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dc.contributor.authorHilko, David H
dc.contributor.authorBornaghi, Laurent F
dc.contributor.authorPoulsen, Sally-Ann
dc.date.accessioned2021-02-25T04:17:13Z
dc.date.available2021-02-25T04:17:13Z
dc.date.issued2018
dc.identifier.issn0022-3263
dc.identifier.doi10.1021/acs.joc.8b01834
dc.identifier.urihttp://hdl.handle.net/10072/382487
dc.description.abstract2′-Deoxy-2′,5-disubstituted arabinosyl uridine derivatives bearing a halogen (Cl, Br or I) at C2′ and an ethynyl group at C5 have been synthesized in 6 steps from 2′,3′,5′-tri-O-acetyl-5-iodo-uridine in overall yields of 61% (compound 3, Cl), 47% (compound 4, Br), and 19% (compound 5, I). Stabilization of a 2′-O-triflyl leaving group intermediate to overcome spontaneous intramolecular 2,2′-anhydro uridine formation was pivotal to the synthesis. Specifically, to favor SN2 reaction with a halogen nucleophile over intramolecular cyclization, the nucleophilicity of O-2 oxygen was reduced by incorporation of an adjacent electron withdrawing nitro substituent at N-3. The introduction of the 3-N-nitro group proceeded rapidly (nitronium trifluoroacetate, 1 min) and in quantitative yield. A one-pot method to remove the 3-N-nitro group by reductive nitration (zinc metal in acetic acid, 5 min) and the silyl protecting groups of the alkyne and 3′,5′ hydroxyls (fluoride reagent, 16 h) was established as the final synthetic step. This application of the 3-N-nitro protecting group addresses the significant shortfalls of the conventional approach to synthesis of 2′ modified nucleosides, wherein condensation of a 2′ modified sugar fragment with a pyrimidine base provides poor stereocontrol of N-glycosylation, low yields and incompatibility with 2′ iodo sugars.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom11944
dc.relation.ispartofpageto11955
dc.relation.ispartofissue19
dc.relation.ispartofjournalJournal of Organic Chemistry
dc.relation.ispartofvolume83
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchOrganic chemistry not elsewhere classified
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode340599
dc.titleStereoselective Synthesis of Highly Functionalized Arabinosyl Nucleosides through Application of an N-Nitro Protecting Group
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionAccepted Manuscript (AM)
gro.facultyGriffith Sciences, Griffith Institute for Drug Discovery
gro.rights.copyrightThis document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Organic Chemistry, copyright 2018 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.joc.8b01834
gro.hasfulltextFull Text
gro.griffith.authorPoulsen, Sally-Ann
gro.griffith.authorHilko, David H.


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