{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pirrone MG"],"funding":["NIAID NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["16043-16059"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7749010"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["85(24)"],"pubmed_abstract":["With a view to facilitating prediction of the exocyclic bond to the pyranoside ring in higher carbon sugars, a model is advanced that relates the relative configuration of the three stereogenic centers comprised of the branchpoint and of the two flanking centers (C4-C5-C6 in aldoheptoses and higher and C5-C6-C7 in sialic and ulosonic acids) to that of the simple ring-opened pentoses. Assignment of a given stereotriad as arabino, lxyo, ribo, or xylo by inspection of the Fischer projection formulas permits prediction of conformation of the exocyclic bond by comparison with the known solution (= crystal in all cases) conformations of the simple pentitols. More remote stereogenic centers in the side chain, as in the 8-position of <i>N</i>-acetylneuraminic acid, have little impact on the conformation of the exocyclic bond. On the basis of this model the conformation of the exocyclic bond in ring I of 6'-homologated 4,5-disubstituted 2-deoxystreptamine class aminoglycoside antibiotics was predicted and was borne out by NMR analysis of newly synthesized derivatives in D<sub>2</sub>O at pD5. The antiribosomal and antibacterial activity of these derivatives is briefly presented and discussed in terms of preorganization of the side chain for binding to the ribosomal decoding A site. It is anticipated that this predictive analysis will also find use in the prediction of the conformation of the exocyclic bonds in other 2-(1-hydroxyalkyl)-3-hydroxytetrahydropyrans and tetrahydrofurans."],"journal":["The Journal of organic chemistry"],"pubmed_title":["Predictive Analysis of the Side Chain Conformation of the Higher Carbon Sugars: Application to the Preorganization of the Aminoglycoside Ring 1 Side Chain for Binding to the Bacterial Ribosomal Decoding A Site."],"pmcid":["PMC7749010"],"funding_grant_id":["R01 GM062160","GM62160","R01 AI123352","AI123352"],"pubmed_authors":["Crich D","Haldimann K","Gysin M","Pirrone MG","Vasella A","Hobbie SN"],"additional_accession":[]},"is_claimable":false,"name":"Predictive Analysis of the Side Chain Conformation of the Higher Carbon Sugars: Application to the Preorganization of the Aminoglycoside Ring 1 Side Chain for Binding to the Bacterial Ribosomal Decoding A Site.","description":"With a view to facilitating prediction of the exocyclic bond to the pyranoside ring in higher carbon sugars, a model is advanced that relates the relative configuration of the three stereogenic centers comprised of the branchpoint and of the two flanking centers (C4-C5-C6 in aldoheptoses and higher and C5-C6-C7 in sialic and ulosonic acids) to that of the simple ring-opened pentoses. Assignment of a given stereotriad as arabino, lxyo, ribo, or xylo by inspection of the Fischer projection formulas permits prediction of conformation of the exocyclic bond by comparison with the known solution (= crystal in all cases) conformations of the simple pentitols. More remote stereogenic centers in the side chain, as in the 8-position of <i>N</i>-acetylneuraminic acid, have little impact on the conformation of the exocyclic bond. On the basis of this model the conformation of the exocyclic bond in ring I of 6'-homologated 4,5-disubstituted 2-deoxystreptamine class aminoglycoside antibiotics was predicted and was borne out by NMR analysis of newly synthesized derivatives in D<sub>2</sub>O at pD5. The antiribosomal and antibacterial activity of these derivatives is briefly presented and discussed in terms of preorganization of the side chain for binding to the ribosomal decoding A site. It is anticipated that this predictive analysis will also find use in the prediction of the conformation of the exocyclic bonds in other 2-(1-hydroxyalkyl)-3-hydroxytetrahydropyrans and tetrahydrofurans.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Dec","modification":"2022-02-11T13:59:00.204Z","creation":"2022-02-11T13:59:00.204Z"},"accession":"S-EPMC7749010","cross_references":{"pubmed":["32902280"],"doi":["10.1021/acs.joc.0c01836"]}}