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Recent Advances in the Synthesis of Oxazole-Based Molecules Via Van Leusen Oxazole Synthesis

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Recent Advances in the Synthesis of Oxazole-Based Molecules Via Van Leusen Oxazole Synthesis molecules Review Recent Advances in the Synthesis of Oxazole-Based Molecules via van Leusen Oxazole Synthesis Xunan Zheng 1,2, Wei Liu 3,* and Dawei Zhang 1,* 1 College of Chemistry, Jilin University, Changchun 130012, China; [email protected] 2 College of Plant Science, Jilin University, Changchun 130062, China 3 Department of Pesticide Science, Plant Protection College, Shenyang Agricultural University, Shenyang 110866, China * Correspondence: [email protected] (W.L.); [email protected] (D.Z.); Tel.: +86-188-1775-2588 (W.L.); +86-431-8783-6471 (D.Z.) Academic Editors: Anna Carbone and Fabio Bertozzi Received: 2 March 2020; Accepted: 23 March 2020; Published: 31 March 2020 Abstract: Oxazole compounds, including one nitrogen atom and one oxygen atom in a five-membered heterocyclic ring, are present in various biological activities. Due to binding with a widespread spectrum of receptors and enzymes easily in biological systems through various non-covalent interactions, oxazole-based molecules are becoming a kind of significant heterocyclic nucleus, which have received attention from researchers globally, leading them to synthesize diverse oxazole derivatives. The van Leusen reaction, based on tosylmethylisocyanides (TosMICs), is one of the most appropriate strategies to prepare oxazole-based medicinal compounds. In this review, we summarize the recent advances of the synthesis of oxazole-containing molecules utilizing the van Leusen oxazole synthesis from 1972, aiming to look for potential oxazole-based medicinal compounds, which are valuable information for drug discovery and synthesis. Keywords: van Leusen; TosMICs; oxazole; synthesis 1. Introduction The oxazole ring, with one nitrogen atom and one oxygen atom, which are widely displayed in natural products and synthetic molecules, is known as a prime skeleton for drug discovery. On the account of structural and chemical diversity, oxazole-based molecules, as a central scaffold, not only enable different types of interactions with various receptors and enzymes, showing broad biological activities, but also occupy a core position in medicinal chemistry, showing their enormous development value and they favored the discovery of newer potential therapeutic agents [1–5]. Consequently, a wide variety of oxazole-containing compounds, as clinical drugs or candidates, have been frequently employed, which play a vital role in the treatment of diverse types of diseases like antibacterial [6–8], antifungal [9–11], anti-inflammatory [12–14], antiviral [15–17], anti-tubercular [18–20], anticancer [21–23], anti-parasitic [24–26], antidiabetic [27–29], and so on. The marketed drugs containing the oxazole ring system with medicinal value are being actively exploited worldwide. Various pharmacological activities and chemical structures of oxazole-based molecules are enumerated in the following Table1. Molecules 2020, 25, 1594; doi:10.3390/molecules25071594 www.mdpi.com/journal/molecules Molecules 2020, 25, x FOR PEER REVIEW 2 of 18 Molecules 2020, 25, x FOR PEER REVIEW 2 of 18 Table 1. The pharmacological activities and chemical structures of typical oxazole-based molecules. Table 1. The pharmacological activities and chemical structures of typical oxazole-based molecules. Molecules 2020MoleculesMolecules, 25Pharmacological, 1594 2020 2020, ,25 25, ,x x FOR FOR PEER PEER REVIEW REVIEW 22 of of 18 218 of 18 MoleculesPharmacological 2020, 25, x FOR PEER REVIEW Chemical Structures 2 of 18 Molecules 2020Activities, 25, x FOR PEER REVIEW Chemical Structures 2 of 18 TableTableActivities 1. 1. The The pharmacological pharmacological activities activities and and chemical chemical structures structures of of typical typical oxazole-based oxazole-based molecules. molecules. Table 1. TheTable pharmacological 1. The pharmacological activities activities and chemical and chemical structures structures of typicalof typical oxazole-based oxazole-based molecules. molecules. TablePharmacological 1. The pharmacological activities and chemical structures of typical oxazole-based molecules. Pharmacological Chemical Structures PharmacologicalActivities Chemical Structures PharmacologicalPharmacologicalActivities Chemical Structures Activities ChemicalChemical Structures Structures ActivitiesActivitiesAntibacterial Antibacterial AntibacterialAntibacterial Antibacterial AntibacterialAntibacterial Antifungal Antifungal AntifungalAntifungal AntifungalAntifungal Antifungal Anti- Anti- inflammatory inflammatory Anti-Anti- Anti-inflammatoryAnti- inflammatoryinflammatory inflammatoryAnti- inflammatory Antiviral Antiviral AntiviralAntiviralAntiviral Antiviral Antiviral Antitubercular