Kinetic resolution is one of the most commonly used methods allowing access to enantioenriched compounds.The last two decades have seen the rapid development of kinetic resolutions enabled by N-heterocyclic carbene ca...Kinetic resolution is one of the most commonly used methods allowing access to enantioenriched compounds.The last two decades have seen the rapid development of kinetic resolutions enabled by N-heterocyclic carbene catalysis,and part of the achievements have been summarized in our previous review paper published in 2017.Since then,a series of new advances have been realized,and this review will provide an update of this field covering reports from mid-2017 to 2023.展开更多
The homochiral compounds play an important role in human health and pharmaceutical industry.Currently,the chromatographic enantioseparation has become one of the most effective and practical approach to obtain pure en...The homochiral compounds play an important role in human health and pharmaceutical industry.Currently,the chromatographic enantioseparation has become one of the most effective and practical approach to obtain pure enantiomers.Herein,the exploration of advanced materials,using as chromatographic chiral stationary phases for racemic separation,has attracted great attention.Thanks to their high enantioselectivity and controllable synthesis,the emerging chiral metal-organic frameworks (CMOFs)have been widely studied as the stationary phase in chromatographic technology.In this review,we will summarize the principles of synthetic strategies and mechanism of chiral microenvironment.In particular,the recent progress and research hotspot of CMOFs regarding as the chiral stationary phases in gas chromatography (GC),high-performance liquid chromatography (HPLC),and capillary electrochromatography (CEC),are elucidated systematically according to the published work.Last but not the least,we also highlight the challenges and perspectives of rational design of CMOFs,as well as their corresponding racemic separation.We envision that the review will provide a further understanding of CMOFs and facilitate the development of chromatographic enantioselective applications.展开更多
Chiral alcohols and amines are important structural units widely existing in pharmaceuticals,agrochemicals,and food additives.Dynamic kinetic resolution(DKR)is an efficient strategy to deliver optically active alcohol...Chiral alcohols and amines are important structural units widely existing in pharmaceuticals,agrochemicals,and food additives.Dynamic kinetic resolution(DKR)is an efficient strategy to deliver optically active alcohols and amines from their racemates.For the development of DKR method,racemization catalyst plays as a crucial element with the requirement of compatibility with the kinetic resolution(KR)system.In this paper,recent advance in the catalytic racemization of secondary alcohols and amines is summarized based on different types of racemizing intermediates,which are redox racemization via ketone/imine intermediates,racemization via radical intermediates,and racemization via carbocation intermediates.Enzymatic racemization of secondary alcohols and amines is also enclosed.展开更多
Introduction:Pulmonary hemorrhage(PHm)is a life-threatening complication that can occur after catheter-based interventions in patients with pulmonary vein stenosis(PVS).Inhaled racemic epinephrine(iRE)and tra-nexamic ...Introduction:Pulmonary hemorrhage(PHm)is a life-threatening complication that can occur after catheter-based interventions in patients with pulmonary vein stenosis(PVS).Inhaled racemic epinephrine(iRE)and tra-nexamic acid(iTXA)have been used in other conditions,but a standardized approach in PVS has not been described.We aimed to describe the current management of PHm after PVS catheter-based interventions.Methods:We present a retrospective review of episodes of PHm from July 2022 to February 2024.PHm was defined as frank blood suctioned from the endotracheal tube including blood-tinged secretions and>3%decrease in saturations and/or ventilatory changes with or without acute chest X-ray changes.Each individual episode of PHm was considered a separate event.Incidence was calculated based on the total number of PVS interventions during the study period.Results:Eleven episodes of PHm were identified out of 108 PVS interventions,resulting in an incidence of 10.2%.Five(45.5%)had primary PVS,and seven(63.6%)had bilateral PVS.The median age at PHm was 23 months(3-91 months).Four episodes were treated with iRE,five with both iRE and iTXA,and two with only iTXA due to a history of suprasystemic right ventricular pressures.Median time on mechanical ventila-tion after PHm was 24 h(15-72 h)and a median ICU stay of 2 days(1-8 days).Hemostasis was achieved in all events.There were no adverse events after iTXA,however,transient hypertension was observed after iRE which was dose-related.Conclusions:The implementation of a standardized protocol for the treatment of PHm in PVS has the potential to improve procedural planning,has a wider availability of medications,and greater awareness by the providers involved,possibly leading to earlier detection of PHm and appropriate treatment.展开更多
