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The aspartimide problem in Fmoc-based SPPS. Part II.

M Mergler·F Dick·B Sax·C Stähelin·T Vorherr
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Abstract

The sequence dependence of base-catalysed aspartmide formation during Fmoc-based SPPS was systematically studied employing the peptide models H-Val-Lys-Asp-Xaa-Tyr-Ile-OH. The extent of formation of aspartimide and related by-products was determined by RP-HPLC. Considerable amounts of by-products were formed in the case of Xaa = Asp(OtBu), Arg(Pbf), Asn(Mtt), Cys(Acm) and unprotected Thr. Aspartimide formation could be diminished by incorporation of Asp(OMpe) or by employing milder methods for Fmoc cleavage, e.g. hexamethyleneimine/N-methylpyrrolidine/HOBt/NMP/DMSO 4:50:4:71:71 (v/v/w/v/v).

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Amino AcidsAspartic AcidBridged Bicyclo Compounds, HeterocyclicChromatography, High Pressure LiquidFluorenesPeptide BiosynthesisPeptidesPiperidinesJournal Article

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M Mergler, F Dick, B Sax, C Stähelin, T Vorherr. 2003. The aspartimide problem in Fmoc-based SPPS. Part II.. https://doi.org/10.1002/psc.473

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