dc.contributor.author | Hilko, David H | |
dc.contributor.author | Bornaghi, Laurent F | |
dc.contributor.author | Poulsen, Sally-Ann | |
dc.date.accessioned | 2021-02-25T04:17:13Z | |
dc.date.available | 2021-02-25T04:17:13Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 0022-3263 | |
dc.identifier.doi | 10.1021/acs.joc.8b01834 | |
dc.identifier.uri | http://hdl.handle.net/10072/382487 | |
dc.description.abstract | 2′-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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Chemical Society | |
dc.publisher.place | United States | |
dc.relation.ispartofpagefrom | 11944 | |
dc.relation.ispartofpageto | 11955 | |
dc.relation.ispartofissue | 19 | |
dc.relation.ispartofjournal | Journal of Organic Chemistry | |
dc.relation.ispartofvolume | 83 | |
dc.subject.fieldofresearch | Medicinal and biomolecular chemistry | |
dc.subject.fieldofresearch | Organic chemistry | |
dc.subject.fieldofresearch | Organic chemistry not elsewhere classified | |
dc.subject.fieldofresearchcode | 3404 | |
dc.subject.fieldofresearchcode | 3405 | |
dc.subject.fieldofresearchcode | 340599 | |
dc.title | Stereoselective Synthesis of Highly Functionalized Arabinosyl Nucleosides through Application of an N-Nitro Protecting Group | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dc.description.version | Accepted Manuscript (AM) | |
gro.faculty | Griffith Sciences, Griffith Institute for Drug Discovery | |
gro.rights.copyright | This 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.hasfulltext | Full Text | |
gro.griffith.author | Poulsen, Sally-Ann | |
gro.griffith.author | Hilko, David H. | |