Parallel synthesis approach

Solid-phase, parallel-synthesis approaches to the imidazole derivatives 49 <96TL937>, 50 and 51 <96TL835>, 52 <96TL751>, and 53 <96TL4865> were also reported in 1996. 

Recently, Yoshida and coworkers demonstrated that the cation pool method can be used to make available Ai-acyliminium ion intermediates for parallel synthesis approaches to molecular libraries [106]. In this work, the cation pool was split into separate flasks following the electrolysis reaction. Different nucleophiles were then added to each flask in order to form a series of products (Scheme 49). 

Baldwin, J.E. Fryer, A.M. Pritchard, G.J. (2000) Novel C-4 heteroaromatic kainoid analogues a parallel synthesis approach. Bioorg. Med. Chem. Lett., 10, 309-11. 

Traditionally, sohd-phase synthesis of peptides is carried out on polymeric supports comprised of small beads of a polymer. In parallel synthesis approaches that are not spatially addressable, there is a need for the easy manipulation of aU members of the array during the course of the synthesis. This is often easier when each member of the array is synthesized on a single macroscopic piece of solid support, or on a small batch of resin enclosed in an appropriate shell. Such macroscopic supports are also easy to label. 

Iterations where more than one position per round was fixed were also examined using 1-, 3- and 9-fixed positions per round (that is, from usual iterative deconvolution to a parallel synthesis approach for 262,144 compounds). Results with three fixed positions per round were identical for the 9-mer compared to one fixed position, and slightly, but not significantly, better for the 6-mer target. Parallel synthesis performed better (80% of simulations gave a best binder for the 9-mer compared with 55% for one and three fixed positions per round), but introduction of the twofold experimental error caused significant deviations from the best binders also for parallel synthesis (10% selection of one of the 16 best binders for the 6-mer, compared with 1% with one or three fixed positions per round). 

This part of our work shows that the construction of SFDs can yield valuable information about the phase formation in the synthesis of mesostructured materials and about the underlying mechanisms. However, constructing the SFDs presented here was a tedious and time-consuming task. Therefore, we have developed a parallel synthesis approach, using an autoclave block which allows the simultaneous preparation of 24 samples under hydrothermal conditions and has considerably shortened the time needed to construct an SFD. ... 

Liu Y, Ali SM, Boge TC, Zygmunt J, Georg GI, Himes RH (2000) A Systematic Study of the Effects of O-10-Substitution on Paclitaxel Bioactivity A Parallel Synthesis Approach. 219th ACS National Meeting, March 26-30. San Francisco, CA, Abstr. MEDI 72... 

The use of parallel synthesis approaches (arrays or focussed libraries) in the lead identification field is widespread with many examples published in the chemistry literature and presented at conferences. 

As shown by these exan les, the use of small focused mixture libraries was found to be a highly effective parallel synthesis approach by providing new, potent enzyme inhibitors while eliminating over 73% of the synthesis and testing effort that would have been required if each confound was prepared and tested individually. 

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