O-Allyl protection in the Fmoc-based synthesis of difficult PNA

Abstract

The synthesis of homothymine PNA-oligomers can be plagued by the occurrence of a significant amount of truncation products, probably because on-resin aggregation hinders access during the coupling reactions. The use of low resin loading and the addition of the chaotropic salt KSCN in DMF allowed a partial remedy by conferring enhancements to the coupling yields. However, protection of the imide group by using O-allyl-protected thymine Fmoc-t^All provided the most significant improvements to the yields, even in cases where the use of non-protected thymine building blocks resulted in 70% truncation products. Deallylation occurs during the TFA cleavage step. Thus, O-allyl-protection can be applied in combination with standard protocols used in automated PNA synthesis.