Stereoselective construction of 2-deoxy-glycosidic linkages has been achieved by the 1,2-sulfur migration/glycosylation and desulfurization strategy;however,current protocols suffer from harsh reaction conditions and ...Stereoselective construction of 2-deoxy-glycosidic linkages has been achieved by the 1,2-sulfur migration/glycosylation and desulfurization strategy;however,current protocols suffer from harsh reaction conditions and unsatisfactory stereoselectivity,particularly during the 1,2-S-migration/glycosylation step.With 2-O-resided(o-alkynyl)benzoate and anomeric p-methoxyphenylsulfenyl groups as the initiating and migrating groups,respectively,a novel protocol for the efficient synthesis of 2-deoxy-glycosides via the 1,2-sulfur migration/glycosylation-desulfurization strategy has been established,which is featured by the mild and catalytic reaction conditions,expanded substrate scope,as well as good to excellent diastereoselectivity.Mechanism studies determined hyperconjugation-stabilized oxocarbenium ion as the key intermediate,achieving high 1,2-trans stereocontrol through thermodynamic,steric,as well as electrostatic effects.This provides the fresh insight for the operative mechanism of the 1,2-sulfur migration/glycosylation and desulfurization strategy,further corroborated by the elaborately designed testing reactions and DFT calculations.Moreover,the synthetic potential of the newly established protocol was examined by the practical synthesis of natural product,culminating in the acquisition of digoxin from acetylated digoxigenin in 25% overall yield through an 8-step longest linear sequence.展开更多
2-Deoxy glycosides are widely presented in natural products and clinical reagents.The presence of 2-deoxy glycosides is essential for bioactivities of these compounds.This report provides an overview of the recent adv...2-Deoxy glycosides are widely presented in natural products and clinical reagents.The presence of 2-deoxy glycosides is essential for bioactivities of these compounds.This report provides an overview of the recent advances in the stereoselective synthesis of 2-deoxy glycosides.Particularly,the contents of this review covered the work published since the earlier reviews on this topic by Marzabadi(2000),Lowary(2009),Ding(2012) and Nagorny(2012).展开更多
Mutants of the strain producing natamycin, Streptomyces gilvosporeus, were obtained after space-flight mutation. With respect to the sand spores and slant spores, the mutation ratios were up to 67.6% and 78.3% and the...Mutants of the strain producing natamycin, Streptomyces gilvosporeus, were obtained after space-flight mutation. With respect to the sand spores and slant spores, the mutation ratios were up to 67.6% and 78.3% and the survival ratio was 43.1% and 3.0%, respectively. An improved mutant producing natamycin, S. gilvosporeus LK-45, was screened, which showed natamycin productivity of 1420mg·L^-1. A mutant resistant to 2-deoxy glucose, S.gilvosporeus LK-119, was further obtained using a＇rational screening procedure. The natamycin productivity of 1940mg·L^-1 was achieved when glucose was used as the carbon source.展开更多
To investigate the malondialdehyde（MDA） levels,paraoxonase1（PON1） activity and 8-hydroxy 2-deoxyguanosine（8-OHd G） levels in the primary open angle glaucoma（POAG） patient.Blood samples from 52 healthy individu...To investigate the malondialdehyde（MDA） levels,paraoxonase1（PON1） activity and 8-hydroxy 2-deoxyguanosine（8-OHd G） levels in the primary open angle glaucoma（POAG） patient.Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHd G by high-performance liquid chromatography（HPLC） and PON1 by spectrophotometry.The data obtained were analyzed statistically.MDA levels were 10.46±8.4 and 4.70±1.79 μmol; PON1 levels were 121 ±39.55 and 161.62 ±60.22 U/m L; and 8-OHd G values were1.32 ±0.53/10~6 d G and 0.47 ±0.27/10~6 d G in the POAG patients and the control group,respectively.The difference was significant in MDA levels,8-OHd G levels and PON1 activity in POAG patients in comparison with controls（P 〈0.001）.We concluded that the observed increase in MDA and 8-OHd G levels may be correlated with decreased PON1 activity.Oxidative stress plays an important role in glaucoma development.展开更多
RNase A catalyzes the hydrolysis of ribonucleic acids to form oligonucleotide fragments containing pyrimidineribonucleoside 2’, 3’-cyclic phosphate at the 3’-termini, which are then further hydrolyzed to produce ol...RNase A catalyzes the hydrolysis of ribonucleic acids to form oligonucleotide fragments containing pyrimidineribonucleoside 2’, 3’-cyclic phosphate at the 3’-termini, which are then further hydrolyzed to produce oligonucleotide fragments with 3’ -phosphate group as the final products. This enzyme can also catalyze the formation of internucleotide linkage from pyrimidineribonucleoside 2’, 3’-cyclic phosphate and a nucleoside component with展开更多
Vascular endothelial growth factor(VEGF)is up-regulated in the vast majority of human tumors.The up-regulation of VEGF not only plays important roles in tumor angiogenesis,but also provides a target for tumor treatmen...Vascular endothelial growth factor(VEGF)is up-regulated in the vast majority of human tumors.The up-regulation of VEGF not only plays important roles in tumor angiogenesis,but also provides a target for tumor treatment with small interfering RNA(siRNA)that targets VEGF;however,it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF.A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line.In this study,we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells,and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents.CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs.The expression of VEGF was effectively suppressed by VEGF-specific siRNAs,measured by ELISA,Western blot analysis and RT-PCR.Furthermore,experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells.VEGF-specific siRNAs were modified with 2′-deoxy,then injected into the tumors,and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs.Tumor growth was reduced significantly after 3 weeks'treatment.These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression,such as CNE,and VEGF-specific siRNAs modified with 2′-deoxy can be used as potential agents for tumor therapy.展开更多
Comprehensive Summary The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate molecules.However,their stereochemistry control in glycosy...Comprehensive Summary The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate molecules.However,their stereochemistry control in glycosylation represents one of the most challenging tasks in carbohydrate chemistry.展开更多
基金financially supported by the National Natural Science Foundation of China(22467012 and 22177042)The generous support from Beijing Municipal Commission of Science and Technology(L212015)was also highly appreciated.
