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Intramolecular Michael Additions in Uridine Derivatives: Isolation of the Labile 5'O-C6 Cyclonucleoside.

ABSTRACT: Uridine derivatives undergo a diastereospecific intramolecular hetero Michael addition onto uracil C6 to give cyclo-adducts. In contrast to the potent amine and thiol nucleophiles at the 5' position of ribose, which readily give the N- and S-cyclonucleosides in good yields, the cyclization reaction from the "natural" 5'-hydroxyl is tedious and has so far been overlooked most probably because of the thermodynamic instability of the O-cyclo-adduct. Here, we show that the O-cyclonucleoside 1 can be isolated, although in low isolated yields, in acidic conditions following an original mechanism. Whether such cyclization reactions occur from biologically relevant pyrimidine-based nucleosides is an open question of interest. Given the structures of thymidine-based antiviral drugs, our results suggest a new hypothetical mode of action for these drugs.

SUBMITTER: Gissot A

PROVIDER: S-EPMC7528289 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Intramolecular Michael Additions in Uridine Derivatives: Isolation of the Labile 5'O-C6 Cyclonucleoside.

Gissot Arnaud A Massip Stéphane S Barthélémy Philippe P

ACS omega 20200915 38

Uridine derivatives undergo a diastereospecific intramolecular hetero Michael addition onto uracil C6 to give cyclo-adducts. In contrast to the potent amine and thiol nucleophiles at the 5' position of ribose, which readily give the N- and S-cyclonucleosides in good yields, the cyclization reaction from the "natural" 5'-hydroxyl is tedious and has so far been overlooked most probably because of the thermodynamic instability of the O-cyclo-adduct. Here, we show that the O< ...[more]

PMID: 33015492

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