Introduction To Trt

Trityl (Trt) is a chemical protecting group with large steric hindrance, which can be used for the protection of amino acids and peptide synthesis. It has unique reaction characteristics and application value, and can protect the amino group of amino acids. Trt can also protect the side chain of amino acids in acylation reactions. In addition, when performing peptide synthesis, Trt can also be used to protect the hydroxyl and thiol groups of amino acids.

Introduction of Trt

Due to the large steric hindrance of Trt, except for Trt-glycine ester with a small amino acid side chain, general Trt-amino acid esters are difficult to saponify. And using very strong conditions (such as high temperature) may cause racemization. Therefore, the introduction of Trt is generally achieved by the following reaction.

Using excess Trt-Cl to generate Trt-amino acid trityl ester, and then the trityl ester is removed by HCl/HOAc treatment to obtain Trt-amino acid.
Trt-amino acid can also be easily obtained by using Trt-Cl/Me₃SiCl/Et₃N or Trt-Cl/TMSCl/Et₃N.

Removal of Trt

Trt can be removed by acidolysis. For example, using HOAc or 50% (or 75%) HOAc aqueous solution at 30 °C or reflux for several minutes can successfully remove the Trt group. Other conditions such as HCl/MeOH, HCl/CHCl₃, HBr/HOAc and trifluoroacetic acid (TFA) can also easily remove Trt group. It is worth noting that the sensitivity of Trt to acid varies with the acid used. For example, Trt is sensitive to acetic acid. In 80% acetic acid, the removal rate of Trt is much faster than Boc, so Trt can be selectively removed in the presence of Boc. However, using 0.1M HBr/HOAc as a reagent, the removal rate of Trt is slower than that of Boc.
Trt can also be removed by catalytic hydrogenolysis. Its removal rate is much slower than that of Cbz.

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