Regioselective Incorporation of Backbone Constraints Compatible with Traditional Solid-Phase Peptide Synthesis

A protected aldehyde was attached via a twocarbon spacer to a peptide backbone amide nitrogen during a traditional Merrifield solid-phase synthesis. Acid-mediated unmasking of the aldehyde triggered the regioselective formation of cyclic N-acyliminiums between the aldehyde and the neighboring peptide amide nitrogen. In the absence of an internal nucleophile, the cyclic iminiums formed dihydropyrazinones, a six-membered peptide backbone constraint between two peptide amides. In the presence of an internal nucleophile, tetrahydropyrazinopyrimidinediones or tetrahydroimidazopyrazinediones were formed via tandem N-acyliminium ion cyclization-nucleophilic addition. The outcome of this nucleophilic addition was dependent on the substituent on the nitrogen nucleophile.Fil: la Venia, Agustina. Palacky University; República Checa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lemrová, Barbora. Palacky University; República ChecaFil: Krchnak, Viktor. Palacky University; República Checa. University Of Notre Dame-Indiana; Estados Unido

Polymer-Supported Stereoselective Synthesis of Tetrahydrobenzopyrazino-thiadiazinone Dioxides via N-Sulfonyl Iminiums

The stereoselective synthesis of 1,2,11,11atetrahydrobenzo[e]pyrazino[1,2-b][1,2,4]thiadiazin-3(4H)- one 6,6-dioxides on a solid support via tandem N-sulfonyl iminium ion cyclization, followed by nucleophilic addition is reported. The synthesis proceeded with full control of stereoselectivity at the newly formed asymmetric carbon, under mild conditions, and using commercially available building blocks. The synthetic route provided high-purity crude productsFil: Cankarova, Nadezda. Palacký University; República ChecaFil: la Venia, Agustina. Palacký University; República Checa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krchnak, Viktor. Palacký University; República Checa. University of Notre Dame; Estados Unido