Parallel monomer-combination method

Fig. 3.4 The parallel monomer-combination method according to Fr chet et al. leads to 2C dendrons (G = number of generations simplified illustration)...

Freeman AW, Christoffels LAJ, Frechet JMJ, A simple method for controlling dendritic architecture and diversity A parallel monomer combination approach, J. Org. Chem., 65 7612-7617, 2000. 

Another troublesome aspect of the reactivity ratios is the fact that they must be determined and reported as a pair. It would clearly simplify things if it were possible to specify one or two general parameters for each monomer which would correctly represent its contribution to all reactivity ratios. Combined with the analogous parameters for its comonomer, the values rj and t2 could then be evaluated. This situation parallels the standard potential of electrochemical cells which we are able to describe as the sum of potential contributions from each of the electrodes that comprise the cell. With x possible electrodes, there are x(x - l)/2 possible electrode combinations. If x = 50, there are 1225 possible cells, but these can be described by only 50 electrode potentials. A dramatic data reduction is accomplished by this device. Precisely the same proliferation of combinations exists for monomer combinations. It would simplify things if a method were available for data reduction such as that used in electrochemistry. 

The split-and-mix strategy appears deceptively similar to parallel synthesis, but can produce libraries of several hundred thousand compounds in one mn. Although it can use the same style of apparatus as for parallel synthesis, there would normally be as many synthesis channels as one has monomers - 20 in the case of natural amino acids (although cysteine is often omitted). However, after the first coupling cycle has been completed, the batches of synthesis beads from each channel would all be combined, mixed well, and re-divided back into the 20 synthesis channels - the step from which the method takes its name. After this, another round of chain extension would commence. In this way all possible sequences are prepared at the same time, but each bead of solid support only contains one sequence. As the number of compounds rises exponentially with each chain extension cycle (hence it is combinatorial), large numbers of monomers limit the number of cycles that can be performed - usually to four rounds (i.e. a tetrapeptide library) with 20 different monomers, = 20" =160 000 compounds. This is because the number of possible sequences should be significantly less than the number of synthesis beads that can be contained in a reasonable volume. 

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