Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry.

ABSTRACT

Tetrahydropyranyl (Thp) is recognized as a useful protecting group for alcohols in organic synthesis. It has several advantages, including low cost, ease of introduction, general stability to most non-acidic reagents, it confers good solubility, and the ease with which it can be removed if the functional group it protects requires manipulation. However, little attention has been paid to Thp in peptide chemistry. Provided here is a concise analysis of the Thp protection of various amino acid functionalities (OH, SH, NH and COOH) and its application to peptide synthesis. Thp is a useful moiety for the side-chain protection of serine, threonine and cysteine and is suitable for the Fmoc/tBu solid-phase peptide synthesis strategy. The immobilized version of 3,4-dihydro-2H-pyran, the so-called Ellman resin, is also discussed as a useful solid support for anchoring the side chains of serine, threonine and tryptophan residues.