Abstract
Stereocontrolled synthesis of some amino acid-based carbocyclic nucleoside analogs containing ring C=C bond has been performed on β- and γ-lactam basis. Key steps were N-arylation of readily available β- or γ-lactam-derived amino ester isomers and amino alcohols with 5-amino-4,6-dichloropyrimidine; ring closure of the formed adduct with HC(OMe)3 and nucleophilic displacement of chlorine with various N-nucleophiles in the resulting 6-chloropurine moiety.
Highlights
Introduction and AimsIn carbocyclic nucleoside analogs, a methylene group replaces the oxygen atom in the carbohydrate ring, thereby increasing stability towards hydrolases and phosphorylases
Taking into account the importance of carbocyclic nucleoside analogs and the bioactivity of peptidyl nucleoside antibiotics containing β-amino acids, our aim was the synthesis of new carbocyclic nucleoside analogs with an amino acid moiety on a β- and γ-lactam basis
This pathway is similar to the first synthesis of carbovir from unsaturated γ-lactam (±)-14 [25,26,27]
Summary
A methylene group replaces the oxygen atom in the carbohydrate ring, thereby increasing stability towards hydrolases and phosphorylases. The synthesis of these molecules is an area of considerable interest to medicinal chemistry, thanks to their bioactivity. Carbocyclic nucleoside analogs with a 6-membered ring received less attention In their case, antiviral activity usually requires the presence of a C=C bond in the ring [1,2,3,5,7,8] (see 3 and 4), enabling the base to occupy a pseudoaxial position [1,5], but some (2-aminocyclohexyl)methanol derivatives (for example, 5 [9]) exhibit bioactivity (Scheme 1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
