In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.

Clarifying the Use of Benzylidene Protecting Group for D-($mathplus$)-Ribono-1,4-Lactone, an Essential Building Block in the Synthesis of C-Nucleosides / S.M. Casati, P. Rota, P. Allevi, A. Mingione, R. Ottria, P. Ciuffreda. - In: MOLECULES. - ISSN 1420-3049. - 26:21(2021 Oct 26), pp. 6447.1-6447.16. [10.3390/molecules26216447]

Clarifying the Use of Benzylidene Protecting Group for D-($mathplus$)-Ribono-1,4-Lactone, an Essential Building Block in the Synthesis of C-Nucleosides

S.M. Casati
Co-primo
;
P. Rota
Co-primo
;
P. Allevi
Secondo
;
A. Mingione;R. Ottria
Penultimo
;
P. Ciuffreda
Ultimo
2021

Abstract

In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.
ribono-1,4-lactone; 1-C-substituted nucleosides; protecting groups; cyclic acetals;
Settore BIO/10 - Biochimica
2015-FDA-0014 - PIANO DI SOSTEGNO ALLA RICERCA 2015-2017 - LINEA 3 "FINANZIAMENTO PER ACQUISTO/RINNOVO ATTREZZATURE SCIENTIFICHE FINALIZZATE ALLA RICERCA" - MARIOTTI, MAURIZIO - PSR2015-17 - Piano di sviluppo di ricerca 2015-17 - 2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/878090
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