Iminosugars,a class of polyhydroxylated cyclic alkaloids with intriguing properties,hold promising therapeutic potentials against a broad spectrum of enveloped viruses,including DENV,HCV,HIV,and influenza viruses.Mech...Iminosugars,a class of polyhydroxylated cyclic alkaloids with intriguing properties,hold promising therapeutic potentials against a broad spectrum of enveloped viruses,including DENV,HCV,HIV,and influenza viruses.Mechanistically,iminosugars act as the competitive inhibitors of host endoplasmic reticularα-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins,which thereby exerts antiviral effects.Remarkably,the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins.Therefore,extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents.This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses,as well as the understandings of their antiviral mechanisms.展开更多
Three new iminosugar-containing KRN7000 （also referred to as α-GalCer） analogues were designed and syn- thesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar struc-...Three new iminosugar-containing KRN7000 （also referred to as α-GalCer） analogues were designed and syn- thesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar struc- tures were connected with ceramide in different manners with a C-glycosidic bond instead of the O-glycosidic bond. To our knowledge, this is the first report in which iminosugars are incorporated in KRN7000 structure modifica- tions. The synthetic compounds were evaluated for their ability to stimulate cytokine release. The results may benefit better understanding of structure-activity relationships and facilitate future design of more KRNT000 derivatives.展开更多
Different novel fused multicyclic iminosugars were synthesized from D-ribose tosylate,aniline and vinyl ethyl ether by one-pot three-component stereoselective[4+2]reaction at different temperatures.The iminium-ion is ...Different novel fused multicyclic iminosugars were synthesized from D-ribose tosylate,aniline and vinyl ethyl ether by one-pot three-component stereoselective[4+2]reaction at different temperatures.The iminium-ion is the key intermediate for the reaction.As a result,several complex fused iminosugars 3a were obtained by aza-Diels-Alder mechanism at 60℃,while a series of aza-C-glycosides 5a were prepared by Mannich reaction at room temperature accompanied by another tetrahydroquinoline-fused iminosugars 4a(tricyclic derivatives)through aza-Diels-Alder cycloaddition.This strategy will help to construct structurally diverse and bioactive iminosugar analogues.展开更多
A series of new N-substituted iminosugars were successfully synthesized through a general synthetic route from D-xylose derivative.This approach provided a convenient access to the synthesis of N-alkylated iminosugars...A series of new N-substituted iminosugars were successfully synthesized through a general synthetic route from D-xylose derivative.This approach provided a convenient access to the synthesis of N-alkylated iminosugars as po-tential glucosidase inhibitors,which included a reaction of reductive amination.Various N-alkylated iminosugars were prepared in good yields with high stereoselectivity.展开更多
2-Oxo-3R,4S,5S,6S-tetraethoxyazepane was conveniently synthesized from D-glucono-1, 5-1actone with a yield of 10% overall. The key step of synthetic route-reductive 1,6-cyclization was completed efficiently by using P...2-Oxo-3R,4S,5S,6S-tetraethoxyazepane was conveniently synthesized from D-glucono-1, 5-1actone with a yield of 10% overall. The key step of synthetic route-reductive 1,6-cyclization was completed efficiently by using Ph3P to give the expected lactam.展开更多
A novel C-branched polyhydroxylated cyclic nitrone 25.which could be a valuable intermediate for the synthesis of C-branched pyrrolidine iminosugars,was synthesized starting from the commercially available i.-arabinos...A novel C-branched polyhydroxylated cyclic nitrone 25.which could be a valuable intermediate for the synthesis of C-branched pyrrolidine iminosugars,was synthesized starting from the commercially available i.-arabinose in 29.0%total yield.展开更多
Secondary metabolites and synthetic iminosugars that structurally resemble monosaccharides are potent inhibitors of a-glucosidase activity. The enzyme is core in cleaving sucrose in phloem feeding insects and it also ...Secondary metabolites and synthetic iminosugars that structurally resemble monosaccharides are potent inhibitors of a-glucosidase activity. The enzyme is core in cleaving sucrose in phloem feeding insects and it also plays a crucial role of reducing osmotic stress via the formation of oligosaccharides. Inhibition of hydrolysis by iminosug- ars should result in nutritional deficiencies and/or disruption of normal osmoregulation. Deoxynojirimycin （DNJ） and 2 N-alkylated analogs [N-butyl DNJ （NB-DNJ） and N-nonyl DNJ （NN-DNJ）] were the major iminosugars used throughout the study. The extensive experiments conducted with a-glucosidase of the whitefly Bemisia tabaci indicated the competitive nature of inhibition and that the hydrophilic DNJ is a potent inhibitor in com- parison to the more hydrophobic NB-DNJ and NN-DNJ compounds. The same inhibitory pattern was observed with the psyllid Cacopsylla bidens a-glucosidase. In contrast to the above pattern, enzymes of the aphids, Myzus persicae and Aphis gossypii were more sen- sitive to the hydrophobic iminosugars as compared to DNJ. In vivo experiments in which adult B. tabaci were fed dietary iminosugars, show that the hydrophilic DNJ was far less toxic than the lipophilic NB-DNJ and NN-DNJ. It is proposed that this pattern is attributed to the better accessibility of the hydrophobic NN-DNJ to the a-glucosidase membrane- bound compartment in the midgut. Based on the inhibitory effects of certain polyhydroxy N-alkylated iminosugars, a-glucosidase of phloem feeding hemipterans could serve as an attractive target site for developing novel pest control agents.展开更多
基金National Key Research and Development Program of China(Nos.2023YFC2606500 to X.Deng)National Natural Science Foundation of China(Nos.22377151 to X.Deng)+2 种基金the Hunan Provincial Key Research and Development Project(Nos.2021WK2005 to X.Deng)the Hunan Provincial Science Fund for Distinguished Young Scholars(Nos.2023JJ10083 to X.Deng)Huxiang High-Level Talent Gathering Project(Nos.2022RC4029)from the Science and Technology Department of Hunan province for the financial supports.
