The aspartimide problem in Fmoc-based SPPS. Part II.
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).
Mergler
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BACHEM AG, Hauptstr. 144, CH-4416 Bubendorf, Switzerland.
Dick
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Sax
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Stähelin
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Vorherr
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D000596:Amino Acids / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000737:chemistry*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry
D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D010880:Piperidines; D001224:Aspartic Acid; C075871:aspartimide; C032727:piperidine; C031033:1,8-diazabicyclo(5.4.0)undec-7-ene