-trienolates (aza-fulvene type) underwent smooth [6+ +2] annulation with electrophilic ketones to afford the product in moderate to good yields under mild conditions. Preliminary DFT studies on the mechanism are also provided.Scheme1.Generation and reaction of various NHC-enolates.

Although NHC-catalyzed umpolung of imines are known, the related reactions under oxidative conditions are limited. Described herein is the two-step process involving the initial formation of aldimines from the corresponding aldehydes and 2-amino benzyl alcohols followed by NHC-catalyzed cyclization proceeding via the imidoyl azoliums under oxidative conditions. The reaction allowed the synthesis of trifluoromethylated 3,1-benzoxazines in good yields and broad scope. The role of NHC in the intramolecular cyclization and preliminary mechanistic experiments are also provided.

This communication reports the use of a rigid organic scaffold to attach two unsymmetrical peptide chains on a single carbon atom. The approach describes the step‐by‐step attachment of peptide chains to the rigid dimedone template (5,5‐dimethyl‐1,3‐cyclohexanedione) – a molecular scaffold that directs orientation of the peptide helices in a well‐defined arrangement via intra‐molecular hydrogen bonding. The overall topology of the final molecules was studied using CD spectroscopy which suggested existence of helical architecture.

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We describe herein design, synthesis and conformational investigations of polypeptides attached on a rigid dimedone template. Two identical peptide chains are attached on a single carbon containing dimedone as a scaffold. Dimedone assists in controlling the secondary interactions through strong intramolecular helical C‐12 and C‐15 membered bifurcated hydrogen bonding on both the peptide chains along with propagating the helical architecture of the peptide chains attached. There exists a C‐6 hydrogen bonding for the single stranded peptides attached to dimedone. Extensive structural investigations involving single crystal X‐ray diffraction, solution‐state NMR and CD studies of oligopeptides have been undertaken.

Abstract:Rapastinel (GLYX‐13) is a natural amidated tetrapeptide (Thr‐Pro‐Pro‐Thr‐NH2)endowed with strong antidepressant property. Rapastinel shows considerable promise for treating drug‐resistant major depressive disorder (MDD), and is under clinical phase III development. Herein, we report the synthesis of a novel class of analogues of the potent antidepressant peptide drug rapastinel featuring rigid dipeptide scaffolds comprising proline (L/D) and amino thiophene carboxylates (Atc). Amino thiophene carboxylate is a conformationally constrained aromatic β‐amino acid, known to rigidify peptide backbones thereby limiting the conformational flexibility of peptides and improving proteolytic stability.

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