O-Allyl protection in the Fmoc-based synthesis of difficult PNA.
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.
Altenbrunn
Frank
F
Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, D-12489, Berlin, Germany.
Seitz
Oliver
O
D000498:Allyl Compounds / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013941:Thymine / Q000737:chemistry
C496789:9-fluorenylmethoxycarbonyl; D000498:Allyl Compounds; D005449:Fluorenes; D020135:Peptide Nucleic Acids; D012997:Solvents; D013941:Thymine