Deviations from chemical parity (PV) were evaluated with the search for very small enantiomeric excesses in a racemate prepared from non chiral materials and were detected by means of the circular dichroism (CD). Thus...Deviations from chemical parity (PV) were evaluated with the search for very small enantiomeric excesses in a racemate prepared from non chiral materials and were detected by means of the circular dichroism (CD). Thus, intensely light-absorbing perylenebiscarboximides were attached to axially chiral biphenyls for the amplification of CD effects by exciton interactions of the adjacent chromophores. A rapidly racemising system was applied for the exclusion of artifacts and compared with an analogous with locked chirally. A very slight enantiomeric excess was detected for the (M) enantiomer. Application of the method for other systems was suggested and relations to natural products discussed.展开更多
Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers...Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.展开更多
The crystal structure of tetrakis[(pyrrol-1-yl)methyl]methane was determined by X-ray diffraction measurement, and the result shows that it belongs to monoclinic crystal system, space group is P2 1/n, with a=0.9284(3...The crystal structure of tetrakis[(pyrrol-1-yl)methyl]methane was determined by X-ray diffraction measurement, and the result shows that it belongs to monoclinic crystal system, space group is P2 1/n, with a=0.9284(3) nm, b=1.0950(6) nm, c=1.8749(8) nm; α=γ= 90.00(4)°, β=103.63(3)°, V=1.8523(14) nm 3, Z=4, ρ calcd. =1.192 kg/m 3, μ=0.072 nm -1 , F(000)=712, R 1=0.0854, wR 2=0.1884. It has been found that the molecules exist in two enantiomeric states. Enantioselective self-assemblies such as one-dimensional molecular stacks in a single handedness, homochiral monolayers and a chiral superlattice are specified in this racemic crystal. In addition, a simple technique is advocated to distinguish chiral states from tetrahedral molecules in the solid state. The present R/S nomenclature of the tetracooradinated carbon centers is used solely for its convenience to distinguish the two enantiomeric states, but not used to determine the absolute configurations.展开更多
Introduction The formation of gelatin-containing mieroemulsionbased gels（MBGs） was first described in 1986 and the physical/structural characterization was carried out by a number of groups with a variety of techni...Introduction The formation of gelatin-containing mieroemulsionbased gels（MBGs） was first described in 1986 and the physical/structural characterization was carried out by a number of groups with a variety of techniques including tracer diffusion, electrical conductivity, NMR, X-ray and small angle neutron scattering. The MBGs were proposed to comprise an extensive, rigid, interconnected network of gelatin/water rods stabilized by a monolayer of surfactant, in coexistence with a po- pulation of conventional W/O microemulsion droplets.展开更多
L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with th...L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.展开更多
The enantioselective esterification of racemic 1-trimethylsilylethanol with acids catalyzed by lipase in organic solvent was successfully performed. The influence of some factors on the reaction was investigated. Amon...The enantioselective esterification of racemic 1-trimethylsilylethanol with acids catalyzed by lipase in organic solvent was successfully performed. The influence of some factors on the reaction was investigated. Among the four lipases explored, Candida rugosa lipase (CRL) showed the highest activity and enantioselectivity. Octanoic acid was the best acyl donor among the eleven acids studied and n-hexane was the most suitable medium for the reaction. The optimum shaking rate and temperature were found to be 150r·min-1 and 20℃ to 30℃, respectively. The enantiomeric excess of the remaining (5)-(-)-1-trimethylsilylethanol was 93% when substrate conversion was 53% upon incubation of the reaction mixture at 30℃, 150r·min-1 for 12 h.展开更多
Venom toxins are widely spread in nature, adopting diverse structures and functions. They often function by blocking or modulating important membrane protein targets thus can be promising therapeutic candidates and bi...Venom toxins are widely spread in nature, adopting diverse structures and functions. They often function by blocking or modulating important membrane protein targets thus can be promising therapeutic candidates and biophysical probes. In this review, we briefly discuss the total chemical synthesis of venom toxins including the different refolding strategies reported during the past decade as well as innovative approaches for structure determination.展开更多
1-Ethyl-2-fluoropyridinium tetrafluoroborate (FEP) was shown to be a very efficient coupling reagent for the synthesis of the hindered peptide with fast reaction speed, low racemization and good yields.
