Synthesis of polyheterocycles via multicomponent reactions.

Polyheterocycles are one of the most desired synthetic targets due to their numerous and valuable applications in various fields. Multicomponent reactions (MCRs) are highly convergent one-pot processes, in which three or more reagents are combined sequentially to construct complex products, with almost all the atoms coming from the starting reagents. In this context, the syntheses of 'heterocycles' via MCR-based processes have been reviewed a number of times. However, there is not a single review (recent or otherwise) covering the synthesis of 'polyheterocycles' via a direct MCR or via a one-pot process involving MCRs coupled to further cyclizations (via ionic, metal-catalyzed, pericyclic, or free-radical-mediated cyclizations). This issue is consequently the main topic of the present review, which considers work from the last decade. The work is categorized according to the key processes involved in the syntheses of polyheterocycles, aiming to give readers an easy understanding of this MCR-based chemistry and to provide insights for further investigations. The reaction mechanisms providing novel elements to these MCR-based methods for the synthesis of polyheterocycles are also discussed.

[1]  X. L. Le Goff,et al.  Straightforward four-component access to spiroindolines. , 2011, Chemical communications.

[2]  R. Rawal,et al.  Diversity-oriented synthesis of fused-imidazole derivatives via Groebke–Blackburn–Bienayme reaction: a review , 2015 .

[3]  M. Haji Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates , 2016, Beilstein journal of organic chemistry.

[4]  P. Andreana,et al.  A one-pot, microwave-influenced synthesis of diverse small molecules by multicomponent reaction cascades. , 2007, Organic letters.

[5]  Wei Wang,et al.  Polycyclic indole alkaloid-type compounds by MCR. , 2010, Chemical communications.

[6]  Stephen R. Johnson,et al.  Molecular properties that influence the oral bioavailability of drug candidates. , 2002, Journal of medicinal chemistry.

[7]  A. Maleki,et al.  Sonochemical rate enhanced by a new nanomagnetic embedded core/shell nanoparticles and catalytic performance in the multicomponent synthesis of pyridoimidazoisoquinolines. , 2017, Ultrasonics sonochemistry.

[8]  S. Shaaban,et al.  Groebke–Blackburn–Bienaymé multicomponent reaction: emerging chemistry for drug discovery , 2015, Molecular Diversity.

[9]  A. Dömling,et al.  Efficient multicomponent reaction synthesis of the schistosomiasis drug praziquantel. , 2010, Chemistry.

[10]  Tanpreet Kaur,et al.  Facile Construction of Imidazo‐benzothia‐/oxazepines by a Quick and Efficient van Leusen Protocol , 2017 .

[11]  L. Grimaud,et al.  Three-component Ugi–Smiles couplings of cyclic imines , 2009 .

[12]  Jieping Zhu Recent Developments in the Isonitrile‐Based Multicomponent Synthesis of Heterocycles , 2003 .

[13]  S. Chemler Copper catalysis in organic synthesis , 2015, Beilstein journal of organic chemistry.

[14]  F. Rutjes,et al.  Recent Advances in Asymmetric Isocyanide-Based Multicomponent Reactions , 2012 .

[15]  T. Bach,et al.  Photochemical reactions as key steps in natural product synthesis. , 2011, Angewandte Chemie.

[16]  A. Islas-Jácome,et al.  Synthesis of unsymmetrical bis-heterocycles containing the imidazo[2,1-b]thiazole framework and their benzo[d]fused analogues by an acid-free Groebke–Blackburn–Bienaymé reaction , 2016 .

[17]  L. D. Miranda,et al.  Multicomponent access to indolo[3,3a-c]isoquinolin-3,6-diones: formal synthesis of (±)-plicamine. , 2016, Organic & biomolecular chemistry.

[18]  Alexander Dömling,et al.  Recent developments in isocyanide based multicomponent reactions in applied chemistry. , 2006, Chemical reviews.

[19]  E. González-Zamora,et al.  Synthesis of cyclic analogues of hexamethylenebis(3-pyridine)amide (HMBPA) in a one-pot process , 2015 .