Antitubercular Antitubercular AntitubercularAntitubercular Antitubercular Antitubercular AnticancerAnticancer MoleculesAnticancer 2020, 25, x FOR PEER REVIEW 3 of 18 Molecules 2020, 25, x FOR PEER REVIEW 3 of 18 AnticancerAnticancer Anticancer Anticancer Antiparasitic AntiparasiticAntiparasitic AntidiabeticAntidiabetic Antidiabetic Due to the diversity of therapeutic response profiles, the chemical synthesis of oxazole and its derivativesDue to hasthe becomediversity a ofkey therapeu objectivetic andresponse has dr profiles,awn much the chemicalattention synthesisof current of pharmacologists oxazole and its andderivatives chemists has around become the a globekey objective to be explored and has exha drawnustively much for attention the benefit of currentof mankind. pharmacologists Until now, manyand chemists ingenious around oxazole the syglobenthesis to bemethodologies explored exha haveustively been for developed, the benefit including of mankind. the van Until Leusen now, reactionmany ingenious [30], Cornforth oxazole reaction synthesis [31], methodologies Fisher reacti onhave [32], been Doyle developed, reaction [33],including Dakin–West the van reaction Leusen [34],reaction as well[30], asCornforth Robinson–Gabriel reaction [31], reaction Fisher [35],reacti etc..on [32],Among Doyle these reaction synthetic [33], Dakin–Weststrategies, it reactionis well- known[34], as thatwell the as vanRobinson–Gabriel Leusen oxazole reaction synthesis, [35], based etc.. on Among tosylmethylisocyanides these synthetic strategies, (TosMICs), it isis one well- of theknown most that convenient the van Leusen and attractive oxazole protocols synthesis, for based the preparationon tosylmethylisocyanides of oxazole-based (TosMICs), molecules, is owingone of tothe its most excellent convenient virtues and like attractive simple operation,protocols for easily the preparationobtained raw of materials,oxazole-based and amolecules, broad substrate owing scope,to its excellent and it has virtues been like developed simple operation, rapidly in easily the pastobtained decades. raw Itmaterials, is worth and mentioning a broad substratethat the pharmacologicalscope, and it has activity been developedoxazole-based rapidly compounds in the past11, 16 decades. and 25 inIt Tableis worth 1 can mentioning be obtained that by vanthe Leusenpharmacological reaction as activity a key step.oxazole-based compounds 11, 16 and 25 in Table 1 can be obtained by van LeusenTosMIC, reaction a kindas a keyof the step. most significant reactants, has many good features at room temperature includingTosMIC, stable a kind solid, of theodorless, most significant and colorless. reactants, Since has it manywas introduced good features and at applied room temperature in organic synthesisincluding bystable the Dutchsolid, odorless,professor andvan Leusencolorless. in Since1972, thisit was reagent introduced is also andknown applied as van in Leusen’s organic reagent.synthesis Today, by the TosMICDutch professor and its devanrivatives Leusen have in 1 972,been this recognized reagent isas also one knownof the mostas van significant Leusen’s buildingreagent. Today,blocks in TosMIC organic and synthesis its de andrivatives a great have deal been of reaction recognized scenarios, as one which of the have most been significant fruitfully employedbuilding blocks in the in preparation organic synthesis of pyrrole-, and a imidazol great deale-, of and reaction oxazole-based scenarios, five-membered which have been heterocyclic fruitfully moleculesemployed [36–40].in the preparation General van of Lepyrrole-,usen synthesis imidazol basee-, and on TosMICsoxazole-based is summarized five-membered in Scheme heterocyclic 1. molecules [36–40]. General van Leusen synthesis base on TosMICs is summarized in Scheme 1. Scheme 1. General van Leusen synthesis base on tosylmethylisocyanides (TosMICs). Scheme 1. General van Leusen synthesis base on tosylmethylisocyanides (TosMICs). Based on our previous research, we have published two reviews about the van Leusen reaction for theBased preparation on our previous of pyrrole- research, and imidazole-based we have published molecules two reviews [41,42]. about Therefore, the van this Leusen review, reaction which coversfor the thepreparation literature of from pyrrole- 1972, andwill imidazole-basedsummarize the recent molecules advances [41,42]. of the Therefore, synthesis this of review,oxazole-based which moleculescovers the literatureutilizing thefrom van 1972, Leusen will summarizeoxazole synthesis the recent as anadvances important of the part synthesis of van ofLeusen oxazole-based reaction, whichmolecules is the utilizing [3+2] cycloadditionthe van Leusen reaction oxazole based synthesis on TosMICs. as an important Meanwhile, part ofit vanis expected Leusen reaction,that this reviewwhich isarticle the [3+2]will be cycloaddition beneficial for reaction
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