A new protecting group for aspartic acid that minimizes piperidine-catalyzed aspartimide formation in Fmoc solid phase peptide synthesis

Karlström, Amelie; Undén, Anders

doi:10.1016/0040-4039(96)00807-6

Cited by 54 publications

(35 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus the corresponding adduct 1e was obtained in high isolated yield (91 to 98%) with up to 94% ee (Table 2, entries 5 to 10). We next turned our attention to the hydrogenation of the even more hindered substrates such as 3-methyldiisopropyl ester 2f [24] and 3-methylpentyl ester (Mpe) 2g [25] hoping to further increase the selectivity of the reaction. However, comparable results to the tert-butyl ester 2e in terms of both yield and enantioselectivity were obtained (Table 2, entries 12 and 13).…”

Section: Mol% Of [Ru(h)a C H T U N G T R E N N U N G (H 6 -Cot)synphos]mentioning

confidence: 99%

Convenient General Asymmetric Synthesis of Roche Ester Derivatives through Catalytic Asymmetric Hydrogenation: Steric and Electronic Effects of Ligands

et al. 2008

View full text Add to dashboard Cite

An efficient and concise asymmetric hydrogenation of acrylate esters promoted by the cat-+ BF 4 À is reported. A full investigation of the effects of catalyst precursors, solvents, temperature, hydrogen pressure, substrates as well as steric and electronic properties of ligands was carried out. The corresponding valuable Roche ester derivatives were obtained in good to excellent isolated yields and high enantioselectivities under mild conditions. The robustness and practicability of this highly enantioselective hydrogenation was demonstrated by the synthesis of the 3-hydroxy-2-methylpropanoic acid tert-butyl ester on a multigram scale, resulting in excellent yield and ee up to 94%.

show abstract

Section: Mol% Of [Ru(h)a C H T U N G T R E N N U N G (H 6 -Cot)synphos]mentioning

confidence: 99%

Convenient General Asymmetric Synthesis of Roche Ester Derivatives through Catalytic Asymmetric Hydrogenation: Steric and Electronic Effects of Ligands

et al. 2008

View full text Add to dashboard Cite

show abstract

“…232 It is removed with 95% TFA and is more sterically hindered than the t Bu group and therefore less prone to aspartimide formation.…”

mentioning

confidence: 99%

Amino Acid-Protecting Groups

2009

View full text Add to dashboard Cite

“…[12b] Aspartimide formation during peptide elongation can be reduced by using bulky groups to protect the Asp side chain, [14] for example, the 2-phenylisopropylester (PhiPr); [12a] however, trityl anchors are also cleaved under the reaction conditions for PhiPr removal. Dmab-protected [15] Asp residues are compatible with trityl anchors, but the backbone protection of the neighboring amino acid is required.…”

mentioning

confidence: 99%

Convergent Solid‐Phase Synthesis of N‐Glycopeptides Facilitated by Pseudoprolines at Consensus‐Sequence Ser/Thr Residues

et al. 2012

View full text Add to dashboard Cite

Dedicated to Professor Hans Paulsen on the occasion of his 90th birthday N-Glycosylation is an important posttranslational modification of proteins. A carbohydrate is transferred to an asparagine within an Asn-X-Ser/Thr consensus sequence.[1]The study of the biological aspects of N-glycosylation often requires the synthesis of N-glycopeptides, [2] which are accessible by two main approaches. In the sequential mode glycosylamino acid cassettes are used for peptide elongation. After incorporation of larger oligosaccharides the solubility and reactivity of the peptide is affected and side reactions, for example, involving free OH groups [3] complicate further elongation. In the convergent mode (Lansbury aspartylation) [4] the sugar is connected to an aspartate after complete assembly of the peptide (Scheme 1). The main drawback of the convergent mode is the formation of cyclic aspartimides during peptide elongation and sugar coupling; [5] this formation depends on the peptide sequence, [6] and the coupling conditions. [7] We found that a pseudoproline (Ypro) [8] at the consensus-sequence Ser/Thr residue (Asn-X-Ser/Thr(Ypro)) efficiently suppresses the formation of aspartimides in the convergent synthesis of N-glycopeptides on the solid phase.The lack of pure N-glycoproteins for biological studies has stimulated research into their synthesis; these syntheses were carried out mainly by ligation techniques.[9] The required glycopeptides and their thioesters are difficult to obtain as the sugar component interferes with the peptide synthesis. The syntheses of longer glycopeptide thioesters are particularly difficult as they require, for example, additional ligation steps [9f, 10] or segment couplings.[3b] For longer N-glycopeptides the convergent approach provides advantages over the sequential approach, [11] especially as the Lansbury aspartylation [4] has been shown to be efficient also on the solid phase.[12]The undesired aspartimide formation can be avoided by peptide backbone (NH) protection, [13] however, this approach is tedious for residues other than glycine, and causes racemization when coupling backbone-protected dipeptides.[12b] Aspartimide formation during peptide elongation can be reduced by using bulky groups to protect the Asp side chain, [14] for example, the 2-phenylisopropylester (PhiPr); [12a] however, trityl anchors are also cleaved under the reaction conditions for PhiPr removal. Dmab-protected [15] Asp residues are compatible with trityl anchors, but the backbone protection of the neighboring amino acid is required. [13a, 16] To provide complex N-glycopeptide thioesters by solidphase Lansbury aspartylation we compared three Asp-sidechain protecting groups for the Fmoc-SPPS of an interleukin-6 (IL-6) 43-48 hexapeptide. The allyl-protected peptide [17] 6 a showed the highest percentage of aspartimide 7 ai formation (15 %), followed by the Dmab peptide 6 b (8 %), and the PhiPr [12a] peptide 6 c (< 1 %; Scheme 2). As well as the protecting group many factors are known to contribute to aspartim...

show abstract

A new protecting group for aspartic acid that minimizes piperidine-catalyzed aspartimide formation in Fmoc solid phase peptide synthesis

Cited by 54 publications

References 13 publications

Convenient General Asymmetric Synthesis of Roche Ester Derivatives through Catalytic Asymmetric Hydrogenation: Steric and Electronic Effects of Ligands

Convenient General Asymmetric Synthesis of Roche Ester Derivatives through Catalytic Asymmetric Hydrogenation: Steric and Electronic Effects of Ligands

Amino Acid-Protecting Groups

Convergent Solid‐Phase Synthesis of N‐Glycopeptides Facilitated by Pseudoprolines at Consensus‐Sequence Ser/Thr Residues

Contact Info

Product

Resources

About