Combinatorial chemistry discussion

There are distinct advantages of these solvent-free procedures in instances where catalytic amounts of reagents or supported agents are used since they provide reduction or elimination of solvents, thus preventing pollution at source . Although not delineated completely, the reaction rate enhancements achieved in these methods may be ascribable to nonthermal effects. The rationalization of microwave effects and mechanistic considerations are discussed in detail elsewhere in this book [25, 193]. A dramatic increase in the number of publications [23c], patents [194—203], a growing interest from pharmaceutical industry, with special emphasis on combinatorial chemistry, and development of newer microwave systems bodes well for micro-wave-enhanced chemical syntheses. 

This chapter will cover the efforts that have been made to use the principles of combinatorial chemistry in the development of new catalysts. In the last few years there has been a lively discussion of what is the correct definition of combinatorial chemistry. Some workers reserve the term combinatorial chemistry for the synthesis and evaluation of mixtures. For the purpose of this chapter, we will employ a liberal interpretation of the term. Since one of the definitions of the word combinatorial is, of or involving combinations (14), we will use the term to include what may be referred to as parallel synthesis. In parallel synthesis, one generates a combination of molecules, be they in separate vials or on separate pins. One view may be that a collection of vessels represents a combination of molecules. It is for this... 

It is important to point out that there is often considerable discussion about the merits of rational approaches where systems are designed, synthesized, and then studied relative to what is sometimes described as the random approach taken with combinatorial chemistry. It is important to view parallel approaches not as a replacement for rational science but as a tool that allows for faster data collection. This data can then be used for the design of better catalysts. 

The great advantage of this approach to synthesis is, of course, speed. Making the 200 compounds in the library just discussed by traditional methods would take a very long time, considerable money, and much labor. In fact, costs and time constraints would probably make the process prohibitive by traditional techniques. In combinatorial chemistry, however, the 200 compounds in the library can be made all at once with relatively little cost and expenditure of time and money. The only problem (and a significant problem it is ) is to find out which of the 200 compounds (if any) meet some predetermined criterion, such as biological potency. 

In this chapter, the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions are reviewed and the scope and mechanisms of these reactions are discussed. It is clear that these carbonylation reactions play important roles in synthetic organic chemistry as well as organometallic chemistry. Some of the reactions have already been used in industrial processes and many others have high potential to become commercial processes in the future. The use of microwave irradiation and substitutes of carbon monoxide has made carbonylation processes suitable for combinatorial chemistry and laboratory syntheses without using carbon monoxide gas. The use of non-conventional reaction media such as SCCO2 and ionic liquids makes product separation and catalyst recovery/reuse easier. Thus, these processes can be operated in an environmentally friendly manner. Judging from the innovative developments in various carbonylations in the last decade, it is easy to anticipate that newer and creative advances will be made in the next decade in carbonylation reactions and processes. 

Although the earlier discussion explains why in recent years the pharma industry have moved away from NP screening, that does not mean that NPs do not hold great promise as pharmaceutical agents in future. Indeed, the opposite is true. There is a growing acceptance that, as the industry enters the twenty-first century, the expectations of the HTS and combinatorial chemistry era have not been fulfilled. Indeed, the screening... 

For a more in depth discussion, see Hoveyda AH (2002) Diversity-based identification of efficient homochiral organometallic catalysts for enantioselective synthesis. In Nicolaou KC, Hanko R, Hartwig W (eds) Handbook of combinatorial chemistry. Wiley-VCH, New York, Chap 33, p 991... 

This chapter is intended to provide an overview of the field of mixture-based combinatorial chemistry. It deals with reports of library preparation and utilization for the period from the beginning of 1995 to mid-1996. As this is the first Report in this planned series, some discussion of pre-1995 work will be included to set the proper context for the more recent work. The discussion will cover the methods of preparation of mixture-based libraries, the means of identifying actives from the mixtures, and the rationale for using mixtures. 

Here, we would like to briefly discuss basic peculiarities of the solid matrices, the various categories of linkers and some reaction types of established significance for combinatorial chemistry. For more comprehensive compilations of solid-phase reactions, the reader is referred to specific reviews [1-5] and commercial electronic databases (e.g. SPORE [6] or SPS [7]). 

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