biostudies-literaturePirrone MGNIAID NIH HHSNational Institutes of HealthNIGMS NIH HHS16043-16059https://www.ebi.ac.uk/biostudies/studies/S-EPMC7749010biostudies-literatureUnknown85(24)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 D₂O 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.The Journal of organic chemistryPredictive 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.PMC7749010R01 GM062160GM62160R01 AI123352AI123352Crich DHaldimann KGysin MPirrone MGVasella AHobbie SNfalsePredictive 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.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 D₂O 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.2020-01-01T00:00:00Z2020 Dec2022-02-11T13:59:00.204Z2022-02-11T13:59:00.204ZS-EPMC77490103290228010.1021/acs.joc.0c01836