Plate-to-plate Fluorous Solid-phase Extraction for Solution-phase Parallel Synthesis

Overview

Journal J Comb Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2005 Nov 15

PMID 16283798

Citations 11

Authors

Wei Zhang

Yimin Lu

Tadamichi Nagashima

Affiliations

Soon will be listed here.

Abstract

A commercially available Argonaut VacMaster-96 plate-to-plate solid-phase extraction (SPE) station equipped with 24 FluoroFlash cartridges is employed for parallel purification of fluorous reaction mixtures. Each cartridge charged with 3 g of fluorous silica gel has the capability to produce up to 100 mg of purified small molecules. The 24-well receiving plate has a standard footprint that can be directly concentrated in a Genevac vacuum centrifuge. Important issues such as sample loading, product cross-contamination, cartridge reuse, and reproducibility are investigated. The SPE system has been demonstrated in the purification of three small libraries that were produced involving amine scavenging reactions with fluorous isatoic anhydride, amide coupling reactions with 2-chloro-4,6-bis[(perfluorohexyl)propyloxy]-1,3,5-triazine (fluorous CDMT), and amide coupling reactions with a newly developed fluorous Mukaiyama condensation reagent.

Citing Articles

Synthesis and Solid State Structure of Fluorous Probe Molecules for Fluorous Separation Applications.

Lehmler H, Telu S, Vyas S, Shaikh N, Rankin S, Knutson B Tetrahedron. 2010; 66(14):2561-2569.

PMID: 20305832 PMC: 2840617. DOI: 10.1016/j.tet.2010.02.018.

The azido acid approach to beta-peptides: parallel synthesis of a tri-beta-peptide library by fluorous tagging.

Wang X, Nelson S, Curran D Tetrahedron. 2009; 63(27):6141-6145.

PMID: 19562094 PMC: 2701693. DOI: 10.1016/j.tet.2007.03.034.

Synthetic applications of fluorous solid-phase extraction (F-SPE).

Zhang W, Curran D Tetrahedron. 2008; 62(51):11837-11865.

PMID: 18509513 PMC: 2396515. DOI: 10.1016/j.tet.2006.08.051.

A fluorous-tagged linker from which small molecules are released by ring-closing metathesis.

Leach S, Cordier C, Morton D, McKiernan G, Warriner S, Nelson A J Org Chem. 2008; 73(7):2753-9.

PMID: 18327951 PMC: 2330080. DOI: 10.1021/jo7026273.

Fluorous 2,4-Dichloro-1,3,5-triazines (F-DCTs) as Nucleophile Scavengers.

Lu Y, Zhang W QSAR Comb Sci. 2007; 25(8-9):728-731.

PMID: 18064294 PMC: 2117359. DOI: 10.1002/qsar.200640042.

References

Werner S, Curran D . Fluorous dienophiles are powerful diene scavengers in Diels-Alder reactions. Org Lett. 2003; 5(18):3293-6. DOI: 10.1021/ol035214a. View

Luo Z, Williams J, Read R, Curran D . Fluorous Boc ((F)Boc) carbamates: new amine protecting groups for use in fluorous synthesis. J Org Chem. 2001; 66(12):4261-6. DOI: 10.1021/jo010111w. View

Matsugi M, Curran D . Synthesis, reaction, and recycle of light fluorous Grubbs-Hoveyda catalysts for alkene metathesis. J Org Chem. 2005; 70(5):1636-42. DOI: 10.1021/jo048001n. View

Brittain S, Ficarro S, Brock A, Peters E . Enrichment and analysis of peptide subsets using fluorous affinity tags and mass spectrometry. Nat Biotechnol. 2005; 23(4):463-8. DOI: 10.1038/nbt1076. View

Zhang W . Fluorous tagging strategy for solution-phase synthesis of small molecules, peptides and oligosaccharides. Curr Opin Drug Discov Devel. 2004; 7(6):784-97. PMC: 1444942. View

McAllister L, McCormick R, Brand S, Procter D . A fluorous-phase pummerer cyclative-capture strategy for the synthesis of nitrogen heterocycles. Angew Chem Int Ed Engl. 2004; 44(3):452-5. DOI: 10.1002/anie.200461930. View

Luo Z, Zhang Q, Oderaotoshi Y, Curran D . Fluorous mixture synthesis: a fluorous-tagging strategy for the synthesis and separation of mixtures of organic compounds. Science. 2001; 291(5509):1766-9. DOI: 10.1126/science.1057567. View

Zhang W, Chen C, Lu Y, Nagashima T . A highly efficient microwave-assisted suzuki coupling reaction of aryl perfluorooctylsulfonates with boronic acids. Org Lett. 2004; 6(9):1473-6. PMC: 1618883. DOI: 10.1021/ol0496428. View

Curran D, Amatore M, Guthrie D, Campbell M, Go E, Luo Z . Synthesis and reactions of fluorous carbobenzyloxy (FCbz) derivatives of alpha-amino acids. J Org Chem. 2003; 68(12):4643-7. DOI: 10.1021/jo0344283. View

10.

Nagashima T, Zhang W . Solution-phase parallel synthesis of an N-alkylated dihydropteridinone library from fluorous amino acids. J Comb Chem. 2004; 6(6):942-9. DOI: 10.1021/cc049885r. View

11.

Villard A, Warrington B, Ladlow M . A fluorous-tagged, acid-labile protecting group for the synthesis of carboxamides and sulfonamides. J Comb Chem. 2004; 6(4):611-22. DOI: 10.1021/cc0499338. View

12.

Zhang W . Fluorous synthesis of disubstituted pyrimidines. Org Lett. 2003; 5(7):1011-3. PMC: 1857353. DOI: 10.1021/ol027469e. View

13.

Chen C, Zhang W . FluoMar, a fluorous version of the Marshall resin for solution-phase library synthesis. Org Lett. 2003; 5(7):1015-7. PMC: 1894904. DOI: 10.1021/ol0274864. View

14.

Zhang W, Lu Y . Fluorous synthesis of hydantoins and thiohydantoins. Org Lett. 2003; 5(14):2555-8. PMC: 1894909. DOI: 10.1021/ol034854a. View

15.

Zhang W . Fluorous synthesis of heterocyclic systems. Chem Rev. 2004; 104(5):2531-56. PMC: 1618880. DOI: 10.1021/cr030600r. View

16.

Zhang W, Luo Z, Chen C, Curran D . Solution-phase preparation of a 560-compound library of individual pure mappicine analogues by fluorous mixture synthesis. J Am Chem Soc. 2002; 124(35):10443-50. DOI: 10.1021/ja026947d. View

17.

Tzschucke C, Markert C, Bannwarth W, Roller S, Hebel A, Haag R . Modern separation techniques for the efficient workup in organic synthesis. Angew Chem Int Ed Engl. 2002; 41(21):3964-4000. DOI: 10.1002/1521-3773(20021104)41:21<3964::AID-ANIE3964>3.0.CO;2-3. View