Esters of amino acids were reacted with 2-cyano-4-nitrobenzenesulfonyl chloride or 2-cyano-4-(trifluoromethyl)benzenesulfonyl chloride and alkylated with various α-haloketones. The corresponding sulfonamides were heated in a solution of ammonium acetate, which yielded imidazo[2,1-a]isoindolones in one step. The key reaction was based on intramolecular C-arylation followed by spontaneous cycloaddition and cyclocondensation. Two approaches have been developed: (i) solid-phase synthesis starting from amino acids immobilized on Wang resin, which allows the rapid preparation of target compounds using the cyclative cleavage strategy, and (ii) traditional solution-phase synthesis using amino acid methyl esters as the starting materials. The advantages and drawbacks of both alternatives are compared.

• Publikační typ
• časopisecké články MeSH

Drug discovery efforts largely depend on access to structural diversity. Multicomponent reactions allow for time-efficient chemical transformations and provide advanced intermediates with three or four points of diversification for further expansion to a structural variety of organic molecules. This review is aimed at solid-phase syntheses of small molecules involving isocyanide-based multicomponent reactions. The majority of all reported syntheses employ the Ugi four-component reaction. The review also covers the Passerini and Groebke-Blackburn-Bienaymé reactions. To date, the main advantages of the solid-phase approach are the ability to prepare chemical libraries intended for biological screening and elimination of the isocyanide odor. However, the potential of multicomponent reactions has not been fully exploited. The unexplored avenues of these reactions, including chiral frameworks, DNA-encoded libraries, eco-friendly synthesis, and chiral auxiliary reactions, are briefly outlined.

• Klíčová slova
• Ugi four-component reaction, convertible isocyanides, drug discovery, multicomponent reactions, post-Ugi transformations, solid-phase synthesis,
• MeSH
• kyanidy chemická syntéza   chemie   MeSH
• objevování léků * metody   MeSH
• syntetické pryskyřice chemie   MeSH
• techniky syntetické chemie * MeSH
• techniky syntézy na pevné fázi * metody   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kyanidy MeSH
• syntetické pryskyřice MeSH