[20]  T. Müller,et al.  Multi-component syntheses of heterocycles by transition-metal catalysis. , 2007, Chemical Society reviews.

[21]  A. Dömling Recent advances in isocyanide-based multicomponent chemistry. , 2002, Current opinion in chemical biology.

[22]  Vishal Rai,et al.  Small heterocycles in multicomponent reactions. , 2014, Chemical reviews.

[23]  T. Müller,et al.  Multicomponent syntheses of functional chromophores. , 2016, Chemical Society reviews.

[24]  I. Ugi,et al.  Multicomponent Reactions with Isocyanides. , 2000, Angewandte Chemie.

[25]  T. Keller,et al.  A practical view of 'druggability'. , 2006, Current opinion in chemical biology.

[26]  A. D. Borthwick 2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products. , 2012, Chemical reviews.

[27]  E. V. Van der Eycken,et al.  Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds. , 2015, Chemical Society reviews.

[28]  A. M. Andersson,et al.  Conductive polyheterocycles as electrode materials in solid state electrochromic devices , 1994 .

[29]  E. V. D. Eycken,et al.  Remote Amide‐Controlled Gold‐Catalyzed Stereoselective Hydro‐heteroarylation of Acrylamides: Access to Pyrido[3,4‐b]indoles , 2015 .

[30]  Irini Akritopoulou-Zanze,et al.  Isocyanide-based multicomponent reactions in drug discovery. , 2008, Current opinion in chemical biology.

[31]  C. Lipinski Lead- and drug-like compounds: the rule-of-five revolution. , 2004, Drug discovery today. Technologies.

[32]  Hugues Bienaymé,et al.  A New Heterocyclic Multicomponent Reaction For the Combinatorial Synthesis of Fused 3-Aminoimidazoles. , 1998, Angewandte Chemie.

[33]  Stefan Wetzel,et al.  Biology-oriented synthesis. , 2011, Angewandte Chemie.

[34]  Jared T. Shaw,et al.  Recent advances in multicomponent reactions for diversity-oriented synthesis. , 2010, Current opinion in chemical biology.

[35]  Agnieszka Ulaczyk-Lesanko,et al.  Wanted: new multicomponent reactions for generating libraries of polycyclic natural products. , 2005, Current opinion in chemical biology.

[36]  A. Islas-Jácome,et al.  A short microwave-assisted synthesis of tetrahydroisoquinolin-pyrrolopyridinones by a triple process: Ugi-3CR–aza Diels–Alder/S-oxidation/Pummerer , 2011 .

[37]  Jieping Zhu,et al.  Rapid synthesis of cyclodepsipeptides containing a sugar amino acid or a sugar amino alcohol by a sequence of a multicomponent reaction and acid-mediated macrocyclization. , 2007, The Journal of organic chemistry.

[38]  Sushobhan Chowdhury,et al.  Advances of azide-alkyne cycloaddition-click chemistry over the recent decade , 2016 .

[39]  S. Pharande,et al.  Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction , 2017 .

[40]  A. Ghose,et al.  A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. , 1999, Journal of combinatorial chemistry.

[41]  M. Yus,et al.  Asymmetric multicomponent reactions (AMCRs): the new frontier. , 2005, Angewandte Chemie.

[42]  L. Grimaud,et al.  Beyond the Ugi reaction: less conventional interactions between isocyanides and iminium species , 2009 .

[43]  O. Roubeau,et al.  Triazoles and tetrazoles: Prime ligands to generate remarkable coordination materials , 2011 .

[44]  R. Martínez,et al.  Synthesis of azepino[4,5-b]indolones via an intermolecular radical oxidative substitution of N-Boc tryptamine. , 2009, Organic & biomolecular chemistry.

[45]  A. de Meijere,et al.  Isocyanides in the synthesis of nitrogen heterocycles. , 2010, Angewandte Chemie.

[46]  C. Hulme,et al.  Synthesis of Diverse Nitrogen-Enriched Heterocyclic Scaffolds Using a Suite of Tunable One-Pot Multicomponent Reactions , 2014, The Journal of organic chemistry.

