On the Necessity of Nucleobase Protection for 2-Thiouracil for Fmoc-Based Pseudo-Complementary Peptide Nucleic Acid Oligomer Synthesis

Robert H E Hudson; Ali Heidari; Timothy Martin-Chan; Gyeongsu Park; James A Wisner

doi:10.1021/acs.joc.9b00821

On the Necessity of Nucleobase Protection for 2-Thiouracil for Fmoc-Based Pseudo-Complementary Peptide Nucleic Acid Oligomer Synthesis

J Org Chem. 2019 Nov 1;84(21):13252-13261. doi: 10.1021/acs.joc.9b00821. Epub 2019 Oct 8.

Authors

Robert H E Hudson¹, Ali Heidari¹, Timothy Martin-Chan¹, Gyeongsu Park¹, James A Wisner¹

Affiliation

¹ Department of Chemistry , The University of Western Ontario , London N6A 5B7 , Ontario , Canada.

PMID: 31547656
DOI: 10.1021/acs.joc.9b00821

Abstract

A selection of benzyl-based protecting groups for thiouracil (^SU) for the synthesis of pseudo-complementary peptide nucleic acid (PNA) has been evaluated. The 4-methoxybenzyl-protecting group that has found use for ^SU during Boc-based oligomerization is also suitable for Fmoc-based oligomerization. Furthermore, it is demonstrated that ^SU protection is unnecessary for the successful synthesis of thiouracil-containing PNA. The new 2-thiothymine (^ST) PNA monomer has also been prepared and incorporated into an oligomer and its binding to complementary PNA evaluated.

Publication types

Research Support, Non-U.S. Gov't