Combinatorial chemistry parallel synthesis

To increase productivity, a registration system should be able to register a compound library as a single transaction. Usually a compound library consists of a group of compounds that are synthesized using parallel synthesis, combinatorial chemistry, or compounds that are acquired from commercial or academic sources. From the compound registration perspective, a library can also be a group of compounds that share some common attributes such as a research project they are synthesized for, the chemist who synthesized them, the creation date, and the notebook information. 

Chemical libraries are libraries of chemical entities to be tested for any biological effect by the customer (i.e., the Pharma company). The libraries comprise molecules from all sources, including modem combinatorial- and parallel synthesis-type chemistries. 

The major impetus for the development of solid phase synthesis centers around applications in combinatorial chemistry. The notion that new drug leads and catalysts can be discovered in a high tiuoughput fashion has been demonstrated many times over as is evidenced from the number of publications that have arisen (see references at the end of this chapter). A number of )proaches to combinatorial chemistry exist. These include the split-mix method, serial techniques and parallel methods to generate libraries of compounds. The advances in combinatorial chemistry are also accompani by sophisticated methods in deconvolution and identification of compounds from libraries. In a number of cases, innovative hardware and software has been developed tor these purposes. 

CHIRSOURCE aims to explore the use of chiral chromatography for combinatorial chemistry approaches. Combinatorial chemistry, as well as parallel synthesis. 

Two main approaches to combinatorial chemistry are used—parallel 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 tfie different wells, thereby making 96 different products. When the reaction sequences are complete, the polymer beads are washed and their products are released. 

These conceptual goals are attained by several combinatorial methods and tools. Characteristic for combinatorial chemistry is the synthesis on solid support or by polymer-supported synthesis, allowing for much higher efficiency in library production. Synthesis can be conducted either in automated parallel synthesis or by split-and-recombine synthesis. Centerpieces of combinatorial methods further include specific analytical methods for combinatorial... 

Combinatorial Chemistry. Figure 2 Chemical libraries are prepared either by parallel synthesis or by the split-and-recombine method. In the latter case, coupling m building blocks in m separated reaction flasks through n synthetic cycles on a beaded polymer carrier generates a combinatorial library with nf individual compounds and one compound per bead. 

Miniaturization and parallelization key approaches for drug development apparatus for combinatorial chemistry UHTS 1536 titer-plate format modular construction of apparatus applications of UHTS fine-chemical synthesis by micro reactors numbering-up nature as model general advantages of micro flow vision of plants-on-a-desk [233]. 

OS 10] [R 10] [P 9] The feasibility of 2 x 2 parallel synthesis using two amines and two acid chlorides for a phase-transfer reaction was demonstrated [23]. This paves the way fornx m parallel reaction combinations as a new micro flow approach for combinatorial chemistry. 

Tietze and coworkers developed two new domino approaches in the field of combinatorial chemistry, which are of interest for the synthesis of bioactive compounds. Combinatorial chemistry can be performed either on solid phase or in solution using parallel synthesis. The former approach has the advantage that purification of the products is simple and an excess of reagents can be used. This is not possible for reactions in solution, but on the other hand all known transformations can be used. The Tietze group has now developed a protocol which combines the... 

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. 

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... 

Parallel to these developments in combinatorial chemistry, microwave-enhanced organic synthesis has attracted a substantial amount of attention in recent years. As evidenced from the other chapters in this book and the large number of review articles available on this subject [7-14], high-speed microwave-assisted synthesis has... 

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