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A Novel Oxazolidine Linker for the Synthesis of Peptide Aldehydes

  • Bruce Merrifield Commemorative Issue
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International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

A reliable method for solid-phase synthesis of peptide aldehydes by using a new oxazolidine linker is described. Based on a comparative study using the usual cleavage protocol as is used for the Fmoc-based peptide synthesis, we found that this new linker is more appropriate for the synthesis of peptide aldehydes compared with the precedent acetal, semicarbazone or threonine linker. Whereas N-Acylated oxazolidines might be partially deprotected to non-N-acylated intermediates in the TFA cocktail containing several soft nucleophiles which cause significant side reactions, the new oxazolidine linker could produce the desired peptide aldehydes by simple Et2O washing and subsequent aqueous workup in high chemical yields and purity. We demonstrate the new method is useful especially for the preparation of highly functionalized long-chain peptide aldehydes which require several scavenger chemicals in the final deprotection step.

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Abbreviations

t-Bu:

tert.-butyl

Boc:

tert.-butyloxycarbonyl

Trt:

trityl

Pbf:

2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl

DIPC:

diisopropylcarbodiimide

EDC:

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

HOBt:

1-hydroxybenzotriazole

DIEA:

diisopropylethylamine

IBX:

2-iodoxybenzoic acid

TMOF:

trimethyl orthoformate

HATU:

O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and 21st Century COE Program ‘Knowledge Information Infrastructure for Genome Science’ which are gratefully acknowledged.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Michinori Tanaka, Shinya Oishi, Hiroaki Ohno & Nobutaka Fujii

Authors
  1. Michinori Tanaka
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  2. Shinya Oishi
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  3. Hiroaki Ohno
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  4. Nobutaka Fujii
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Corresponding author

Correspondence to Nobutaka Fujii.

Additional information

This paper is dedicated to the memory of the late Prof. R. Bruce Merrifield, who passed away May 14, 2006.

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Tanaka, M., Oishi, S., Ohno, H. et al. A Novel Oxazolidine Linker for the Synthesis of Peptide Aldehydes. Int J Pept Res Ther 13, 271–279 (2007). https://doi.org/10.1007/s10989-007-9078-z

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  • DOI: https://doi.org/10.1007/s10989-007-9078-z

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