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 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
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
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.
Seven chiral compounds were resolved on cellulose tris (3,5-dimethylphenylcarbamate) chiral stationary phase (CDMPC-CSP) using n-hexane/alcohol as mobile phase. Solvent strength and structural characteristics of the c...Seven chiral compounds were resolved on cellulose tris (3,5-dimethylphenylcarbamate) chiral stationary phase (CDMPC-CSP) using n-hexane/alcohol as mobile phase. Solvent strength and structural characteristics of the compounds effecting on the retention and resolution were discussed. Satisfactory separation was obtained.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
A one-dimensional chain aluminophosphate C1.5H7.5N1.5Al0.5PO4 containing diprotonated racemic 1, 2-diaminopropane cations was synthesized from an alcoholic system. The compound consists of infinite inorganic [AlP2O8]...A one-dimensional chain aluminophosphate C1.5H7.5N1.5Al0.5PO4 containing diprotonated racemic 1, 2-diaminopropane cations was synthesized from an alcoholic system. The compound consists of infinite inorganic [AlP2O8] chains of alternately connected AlO4 and PO2(=O)2 tetrahedral units and the racemic template molecules. The macroanionic chains contain corner-shared double four-membered rings.展开更多
Enantioseparation of salbutamol solute was carried out in liquid-supported membrane by using a polyvinylidene fluoride hollow-fiber module. The enantioselective transport of solute was facilitated by combinatorial chi...Enantioseparation of salbutamol solute was carried out in liquid-supported membrane by using a polyvinylidene fluoride hollow-fiber module. The enantioselective transport of solute was facilitated by combinatorial chiral selectors, which were dissolved in toluene organic solvent. The effects of molar concentration ratios of salbutamol to combinatorial chiral selectors, and the pH value of buffer solution on enantioseparation were investigated. The results show that when the molar concentration ratio is 2∶1∶1, the maximum separation factor and enantiomer excess are 1.49 and 19.74%, respectively, and the R-enantiomer flux is more than S-enantiomer; the pH value of buffer solution influences the performances of enantioseparartion obviously, and the appropriate range of pH value is 7.07.2.展开更多
The optically active R-4-phenyl-2-hydroxy butyrates were prepared by esterification of the racemic acid or transesterification of the racemic ester catalyzed by lipase from Candida cyclindra (CCL) in organic media.
The present study involves the enantioselective resolution of racemic Felodipine by using free and immobilized forms of microbial cultures as well as an enzyme (Lipase AP6). Among the microbial cultures employed in th...The present study involves the enantioselective resolution of racemic Felodipine by using free and immobilized forms of microbial cultures as well as an enzyme (Lipase AP6). Among the microbial cultures employed in the present study, Aspergillus niger, Sphingomonas paucimobilis, Cunninghamella elegans, Escherichia coli, Pseudomonas putida and Cunninghamella blakesleeana were found to possess capability of enantioselective resolution of racemic Felodipine. The enantiomeric excess (ee%) of Felodipine after reaction catalyzed by whole-cell A. niger and S. paucimobilis was found as 81.59 and 71.67%, respectively. Immobilization enhanced the enantioselectivity (enantiomeric ratio (E)) of the biocatalysts and hence this led to enhanced enantiomeric purity of the drug. The ee% values were found to be enhanced in reactions catalyzed by A. niger and S. paucimobilis cultures after immobilization as 98.27 and 93.56%, respectively. Enantiomeric ratio (E) of the reactions catalyzed by all the biocatalysts has been improved after immobilization. E value of the reaction catalyzed by immobilized A. niger was found to be excellent (E > 100) and hence the drug showed high enantiomeric purity. In lipase AP6 catalyzed study, the enantioselectivity was enhanced after immobilization with excellent E value, which led to enhanced enantiomeric purity of the drug (99.21% ee%).展开更多
Chirality is a common phenomenon in nature,playing a crucial role in fields such as pharmaceuticals[1],materials science[2],and life sciences[3].The catalytic synthesis of chiral molecules,particularly those bearing m...Chirality is a common phenomenon in nature,playing a crucial role in fields such as pharmaceuticals[1],materials science[2],and life sciences[3].The catalytic synthesis of chiral molecules,particularly those bearing multiple stereogenic elements(e.g.,central,axial,planar,helical,or inherent chirality),has gained tremendous attention in organic synthesis[4].展开更多
