Synthesis of Cyclobutane Analogue 4: Preparation of Purine and Pyrimidine Carbocyclic Nucleoside Derivatives

The coupling of 2-bromo-3-benzoyloxycyclobutanone with purine under basic conditions produces two regioisomers consisting of the and alkylated products in equal amounts in their racemic forms. The distribution of the isomers is consistent with the charge delocalization between the and positions of t...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-09, Vol.24 (18), p.3235
Main Authors: Hasaneen, Noha, Ebead, Abdelaziz, Hassan, Murtaza, Afifi, Hanan, Hunter, Howard, Lee-Ruff, Edward, El-Gohary, Nadia S, Maarouf, Azza R, El-Emam, Ali A
Format: Article
Language:English
Subjects:
Alcohol
Alkylation
Chemistry Techniques, Synthetic
Chromatography
Cyclobutane
cyclobutanes
Cyclobutanes - chemical synthesis
Cyclobutanes - chemistry
Experiments
Isomers
Magnetic Resonance Spectroscopy
Molecular Structure
NMR
Nuclear magnetic resonance
Nucleoside analogs
Nucleosides
purine
Purines - chemistry
Pyrimidine Nucleosides - chemistry
Sodium
Stereochemistry
Stereoisomerism
Stereoselectivity
Thymine
Transesterification
Uracil
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Summary:The coupling of 2-bromo-3-benzoyloxycyclobutanone with purine under basic conditions produces two regioisomers consisting of the and alkylated products in equal amounts in their racemic forms. The distribution of the isomers is consistent with the charge delocalization between the and 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 and substituents in each regioisomer was the orientation consistent with steric factors in the coupling step. The regioisomer was reduced with sodium borohydride to give the all 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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24183235