Research route

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Process research route and sequence selection, analytical method development ON I VO 3 ... 

Figure 11.4 An outline of the initial research route for the synthesis of ICI 180080 and other analogues. The intermediates and products were produced as racemates. Geometric stereoisomers...

Those who choose the applied research route for a particular project or for themselves (e.g. by taking up employment in apphed research organizations or in the industry), have to remind themselves occasionally what their decision implies. Applied research aims at useful applications and probably patentable inventions rather than at discoveries and rapid publications. In contrast to flmdamental research which concentrates on a very specific topic, applied research embraces several disciplines and focusses them towards one conunon goal. Thus, efficient collaboration is essential. The success of the project is at stake, if an individual scientist prefers to work in isolation. 

Figure 19-16. Comparison of drug discovery and process research route of Ro 31-9790.

Developers may initially adopt the research synthesis to make clinical supplies and subsequently adapt it to become the manufacturing synthesis. Frequently they improve it dramatically but sometimes abandon it utterly. Certainly every aspect of the research route receives scrutiny before chemical developers discard the synthesis or implement it on a manufacturing scale. All this takes time, so that efforts to prepare clinical supplies overlap with trials of new or improved processes. Different groups of scientists, comprising chemists at all degree levels, may work simultaneously on the two different tasks. A chemical development project typically lasts for 1 to 3 years and ceases when a suitable production synthesis results. 

The research route of biomimetic materials is a process that derives from nature but beyond nature ultimately. Scientists first discover the special property of bio-system and give a scientific explanation of the mechanism behind the property. Based on the understanding, researchers mimic the chemical composition and microstructures of the bio-system to recur the desired bio-function. Then abundant artificial fabrication approaches can be used to create new materials that possess better performance or more functionalities than natural materials. McKinley and Cohen et al. synthesized a series of fiuorinated polyhedral oligomeric silsesquioxanes (fiuoroPOSS) that were of very low free energy (Fig. 18.10a). Because pure fiuoroPOSS was not spinnable, they blended the fiuoroPOSS with... 

Once complex le was selected for clinical development, a synthetic route amenable to scale up was required. The research route i ch, as already discussed, roughly follows that of complex la (see Figure 1) was critically analyzed. A not so appealing scenario appeared i) the overall yield was very low (i,e. 6% from L glutamic acid) ii) a large number of chemical steps (Le. 12) and several isolated intermediates (Le. 10), most of which were purified by silica gel chromatography, were involved. Although the latter issues are ordinary life in process research and development, the low overall yield deserves some further comments. 

The monoacid pentaester 6 is a versatile intermediate, nearly perfect for the synthesis of a series of compounds like tiiose above described. However, its synthesis (14) largely accounts for the low yield observed in the preparation of Ic. Furthermore, the conversion of methyl deoxycholate into the corresponding 3/ -NH2 derivative 14 (see Figure 5 Research route) involves the intermediate production of the SjS-Ns derivative 15. Although the latter proved a perfectly safe compound, we must underline that i) the reagent (Le. diphenylphosphoryl azide) which is used in the Mitsunobu reaction is extremely expensive ii) alternative approaches to generate the azide by phase tiansfer catalysed... 

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