Asymmetric kinetic resolution polymerization(AKRP)provides an ideal way to obtain highly isotactic polymers and optically pure monomers.However,highly enantioselective AKRP process is still rarely reported to date.And...Asymmetric kinetic resolution polymerization(AKRP)provides an ideal way to obtain highly isotactic polymers and optically pure monomers.However,highly enantioselective AKRP process is still rarely reported to date.And the AKRP of racemic lactide(rac-LA)remains a challenge.Here,in this paper,the AKRP of rac-LA was achieved by means of an enhanced enantiomorphic site control,delivering isotactic polylactide(PLA)and enantiomeric enriched lactide(LA)with the highest kinetic resolution coefficients(k_(rel))to date.Different from common(Salen)Al complex,a series of new chiral(BisSalen)Al complexes were designed and synthesized to form a more confined chiral microenvironment and further improve specific discrimination of rac-LA.The NMR analysis,kinetic studies,the activation parameters and thermal properties of the resulting PLAs provided strong evidence for enhanced enantiomorphic site control.This work enables highly enantioselective AKRP of rac-LA.展开更多
Dielectric chiral metasurface is a new type of planar and efficient chiral optical device that shows strong circular dichroism or optical activity,which has important application potential in optical sensing and displ...Dielectric chiral metasurface is a new type of planar and efficient chiral optical device that shows strong circular dichroism or optical activity,which has important application potential in optical sensing and display.However,the two types of chiral optical responses in conventional chiral metasurfaces are often interdependent,as their modulation of the amplitudes and phases of orthogonal circularly polarized components is correlated,which limits the further progress of chiral meta-devices.Here we propose a new scheme for independently designing the circular dichroism and optical activity of chiral metasurfaces to further control the polarization and wavefront of transmitted waves.Inspired by mixtures of chiral molecular isomers,we use the dielectric isomer resonators to form“super-units”instead of single meta-atoms for chiral responses in terahertz band,which is called racemic metasurface.By introducing two levels of Pancharatnam-Berry phases between meta-atoms and“super-units”,the polarization rotation angle and wavefront of the beam can be designed without the far-field circular dichroism.We demonstrate the strong control ability on terahertz waves of this scheme through simulation and experiments.In addition,this new type of device with near-field chirality but no far-field circular dichroism may also have important value in optical sensing and other technologies.展开更多
Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by usi...Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by using hydrazide based native chemical ligation. The crystal structure of Calciseptine was determined by racemic protein crystallography technique. Compared to the structure of its homologous family protein, we found that Calciseptine is adopting a typical three-finger structure.展开更多
Background Pediatric patients with croup are frequently admitted if they require two doses of racemic epinephrine(RE)in the emergency department(ED).We aimed to identify factors associated with the need for additional...Background Pediatric patients with croup are frequently admitted if they require two doses of racemic epinephrine(RE)in the emergency department(ED).We aimed to identify factors associated with the need for additional therapy(>2 RE doses)among pediatric patients with croup.Methods We performed a single-center retrospective study of consecutive patients admitted from the ED with a diagnosis of croup between January 1,2011 and December 31,2015.Primary outcome was need for>2 doses of RE.Secondary out-comes included time to third RE and 72-hour return visits.We performed logistic regression to identify factors associated with use of>2 RE doses during hospitalization,and survival analysis to identify time to dosing of 3rd RE from 2nd RE.Results Of 353 included admissions[250(70.8%)males,median age 1.48,interquartile range 0.97-2.51 years],106/353(30.0%)required>2 RE.In univariate logistic regression,only recent use of steroids within 1 day prior to presentation(4.18,1.48-11.83;P=0.007)was associated with need for>2 RE.Survival from third RE was 0.74(95%CI 0.69-0.78),which was similar to the survival at 12 hours(0.70,95%CI 0.65-0.75).Return visits occurred in 19(5.4%)patients,of whom 12/19(63.2%)were given RE.Conclusions Patients hospitalized for croup with recent use of steroids prior to ED presentation have a greater need for>2 RE during hospitalization.The majority who require inpatient RE will do so within 8-12 hours.These data provide informa-tion for risk stratification and duration of monitoring for patients hospitalized with croup.展开更多
