2. Academic Validation
  3. Tetrahydropyranyl: A Non-aromatic, Mild-Acid-Labile Group for Hydroxyl Protection in Solid-Phase Peptide Synthesis

Tetrahydropyranyl: A Non-aromatic, Mild-Acid-Labile Group for Hydroxyl Protection in Solid-Phase Peptide Synthesis

  • ChemistryOpen. 2017 Mar 8;6(2):206-210. doi: 10.1002/open.201600157.
Anamika Sharma 1,  Iván Ramos-Tomillero 2,  Ayman El-Faham 3 4,  Hortensia Rodríguez 5,  Beatriz G de la Torre 1 6,  Fernando Albericio 1 2 3 7 8
Affiliations

Affiliations

  • 1 Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal Durban 4001 South Africa.
  • 2 Inorganic and Organic Department University of Barcelona Martí Franqués 1-11 08028 Barcelona Spain.
  • 3 Department of Chemistry College of Science King Saud University P.O. Box 2455 Riyadh 11451 Saudi Arabia.
  • 4 Department of Chemistry Faculty of Science Alexandria University P.O. Box 426, Ibrahimia Alexandria 21321 Egypt.
  • 5 School of Chemistry Yachay Tech Yachay City of Knowledge Urcuqui Ecuador.
  • 6 School of Laboratory of Medicine & Medical Sciences University of KwaZulu-Natal Durban 4001 South Africa.
  • 7 School of Chemistry & Physics University of KwaZulu-Natal Durban 4001 South Africa.
  • 8 CIBER-BBN, Networking Centre on Bioengineering Biomaterials and Nanomedicine Barcelona Science Park Baldiri Reixac 10-12 08028 Barcelona Spain.
PMID: 28413752 DOI: 10.1002/open.201600157
Abstract

The use of the tetrahydropyranyl (Thp) group for the protection of serine and threonine side-chain hydroxyl groups in solid-phase peptide synthesis has not been widely investigated. Ser/Thr side-chain hydroxyl protection with this acid-labile and non-aromatic moiety is presented here. Although Thp reacts with free carboxylic acids, it can be concluded that to introduce Thp ethers at the hydroxyl groups of N-protected Ser and Thr, protection of the C-terminal carboxyl group is unnecessary due to the lability of Thp esters. Thp-protected Ser/Thr-containing tripeptides are synthesized and the removal of Thp studied in low concentrations of trifluoroacetic acid in the presence of cation scavengers. Given its general stability to most non-acidic reagents, improved solubility of its conjugates and ease with which it can be removed, Thp emerges as an effective protecting group for the hydroxyl groups of Ser and Thr in solid-phase peptide synthesis.

Keywords

protecting groups; serine; solid-phase peptide synthesis; tetrahydropyranyl group; threonine.

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