Incorporation of Sensitive Ester and Chloropurine Groups into Oligodeoxynucleotides through Solid‐Phase Synthesis. Issue 31 (16th August 2018)

• Record Type: Journal Article
• Authors: Halami, Bhaskar; Shahsavari, Shahien; Nelson, Zack; Prehoda, Lucas; Eriyagama, Dhananjani Nisansala Adikar Mudiyanselage; Fang, Shiyue
• Is Part Of: ChemistrySelect. Volume 3:Issue 31(2018)
• Page Start: 8857
• Page End: 8862
• Publication Date: 2018-08-16
• Subjects: Synthetic Method -- Solid Phase Synthesis -- Oligonucleotide -- Oxidation -- Dmoc; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201801484
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Nucleosides containing ester groups that are sensitive to nucleophiles were incorporated into oligodeoxynucleotides (ODNs) through solid phase chemical synthesis. The sensitive esters are located on a purine nucleobase. They are the esters of ethyl, 2‐methoxyethyl, 4‐methoxyphenyl and phenyl groups, and a thioester. These esters cannot survive the deprotection and cleavage conditions used in known ODN synthesis technologies, which involve strong nucleophiles such as ammonium hydroxide and potassium methoxide (potassium carbonate in anhydrous methanol). To incorporate these sensitive groups into ODNs, the Dmoc (i. e. dimethyl‐1, 3‐dithian‐2‐ylmethoxycarbonyl) phosphoramidites and linker were used for solid phase synthesis, which allowed ODN deprotection and cleavage to be carried out under non‐nucleophilic oxidative conditions. Sixteen ODN sequences containing these groups were synthesized and characterized with MALDI MS. In addition, the synthesis and characterization of three ODNs containing a nucleophile sensitive 6‐chloropurine using the same strategy are described. Abstract : Due to the use of acyl protection and deprotection with nucleophiles, known technologies are unsuitable for the synthesis of oligos containing electrophilic groups. This challenge is now overcome. Using Dmoc for protection, which allows deprotection under non‐nucleophilic conditions, electrophilic groups including the highly sensitive phenyl esters can now be reliably incorporated into oligos.