Chemical library purification strategies based on principles of complementary molecular reactivity and molecular recognition

Journal of the American Chemical Society

Volumn 119, Issue 21, 1997, Pages 4874-4881

  Flynn, Daniel L ^a   Crich, Joyce Z ^a   Devraj, Rajesh V ^a   Hockerman, Susan L ^a   Parlow, John J ^a   South, Michael S ^a   Woodard, Scott ^b  

^a PFIZER INC   (United States)

^b Ceregen   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RESIN;

ACYLATION; ARTICLE; AUTOMATION; METHODOLOGY; MOLECULAR RECOGNITION; OXIDATION; PURIFICATION; REACTION ANALYSIS; SYNTHESIS;

EID: 0030952762     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja963462e     Document Type: Article

References (28)

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21. After this manuscript was submitted, a report was published which disclosed the use of scavenging resins to remove excess amines or electrophiles from parallel solution-phase reactions: Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron. Lett. 1996, 37, 7193-7196.
22. The simultaneous use of multiple polymers in organic synthesis has been reported. In fact, multiple polymers containing mutually-incompatible functionality have been shown to be effective because of their spatial separation from each other. See: (a) Cohen, B. J.; Kraus, M. A, Patchornik, A. J. Am. Chem. Soc. 1981, 103, 7620-7629. (b) Parlow, J. J. Tetrahedron. Lett. 1995, 36, 1395-1396.
23. The simultaneous use of multiple polymers in organic synthesis has been reported. In fact, multiple polymers containing mutually-incompatible functionality have been shown to be effective because of their spatial separation from each other. See: (a) Cohen, B. J.; Kraus, M. A, Patchornik, A. J. Am. Chem. Soc. 1981, 103, 7620-7629. (b) Parlow, J. J. Tetrahedron. Lett. 1995, 36, 1395-1396.
24. The alternative sequestration strategy where product is trapped by polymer away from solution-phase reagents has recently been described: Keating, T. A.; Armstrong, R. W. J. Am. Chem. Soc. 1996, 118, 2574-2583.
25. While the present sequestration purification strategy for solution-phase chemical libraries does rely on CMR/R resins to remove reactants and reagents, there is not the same concern about resin-loading capacity as in the substrate-linked solid-phase synthesis method. High-density functionalized resins can be used for CMR/R purification as there is not the concern about site-isolation that plagues substrate-linked solid-phase synthesis.
26. The terms reactant and reagent have explicit meanings in the context of this strategy. A reactant is a starting material which becomes chemically incorporated into the product. A reagent is a chemical which mediates a transformation but does not become incorporated into the product.
27. In contrast to substrate-linked solid-phase synthesis where every permutation of substrate diversity ultimately is attached to the polymer support, the present purification strategy requires the attachment of only a single representative functionality that finds general utility for all reactions being sequestered for that particular reaction type.
28. Alternative use of polystyrene sulfonate sodium salt to directly sequester the EDC amine hydrochloride and byproduct urea hydrochloride gave inferior results.