Name: Franziska Weichelt Topic: Safety-CAtch Linker (SCAL) Related Top - PDF document

Name: Franziska Weichelt Topic: Safety-CAtch Linker (SCAL) Related Topics: Linker types (monofunctional linker, multidirectional linker, cleavage linker)Definition: The term “safety catch principle” was introduced by Kenner in 1971 for peptide chemistry to describe a strategy that allows a linker to remain stable until it is activated for cleavage by a chemical modification. Currently, the term safety-catch is applied to a linker that is cleaved by performing two different reactions instead of the normal single step, that means that the linker is unreactive to the conditions of the library synthesis but may be activated by a simple chemical transformation to permit cleavage of the library from the solid phase to take place. Safety-catch linkers are used especially for solid-phase-syntheses, which are nowadays very important and can be used for nearly every known reaction (syntheses of alcohols, phenols, guanidines, aldehydes, carboxylic acids, amides, esters, …). Advantages of safety-catch linkers: · greater control over the timing of compound release· stable to both strongly acidic and basic conditions· the linker group is often reduced to a single atom · sufficient stability of the linker-substrate-bond impedes hydrolysis or similar side reactions · mild chemical conditions allowing unscathed liberation of the precious products Developments regarding the linker, coupling conditions, activation methods, cleavage conditions and possible substrates established this linker and its modifications in modern chemistry and will without doubt be present in the future. Mechanism [1]: Examples: · sulfone-linker for solid-phase synthesis of the 2-Aminobenzoxazole Library · Kenner’s safety-catch linkerfor N-Acyl-N-alkyl-sulfonamide anchors and for synthesis of primary amides, hydrazones and carboxylic acids [4] · reverse Kenner safety-catch linker for Suzuki coupling and thiazolidinone formation [4] · sulfide safety-catch linker [3] · selenium safety-catch linkers for annulations, Knoevenagel condensation, Pd-catalyzed cross couplings, reductive aminations, Mitsonobu inversions, glycosidations, organometallic additions · safety-catch linker for Hofmann-elimination [3] Publications: [1] Combinatorial Chemistry N. K. Terret, 1998, Oxford Chemistry Masters [2] Combinatorial Chemistry – A practical approach W. Bannwarth, E. Felder, 2000, Wiley-VCH Web-Links: [3] http://phoenix.tuwien.ac.at/combichem/Combi_2004_5_linkers2.pdf [4] http://www.scs.uiuc.edu/chem/gradprogram/chem435/spring03/Elmer.pdf [5] http://www.combichemistry.com/glossary_s.html [6] http://www.mdpi.net/ecsoc/ecsoc-5/Papers/e0027/e0027.htm [7] http://www.5z.com/moldiv/volume5/abstract25-34.pdf