Parallel synthesis, and combinatorial

This issue highlights the characterization difference between parallel synthesis and combinatorial synthesis. Parallel synthesis is automated traditional organic chemistry. Each compound is made in a separate reactor, purified and characterized. There is no excuse for not fully characterizing compounds made by parallel synthesis. Jonathan Ellman s laboratory at UC Berkeley has been a pioneering academic center for solid-phase chemistry development. His philosophy is to synthesize libraries of discrete compounds in a spatially separate fashion, rather than libraries of compound mixtures, to allow for rigorous analytical characterization [48,49],... 

Advances in parallel synthesis and combinatorial chemistry have given pharmaceutical companies the ability to generate an unprecedented number of compounds. In lead compound optimization efforts. 

In conclusion, the advantages of microfluidic devices, parallel synthesis, and combinatorial approaches can be merged to integrate a fluorescent chemical sensor array in a microfluidic chip. Fluorescent microchannel array can be produced by parallel synthesis of fluorescent monolayers covalent attached to the walls of glass microchannels. 

Traditional medicinal chemistry laboratories are beginning to practice parallel synthesis and combinatorial chemistry more often. The development of manual and semiautomated devices, which improve the productivity of the synthesis process, is a reflection of this recent trend. Fully automated systems are expensive, and it is also not always easy to find adequate space in the laboratory to locate such systems. The synthesizers may have counterintuitive software and require a lot of maintenance therefore, it is often necessary to have dedicated users to operate them. Ad hoc usage by everyone in need is difficult due to the complexity of the software and scheduling issues, but the market is beginning to respond by offering smaller, substantially less expensive devices that are easy to use without learning complex software. 

Solid-phase reactions play an important role in parallel synthesis and combinatorial chemistry, particularly in the area of medicinal chemistry, where their potential has emerged as a result of the possibility of automation. Considerable attention has been focused on adapting and exploiting the advantages of solid-phase synthesis (SPS) to produce libraries of such organic compounds. In this context, transition metal-pro-... 

Parallel synthesis and combinatorial chemistry are two closely related concepts, result of intentions to automatically perform more synthetic reactions. Parallel synthesis enables preparation of a set of defined compounds in a number of physically separated reaction vessels or micro-departments. Combinatorial chemistry instead uses a combinatorial process for preparation of a large number of compounds from a defined set of building blocks. Combinatorial chemical synthesis generates a large number of compounds, so-called libraries, at the same time and in predictable mode. 

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. 

Parallel processing of synthetic operations has been one of the cornerstones in combinatorial chemistry for years [1-6]. In the parallel synthesis of combinatorial libraries, compounds are synthesized using ordered arrays of spatially separated reaction vessels adhering to the traditional one vessel-one compound philosophy. The defined location of the compound in the array provides the structure of the compound. A commonly used format for parallel synthesis is the 96-well microtiter plate, and today combinatorial libraries comprising hundreds to thousands of compounds can be synthesized by parallel synthesis, often in an automated fashion [6]. 

As demonstrated in the previous sections of this review, microwave-assisted reactions allow rapid product generation in high yield under uniform conditions. Therefore, they should be ideally suited for parallel synthesis and/or combinatorial chemistry applications. The first example of parallel reactions performed under micro-wave irradiation conditions involved the nucleophilic substitution of an alkyl iodide with 60 diverse piperidine or piperazine derivatives (Scheme 12.22) [71]. Reactions were performed in a multimode microwave reactor in individual sealed polypropy-... 

There are two basic combinatorial chemistry techniques (1) parallel synthesis and (2) split and mix methods. They are illustrated next. 

Gooding, O. W. (2004), Process optimization using combinatorial design principles Parallel synthesis and design of experiment methods, Curr. Opin. Chem. Biol., 8, 297-304. 

The radical cascade synthesis was applied to the preparation of drugs such as irinotecan [62], and drug candidates such as lurtotecan [66], silatecan DB-67 [67] and homosilatecans [68]. Moreover, a convergent synthesis could be applied to a combinatorial synthesis, in which over one hundred homosilatecans were prepared by parallel synthesis and automated purification [69]. 

Parallel synthesis of combinatorial libraries is a synthetic sequence where the assembly of library is performed using an ordered array of spatially separated reaction vessels under the same reaction conditions. In sequential synthesis, the general reaction conditions can be modified for each building block combination according to the reactivity of the reagents in each reaction vessel. Parallel synthesis can be carried out with both conventional and MAOS and either in solid-phase or solntion-phase synthesis. 

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... 

TOOLS Program for combinatorial chemistry and parallel synthesis and custom chemical synthesis and manufacturing. 

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