文摘Iminosugars,a class of polyhydroxylated cyclic alkaloids with intriguing properties,hold promising therapeutic potentials against a broad spectrum of enveloped viruses,including DENV,HCV,HIV,and influenza viruses.Mechanistically,iminosugars act as the competitive inhibitors of host endoplasmic reticularα-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins,which thereby exerts antiviral effects.Remarkably,the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins.Therefore,extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents.This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses,as well as the understandings of their antiviral mechanisms.
基金This work was financially supported by the National Natural Science Foundation of China （No. 21232002）.
文摘Three new iminosugar-containing KRN7000 （also referred to as α-GalCer） analogues were designed and syn- thesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar struc- tures were connected with ceramide in different manners with a C-glycosidic bond instead of the O-glycosidic bond. To our knowledge, this is the first report in which iminosugars are incorporated in KRN7000 structure modifica- tions. The synthetic compounds were evaluated for their ability to stimulate cytokine release. The results may benefit better understanding of structure-activity relationships and facilitate future design of more KRNT000 derivatives.
基金supported by the National Natural Science Foundation of China(NSFC)(21772031)the Natural Science Foundations of Hebei Province(B2019201398).
文摘Different novel fused multicyclic iminosugars were synthesized from D-ribose tosylate,aniline and vinyl ethyl ether by one-pot three-component stereoselective[4+2]reaction at different temperatures.The iminium-ion is the key intermediate for the reaction.As a result,several complex fused iminosugars 3a were obtained by aza-Diels-Alder mechanism at 60℃,while a series of aza-C-glycosides 5a were prepared by Mannich reaction at room temperature accompanied by another tetrahydroquinoline-fused iminosugars 4a(tricyclic derivatives)through aza-Diels-Alder cycloaddition.This strategy will help to construct structurally diverse and bioactive iminosugar analogues.
基金This work was supported by the National Natural Science Foundation of China(Nos.21372215 and 20972151).
文摘A series of new N-substituted iminosugars were successfully synthesized through a general synthetic route from D-xylose derivative.This approach provided a convenient access to the synthesis of N-alkylated iminosugars as po-tential glucosidase inhibitors,which included a reaction of reductive amination.Various N-alkylated iminosugars were prepared in good yields with high stereoselectivity.
基金the Graduate Education Innovation Foundation of Nanjing University of Science & Technology (No.200705).
文摘2-Oxo-3R,4S,5S,6S-tetraethoxyazepane was conveniently synthesized from D-glucono-1, 5-1actone with a yield of 10% overall. The key step of synthetic route-reductive 1,6-cyclization was completed efficiently by using Ph3P to give the expected lactam.
基金Financial support from National Basic Research Program of China(No.2012CB822101)the National Natural Science Foundation of China(No.21272240)+1 种基金National Science and Technology Major Projects for "Major New Drugs Innovation and Development"(No.2013ZX09508104)National Engineering Research Center for Carbohydrate Synthesis of Jiangxi Normal University
文摘A novel C-branched polyhydroxylated cyclic nitrone 25.which could be a valuable intermediate for the synthesis of C-branched pyrrolidine iminosugars,was synthesized starting from the commercially available i.-arabinose in 29.0%total yield.
文摘Secondary metabolites and synthetic iminosugars that structurally resemble monosaccharides are potent inhibitors of a-glucosidase activity. The enzyme is core in cleaving sucrose in phloem feeding insects and it also plays a crucial role of reducing osmotic stress via the formation of oligosaccharides. Inhibition of hydrolysis by iminosug- ars should result in nutritional deficiencies and/or disruption of normal osmoregulation. Deoxynojirimycin （DNJ） and 2 N-alkylated analogs [N-butyl DNJ （NB-DNJ） and N-nonyl DNJ （NN-DNJ）] were the major iminosugars used throughout the study. The extensive experiments conducted with a-glucosidase of the whitefly Bemisia tabaci indicated the competitive nature of inhibition and that the hydrophilic DNJ is a potent inhibitor in com- parison to the more hydrophobic NB-DNJ and NN-DNJ compounds. The same inhibitory pattern was observed with the psyllid Cacopsylla bidens a-glucosidase. In contrast to the above pattern, enzymes of the aphids, Myzus persicae and Aphis gossypii were more sen- sitive to the hydrophobic iminosugars as compared to DNJ. In vivo experiments in which adult B. tabaci were fed dietary iminosugars, show that the hydrophilic DNJ was far less toxic than the lipophilic NB-DNJ and NN-DNJ. It is proposed that this pattern is attributed to the better accessibility of the hydrophobic NN-DNJ to the a-glucosidase membrane- bound compartment in the midgut. Based on the inhibitory effects of certain polyhydroxy N-alkylated iminosugars, a-glucosidase of phloem feeding hemipterans could serve as an attractive target site for developing novel pest control agents.