Based on chemical thermodynamic theory, racemic ofloxacin is separated in chiral sys-tems by hollow fiber liquid-supported membrane technology combining with countercurrently frac-tional extraction. The two chiral sol...Based on chemical thermodynamic theory, racemic ofloxacin is separated in chiral sys-tems by hollow fiber liquid-supported membrane technology combining with countercurrently frac-tional extraction. The two chiral solutions containing L-dibenzoyltartaric acid and D-dibenzoylta- rtaric acid in 1-octanol, flow through the lumen side and the shell side of fibers, respectively. The solution which flows through the lumen side of fibers also contains racemic ofloxacin. The wall of hollow fibers is filled with an aqueous of 0.1 mol/L Na2HPO4/H3PO4 buffer solution of pH = 6.86 containing 2 mmol/L of cetyltrimethyl ammonium bromide for 48 h. The fairly polar ofloxacin can cross the membrane back and forth, but dibenzoyltartaric acids cannot cross it. Fractional chiral extraction theory, mass transfer performance of hollow fiber membrane and enantioselectivity are investigated. Mathematical model of R/S = 0.96e0.03NTU for racemic ofloxacin separation by hollow fiber extraction, is established. The optical purity for ofloxacin enantiomers is up to 90% when 11 hollow fiber membrane modules of 22 cm in length in series are used.展开更多
1 Results It has been reported that crystalline form racemates can be resoluted by various methods[1],but for optical resolution of liquid form racemates,the method is limited in chromatograph.So chiral compounds cann...1 Results It has been reported that crystalline form racemates can be resoluted by various methods[1],but for optical resolution of liquid form racemates,the method is limited in chromatograph.So chiral compounds cannot be obtained on large scale by such method.In our previous paper,(+)-3-chloro-1,2-propanediol has been obtained by optical resolution of its racemata (liquid) with a chiral biopolymer,casein[2].展开更多
A new chemical transformation for the construction of diversely functionalized cyclopropane-phosphorus derivatives utilizing chiron 4 and racemic diethyl α-hydroxylbenzylphosphonate as the key precursors is described...A new chemical transformation for the construction of diversely functionalized cyclopropane-phosphorus derivatives utilizing chiron 4 and racemic diethyl α-hydroxylbenzylphosphonate as the key precursors is described. The diastereomeric pure phosphorus-containing derivatives 5a, 5′a, 5b and 5′b were obtained respectively, in good yields with d. e. 98% via asymmetric tandem double Michael addition/internal nucleophilic substitution of the corresponding compounds and further through the separation of the diastereomeric mixture by column chromatography. The diversely functionalized phosphorus derivatives are identified on the basis of their elemental analysis and spectroscopic data, such as K, 1H NMR, 13C NMR and MS. The absolute configuration of the interesting cyclopropane-phosphorus compound 5a was established by X-ray crystallography. Thus, these results provide a valuable strategy for synthesizing some biologically active molecules.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
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
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.
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.
文摘Seven chiral compounds were resolved on cellulose tris (3,5-dimethylphenylcarbamate) chiral stationary phase (CDMPC-CSP) using n-hexane/alcohol as mobile phase. Solvent strength and structural characteristics of the compounds effecting on the retention and resolution were discussed. Satisfactory separation was obtained.
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.
基金This work was financially supported by the National Natural Science Foundation of China.
文摘A one-dimensional chain aluminophosphate C1.5H7.5N1.5Al0.5PO4 containing diprotonated racemic 1, 2-diaminopropane cations was synthesized from an alcoholic system. The compound consists of infinite inorganic [AlP2O8] chains of alternately connected AlO4 and PO2(=O)2 tetrahedral units and the racemic template molecules. The macroanionic chains contain corner-shared double four-membered rings.
文摘Enantioseparation of salbutamol solute was carried out in liquid-supported membrane by using a polyvinylidene fluoride hollow-fiber module. The enantioselective transport of solute was facilitated by combinatorial chiral selectors, which were dissolved in toluene organic solvent. The effects of molar concentration ratios of salbutamol to combinatorial chiral selectors, and the pH value of buffer solution on enantioseparation were investigated. The results show that when the molar concentration ratio is 2∶1∶1, the maximum separation factor and enantiomer excess are 1.49 and 19.74%, respectively, and the R-enantiomer flux is more than S-enantiomer; the pH value of buffer solution influences the performances of enantioseparartion obviously, and the appropriate range of pH value is 7.07.2.
文摘The optically active R-4-phenyl-2-hydroxy butyrates were prepared by esterification of the racemic acid or transesterification of the racemic ester catalyzed by lipase from Candida cyclindra (CCL) in organic media.
