2-Diphenylmethylsilylethyl (DPSE): a versatile protecting group for oligodeoxyribonucleotide synthesis

Area of Science:

• Organic Chemistry
• Biochemistry
• Synthetic Chemistry

Background:

• The synthesis of oligodeoxyribonucleotides is crucial for molecular biology and therapeutics.
• Protecting groups are essential for controlling reactivity during oligonucleotide synthesis.
• Existing protecting groups may have limitations in stability or removal conditions.

Purpose of the Study:

• To introduce and evaluate a novel protecting group for internucleotidic bonds in oligodeoxyribonucleotide synthesis.
• To assess the stability and cleavage conditions of the new protecting group.

Main Methods:

• The phosphoramidite approach was employed for solid-support and solution-phase synthesis.
• The 2-diphenylmethylsilylethyl (DPSE) group was utilized as a protecting group for internucleotidic bonds.
• Cleavage conditions involving aqueous ammonia and tetrafluorosilane in acetonitrile were investigated.

Main Results:

• The DPSE protecting group demonstrated stability under acidic conditions.
• Efficient removal of the DPSE group was achieved via a beta-fragmentation mechanism.
• Mild conditions using aqueous ammonia or tetrafluorosilane in acetonitrile successfully cleaved the DPSE group.

Conclusions:

• The 2-diphenylmethylsilylethyl (DPSE) group is a viable and effective protecting group for oligodeoxyribonucleotide synthesis.
• DPSE offers advantages in terms of stability and versatile, mild cleavage conditions.
• This protecting group facilitates both solid-support and solution-phase synthesis via the phosphoramidite approach.