Solution phase combinatorial

Also in this case, Curran and coworkers produced a library of 64 mappicine analogues by automated solution-phase combinatorial synthesis, as well as a 48-mem-ber library of mappicine ketone derivatives [88]. Furthermore, these authors were successful in building up a 115-member library of rac-homosilatecans 3-216 using different iodopyridones 3-214 and aryl isocyanides as substrates 3-215 (Scheme 3.56) [89]. 

Applications of the cross-metathesis reaction in more diverse areas of organic chemistry are beginning to appear in the literature. For example, the use of alkene metathesis in solution-phase combinatorial synthesis was recently reported by Boger and co-workers [45]. They assembled a chemical library of 600 compounds 27 (including cisttrans isomers) in which the final reaction was the metathesis of a mixture of 24 oo-alkene carboxamides 26 (prepared from six ami-nodiacetamides, with differing amide groups, each functionalised with four to-alkene carboxylic acids) (Eq.27). 

Since glycosylated derivatives of this porphyrin core have been shown to be effective photosensitisers, inducing necrosis and/or apoptosis in several cancer cell lines, Drain s group used TPPF20 as a core platform to efficiently generate a variety of solution-phase combinatorial libraries.83 This... 

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

Zhao, Y.-Z., van Breemen, R.B., Nikolic, D., Huang, C.-R., Woodbury, C.P., Schilling, A., Venton, D.L. Screening solution-phase combinatorial libraries using pulsed ultrafiltration/electrospray mass spectrometry. J. Med. Chem. 1997, 40, 4006-4012. 

Schilling A, Venton DL Screening solution-phase combinatorial libraries using pulsed ultrafiltration/ electrospray mass spectrometry. J Med Chem 1997, 40, 4006-4012. 

Goldberg, J. Jin, Q. Ambroise, Y. Satoh, S. Desharnais, J. Capps, K. Boger, D. T. Erythropoietin Mimetics Derived from Solution Phase Combinatorial Tibraries. J. Am. Chem. Soc. 2002, 124, 544-555. 

Parlow, J. J. Naing, W. South, M. S. Flynn, D. L. In Situ Chemical Tagging Tetrafluorophthalic Anhydride as a Sequestration Enabling Reagent (SER) in the Purification of Solution-Phase Combinatorial Libraries, Tetrahedron Lett. 1997, 38, 7959. 

Kulkarni, B. A. Ganesan, A. Solution-Phase Combinatorial Synthesis of 4-Hydroxyquinolin-2(l//)-ones, Chem. Commun. 1998, 785. 

Solution-phase combinatorial synthesis provides a homogeneous reaction medium and overcomes the drawbacks of a solid-phase strategy. An easy and reliable purification method is required in solution-phase combinatorial (parallel) synthesis to facihtate automation. The throughput in solution-phase automated synthesis is directly related to the facility of performing a purification process (work-up), compound separation, etc.15... 

This chapter will cover an overview of recent advances in solid-phase-assisted solution-phase combinatorial synthesis, specifically the use of scavenger resins in assisting in the isolation of pure product without the need for chromatography. In addition, an experimental section has been included. 

During the past few years, polymer-assisted solution-phase synthesis has become the prevalent method for the parallel synthesis of chemical libraries as confirmed by the increasing number of publications and reviews on the subject.16-29 A key step in the parallel solution-phase combinatorial... 

One of the most used resins in solid-phase combinatorial organic synthesis, which has found a myriad of applications, is the Merrifield resin (17).61 This resin is also the building block for a tremendous amount of novel resins being developed in combinatorial chemistry with applications in both solid-phase as well as solid-phase-assisted solution-phase combinatorial chemistry. A recent, useful, and novel example is the report of its being employed as a triphenylphosphine scavenging resin.76 During the conversion of azidomethylbenzene (51) into benzylamine, excess triphenyl-phosphine is allowed to react with Merrifield resin (17) in the presence of sodium iodide in acetone. A phosphonium-substituted resin (52) is thus formed. Upon simple filtration, pure benzylamine is isolated as shown in Fig. 22. 

The earliest report of a solution-phase combinatorial library of small drug-like molecules was by Smith et al. [2], The reaction of 40 individual acid chlorides with an equimolar mixture of 40 nucleophiles (alcohols or amines) and of the individual nucleophiles with an equimolar mixture of the acid chlorides produced a library of 1600 amides and esters as pools of 40 compounds. The orthogonal design strategy determined that each possible product should appear in a unique pair of samples to allow the rapid identification of lead compounds after screening. 

Song, G., Cai, Y., and Peng, Y. (2005) Amino-functionalized ionic liquid as a nucleophilic scavenger in solution phase combinatorial synthesis./. Comb. Chem., 7, 561-566. 

Solution Phase Combinatorial Libraries of Small Organic Molecules... 

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