文摘The present study involves the enantioselective resolution of racemic Felodipine by using free and immobilized forms of microbial cultures as well as an enzyme (Lipase AP6). Among the microbial cultures employed in the present study, Aspergillus niger, Sphingomonas paucimobilis, Cunninghamella elegans, Escherichia coli, Pseudomonas putida and Cunninghamella blakesleeana were found to possess capability of enantioselective resolution of racemic Felodipine. The enantiomeric excess (ee%) of Felodipine after reaction catalyzed by whole-cell A. niger and S. paucimobilis was found as 81.59 and 71.67%, respectively. Immobilization enhanced the enantioselectivity (enantiomeric ratio (E)) of the biocatalysts and hence this led to enhanced enantiomeric purity of the drug. The ee% values were found to be enhanced in reactions catalyzed by A. niger and S. paucimobilis cultures after immobilization as 98.27 and 93.56%, respectively. Enantiomeric ratio (E) of the reactions catalyzed by all the biocatalysts has been improved after immobilization. E value of the reaction catalyzed by immobilized A. niger was found to be excellent (E > 100) and hence the drug showed high enantiomeric purity. In lipase AP6 catalyzed study, the enantioselectivity was enhanced after immobilization with excellent E value, which led to enhanced enantiomeric purity of the drug (99.21% ee%).
基金supported by the National Key R&D Program of China(2022YFA1503200)the Naural Science Foundation of Jiangsu Province(BK20230078)+3 种基金the National Naural Science Foundation of China(22271146)the Fundamental Research Funds for the Central Universities(491916003301)the High Performance Computing Center(HPCC)of Nanjing Universitythe Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University。
文摘Chirality is a common phenomenon in nature,playing a crucial role in fields such as pharmaceuticals[1],materials science[2],and life sciences[3].The catalytic synthesis of chiral molecules,particularly those bearing multiple stereogenic elements(e.g.,central,axial,planar,helical,or inherent chirality),has gained tremendous attention in organic synthesis[4].
基金supported by the National Natural Science Foundation of China(21901249)Taishan Scholars Program of Shandong Province(tsqn201812112)+1 种基金the Major Science and Technology Innovation Program of Shandong Province(2022CXGC020604)the Natural Science Foundation of Shandong Province(ZR2023ME008)。
文摘Asymmetric kinetic resolution polymerization(AKRP)provides an ideal way to obtain highly isotactic polymers and optically pure monomers.However,highly enantioselective AKRP process is still rarely reported to date.And the AKRP of racemic lactide(rac-LA)remains a challenge.Here,in this paper,the AKRP of rac-LA was achieved by means of an enhanced enantiomorphic site control,delivering isotactic polylactide(PLA)and enantiomeric enriched lactide(LA)with the highest kinetic resolution coefficients(k_(rel))to date.Different from common(Salen)Al complex,a series of new chiral(BisSalen)Al complexes were designed and synthesized to form a more confined chiral microenvironment and further improve specific discrimination of rac-LA.The NMR analysis,kinetic studies,the activation parameters and thermal properties of the resulting PLAs provided strong evidence for enhanced enantiomorphic site control.This work enables highly enantioselective AKRP of rac-LA.
基金supported by the Scientific Research Foundation of Chengdu University of Information Technology(No.KYTZ202245)Information Materials and Device Applications Key Laboratory of Sichuan Provincial Universities(No.2023XXCL002)+4 种基金the Key Research and Development Project of Sichuan Province:Research on Development and Application Technology of VO2 Nano powder/Slurry with Intelligent Temperature Control(Subproject No.2022Z091)Sichuan Science and Technology Program(No.2023ZYD0020)National Natural Science Foundation of China(No.62201378,12364045,12304420)Natural Science Foundation of Jiangxi Province(No.20232BAB211025 and 20232BAB201040)Young Elite Scientists Sponsorship Program by JXAST(No.2023QT11).
文摘Dielectric chiral metasurface is a new type of planar and efficient chiral optical device that shows strong circular dichroism or optical activity,which has important application potential in optical sensing and display.However,the two types of chiral optical responses in conventional chiral metasurfaces are often interdependent,as their modulation of the amplitudes and phases of orthogonal circularly polarized components is correlated,which limits the further progress of chiral meta-devices.Here we propose a new scheme for independently designing the circular dichroism and optical activity of chiral metasurfaces to further control the polarization and wavefront of transmitted waves.Inspired by mixtures of chiral molecular isomers,we use the dielectric isomer resonators to form“super-units”instead of single meta-atoms for chiral responses in terahertz band,which is called racemic metasurface.By introducing two levels of Pancharatnam-Berry phases between meta-atoms and“super-units”,the polarization rotation angle and wavefront of the beam can be designed without the far-field circular dichroism.We demonstrate the strong control ability on terahertz waves of this scheme through simulation and experiments.In addition,this new type of device with near-field chirality but no far-field circular dichroism may also have important value in optical sensing and other technologies.
