Synthesis of Cyclobutane Analogue 4: Preparation of Purine and Pyrimidine Carbocyclic Nucleoside Derivatives.
Molecules
; 24(18)2019 Sep 05.
Article
en En
| MEDLINE
| ID: mdl-31491981
ABSTRACT
The coupling of 2-bromo-3-benzoyloxycyclobutanone with purine under basic conditions produces two regioisomers consisting of the N-7 and N-9 alkylated products in equal amounts in their racemic forms. The distribution of the isomers is consistent with the charge delocalization between the N-7 and N-9 positions of the purinyl anion. The structural assignments and relative stereochemistry of each regioisomer were based on 1 and 2D NMR techniques. The relative stereochemistry of the C-2 and C-3 substituents in each regioisomer was the trans orientation consistent with steric factors in the coupling step. The N-9 regioisomer was reduced with sodium borohydride to give the all trans cyclobutanol as the major product in a stereoselective manner. The alcohol was debenzoylated with sodium methoxide in a transesterification step to give the nucleoside analogue. The regioisomeric pyrimidine nucleosides were prepared by Vorbrüggen coupling of the 3-hydroxymethylcyclobutanone triflate with either thymine or uracil followed by stereoselective hydride addition. Regiospecificity of the coupling at the N-1 position was observed and stereoselective reduction to the trans-disubstituted cyclobutanol structure assignments was based on NMR data.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Ciclobutanos
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá