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Current Organic Synthesis


ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Research Article

Thietanyl Protection in the Synthesis of 8-Substituted 1-Benzyl-3-methyl-3,7-dihydro- 1H-purine-2,6-diones

Author(s): Ferkat Khaliullin* and Yuliya Shabalina

Volume 17 , Issue 7 , 2020

Page: [535 - 539] Pages: 5

DOI: 10.2174/1570179417666200628015511

Price: $65


Aim and Objective: 1-Аlkyl-3,7-dihydro-1H-purine-2,6-diones containing no substituents in the N7 position can be synthesized only using protecting groups, for example, benzyl protection. However, in the case of synthesis of 1-benzyl-3,7-dihydro-1H-purine-2,6-diones, the use of benzyl protection may lead to simultaneous debenzylation of both N1 and N7 positions. Therefore, it is necessary to use other protective groups for the synthesis of 1-benzyl-3,7-dihydro-1H-purine-2,6-diones.

Materials and Methods: 8-Bromo- and 8-amino-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones unsubstituted in the N7 position were synthesized with the use of thietanyl protecting group. The thietane ring was introduced via the reaction of 8-bromo-3-methyl-3,7-dihydro-1H-purine-2,6-dione with 2-chloromethylthiirane, giving rise to 8-bromo-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-dione. The subsequent alkylation with benzyl chloride yielded 1-benzyl-8-bromo-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-dione, which was oxidized with hydrogen peroxide to be converted to 1-benzyl-8-bromo-3-methyl-7-(1,1-dioxothietan- 3-yl)-3,7-dihydro-1H-purine-2,6-dione. This product reacted with amines to give 8-amino-substituted 1-benzyl-3- methyl-7-(1,1-dioxothietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones. The reaction of 8-substituted 1-benzyl-3- methyl-7-(1,1-dioxothietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones with sodium isopropoxide resulted in the removal of the thietanyl protection and afforded target 8-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6- diones. The structures of the targets compounds have been deduced upon their elemental analysis and spectral data (IR, 1H NMR, 13C NMR and 15N NMR).

Results and Discussion: A new 8-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones unsubstituted in the N7 position were synthesized using thietanyl protecting group.

Conclusion: The present study described a new route to synthesize some new 1,8-disubstituted 3-methyl-3,7- dihydro-1H-purine-2,6-diones unsubstituted in the N7 position starting from available 8-bromo-3-methyl-3,7- dihydro-1H-purine-2,6-dione with use of thietanyl protecting group. The advantages of this protocol are the possibility of the synthesis of 1-benzyl-substituted 3,7-dihydro-1H-purine-2,6-diones, the stability of the thietanyl protecting group upon nucleophilic substitution by amines of the bromine atom in the position 8, as well as mild conditions, and simple execution of experiments.

Keywords: Alkylation, amines, nucleophilic substitution, oxidation, protecting groups, purine-2, 6-diones, thietanes.

Graphical Abstract
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