Groebke–Blackburn–Bienaymé multicomponent reaction: emerging chemistry for drug discovery

Abstract

The Groebke-Blackburn-Bienaymé reaction (GBBR) is used for the one-pot synthesis of therapeutically relevant fused imidazoles bridgehead nitrogen heterocyclic compounds from readily available aldehyde, isocyanide and amidine building blocks. The reaction is driven by a wide range of catalysts and can be performed either under solvent or solvent-free conditions, or under microwave irradiation as heat source. The GBBR products can be used for the synthesis of a variety of more complex scaffolds via postmodification reactions. These include cyclization and nucleophilic substitution as well as further MCRs. The GBBR reaction has seen diverse applications in combinatorial and medicinal chemistry and its products are of great use in drug discovery. In this review, we summarize the efforts of the chemistry community in the progress and applications of GBBR since 1998. This review also includes some biological profiles and synthetic scopes of GBBR products. The component variations, postmodifications and secondary transformations will also be discussed throughout this review.

Silica‐Supported P2O5 as an Efficient Heterogeneous Catalyst for the One Pot Synthesis of 3‐Amino‐imidazo[2,1‐b](1,3)benzothiazole under Green Conditions

“…New application of P 2 O 5 /SiO 2 as an efficient catalyst in the three‐component one‐pot preparation of 3‐amino‐imidazo[2,1‐ b ](1,3)benzothiazole derivatives have been reported. Use of silica‐supported P 2 O 5 as a heterogeneous catalyst in methanol under reflux helped in synthesis of expected derivatives in good yields.…”

“…Additionally, several other catalysts were used, such as MgCl 2 [9a], InCl 3 [9b], ZnCl 2 [9c], RuCl 3 [9d], SnCl 2 . 2H 2 O [9e], and trimethylsilyl chloride [1,9f]. The reaction has also been carried out under microwave irradiation in the presence of a solid acid, Montmorillonite K10 ; in this method, special instrumentation is required.…”

Synergy Effects in the Chemical Synthesis and Extensions of Multicomponent Reactions (MCRs)—The Low Energy Way to Ultra-Short Syntheses of Tailor-Made Molecules

“…MCRs have been also applied in polymer [74], nucleoside [75] and carbohydrate [76] chemistry. Main field of application remains the production of heterocyclic compounds and many natural products by means of MCR [38,[77][78][79][80][81][82][83][84][85][86][87][88][89], leading directly towards drug design and discovery [90][91][92][93][94]. Scheme 9 presents a current brief of well-known multicomponent reactions [35,40,9,[95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110].…”

Multicomponent Tandem Polymerization of Aromatic Alkynes, Carbonyl Chloride, and Fischer's Base toward Poly(diene merocyanine)s

“…In the past decade, inspired by the advantages of multicomponent reactions (MCRs) such as high efficiency, mild condition, atom economy, simple reactants, and structural diversity, they were introduced to polymer chemistry and a large number of multicomponent polymerizations (MCPs) were developed which bring new functional polymer structures and materials . Typical MCPs include Ugi four‐component polymerizations, Passerini three‐component polymerizations, A 3 ‐polycouplings of alkynes, aldehydes, and amines, MCPs based on alkynes and sulfonyl azides, catalyst‐free MCPs of elemental sulfur, amine, and alkynes/isocyanides, and many other MCPs .…”