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A mild removal of Fmoc group using sodium azide

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Abstract

A mild method for effectively removing the fluorenylmethoxycarbonyl (Fmoc) group using sodium azide was developed. Without base, sodium azide completely deprotected N α-Fmoc-amino acids in hours. The solvent-dependent conditions were carefully studied and then optimized by screening different sodium azide amounts and reaction temperatures. A variety of Fmoc-protected amino acids containing residues masked with different protecting groups were efficiently and selectively deprotected by the optimized reaction. Finally, a biologically significant hexapeptide, angiotensin IV, was successfully synthesized by solid phase peptide synthesis using the developed sodium azide method for all Fmoc removals. The base-free condition provides a complement method for Fmoc deprotection in peptide chemistry and modern organic synthesis.

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Acknowledgments

This work is supported by Grants from National Science Council (NSC 101-2113-M-110-007- MY2) and National Sun Yat-sen University (01C030703 and 01A06802). Authors thank Prof. Shiue-Shien Weng’s help in chiral HPLC experiments. Authors thank Prof. Chi-Wi Ong’s help in the preparation of manuscript.

Conflict of interest

The authors declare no conflict of interest. The authors alone are responsible for the content and writing of this manuscript.

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Authors and Affiliations

  1. Department of Chemistry, National Sun Yat-sen University, Kaohsiung, 804, Taiwan

    Chun-Chi Chen, Basker Rajagopal, Xuan Yu Liu, Kuan Lin Chen, FuI Lin & Po-Chiao Lin

  2. National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan

    Yu-Chang Tyan & Po-Chiao Lin

  3. Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Yu-Chang Tyan

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  1. Chun-Chi Chen
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  2. Basker Rajagopal
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  3. Xuan Yu Liu
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  4. Kuan Lin Chen
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  5. Yu-Chang Tyan
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  6. FuI Lin
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  7. Po-Chiao Lin
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Corresponding author

Correspondence to Po-Chiao Lin.

Additional information

C.-C. Chen and B. Rajagopal contributed equally.

Electronic supplementary material

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Experimental data and characterization of all compounds and angiotensin IV are available free of charge.

Supplementary material 1 (DOC 3633 kb)

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Chen, CC., Rajagopal, B., Liu, X.Y. et al. A mild removal of Fmoc group using sodium azide. Amino Acids 46, 367–374 (2014). https://doi.org/10.1007/s00726-013-1625-7

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  • DOI: https://doi.org/10.1007/s00726-013-1625-7

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