The deletion of the C-terminal arginine of the anaphylatoxin protein C5a reduces it receptor binding affinity.Understanding how C-terminal arginine affects the structure and bioactivity of C5a is important for the dev...The deletion of the C-terminal arginine of the anaphylatoxin protein C5a reduces it receptor binding affinity.Understanding how C-terminal arginine affects the structure and bioactivity of C5a is important for the development of C5a C-terminal mimics as drug candidates.Herein,we report the total chemical synthesis of rat C5a and its D-enantiomer with its C-terminal arginine deleted,namely L-rC5a-desArg and D-rC5a-desArg.The structure of rC5a-desArg was then determined by racemic crystallography for the first time.The C-terminal residues of rC5a-Arg were found to expand from the fourth helix in a continuous helical confo rmation.This C-terminal conformation is significantly different from that of the previously reported full-length of C5a,indicating that the deletion of C-terminal arginine residue could result in the destruction of a positively charged surface formed by two adjacent Arg residues in C5a.展开更多
Density functional theory （DFT） was applied to study the ground state geometries and isomerization processes of 1,1＇-binaphthalene-8,8＇-diol. Three isomers, denoted as ISO1, ISO2, and ISO3, were found, distinguish...Density functional theory （DFT） was applied to study the ground state geometries and isomerization processes of 1,1＇-binaphthalene-8,8＇-diol. Three isomers, denoted as ISO1, ISO2, and ISO3, were found, distinguished by different orientations of the OH groups, and each OH-orientational isomer has R- and S-enantiomer. The conformational stabilities of these isomers were investigated by tracking the energy change with respect to the ring-to-ring torsion. The inter-conversions between the three OH-orientational S-isomers were found to have quite low barriers owing to the nearly free rotation of OH groups around the O-C single bonds. The S-R enantiomerization of ISO1 and ISO2 can take place through the ring-ring torsion around the C1-C1/ single bond, either in the anti-rotation manner or in the syn-rotation manner. The barriers of the anti routes are lower than those of the corresponding syn routes by 87.95 and 75.04 kJ/mol. For the S-R enantiomerization of ISO3, only the anti route was found. The barriers for the anti route enantiomerizations of ISO1, ISO2, and ISO3 are 119.61, 120.43, and 121.59 kJ/mol, respectively. A parallel reaction mechanism via three anti enantiomerization routes was proposed for the racemization of 1,1＇-binaphthalene-8,8＇-diol.展开更多
The chiral oxiranecarboxylic acids or esters 2a-e were obtained with lipase (CCL) in aqueous-organic system.The ee and the absolute configurations of the products were determined.
Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid peptide approved by the FD...Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation(IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Drug molecule design based on structural information plays a crucial role and the activity of linaclotide still need to improve, while the structure of linaclotide remains unknown. In this work, linaclotide and its D-enantiomer were obtained through Fmoc solid phase peptide synthesis method and co-crystalized through racemic crystallization. The crystal structure showed that linaclotide has a tight, three-beta turns structure immobilized by three pairs of disulfide bonds.展开更多
The new shortcut synthesis route of(±)raphidecursinol 1,a racemic 8,4′-oxyneolignan compound,can be more easily achieved by the synthesis route,starting from readily available inexpensive 3,4,5-trimethoxybenzald...The new shortcut synthesis route of(±)raphidecursinol 1,a racemic 8,4′-oxyneolignan compound,can be more easily achieved by the synthesis route,starting from readily available inexpensive 3,4,5-trimethoxybenzaldehyde and 1,2,3-trihydroxybenzene.All structures were confirmed by ~1H NMR,IR and MS.展开更多
A system of structure depiction, as an extension of the wedge and hashed wedge bonds (Natta projection), and text notation is herein suggested that embodies more explicit information—or reduced over-statement as circ...A system of structure depiction, as an extension of the wedge and hashed wedge bonds (Natta projection), and text notation is herein suggested that embodies more explicit information—or reduced over-statement as circumstances warrant—on the stereochemical nature of the system at hand, in particular, for those cases where only the relative stereochemistry of a compound is known.展开更多
A new layered zincophosphate was synthesized under solvothermal conditions by employing racemic 1,2-diaminopropane as the structure-directing agent. The structure of the compound was solved by means of single-crystal ...A new layered zincophosphate was synthesized under solvothermal conditions by employing racemic 1,2-diaminopropane as the structure-directing agent. The structure of the compound was solved by means of single-crystal X-ray diffraction analysis. It crystallized in the monoclinic space group P2_1/c (No. 14) with a= 1.047 0(3) nm, b=0.787 31(18) nm, c=0.662 68(16) nm, β=103.120(5)°, V=0.532 0(2) nm 3 and Z=4. The structure is made up of anionic zincophosphate sheets stacked in an AAAA sequence. The individual sheet contains three- and four-membered rings and the infinite Zn-O-Zn chains can also be envisaged in the sheet. The charge-balancing diprotonated racemic 1,2-diaminopropane cations are sandwiched between the layers, whereas the inorganic layers are stabilized by strong H-bonds formed between the N atoms of the amine and the O atoms in the inorganic sheets.展开更多
文摘Kinetic resolution is one of the most commonly used methods allowing access to enantioenriched compounds.The last two decades have seen the rapid development of kinetic resolutions enabled by N-heterocyclic carbene catalysis,and part of the achievements have been summarized in our previous review paper published in 2017.Since then,a series of new advances have been realized,and this review will provide an update of this field covering reports from mid-2017 to 2023.
