Combinatorial chemistry, small parallel synthesis

Combinatorial chemistry and parallel synthesis are now the dominant methods of compound synthesis at the lead discovery stage [2]. The method of chemistry synthesis is important because it dictates compound physical form and therefore compound aqueous solubility. As the volume of chemistry synthetic output increases due to combinatorial chemistry and parallel synthesis, there is an increasing probability that resultant chemistry physical form will be amorphous or a neat material of indeterminate solid appearance. There are two major styles of combinatorial chemistry - solid-phase and solution-phase synthesis. There is some uncertainty as to the true relative contribution of each method to chemistry output in the pharmaceutical/biotechnology industry. Published reviews of combinatorial library synthesis suggest that solid-phase synthesis is currently the dominant style contributing to about 80% of combinatorial libraries [3]. In solid-phase synthesis the mode of synthesis dictates that relatively small quantitities of compounds are made. 

Emergence of combinatorial chemistry and parallel synthesis in early nineties and synthesis of small molecules inspired by the structural architectures of natural products in the beginning of this century called for further developments in the solid-phase synthesis protocols. Synthesis of compound libraries possessing enantiopure molecules embodying a complex framework and decorated with more than one stereocenters in a combinatorial and parallel fashion calls for highly feasible solid-phase synthesis methods." In particular, these efforts must address the stereocontrol of the reaction course in order to minimize isomer... 

There are two main approaches to combinatorial chemistry-—pcra/te/ synthesis and split synthesis. In parallel synthesis, each compound is prepared independently. Typically, a reactant is first linked to the surface of polymer beads, which are then placed into small wells on a 96-well glass plate. Programmable robotic instruments add different sequences of building blocks to the different wells, thereby making 96 different products. When the reaction sequences are complete, the polymer beads are washed and their products are released. 

MATHEY Phosphorus-Carbon Heterocyclic Chemistry The Rise of a New Domain McKILLOP Advanced Problems in Organic Reaction Mechanisms OBRECHT Solid Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries... 

Combinatorial chemistry is the production of libraries of compounds that represent permutations of a set of chemical variables. These variables include the nature of the substituent in a particular molecule, both in type and size, changes in the components in a mixture of materials, e.g. in ceramics and changes in process parameters, e.g. temperature, pH etc. Chemical libraries are usually created by one of two methods split and mix or parallel synthesis . Split and mix synthesis is used to produce small quantities of a relatively large number of compounds and requires assays to be performed on pools of compounds. Parallel synthesis is used to produce libraries... 

The tremendous development of combinatorial chemistry during the last few years has contributed to increasing steadily the options for a chemist to synthesize a chemical library, and many excellent reviews have dealt extensively with different aspects of this exciting new discipline. Solid-phase [1] or solution-phase [2] libraries, parallel synthesis [3] or mixtures of compounds [4] and large or small libraries, are only a few of the alternatives, and each one of... 

These libraries contain a relatively small number of individuals (typically tens to hundreds) and are almost always prepared as discrete libraries using parallel synthesis and automated or semiautomated devices. Focused libraries are predominantly prepared in solution because of the easier shift from classical organic synthesis to solution-phase combinatorial chemistry, while automated purification procedures for relatively small arrays of discrete compounds in solution are common nowadays. The... 

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