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

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 (ImN(N)). Since the ImN(N) 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 ImN(N) 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 ImN(N) were obtained in good yield. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Noriko Tarashima, Yosuke Higuchi, Yasuo Komatsu, Noriaki Minakawa. A practical post-modification synthesis of oligodeoxynucleotides containing 4,7-diaminoimidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside. Bioorganic & medicinal chemistry. 2012 Dec 15;20(24):7095-100

Mesh Tags

Substances

PMID: 23142321

search → result