[47]  F. J. Luque,et al.  Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds. , 2016, Angewandte Chemie.

[48]  A. Váradi,et al.  Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles , 2015, Molecules.

[49]  H. Meshram,et al.  Sulfamic acid catalyzed one-pot, three-component green approach: synthesis and cytotoxic evaluation of pyrazolyl-thiazole congeners , 2017 .

[50]  L. D. Miranda,et al.  Synthesis of novel tryptamine-based macrocycles using an Ugi 4-CR/microwave assisted click-cycloaddition reaction protocol. , 2015, Organic & biomolecular chemistry.

[51]  L. Grimaud,et al.  New Ugi/Pictet-Spengler Multicomponent Formation of Polycyclic ­Diketopiperazines from Isocyanides and α-Keto Acids , 2007 .

[52]  J. Vaquero,et al.  Novel environmentally benign procedures for the synthesis of styryl dyes , 2008 .

[53]  S. Martin,et al.  Applications of multicomponent reactions to the synthesis of diverse heterocyclic scaffolds. , 2009, Chemistry.

[54]  Xuechen Li,et al.  A fascinating journey into history: exploration of the world of isonitriles en route to complex amides. , 2012, Angewandte Chemie.

[55]  J. Sapi,et al.  Indole based multicomponent reactions towards functionalized heterocycles , 2004 .

[56]  R. Santillán,et al.  Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel , 2016, Molecules.

[57]  Rocío Gámez-Montaño,et al.  The Ugi Reaction of Cyanoacetic Acid as a Route to Tetramic Acid Derivatives , 2015 .

[58]  A. Islas-Jácome,et al.  Selective reaction route in the construction of the pyrrolo[3,4-b]pyridin-5-one core from a variety of 5-aminooxazoles and maleic anhydride. A DFT study , 2016 .

[59]  C. Hulme,et al.  Bifunctional building blocks in the Ugi-azide condensation reaction: a general strategy toward exploration of new molecular diversity. , 2013, Organic & biomolecular chemistry.

[60]  L. Wessjohann,et al.  Multiple multicomponent macrocyclizations (MiBs): a strategic development toward macrocycle diversity. , 2009, Chemical reviews.

[61]  Ivan Marziano,et al.  Critical assessment of pharmaceutical processes--A rationale for changing the synthetic route. , 2006, Chemical reviews.

[62]  E. González-Zamora,et al.  Synthesis of a tetracyclic lactam system of Nuevamine by four-component reaction and free radical cyclization , 2010 .

[63]  A. Andreani,et al.  Synthesis and fungicide activity of 2,3-dihydroimidazo [2,1-b]thiazole-5-carboxamides. , 1995, Pharmaceutica acta Helvetiae.

[64]  A. Ramazani,et al.  Synthetic Applications of Passerini Reaction , 2012 .

[65]  H. Eckert Diversity Oriented Syntheses of Conventional Heterocycles by Smart Multi Component Reactions (MCRs) of the Last Decade , 2012, Molecules.

[66]  C. Hulme,et al.  Ugi/aldol sequence: expeditious entry to several families of densely substituted nitrogen heterocycles. , 2012, Angewandte Chemie.

[67]  E. V. D. Eycken,et al.  Synthesis of novel imidazole-based triheterocycles via a domino Ugi/Michael reaction and silver-catalyzed heteroannulation , 2016 .

[68]  A. Andreani,et al.  Synthesis of imidazo[2,1-b]thiazoles as herbicides , 1996 .

[69]  L. Weber,et al.  Synthesis of Imidazo[1,2-a] annulated Pyridines, Pyrazines and Pyrimidines by a Novel Three-Component Condensation , 1998 .

[70]  A. Islas-Jácome,et al.  Synthesis of azepino[4,5-b]indol-4-ones via MCR/free radical cyclization and in vitro-in silico studies as 5-Ht₆R ligands. , 2016, Bioorganic & medicinal chemistry letters.

[71]  Y. Ivanenkov,et al.  Multicomponent reactions of isocyanides in the synthesis of heterocycles , 2010 .