文摘Stereoselective construction of 2-deoxy-glycosidic linkages has been achieved by the 1,2-sulfur migration/glycosylation and desulfurization strategy;however,current protocols suffer from harsh reaction conditions and unsatisfactory stereoselectivity,particularly during the 1,2-S-migration/glycosylation step.With 2-O-resided(o-alkynyl)benzoate and anomeric p-methoxyphenylsulfenyl groups as the initiating and migrating groups,respectively,a novel protocol for the efficient synthesis of 2-deoxy-glycosides via the 1,2-sulfur migration/glycosylation-desulfurization strategy has been established,which is featured by the mild and catalytic reaction conditions,expanded substrate scope,as well as good to excellent diastereoselectivity.Mechanism studies determined hyperconjugation-stabilized oxocarbenium ion as the key intermediate,achieving high 1,2-trans stereocontrol through thermodynamic,steric,as well as electrostatic effects.This provides the fresh insight for the operative mechanism of the 1,2-sulfur migration/glycosylation and desulfurization strategy,further corroborated by the elaborately designed testing reactions and DFT calculations.Moreover,the synthetic potential of the newly established protocol was examined by the practical synthesis of natural product,culminating in the acquisition of digoxin from acetylated digoxigenin in 25% overall yield through an 8-step longest linear sequence.
基金supported by the National Natural Science Foundation of China(21272082,21402055,21472054,21672077)the State Key Laboratory of Bio-organic and Natural Products Chemistry(SKLBNPC13425)+3 种基金Natural Science Funds of Hubei Province for Distinguished Young Scholars(2015CFA035)"Thousand Talents Program"Young Investigator AwardWuhan Creative Talent Development FundHuazhong University of Science and Technology(2014ZZGH015)
文摘2-Deoxy glycosides are widely presented in natural products and clinical reagents.The presence of 2-deoxy glycosides is essential for bioactivities of these compounds.This report provides an overview of the recent advances in the stereoselective synthesis of 2-deoxy glycosides.Particularly,the contents of this review covered the work published since the earlier reviews on this topic by Marzabadi(2000),Lowary(2009),Ding(2012) and Nagorny(2012).
文摘Mutants of the strain producing natamycin, Streptomyces gilvosporeus, were obtained after space-flight mutation. With respect to the sand spores and slant spores, the mutation ratios were up to 67.6% and 78.3% and the survival ratio was 43.1% and 3.0%, respectively. An improved mutant producing natamycin, S. gilvosporeus LK-45, was screened, which showed natamycin productivity of 1420mg·L^-1. A mutant resistant to 2-deoxy glucose, S.gilvosporeus LK-119, was further obtained using a＇rational screening procedure. The natamycin productivity of 1940mg·L^-1 was achieved when glucose was used as the carbon source.
文摘To investigate the malondialdehyde（MDA） levels,paraoxonase1（PON1） activity and 8-hydroxy 2-deoxyguanosine（8-OHd G） levels in the primary open angle glaucoma（POAG） patient.Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHd G by high-performance liquid chromatography（HPLC） and PON1 by spectrophotometry.The data obtained were analyzed statistically.MDA levels were 10.46±8.4 and 4.70±1.79 μmol; PON1 levels were 121 ±39.55 and 161.62 ±60.22 U/m L; and 8-OHd G values were1.32 ±0.53/10~6 d G and 0.47 ±0.27/10~6 d G in the POAG patients and the control group,respectively.The difference was significant in MDA levels,8-OHd G levels and PON1 activity in POAG patients in comparison with controls（P 〈0.001）.We concluded that the observed increase in MDA and 8-OHd G levels may be correlated with decreased PON1 activity.Oxidative stress plays an important role in glaucoma development.
基金Project supported by the National Natural Science Foundation of China
文摘RNase A catalyzes the hydrolysis of ribonucleic acids to form oligonucleotide fragments containing pyrimidineribonucleoside 2’, 3’-cyclic phosphate at the 3’-termini, which are then further hydrolyzed to produce oligonucleotide fragments with 3’ -phosphate group as the final products. This enzyme can also catalyze the formation of internucleotide linkage from pyrimidineribonucleoside 2’, 3’-cyclic phosphate and a nucleoside component with
基金Natural Science Foundation of Guangdong Province,China(Grant No.012402)
文摘Vascular endothelial growth factor(VEGF)is up-regulated in the vast majority of human tumors.The up-regulation of VEGF not only plays important roles in tumor angiogenesis,but also provides a target for tumor treatment with small interfering RNA(siRNA)that targets VEGF;however,it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF.A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line.In this study,we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells,and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents.CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs.The expression of VEGF was effectively suppressed by VEGF-specific siRNAs,measured by ELISA,Western blot analysis and RT-PCR.Furthermore,experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells.VEGF-specific siRNAs were modified with 2′-deoxy,then injected into the tumors,and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs.Tumor growth was reduced significantly after 3 weeks'treatment.These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression,such as CNE,and VEGF-specific siRNAs modified with 2′-deoxy can be used as potential agents for tumor therapy.
基金supported by the National Natural Science Foundation of China(Nos.21977115 and 21672248).
文摘Comprehensive Summary The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate molecules.However,their stereochemistry control in glycosylation represents one of the most challenging tasks in carbohydrate chemistry.
