Synthesis of Natural Compounds Based on the [3,7]‐Diazabicyclo[3.3.1]nonane (Bispidine) Core

Abstract

The [3,7]‐diazabicyclo[3.3.1]nonane (bispidine) structure is found in several interesting naturally occurring alkaloids. The most representative components are the tetracyclic alkaloid (−)‐sparteine and the tricyclic (−)‐cytisine alkaloids. Their biological activities have been known for a long time. In the literature, different syntheses of both tetracyclic and tricyclic structures have been reported, especially in the last few years, when a number of new reports renewed the interest in these fascinating molecules. Bicyclic bispidine derivatives have been thoroughly investigated in recent times also for their applications as catalysts, metal chelating agents, and lately in coordination polymers chemistry. In this review, we describe the most relevant strategies for the synthesis of molecules based on the [3,7]‐diazabicyclo[3.3.1]nonane core, related to (−)‐sparteine and (−)‐cytisine alkaloids.

Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

“…3,7-Diazabicyclo[3.3.1]nonanes (bispidins) and related compounds are widely used as biologically active compounds [38,39], complexing agents for metals [40], radionuclides [41], as initial reagents for the synthesis of natural compounds [42], materials for imaging in positron emission tomography [43], platforms for chiral catalysts [44,45]. Recently, 3,7-diazabicyclononane derivatives have been successfully used as initial templates for constructing complex supramolecular assemblies [46][47][48][49].…”

Synthesis and Characterization of New Triazole-Bispidinone Scaffolds and Their Metal Complexes for Catalytic Applications

“…The importance of 1,2,3-triazole-based ligands in catalyzed chemical transformations has recently been reported in the literature [18]. Moreover, the presence of three consecutive sp 2 nitrogen atoms has been shown to confer to the 1,2,3-triazole ring particular electron-donating capabilities [19].…”

“…It can be conveniently prepared by a classical multi-Mannich reaction approach, allowing for the obtainment of many differently decorated structures capable of efficiently coordinating metals in a highly preorganized way. By the introduction of specific substituents, many tetra-, penta-, hexa-, hepta-, and octadentate ligands have been reported in the literature [1][2][3][4][5][6][7][8]. Most of their applications are related to the rigidity of the bispidine backbone, which confers unique structural and electronic properties to the ligand, namely a relatively large cavity allowing for efficient metal ion encapsulation.…”

“…To expand the number of coordination sites on the bispidine core, a classical approach is to introduce additional sp 2 nitrogen atoms, usually by adding one or more pyridine rings in different positions of the diazabicyclo scaffold [2,13]. For the same purpose, pyrazole rings, macrocyclic amides, and oxygen-containing substituents such as alcohols or Molecules 2023, 28, 6351 2 of 21 carboxylate groups have also been proposed [2,13]. Recently, the introduction of the picoline residue by Comba allowed coordination numbers higher than eight to be achieved [5].…”

“…In our ongoing studies on the properties and applications of bispidines [2,6,11], we decided to introduce the 1,2,3-triazole ring on the bispidine core to expand the coordination capabilities of this ligand. The 1,2,3-triazole has gained great interest in the last decades due to the success of the Cu alkyne-azide cycloaddition, the so-called CuAAC click-reaction [14].…”