Synthesis and Discovery

There are many challenging intellectual opportunities for the research community to create new knowledge in molecular structure-property relations, and to enlarge the toolbox of product engineering, that promise to inspire and accelerate new product innovations. 

There is a suspicion that there are inexhaustible families of material structures waiting to be discovered and to be used. Periodically, this suspicion is confirmed by the announcement of yet another family of interesting materials. 

The synthesis of new material can also be divided into the twin paths of incremental synthesis of the derivatives of known structures and the wildcat synthesis of totally unrelated structures. The incremental approach is used when a material with interesting properties is discovered, and research chemists will swarm around it to make every conceivable derivative to see whether they can enlarge the menu to choose from, and to ensure that the new province is well explored. The opposite wildcat approach seeks new and exciting families of material that would not be found by adhering exclusively to known provinces. 

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The synthesis and discovery of the antipsychotic effects of the piperazinyl-dibenzoazepine, clozapine (Fig. 13.1) and its launch in 1972 was an important turning point in the drug treatment of schizophrenia [1-3]. Clozapine was called an atypical antipsychotic as it did not produce side effects characteristic for compounds of the chlorpromazine- or haloperidol-type (i.e., extrapyramidal symptoms) either in animal models or in the clinic. Its use, however, became very limited when it was recognized that clozapine might cause a severe, and sometimes fatal, form of agranulocytosis. 

Kumar RR, Perumal S, Senthilkumar P et al (2008) A highly atom economic, chemo-, regio-and stereoselective synthesis, and discovery of spiro-pyrido-pyrrolizines and pyrrolidines as antimycobacterial agents. Tetrahedron 64 2962-2971... 

Kumar RS, Rajesh SM, Perumal S et al (2010) Novel three-component domino reactions of ketones, isatin and amino acids synthesis and discovery of antimycobacterial activity of highly functionalised novel dispiropyrrolidines. Eur J Med Chem 45 411 22... 

D. Macmillan, A.M. Daines, Recent developments in the synthesis and discovery of oligosaccharides and glycoconjugates for the treatment of disease, Curr. Med. Chem. 2003, 10, 2733-2773. 

Y. Cbun (2002). Design, synthesis, and discovery of novel frans-stilbene analogues as potent and selective human cytoehrome P450 IBl inhibitors. J. Med. Chem. 45, 160-164. 

Such small-molecule hgands, primarily natural products or synthetic variants of them or rationally designed molecules or randomly synthesized molecules, can either inactivate or activate protein function. Efficient methods of ligand synthesis and discovery are requhed to provide a smaU-molecule partner for every gene product or target. 

The methods of combinatorial chemistry which were developed to speed the synthesis and discovery of pharmaceutical active compoimds, have recently been adapted for catalyst development. Techniques are apphed that quickly generate a vast collection of compounds that might be catalyTically active, a so-called library of catalysts. 

Naya, A., Sagara, Y, Ohwaki, K., Saeki, T., Ichikawa, D. et al. (2001) Design, synthesis, and discovery of a novel CCRl antagonist. Journal of Medicinal Chemistry, 44, 1429-1435. 

The synthesis and discovery of new phosphate structures have accelerated greatly over the past two decades. It is now evident that phosphates will surpass silicates both in variety and in complexity, although their thermal stability is often less than that of the latter. 

Application of Mechanochemistry in the Synthesis and Discovery of New Pharmaceutical Forms Co-crystals, Salts and Coordination Compounds... 

Eicosapentaenoic acid derived isoprostanes Synthesis and discovery of two major isoprostanes... 

Design, synthesis and discovery of novel fluorescent HDAC inhibitors that challenge current HDAC mechanisms... 

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