Synthesis and properties of 3′-C-methylnucleosides and their phosphoric esters

Mikhailov, Sergey N.; Beigelman, Leon N.; Gurskaya, G. V.; Padyukova, N. Sh.; Yakovlev, G. I.; Karpeisky, M.Ya.

doi:10.1016/0008-6215(83)88357-8

Cited by 27 publications

(12 citation statements)

References 47 publications

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“…6). (Mikhailov et al, 1983) From these initial SAR studies, it was found that 3′- C -methyladenosine served as a potent anticancer agent against numerous human leukemia and carcinoma cell lines, with IC 50 values of ∼18 µM (Franchetti et al, 2005; Cappellacci et al, 2006). Further analysis found that shifting the methyl from the 3′ position of 3′- C -methyladenosine to another position on the sugar ring was associated with a decrease in activity, thus highlighting the importance of this moiety (Cappellacci et al, 2006).…”

Section: Modifications To the Sugar Scaffoldmentioning

confidence: 99%

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

2018

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This is the first of two invited articles reviewing the development of nucleoside-analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. Rather than providing a simple chronological account, we have examined and attempted to explain the thought processes, advances in synthetic chemistry and lessons learned from antiviral testing that led to a few molecules being moved forward to eventual approval for human therapies, while others were discarded. The present paper focuses on early, relatively simplistic changes made to the nucleoside scaffold, beginning with modifications of the nucleoside sugars of Ara-C and other arabinose-derived nucleoside analogues in the 1960's. A future paper will review more recent developments, focusing especially on more complex modifications, particularly those involving multiple changes to the nucleoside scaffold. We hope that these articles will help virologists and others outside the field of medicinal chemistry to understand why certain drugs were successfully developed, while the majority of candidate compounds encountered barriers due to low-yielding synthetic routes, toxicity or other problems that led to their abandonment.

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Section: Modifications To the Sugar Scaffoldmentioning

confidence: 99%

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

2018

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“…Early examples of modifications at the 3′ position of nucleoside sugars led to the development of novel analogues such as the 3′-methyl nucleosides ( Mikhailov et al, 1983 ; Franchetti et al, 2005 ; Cappellacci et al, 2006 ), however, the 2′, 3′-dideoxy nucleosides ( Veal et al, 1995 ; Horwitz et al, 1967 ; Mitsuya and Broder, 1986 ) and 2′-deoxy-3′-modified nucleosides ( Smith et al, 2008 ; Hostetler et al, 1994 ) ultimately proved to be more promising. The development of these analogues was covered extensively in the previous review and is not discussed here ( Seley-Radtke and Yates, 2018 ).…”

Section: ′ Modificationsmentioning

confidence: 99%

“…Another common isosteric modification in nucleoside drug design is the substitution of a methyl group for a hydrogen. While this modification has been explored at the 1′ ( Cappellacci et al, 2002 ), 2′ ( Zhang et al, 2011 ; Carroll et al, 2003 ; Migliaccio et al, 2003 ; Eldrup et al, 2004a , 2004b ; Pierra et al, 2006 ), and 3’ ( Mikhailov et al, 1983 ; Franchetti et al, 2005 ; Cappellacci et al, 2006 ; Orlov et al, 2017 ) positions on the furanose ring, little research had been reported on the presence of a methyl group at the 4′ position. As mentioned previously, it was found that the addition of a 4′-modification altered the reactivities of the 3′ and 5′-hydroxyl groups compared to natural nucleosides due to steric effects ( Waga et al, 1993 ), thus 4′-methyl modifications were considered an interesting avenue to pursue.…”

Section: ′ Modificationsmentioning

confidence: 99%

The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold

2019

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This is the second of two invited articles reviewing the development of nucleoside analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. As with the first paper, rather than providing a chronological account, we have chosen to examine particular examples of structural modifications made to nucleoside analogues that have proven fruitful as various antiviral, anticancer, and other therapeutics. The first review covered the more common, and in most cases, single modifications to the sugar and base moieties of the nucleoside scaffold. This paper focuses on more recent developments, especially nucleoside analogues that contain more than one modification to the nucleoside scaffold. We hope that these two articles will provide an informative historical perspective of some of the successfully designed analogues, as well as many candidate compounds that encountered obstacles.

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“…However, some examples of the low reactivity of the corresponding tertiary 3'-hydroxyl have been reported in the 3'-C-β-methylribofuranosyl series. [12][13][14] In conclusion, compound 6 does not seem to be a promising substrate for 2'-modification. To solve the problem of regioselective modification of the 2',3'-diol system in 2'-C-β-methyl-D-ribonucleosides, we decided to take advantage of this low reactivity of 2'-hydroxyl group, assuming that this position could remain unprotected during 3'-modification.…”

Section: Scheme 1 Reagents and Conditions: (A) (Chmentioning

confidence: 99%

Partial acylation of cytidine and its 2'-C-methyl analogue as a tool to functionalize the ribonucleosidic 2’,3’-cis-diol system

Fogt¹,

Januszczyk²,

Onishi³

et al. 2008

Arkivoc

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Dedicated to Professor Harri Lönnberg on the occasion of his 60 th anniversary AbstractPrecisely controlled conditions of acylation and 2',3'-O-isomerization allowed to synthesize tripivaloyl derivatives of cytidine with free 2'-or 3'-hydroxyl group in a simple manner. Acylation of 2'-C-β-methylcytidine proceeded in a different way and resulted in the formation of tripivaloyl 2'-hydroxy nucleoside, or dipivaloyl 2',3'-dihydroxy compound. All these products may be applied as key intermediates in the regioselective modification of 2',3'-cis-diol system.

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Synthesis and properties of 3′-C-methylnucleosides and their phosphoric esters

Cited by 27 publications

References 47 publications

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold

Partial acylation of cytidine and its 2'-C-methyl analogue as a tool to functionalize the ribonucleosidic 2’,3’-cis-diol system

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