基金supported by the National Natural Science Foundation of China (21572043, 21473176)the Ministry of Science and Technology (2016YFA0400900, 2015CB910103)the Fundamental Research Funds for the Central Universities (PA2017GDQT0021)
文摘Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by using hydrazide based native chemical ligation. The crystal structure of Calciseptine was determined by racemic protein crystallography technique. Compared to the structure of its homologous family protein, we found that Calciseptine is adopting a typical three-finger structure.
文摘Background Pediatric patients with croup are frequently admitted if they require two doses of racemic epinephrine(RE)in the emergency department(ED).We aimed to identify factors associated with the need for additional therapy(>2 RE doses)among pediatric patients with croup.Methods We performed a single-center retrospective study of consecutive patients admitted from the ED with a diagnosis of croup between January 1,2011 and December 31,2015.Primary outcome was need for>2 doses of RE.Secondary out-comes included time to third RE and 72-hour return visits.We performed logistic regression to identify factors associated with use of>2 RE doses during hospitalization,and survival analysis to identify time to dosing of 3rd RE from 2nd RE.Results Of 353 included admissions[250(70.8%)males,median age 1.48,interquartile range 0.97-2.51 years],106/353(30.0%)required>2 RE.In univariate logistic regression,only recent use of steroids within 1 day prior to presentation(4.18,1.48-11.83;P=0.007)was associated with need for>2 RE.Survival from third RE was 0.74(95%CI 0.69-0.78),which was similar to the survival at 12 hours(0.70,95%CI 0.65-0.75).Return visits occurred in 19(5.4%)patients,of whom 12/19(63.2%)were given RE.Conclusions Patients hospitalized for croup with recent use of steroids prior to ED presentation have a greater need for>2 RE during hospitalization.The majority who require inpatient RE will do so within 8-12 hours.These data provide informa-tion for risk stratification and duration of monitoring for patients hospitalized with croup.
文摘Based on chemical thermodynamic theory, racemic ofloxacin is separated in chiral sys-tems by hollow fiber liquid-supported membrane technology combining with countercurrently frac-tional extraction. The two chiral solutions containing L-dibenzoyltartaric acid and D-dibenzoylta- rtaric acid in 1-octanol, flow through the lumen side and the shell side of fibers, respectively. The solution which flows through the lumen side of fibers also contains racemic ofloxacin. The wall of hollow fibers is filled with an aqueous of 0.1 mol/L Na2HPO4/H3PO4 buffer solution of pH = 6.86 containing 2 mmol/L of cetyltrimethyl ammonium bromide for 48 h. The fairly polar ofloxacin can cross the membrane back and forth, but dibenzoyltartaric acids cannot cross it. Fractional chiral extraction theory, mass transfer performance of hollow fiber membrane and enantioselectivity are investigated. Mathematical model of R/S = 0.96e0.03NTU for racemic ofloxacin separation by hollow fiber extraction, is established. The optical purity for ofloxacin enantiomers is up to 90% when 11 hollow fiber membrane modules of 22 cm in length in series are used.
文摘1 Results It has been reported that crystalline form racemates can be resoluted by various methods[1],but for optical resolution of liquid form racemates,the method is limited in chromatograph.So chiral compounds cannot be obtained on large scale by such method.In our previous paper,(+)-3-chloro-1,2-propanediol has been obtained by optical resolution of its racemata (liquid) with a chiral biopolymer,casein[2].
文摘A new chemical transformation for the construction of diversely functionalized cyclopropane-phosphorus derivatives utilizing chiron 4 and racemic diethyl α-hydroxylbenzylphosphonate as the key precursors is described. The diastereomeric pure phosphorus-containing derivatives 5a, 5′a, 5b and 5′b were obtained respectively, in good yields with d. e. 98% via asymmetric tandem double Michael addition/internal nucleophilic substitution of the corresponding compounds and further through the separation of the diastereomeric mixture by column chromatography. The diversely functionalized phosphorus derivatives are identified on the basis of their elemental analysis and spectroscopic data, such as K, 1H NMR, 13C NMR and MS. The absolute configuration of the interesting cyclopropane-phosphorus compound 5a was established by X-ray crystallography. Thus, these results provide a valuable strategy for synthesizing some biologically active molecules.
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.
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.
