A1 Refereed original research article in a scientific journal
Solid-phase synthesis of 7-substituted 3H-imidazo[2,1-i]purines
Authors: Karskela T, Lonnberg H
Publisher: ROYAL SOC CHEMISTRY
Publication year: 2006
Journal:: Organic and Biomolecular Chemistry
Journal name in source: ORGANIC & BIOMOLECULAR CHEMISTRY
Journal acronym: ORG BIOMOL CHEM
Volume: 4
Issue: 24
First page : 4506
Last page: 4513
Number of pages: 8
ISSN: 1477-0520
DOI: https://doi.org/10.1039/b612655c
Abstract
A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i] purin-7-yl) methyl amines has been developed. The key features of this library synthesis are: (i) immobilization of commercially available N-6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 3'-(2-cyanoethyl N, N-diisopropylphosphoramidite) by phosphitylation to a hydroxyl-functionalized support, ( ii) quantitative conversion of the deprotected adenine base to 3H-imidazo[2,1- i] purine-7-carbaldehyde with bromomalonaldehyde in DMF in the presence of formic acid and 2,6-lutidine, (iii) reductive amination of the formyl group followed by N-alkylation or N-acylation, and (iv) release from the support by acidolytic cleavage of the N-glycosidic bond. Steps ( ii) and ( iii) have been optimized in some detail by using (adenin-9-yl) acetic acid anchored to a Phe-Wang resin as a model compound.
A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i] purin-7-yl) methyl amines has been developed. The key features of this library synthesis are: (i) immobilization of commercially available N-6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 3'-(2-cyanoethyl N, N-diisopropylphosphoramidite) by phosphitylation to a hydroxyl-functionalized support, ( ii) quantitative conversion of the deprotected adenine base to 3H-imidazo[2,1- i] purine-7-carbaldehyde with bromomalonaldehyde in DMF in the presence of formic acid and 2,6-lutidine, (iii) reductive amination of the formyl group followed by N-alkylation or N-acylation, and (iv) release from the support by acidolytic cleavage of the N-glycosidic bond. Steps ( ii) and ( iii) have been optimized in some detail by using (adenin-9-yl) acetic acid anchored to a Phe-Wang resin as a model compound.
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