基金supported by the Science and Technology Project of Education Department of Jiangxi Province (No.GJJ201249)。
文摘The homochiral compounds play an important role in human health and pharmaceutical industry.Currently,the chromatographic enantioseparation has become one of the most effective and practical approach to obtain pure enantiomers.Herein,the exploration of advanced materials,using as chromatographic chiral stationary phases for racemic separation,has attracted great attention.Thanks to their high enantioselectivity and controllable synthesis,the emerging chiral metal-organic frameworks (CMOFs)have been widely studied as the stationary phase in chromatographic technology.In this review,we will summarize the principles of synthetic strategies and mechanism of chiral microenvironment.In particular,the recent progress and research hotspot of CMOFs regarding as the chiral stationary phases in gas chromatography (GC),high-performance liquid chromatography (HPLC),and capillary electrochromatography (CEC),are elucidated systematically according to the published work.Last but not the least,we also highlight the challenges and perspectives of rational design of CMOFs,as well as their corresponding racemic separation.We envision that the review will provide a further understanding of CMOFs and facilitate the development of chromatographic enantioselective applications.
基金the National Natural Science Foundation of China (No. 22271054)the “1000-Youth Talents Plan”Fudan University (start-up grant) for financial support.
文摘Chiral alcohols and amines are important structural units widely existing in pharmaceuticals,agrochemicals,and food additives.Dynamic kinetic resolution(DKR)is an efficient strategy to deliver optically active alcohols and amines from their racemates.For the development of DKR method,racemization catalyst plays as a crucial element with the requirement of compatibility with the kinetic resolution(KR)system.In this paper,recent advance in the catalytic racemization of secondary alcohols and amines is summarized based on different types of racemizing intermediates,which are redox racemization via ketone/imine intermediates,racemization via radical intermediates,and racemization via carbocation intermediates.Enzymatic racemization of secondary alcohols and amines is also enclosed.
文摘Introduction:Pulmonary hemorrhage(PHm)is a life-threatening complication that can occur after catheter-based interventions in patients with pulmonary vein stenosis(PVS).Inhaled racemic epinephrine(iRE)and tra-nexamic acid(iTXA)have been used in other conditions,but a standardized approach in PVS has not been described.We aimed to describe the current management of PHm after PVS catheter-based interventions.Methods:We present a retrospective review of episodes of PHm from July 2022 to February 2024.PHm was defined as frank blood suctioned from the endotracheal tube including blood-tinged secretions and>3%decrease in saturations and/or ventilatory changes with or without acute chest X-ray changes.Each individual episode of PHm was considered a separate event.Incidence was calculated based on the total number of PVS interventions during the study period.Results:Eleven episodes of PHm were identified out of 108 PVS interventions,resulting in an incidence of 10.2%.Five(45.5%)had primary PVS,and seven(63.6%)had bilateral PVS.The median age at PHm was 23 months(3-91 months).Four episodes were treated with iRE,five with both iRE and iTXA,and two with only iTXA due to a history of suprasystemic right ventricular pressures.Median time on mechanical ventila-tion after PHm was 24 h(15-72 h)and a median ICU stay of 2 days(1-8 days).Hemostasis was achieved in all events.There were no adverse events after iTXA,however,transient hypertension was observed after iRE which was dose-related.Conclusions:The implementation of a standardized protocol for the treatment of PHm in PVS has the potential to improve procedural planning,has a wider availability of medications,and greater awareness by the providers involved,possibly leading to earlier detection of PHm and appropriate treatment.
