Synthetic Strategies for Preparing Bicyclic Guanidines

Abstract

Different synthetic approaches leading to compounds containing bicyclic guanidine scaffolds are summarised. Because of the diversity within this group of target molecules and the wide range of individually reported synthetic routes, this review is divided into three subsections according to the key intermediate used to obtain the bicyclic structure. The first section is dedicated to strategies in which monocyclic guanidine derivatives are used as the key intermediates. The second section presents direct syntheses of bicyclic guanidines from acyclic or non‐guanidine starting materials. The last part of the text addresses the synthesis of target compounds through the use of polymer‐supported chemistry. The applicability of each synthetic approach for the preparation of target molecules with certain x+y combinations of individual cycles is specified.

An Expeditious and Greener Synthesis of 2-Aminoimidazoles in Deep Eutectic Solvents

“…As such, novel synthetic approaches for the construction of 2-AI scaffolds are continuously proposed. Classical methods rely upon condensation reactions, decoration of imidazole derivatives and heterocyclic exchange reactions [10,11,12,13]. More recently, various metal-mediated cycloguanylation reactions have also been proposed [14,15,16,17,18,19].…”

Catalytic Synthesis of Cyclic Guanidines via Hydrogen Atom Transfer and Radical-Polar Crossover

“…Moreover, its cyclic form is present in potent bioactive compounds and natural products, such as saxitoxin (blocker of voltage-gated sodium channels) and teixobactin (an antibiotic for resistant bacteria) (Scheme ). Because of these chemical and medicinal properties of cyclic guanidines, the development of a useful method for their synthesis has been of long-standing interest in organic synthesis. , There are various methods for synthesizing cyclic guanidines, such as intramolecular displacement, halocyclization, and others . Metal-catalyzed processes were developed, including alkene hydroamination (Ag), alkene carboamination (Pd), alkene diamination (Pd), alkyne hydroamination (Ag, Rh), alkyne carboamination (Pd), C–H amination (Rh), cyclization via (π-allyl) palladium intermediate, and carbenylative amination (Pd) .…”

Tandem Radical Fragmentation/Cyclization of Guanidinylated Monosaccharides Grants Access to Medium-Sized Polyhydroxylated Heterocycles

“…The most remarkable natural compounds within this group are those presenting a cyclic guanidinium, such as saxitoxin ( I ), tetrodotoxin ( II ), or crambescin A ( III ) (Figure ). Due to the complexity of their structures, these natural products have posed a synthetic challenge for organic chemists, which in turn has led to the development of numerous synthetic methodologies, especially in the synthesis of 5- and 6-membered cyclic guanidines . Natural products containing higher-order cyclic guanidines are, to the best of our knowledge, much scarcer, and in fact only monanchorin ( IV ), which contains a bridged 7-membered ring, is reported in the literature.…”