Stereoselective chemical glycosylation reactions are pivotal for preparing manifold biologically and medically important compounds,while mechanisms of chemical glycosylation reactions remain obscure and largely specul...Stereoselective chemical glycosylation reactions are pivotal for preparing manifold biologically and medically important compounds,while mechanisms of chemical glycosylation reactions remain obscure and largely speculative.Herein,we performed DFT calculations to delve into the multifaceted mechanistic details of glycosylation reactions,including the equilibria among reactive glycosyl triflate intermediates in solution,the stereoselectivity imparting protecting groups,solvent effects,base,and the anomeric effect.Our results provided theoretical corroboration to 2-OAc neighbouring group participation(NGP),the arming/disarming effect,the coordination theory of solvent effect on glycosylation stereochemistry,and the influence of solvent polarity on the reaction kinetics spanning the S_(N)1-S_(N)2 continuum.For the first time,the existence of putative contact-ion-pairs(CIP)of glycosyl oxocarbenium and triflate anion in organic solutions was theoretically confirmed with the identification of multiple ground state structures employing an implicit Solvation Model based on Density(SMD).Kinetics of nucleophilic attack of model glucosyl triflates by simple alcohol acceptors ethanol(EtOH)and trifluoroethanol(TFE),complexed with 2,4,6-tri-tert-butylpyrimidine(TTBP)were explored,revealing the essential role of the close accompanying base for rendering glycosidic bond formation thermodynamically favourable.Our work deepens the comprehension of the glycosylation mechanism,paving the way for the rational design and future advancement of efficient and environmentally friendly stereoselective glycosylation reactions.展开更多
Twenty one 1,3 dioxolanes with varieties of substituents at 2,4 positions were synthesized by acid catalyzed acetalization and ketalization reactions of glycerol and its modified derivatives. The assignment and qua...Twenty one 1,3 dioxolanes with varieties of substituents at 2,4 positions were synthesized by acid catalyzed acetalization and ketalization reactions of glycerol and its modified derivatives. The assignment and quantitative analyses of thermodynamically equilibrated cis and trans 1,3 dioxolanes were completed by 1H NMR. The stereoselective regularity was found in acetalization and ketalization reactions of glycerol and its modified derivatives. The stereoselective regularity of the condensation reactions was reasonably explained by anomeric effect and 2,4 nonbonded interaction.展开更多
Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of(+)-aigialospirol featuring a cyclic acetal tethered ring-closing metathesis.Through modeling,we were able to...Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of(+)-aigialospirol featuring a cyclic acetal tethered ring-closing metathesis.Through modeling,we were able to turn these two unexpected epimerizations to our advantage via modeling to ensure a successful and concise total synthesis,thereby firmly establishing cyclic acetal tethered RCM as a powerful strategy in natural product synthesis.Most importantly,calculations allowed us to fully understand the nature and the mechanistic course of these two epimerizations that were imperative to the total synthesis efforts.展开更多
基金X.W.L.would like to sincerely appreciate Nanyang Technological University(No.MOE Tier 1,RG9/20)Ministry of Education,Singapore(No.MOE-T2EP30120-0007)+1 种基金A*STAR(No.A20E5c0087)for their generous financial supportT.P.L.thanks the Startup Grant(No.21470001)from Henan University of Technology for the financial support.
文摘Stereoselective chemical glycosylation reactions are pivotal for preparing manifold biologically and medically important compounds,while mechanisms of chemical glycosylation reactions remain obscure and largely speculative.Herein,we performed DFT calculations to delve into the multifaceted mechanistic details of glycosylation reactions,including the equilibria among reactive glycosyl triflate intermediates in solution,the stereoselectivity imparting protecting groups,solvent effects,base,and the anomeric effect.Our results provided theoretical corroboration to 2-OAc neighbouring group participation(NGP),the arming/disarming effect,the coordination theory of solvent effect on glycosylation stereochemistry,and the influence of solvent polarity on the reaction kinetics spanning the S_(N)1-S_(N)2 continuum.For the first time,the existence of putative contact-ion-pairs(CIP)of glycosyl oxocarbenium and triflate anion in organic solutions was theoretically confirmed with the identification of multiple ground state structures employing an implicit Solvation Model based on Density(SMD).Kinetics of nucleophilic attack of model glucosyl triflates by simple alcohol acceptors ethanol(EtOH)and trifluoroethanol(TFE),complexed with 2,4,6-tri-tert-butylpyrimidine(TTBP)were explored,revealing the essential role of the close accompanying base for rendering glycosidic bond formation thermodynamically favourable.Our work deepens the comprehension of the glycosylation mechanism,paving the way for the rational design and future advancement of efficient and environmentally friendly stereoselective glycosylation reactions.
文摘Twenty one 1,3 dioxolanes with varieties of substituents at 2,4 positions were synthesized by acid catalyzed acetalization and ketalization reactions of glycerol and its modified derivatives. The assignment and quantitative analyses of thermodynamically equilibrated cis and trans 1,3 dioxolanes were completed by 1H NMR. The stereoselective regularity was found in acetalization and ketalization reactions of glycerol and its modified derivatives. The stereoselective regularity of the condensation reactions was reasonably explained by anomeric effect and 2,4 nonbonded interaction.
基金PRF-AC(42106) for support and Dr.Victor Young and Ben Kucera(University of Minnesota) for X-ray analysis.CCG thanks UW for an NIH-CBI Training Grant
文摘Two remarkable epimerization processes were uncovered during our pursuit of an enantioselective synthesis of(+)-aigialospirol featuring a cyclic acetal tethered ring-closing metathesis.Through modeling,we were able to turn these two unexpected epimerizations to our advantage via modeling to ensure a successful and concise total synthesis,thereby firmly establishing cyclic acetal tethered RCM as a powerful strategy in natural product synthesis.Most importantly,calculations allowed us to fully understand the nature and the mechanistic course of these two epimerizations that were imperative to the total synthesis efforts.
