Peptidomimetics via Iminium Ion Chemistry on Solid Phase: Single, Fused, and Bridged Heterocycles

Copper‐Free Solid‐Phase Synthesis of Triazolo[1,5‐a][1,4]diazepin‐6‐ones

“…Inspired by this fact, we decided to develop an alternative and more robust approach consisting of the preparation of immobilized linear intermediates using convenient solid‐phase synthesis with on‐resin Huisgen cyclization being the final step. Apart from the applicability of the proposed methodology to easily obtaining collections of small molecules resembling the structure of biologically active triazolopiperazines with antiviral [17] and antidiabetic properties, [18] we also tested the application of our method to prepare constrained peptidomimetics, [19] which have recently found wide application in medicinal chemistry [20] . In this regard, it was already proven that the triazolodiazepinone scaffold serves as a constrained histidine mimic [16] .…”

Traceless Solid-Phase Synthesis of [6,7,8 + 5,6,7]-Fused Molecular Frameworks

“…Natural products comprising fused and bridged carbo- and heterocycles represent particularly intriguing molecular scaffolds with 3D architecture. Among the various chemical routes used to synthesize diverse nitrogenous heterocycles, tandem iminium ion cyclization-nucleophilic addition represents one of the most versatile strategies [ 8 , 9 , 10 , 11 ]. Typically, a cyclic iminium is formed from an amide nitrogen and an aldehyde attached to acyclic intermediate.…”

“…Incorporation of fused lactam rings was also frequently applied for the synthesis of peptidomimetics [ 8 , 21 ]. The constrained structures were designed to mimic β-turns, the most frequent secondary structure found in proteins.…”

Configuration-Dependent Medium-Sized Ring Formation: Chiral Molecular Framework with Three-Dimensional Architecture

“…Tandem iminium ion cyclizations followed by nucleophilic additions have been one of the most attractive methods because it generates two rings in one step and induces the formation of a new stereogenic center, typically with full control of the stereochemistry. 8−11 Several groups, including ours, have been involved in the synthesis of chiral molecular scaffolds comprising fused/bridged rings using iminium chemistry (see reviews in the literature 10,12,13 ).…”

“…Today the search for new drugs is focused on the design and synthesis of compounds structurally resembling natural products, which is referred to as biology-oriented synthesis. − The structural analysis of compound collections used for hit/lead generation revealed that chiral molecular scaffolds with three-dimensional (3D) architecture that mimic natural products show greater potential for finding promising starting compounds for the discovery of novel lead compounds. , Several synthetic strategies have been devised for accessing chiral 3D molecular frameworks. Tandem iminium ion cyclizations followed by nucleophilic additions have been one of the most attractive methods because it generates two rings in one step and induces the formation of a new stereogenic center, typically with full control of the stereochemistry. − Several groups, including ours, have been involved in the synthesis of chiral molecular scaffolds comprising fused/bridged rings using iminium chemistry (see reviews in the literature ,, ).…”