[72]  D. Denning,et al.  Electrophilic, Activation-Free Fluorogenic Reagent for Labeling Bioactive Amines. , 2016, Bioconjugate chemistry.

[73]  Eelco Ruijter,et al.  Multicomponent reaction design in the quest for molecular complexity and diversity. , 2011, Angewandte Chemie.

[74]  Jianxian Gong,et al.  One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction , 2016, Beilstein journal of organic chemistry.

[75]  M. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001 .

[76]  P. Mirzaei,et al.  CATALYST-FREE THREE-COMPONENT REACTION BETWEEN 2-AMINOPYRIDINES (OR 2-AMINOTHIAZOLES), ALDEHYDES, AND ISOCYANIDES IN WATER , 2007 .

[77]  A. Islas-Jácome,et al.  Synthesis of 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones in two reaction steps: (Ugi-azide/N-acylation/SN2)/free radical cyclization and docking studies to a 5-Ht(6) model. , 2013, Organic & biomolecular chemistry.

[78]  A. Andreani,et al.  5-Formylimidazo[2,1- b ]thiazoles and derivatives with herbicidal activity , 1991 .

[79]  N. Isambert,et al.  Multicomponent Access to Functionalized Mesoionic Structures Based on TFAA Activation of Isocyanides : Novel Domino Reactions , 2009 .

[80]  A. Dömling,et al.  Efficient and diverse synthesis of indole derivatives. , 2009, The Journal of organic chemistry.

[81]  A. Maleki,et al.  A review of syntheses of 1,5-disubstituted tetrazole derivatives , 2015, Molecular Diversity.

[82]  K. Nicolaou,et al.  Samarium diiodide mediated reactions in total synthesis. , 2009, Angewandte Chemie.

[83]  A. A. Shestopalov,et al.  Multicomponent Reactions of Carbonyl Compounds and Derivatives of Cyanoacetic Acid : Synthesis of Carbo-and Heterocycles , 2008 .

[84]  H. Bienaymé,et al.  A novel multicomponent synthesis of polysubstituted 5-aminooxazole and its new scaffold-generating reaction to pyrrolo[3,4-b]pyridine. , 2001, Organic letters.

[85]  G. Mlostoń,et al.  Synthesis of optically active polyheterocycles containing pyrrolidine, imidazole, and 1,2,3-triazole rings ☆ , 2015 .

[86]  A. Maleki,et al.  Synthesis of tetrazoles via isocyanide-based reactions , 2015 .

[87]  Liyao Zheng,et al.  Synthesis of Natural Product-like Polyheterocycles via One-Pot Cascade Oximation, C-H Activation, and Alkyne Annulation. , 2016, The Journal of organic chemistry.

[88]  C. Blackburn,et al.  Parallel synthesis of 3-aminoimidazo[1,2-a]pyridines and pyrazines by a new three-component condensation , 1998 .

[89]  E. V. D. Eycken,et al.  A domino Ugi/Michael approach for the synthesis of α,β-unsaturated γ-lactams , 2016 .

[90]  Seung Bum Park,et al.  A design strategy for drug-like polyheterocycles with privileged substructures for discovery of specific small-molecule modulators. , 2011, Chemical communications.

[91]  S. Pharande,et al.  An efficient Ugi-3CR/aza Diels-Alder/Pomeranz-Fritsch protocol towards novel aza-analogues of (±)-nuevamine, (±)-lennoxamine and magallanesine: a diversity oriented synthesis approach. , 2017, Organic & biomolecular chemistry.

[92]  S. Danishefsky,et al.  On the reach of chemical synthesis: creation of a mini-pipeline from an academic laboratory. , 2010, Angewandte Chemie.

[93]  A. Basso,et al.  Synthesis of seven-membered nitrogen heterocycles through the Ugi multicomponent reaction , 2017, Chemistry of Heterocyclic Compounds.

[94]  N. Isambert,et al.  Heterocycles as key substrates in multicomponent reactions: the fast lane towards molecular complexity. , 2008, Chemistry.

[95]  M. Heravi,et al.  Recent application of isocyanides in synthesis of heterocycles , 2011 .