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Synthetic chemistry in water: applications to peptide synthesis and nitro-group reductions

Nature Protocols volume 14, pages 1108–1129 (2019)Cite this article

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Abstract

Amide bond formation and aromatic/heteroaromatic nitro-group reductions represent two of the most commonly used transformations in organic synthesis. Unfortunately, such processes can be especially wasteful and hence environmentally harmful, and may present safety hazards as well, given the reaction conditions involved. The two protocols herein describe alternative technologies that offer solutions to these issues. Polypeptides can now be made in water at ambient temperatures using small amounts of the designer surfactant TPGS-750-M, thereby eliminating the use of organic solvents as the reaction medium. Likewise, a safe, inexpensive and efficient procedure is outlined for nitro-group reductions, using industrial iron in the form of carbonyl iron powder (CIP), an inexpensive item of commerce. The peptide synthesis will typically take, overall, 3–4 h for a simple coupling and 8 h for a two-step deprotection/coupling process. The workup usually consists of a simple extraction and acidic/basic aqueous washings. The nitro reduction procedure will typically take 6–8 h to complete, including setup, reaction time and workup.

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The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files.

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Author information

Author notes

  1. These authors contributed equally: Margery Cortes-Clerget, Nicholas R. Lee.

Authors and Affiliations

  1. Department of Chemistry & Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, USA

    Margery Cortes-Clerget, Nicholas R. Lee & Bruce H. Lipshutz

Authors
  1. Margery Cortes-Clerget
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  2. Nicholas R. Lee
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  3. Bruce H. Lipshutz
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Contributions

M.C.-C., N.R.L. and B.H.L. wrote, reviewed and edited the manuscript.

Corresponding author

Correspondence to Bruce H. Lipshutz.

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The authors declare no competing interests.

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Key references using this protocol

Gabriel, C. M., Keener, M., Gallou, F. & Lipshutz, B. H. Org. Lett. 17, 3968–3971 (2015): https://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01812

Cortes-Clerget, M., Berthon, J.-Y., Krolikiewicz-Renimel, I., Chaisemartin, L. & Lipshutz, B. H. Green Chem. 19, 4263−4267 (2017): https://pubs.rsc.org/en/content/articlelanding/2017/gc/c7gc01575e#!divAbstract

Lee, N. R., Bikovtseva, A. A., Cortes-Clerget, M., Gallou, F. & Lipshutz, B. H. Org. Lett. 19, 6518–6521 (2017): https://pubs.acs.org/doi/abs/10.1021/acs.orglett.7b03216

Video tutorials

Peptide synthesis in water—episode 1: coupling: https://youtu.be/WvRVfaR7dwM

Peptide synthesis in water—episode 2: 1-pot deprotection/coupling: https://youtu.be/eNqan3L4LrQ

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Cortes-Clerget, M., Lee, N.R. & Lipshutz, B.H. Synthetic chemistry in water: applications to peptide synthesis and nitro-group reductions. Nat Protoc 14, 1108–1129 (2019). https://doi.org/10.1038/s41596-019-0130-1

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