文摘Deviations from chemical parity (PV) were evaluated with the search for very small enantiomeric excesses in a racemate prepared from non chiral materials and were detected by means of the circular dichroism (CD). Thus, intensely light-absorbing perylenebiscarboximides were attached to axially chiral biphenyls for the amplification of CD effects by exciton interactions of the adjacent chromophores. A rapidly racemising system was applied for the exclusion of artifacts and compared with an analogous with locked chirally. A very slight enantiomeric excess was detected for the (M) enantiomer. Application of the method for other systems was suggested and relations to natural products discussed.
基金Supported by Zhejiang Provincial Bureau of Education, No. 20070227Zhejiang Medical Association, No.2007ZYC18Association of Zhejiang Hospital Administration, No. 2007AZHA-KEB312
文摘Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.
基金the National Natural Science Foundation of China(No.6 0 1710 0 8) and Shanghai Science and TechnologyCom mittee(No.0 2 14 nm0 0 5 )
文摘The crystal structure of tetrakis[(pyrrol-1-yl)methyl]methane was determined by X-ray diffraction measurement, and the result shows that it belongs to monoclinic crystal system, space group is P2 1/n, with a=0.9284(3) nm, b=1.0950(6) nm, c=1.8749(8) nm; α=γ= 90.00(4)°, β=103.63(3)°, V=1.8523(14) nm 3, Z=4, ρ calcd. =1.192 kg/m 3, μ=0.072 nm -1 , F(000)=712, R 1=0.0854, wR 2=0.1884. It has been found that the molecules exist in two enantiomeric states. Enantioselective self-assemblies such as one-dimensional molecular stacks in a single handedness, homochiral monolayers and a chiral superlattice are specified in this racemic crystal. In addition, a simple technique is advocated to distinguish chiral states from tetrahedral molecules in the solid state. The present R/S nomenclature of the tetracooradinated carbon centers is used solely for its convenience to distinguish the two enantiomeric states, but not used to determine the absolute configurations.
基金Supported by the Natural Science Foundation of Shandong Province in China(No.Y2003B01).
文摘Introduction The formation of gelatin-containing mieroemulsionbased gels（MBGs） was first described in 1986 and the physical/structural characterization was carried out by a number of groups with a variety of techniques including tracer diffusion, electrical conductivity, NMR, X-ray and small angle neutron scattering. The MBGs were proposed to comprise an extensive, rigid, interconnected network of gelatin/water rods stabilized by a monolayer of surfactant, in coexistence with a po- pulation of conventional W/O microemulsion droplets.
基金Research supported by The Analysis & Test Fund of Zhejiang Province.
文摘L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.
基金Supported by the National Natural Science Foundation of China (No. 20076019) the Natural Science Foundation of Guangdong Province (No. 000444).
文摘The enantioselective esterification of racemic 1-trimethylsilylethanol with acids catalyzed by lipase in organic solvent was successfully performed. The influence of some factors on the reaction was investigated. Among the four lipases explored, Candida rugosa lipase (CRL) showed the highest activity and enantioselectivity. Octanoic acid was the best acyl donor among the eleven acids studied and n-hexane was the most suitable medium for the reaction. The optimum shaking rate and temperature were found to be 150r·min-1 and 20℃ to 30℃, respectively. The enantiomeric excess of the remaining (5)-(-)-1-trimethylsilylethanol was 93% when substrate conversion was 53% upon incubation of the reaction mixture at 30℃, 150r·min-1 for 12 h.
文摘Venom toxins are widely spread in nature, adopting diverse structures and functions. They often function by blocking or modulating important membrane protein targets thus can be promising therapeutic candidates and biophysical probes. In this review, we briefly discuss the total chemical synthesis of venom toxins including the different refolding strategies reported during the past decade as well as innovative approaches for structure determination.
基金This work was financially supported by the National Natural Science Foundation of China!(9772045 )
文摘1-Ethyl-2-fluoropyridinium tetrafluoroborate (FEP) was shown to be a very efficient coupling reagent for the synthesis of the hindered peptide with fast reaction speed, low racemization and good yields.
