Project description:This review covers sixty original publications dealing with the application of multicomponent reactions (MCRs) in the synthesis of novel nucleoside analogs. The reported approaches were employed for modifications of the parent nucleoside core or for de novo construction of a nucleoside scaffold from non-nucleoside substrates. The cited references are grouped according to the usually recognized types of the MCRs. Biochemical properties of the novel nucleoside analogs are also presented (if provided by the authors).
Project description:Here, we have demonstrated a metal-free energy-efficient mechanochemical approach for expedient access to a diverse set of 2-amino-3-cyano-aryl/heteroaryl-4H-chromenes, tetrahydrospiro[chromene-3,4'-indoline], 2,2'-aryl/heteroarylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) as well as tetrahydro-1H-xanthen-1-one by employing the reactivity of 5,5-dimethylcyclohexane-1,3-dione/cyclohexane-1,3-dione with TsOH⋅H2O as Brønsted acid catalyst under water-assisted grinding conditions at ambient temperature. The ability to accomplish multiple C-C, C=C, C-O, and C-N bonds from readily available starting materials via a domino multicomponent strategy in the absence of metal-catalyst as well as volatile organic solvents with an immediate reduction in the cost of the transformation without necessitates complex operational procedures, features the significant highlights of this approach. The excellent yield of the products, broad functional group tolerances, easy set-up, column-free, scalable synthesis with ultralow catalyst loading, short reaction time, waste-free, ligand-free, and toxic-free, are other notable advantages of this approach. The greenness and sustainability of the protocol were also established by demonstrating several green metrics parameters.
Project description:One of the highlights of green chemistry is the development of techniques and procedures with low environmental impact. In the last years, deep eutectic solvents (DES) have become an important alternative to conventional organic solvents. For a period ionic liquids have provoked remarkable interest, but they have been displaced by DES because they show easier preparation methods, lower prices, many of them are biodegradable and compatible with biological systems. In addition, they show adjustable physicochemical properties, high thermal stability, low volatility and are compatible with water. In this paper is reviewed the state of the art of the use of DES paying special attention to the role of reaction media in organic synthesis.
Project description:We developed synthetic chemistry to access the marine alkaloid rigidins and over 40 synthetic analogues based on the 7-deazaxanthine, 7-deazaadenine, 7-deazapurine, and 7-deazahypoxanthine skeletons. Analogues based on the 7-deazahypoxanthine skeleton exhibited nanomolar potencies against cell lines representing cancers with dismal prognoses, tumor metastases, and multidrug resistant cells. Studies aimed at elucidating the mode(s) of action of the 7-deazahypoxanthines in cancer cells revealed that they inhibited in vitro tubulin polymerization and disorganized microtubules in live HeLa cells. Experiments evaluating the effects of the 7-deazahypoxanthines on the binding of [(3)H]colchicine to tubulin identified the colchicine site on tubulin as the most likely target for these compounds in cancer cells. Because many microtubule-targeting compounds are successfully used to fight cancer in the clinic, we believe the new chemical class of antitubulin agents represented by the 7-deazahypoxanthine rigidin analogues have significant potential as new anticancer agents.
Project description:Using the Passerini and Ugi reactions as representative tests, the utility of several alpha-substituted ketones R-CO-CH(2)-X (X = sulfonyloxy, acyloxy, azido, halo, hydroxy, and sulfonyl) in isonitrile-based multicomponent reactions was explored. In a relative rate study (R = PhCH(2)CH(2)), each of the alpha-substituted ketones underwent Passerini condensation more rapidly than the parent ketone. Short, highly convergent routes to oxazoline, beta-lactam, di-O-acylglyceramides, and other molecular frameworks were developed.
Project description:The aldol reaction has been evaluated in combination with the Ugi multicomponent reaction to assemble richly decorated mono- and polycyclic systems via expeditious cascade pathways. A small collection of pyrrolinones was generated thereof, and the scarcely accessible pyridoquinoxalinedione scaffold was also prepared by designing an additional nucleophilic substitution step in this domino sequence requiring minimal operational effort.
Project description:The synthesis of a [2]rotaxane through three- or five-component coupling reactions has been adapted to an organic chemistry experiment for upper-division students. The experimental procedure addresses the search for the most favorable reaction conditions for the synthesis of the interlocked compound, which is obtained in a yield of up to 71%. Moreover, the interlocked nature of the rotaxane is proven by NMR spectroscopy. The content of the sessions has been designed on the basis of a proactive methodology whereby upper-division undergraduate students have a dynamic role. The laboratory experience not only introduces students to the chemistry of the mechanical bond but also reinforces their previous knowledge of basic organic laboratory procedures and their skills with structural elucidation techniques such as NMR and FT-IR spectroscopies. The experiment has been designed in such a customizable way that both experimental procedures and laboratory material can be adapted to a wide range of undergraduate course curricula.
Project description:A demonstration experiment of the synthesis of a novel tetrazole derivative via a multicomponent reaction (Ugi tetrazole four component reaction, UT-4CR) bearing a luminol moiety and a subsequent exploitation of its chemiluminescent properties is described. A complex product is generated in just one simple step, so simple that children can do it: "kinderleicht", German for dead easy. Students are stimulated, inspired, and involved in a multilevel active learning process using the Steps to Inquiry framework as a metacognitive tool that raises student awareness regarding scientific process and prompts them to ask their own questions discussing the merits of a mechanism and evaluating its effectiveness before they start their own cycles of inquiry.
Project description:Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.
Project description:Multicomponent reactions are powerful synthetic tools for the efficient creation of complex organic molecules in an one-pot one-step fashion. Moreover, the amount of solvents and energy needed for separation and purification of intermediates is significantly reduced what is beneficial from the green chemistry issues point of view. This review highlights the development of multicomponent reactions conducted using aqueous micelles systems during the last two decades.