Convergent combinatorial synthesis

Scheme 3.9. Example of a convergent combinatorial synthesis in solution.

Boger, D.L., Jiang, W., and Goldberg, J. Convergent solution-phase combinatorial synthesis with multiplication... 

Boger, D. L. Chai, W. Jin, Q. Multistep Convergent Solution-Phase Combinatorial Synthesis and Deletion Synthesis Deconvolution, J. Am. Chem. Soc. 1998, 120, 7220. 

An asymmetric C-C coupling, one of the most important and challenging problems in synthetic organic chemistry, seems to be most appropriate for the creation of a complete set of diastereomers because of the applicability of a convergent, combinatorial strategy [38-40]. In Nature, such reactions are facilitated by lyases which catalyze the (usually reversible) addition of carbo-nucleophiles to C=0 double bonds, in a manner mechanistically most often categorized as aldol and Claisen additions or acyloin reactions [41], The most frequent reaction type is the aldol reaction, and some 30 lyases of the aldol type ( aldolases ) have been identified so far [42], of which the majority are involved in carbohydrate, amino acid, or hydroxy acid metabolism. This review will focus on the current state of development of this type of enzyme and will outline the scope and limitations for their preparative application in asymmetric synthesis. 

Boger DL, Chai W, Qing J, Multistep convergent solution-phase combinatorial synthesis and deletion synthesis deconvolution, J. Am. Chem. Soc., 120 7220-7225, 1998. 

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]. 

Both chemistry and biology have converged on a common 96-well format as a convenient means of combinatorial synthesis, purification, compound storage, and drug screening. The development of assay plates with the same footprint but increasingly high density arrays (e.g., 384, 864, and 1536) has... 

It has been pointed out previously that solution-phase combinatorial synthesis is open to convergent strategies. A corresponding example is shown in Scheme 3.9 [24],... 

Linear strategies in combinatorial synthesis have been extensively summarised and since the present work focuses more on convergent strategies for the synthesis of small molecules we will try in this chapter to summarise only the most important aspects of this very broad field. 

Scheme 1 Retro-synthetic analysis for the convergent and combinatorial synthesis of anthracyclinones and analoguous linearly condensed polycyclic compounds...

Just as in one at a time synthesis, linear syntheses are the most risky and produce the lowest yields. Converging methodologies address these limitations successfully, and in combinatorial work, Ugi (four-component) and Passerini (three-component) reactions are very flexible and popular. Generally one has less control over the specific products being produced by such reactions but this is largely compensated for by the molecular diversity available in this way. 

Gibson,M. I.,Damal>t,etal. Sequentially Modified, Polymer-Stabilized Gold Nanoparticle Libraries Convergent Synthesis andAggregation Behavior. ACS Combinatorial Sci-ence,13(3), 286-297 (2011). 

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