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Download Anchors and Linkers for Solid
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Anchors and Linkers for Solid-Phase Synthesis General, Examples for Functional Groups Carolin Pauker Definitions Spacer Located between resin carrier and linker Reduces steric hinderance Modifies for example hydrophilicity and hydrophobicity Remains after cleavage at the resin carrier Linker Bifunctional molecule one hand binds irreverible to resin, other hand binds reversible to desired molecule Remains after cleavage at the resin Anchor Resin-immobilized functional group forming a cleavable coupling Linker becomes anchor after immobilizing Direct syntheses on resin Conditions for Linkers Remaining stable during removal of Nterminal-protecting group and the whole syntheses Removable under mild conditions without damaging the final product Resin with different anchor structures requires orthogonal cleavage conditions > multiple products Difficulties Very large number (over 400 linkers) Many trival names (IUPAC nomenclature is complicated and inconvenient) Difficult to find appropriate anchor for specific reaction conditions Very large number of different applications Cleavage Methods Acid Base or nucleophilic Hydrogenolysis Enzymatic Palladium catalysed Photochemical Oxidative or reductive Depending on desired functional group in the product Acid-labile Anchors Mostly involved in peptide and combinatorial chemistry Cleavage reagents: HF, HBr, TFA and others High number of products possible Electropositive substituents (methoxy, amino or hydroxy groups) raise the stability formed cations > usage of weaker acid Examples for Acid Labile Anchors Anchors Cleaved by Nucleophiles Based on β-elimination, hydrolysis, re-esterfication or aminolysis Cleavage reagents NaOH Amine/NH3 Hydrazine Alcohol Product Carboxylic Acid Carboxamine Hydrazide Carboxylic acid ester Examples for Linkers Cleaved by Base or Nucleophiles Reduktive Cleavage Orthogonal to many other methods Example: Desulfurization by using Raney Ni/H2 Oxidative Cleavage Different approaches like ozonolysis of alkene Not compatible with groups modified by oxidizing agents Other Likers Photolabile linkers Traceless linkers Safty catch linkers Multifunctional anchors (various endgroups can be generated by the use of different cleavage strategies) Literature Jung G. (ed.): Combinatorial Chemistry, Synthesis, Analysis, Screening, Wiley-VCH, Weinheim, 1999 Jung G. (ed.): Combinatorial Peptide and non Peptide Libraries, A Handbook, Wiley-VCH, Weinheim, 1996 Guillier, Orain, Bradley : Linkers and Cleavage Strategies in Solid Phase Organic Synthesis and Combinatorial Chemistry. Chem. Rev. 2000, 100, 2091-2157 Handout: Combinatorial Chemistry and Synthesis on Solid Support, B. König, SS 2006 Thank you for attention
