A practical post-modification synthesis of oligodeoxynucleotides containing 4,7-diaminoimidazo[5′,4′:4,5]pyrido[2,3-d]pyrimidine nucleoside

• Published in: Bioorganic & medicinal chemistry Vol. 20; no. 24; pp. 7095 - 7100
• Main Authors: Tarashima, Noriko, Higuchi, Yosuke, Komatsu, Yasuo, Minakawa, Noriaki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-12-2012; Elsevier
• Subjects: Amino groups; Ammonium; ammonium hydroxide; Biological and medical sciences; chemistry; CpG islands; glass; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazopyridopyrimidine; Medical sciences; Nucleoside; nucleosides; Oligodeoxynucleotide; oligodeoxyribonucleotides; Oligodeoxyribonucleotides - chemical synthesis; Oligodeoxyribonucleotides - chemistry; Oligonucleotides; Pharmacology. Drug treatments; Pores; Post-modification synthesis; Protecting groups; pyrimidine nucleosides; Pyrimidine Nucleosides - chemical synthesis; Pyrimidine Nucleosides - chemistry; Solid phase methods; Stereoisomerism; Oligodeoxynucleotide; Nucleoside; Imidazopyridopyrimidine; Post-modification synthesis; DNA; Oligonucleotide; Oligodeoxyribonucleotide; Chemical synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.10.035

We describe herein the practical post-modification synthesis of oligodeoxynucleotides (ODNs) containing 4,7-diaminoimidazo[5′,4′:4,5]pyrido[2,3-d]pyrimidine nucleoside (ImNN). Since the ImNN nucleoside unit possessing tribenzoyl groups on its exocyclic amino groups as the protecting group was quite unstable under acidic conditions, cleavage of its glycosidic linkage in ODN has been suggested throughout the conditions of solid-phase synthesis. As an alternative approach, we investigated a post-modification synthesis of the desired ODNs containing the ImNN unit. Starting with protected 4-amino-7-chloro-1-(2-deoxy-β-d-ribofuranosyl)imidazo[5′,4′:4,5]pyrido[2,3-d]pyrimidine derivative 1, conversion into the corresponding phosphoramidite unit was examined. The p-bromobenzoyl group (p-BrBz) was the best protecting group of 4-amino group of 1 to give the phosphoramidite unit 9 for the post-modification synthesis. After carrying out the ODN synthesis linked to the controlled pore glass (CPG) support, the support was treated with ammonium hydroxide at 55°C to remove the protecting groups, detach the ODN form the CPG support, and convert the 7-chloro group into a desired amino group. As a result, the desired ODNs containing ImNN were obtained in good yield.