基金supported by the National Key R&D Program of China(No.2017YFA0505200)the National Natural Science Foundation of China(Nos.21532004,21807001,91753205,81621002,21621003)。
文摘The deletion of the C-terminal arginine of the anaphylatoxin protein C5a reduces it receptor binding affinity.Understanding how C-terminal arginine affects the structure and bioactivity of C5a is important for the development of C5a C-terminal mimics as drug candidates.Herein,we report the total chemical synthesis of rat C5a and its D-enantiomer with its C-terminal arginine deleted,namely L-rC5a-desArg and D-rC5a-desArg.The structure of rC5a-desArg was then determined by racemic crystallography for the first time.The C-terminal residues of rC5a-Arg were found to expand from the fourth helix in a continuous helical confo rmation.This C-terminal conformation is significantly different from that of the previously reported full-length of C5a,indicating that the deletion of C-terminal arginine residue could result in the destruction of a positively charged surface formed by two adjacent Arg residues in C5a.
文摘Density functional theory （DFT） was applied to study the ground state geometries and isomerization processes of 1,1＇-binaphthalene-8,8＇-diol. Three isomers, denoted as ISO1, ISO2, and ISO3, were found, distinguished by different orientations of the OH groups, and each OH-orientational isomer has R- and S-enantiomer. The conformational stabilities of these isomers were investigated by tracking the energy change with respect to the ring-to-ring torsion. The inter-conversions between the three OH-orientational S-isomers were found to have quite low barriers owing to the nearly free rotation of OH groups around the O-C single bonds. The S-R enantiomerization of ISO1 and ISO2 can take place through the ring-ring torsion around the C1-C1/ single bond, either in the anti-rotation manner or in the syn-rotation manner. The barriers of the anti routes are lower than those of the corresponding syn routes by 87.95 and 75.04 kJ/mol. For the S-R enantiomerization of ISO3, only the anti route was found. The barriers for the anti route enantiomerizations of ISO1, ISO2, and ISO3 are 119.61, 120.43, and 121.59 kJ/mol, respectively. A parallel reaction mechanism via three anti enantiomerization routes was proposed for the racemization of 1,1＇-binaphthalene-8,8＇-diol.
文摘The chiral oxiranecarboxylic acids or esters 2a-e were obtained with lipase (CCL) in aqueous-organic system.The ee and the absolute configurations of the products were determined.
基金supported by the National Natural Science Foundation of China (NSFC No. 21572043)the Fundamental Research Funds for the Central Universities (No. PA2017GDQT0021)
文摘Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. Linaclotide is a 14-amino acid peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation(IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Drug molecule design based on structural information plays a crucial role and the activity of linaclotide still need to improve, while the structure of linaclotide remains unknown. In this work, linaclotide and its D-enantiomer were obtained through Fmoc solid phase peptide synthesis method and co-crystalized through racemic crystallization. The crystal structure showed that linaclotide has a tight, three-beta turns structure immobilized by three pairs of disulfide bonds.
基金the National Natural Science Foundation of China(No.29972013)
文摘The new shortcut synthesis route of(±)raphidecursinol 1,a racemic 8,4′-oxyneolignan compound,can be more easily achieved by the synthesis route,starting from readily available inexpensive 3,4,5-trimethoxybenzaldehyde and 1,2,3-trihydroxybenzene.All structures were confirmed by ~1H NMR,IR and MS.
文摘A system of structure depiction, as an extension of the wedge and hashed wedge bonds (Natta projection), and text notation is herein suggested that embodies more explicit information—or reduced over-statement as circumstances warrant—on the stereochemical nature of the system at hand, in particular, for those cases where only the relative stereochemistry of a compound is known.
基金Supported by the National Natural Science Foundation of China( No.2 993 10 10 )
文摘A new layered zincophosphate was synthesized under solvothermal conditions by employing racemic 1,2-diaminopropane as the structure-directing agent. The structure of the compound was solved by means of single-crystal X-ray diffraction analysis. It crystallized in the monoclinic space group P2_1/c (No. 14) with a= 1.047 0(3) nm, b=0.787 31(18) nm, c=0.662 68(16) nm, β=103.120(5)°, V=0.532 0(2) nm 3 and Z=4. The structure is made up of anionic zincophosphate sheets stacked in an AAAA sequence. The individual sheet contains three- and four-membered rings and the infinite Zn-O-Zn chains can also be envisaged in the sheet. The charge-balancing diprotonated racemic 1,2-diaminopropane cations are sandwiched between the layers, whereas the inorganic layers are stabilized by strong H-bonds formed between the N atoms of the amine and the O atoms in the inorganic sheets.
