Multiple parallel synthesis

Mitscher, L.A. and Dutta, A., Combinatorial chemistry and multiple parallel synthesis, in Burger s Medicinal Chemistry and Drug Discovery, Abraham, D.J., Ed., 6th ed., Vol. 2, Drug Development, Wiley, New York, 2003. 

Requirements of Multiple Parallel Synthesis or Combinatorial Chemistry... 

While NMR spectra possess a high information content, this confers a level of complexity that can be obstructive if a quick and simple answer is required. The use of NMR flow probes has reduced the time taken to acquire a spectrum to 2-3 min and flow NMR has consequently found considerable application in robot synthesis, multiple parallel synthesis (MPS) or combinatorial chemistry. Since H possesses 5600 times the receptivity of it is inevitable that it will continue to be the nucleus of choice in this area, complicating the analysis. Unless automatic analysis is able to transcend the aid to interpretation role and into the confirm or refute the structure role, the higher information content of the NMR spectrum constitutes a threat rather than an opportunity. 

REQUIREMENTS OF MULTIPLE PARALLEL SYNTHESIS OR COMBINATORIAL CHEMISTRY... 

Multiple Parallel Synthesis (MPS) is typically carried out in a plate containing a matrix of 8 x 12 wells. It is typical for each well to contain a different combination of reactants (say an acid and an amine). Since the number of outcomes is then restricted (to say 96 amides) it could reasonably be argued that a full analysis of individual spectra need not take place in order to validate the plate for further work. Indeed, it may well be that the plate is destined for high throughput (biological activity) screening, and only hits from that process would then warrant a more rigorous approach. 

Natural products as leads for new pharmaceuticals, 847-900 chapter by Mitscher, LA. Dutta, A. Combinational chemistry and multiple parallel synthesis. Volume 2, 1-36. 

Although it uses an all-liquid environment, like traditional procedures, the methods of solution-phase synthesis (also called parallel synthesis or multiple parallel synthesis ) are distinct. The difference is illustrated below. 

Mitscher, Lester A., and Apurba Dutta. Combinatorial Chemistry and Multiple Parallel Synthesis, John Wiley fit Sons, Inc. Available online. URL http //media.wiley.eom/product data/excerpt/82/04713702/ 0471370282.pdf. Originally published in Burger s Medicinal Chemistry and Drug Discovery, edited by Donald J. Abraham. Vol. 2, Drug Discovery and Development. Hoboken, N.J. Wiley, 2003. 

Mimotopes has been involved in the development, use, and commercialization of radiation-grafted polymer surfaces for multiple parallel synthesis since the late 1980s.10-12 Although other workers have reported the use of radiation-graft polymers in solid-phase synthesis,13,14 as far as we are aware, the graft polymer devices manufactured and sold by Mimotopes (SynPhase Crowns, SynPhase Lanterns) are the only current commercial products of this type. These products are presented in Fig. 1. The SynPhase Lanterns are the current design for small molecule synthesis. The initial... 

The introduction of a new pharmaceutical is a lengthy and expensive undertaking. Methods which promise to shorten the time or the cost are eagerly taken up, and this is clearly the case with combinatorial chemistry and multiple parallel synthesis. 

Figure 1.2. A multiple parallel synthesis library constructed from six participants.

As noted above, the field of combinatorial chemistry and multiple parallel synthesis started with libraries of peptides. In time, unusual residues crept into the products. While this evolutionis still ongoing, it is now accompanied by a major effort to produce libraries of small, drug-like molecules in library form. Many of the methods used for large molecules carry over but the largely non-iterative nature of small molecule synthesis is a significant complication. 

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