Optically pure(R)-γ-and(R)-δ-lactones can be prepared by intramolecular cyclization of chiral hydroxy acids/esters reduced asymmetrically from γ-and δ-keto acids/esters using Saccharomyces cerevisiae(S.cerevisiae)...Optically pure(R)-γ-and(R)-δ-lactones can be prepared by intramolecular cyclization of chiral hydroxy acids/esters reduced asymmetrically from γ-and δ-keto acids/esters using Saccharomyces cerevisiae(S.cerevisiae) as a whole-cell biocatalyst.However,some of the enzymes catalyzing these reactions in S.cerevisiae are still unknown up to date.In this report,two carbonyl reductases,OdCRl and OdCR2,were successfully discovered,and cloned from S.cerevisiae using a genome-mining approach,and overexpressed in Escherichia coli(E.coli).Compared with OdCR1,OdCR2 can reduce 4-oxodecanoic acid and 5-oxodecanoic acid asymmetrically with higher stereoselectivity,generating(R)-γ-decalactone(99% ee) and(R)-δ-decalactone(98% ee) in 85% and 92%yields,respectively.This is the first report of native enzymes from S.cerevisiae for the enzymatic synthesis of chiral γ-and δ-lactones which is of wide uses in food and cosmetic industries.展开更多
High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might ...High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.展开更多
Background:The effects of keto acid(KA)supplements on Chinese patients receiving maintenance hemodialysis(MHD)are unclear.This study aimed to evaluate the effects of KA supplementation on nutritional status,inflammato...Background:The effects of keto acid(KA)supplements on Chinese patients receiving maintenance hemodialysis(MHD)are unclear.This study aimed to evaluate the effects of KA supplementation on nutritional status,inflammatory markers,and bioelectric impedance analysis(BIA)parameters in a cohort of Chinese patients with MHD without malnutrition.Methods:This was a prospective,randomized,controlled,single-center clinical study conducted in 2011 till 2014.Twenty-nine patients with MHD were randomly assigned to a control(n=14)or a KA(n=15)group.The control group maintained a dietary protein intake of 0.9 g/kg/day.The KA group received additional KA supplement(0.1 g/kg/day).BIA was used to determine the lean tissue mass,adipose tissue mass,and body cell mass.The patients,nutritional status,dialysis adequacy,and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.Results:The daily total energy intake for both groups was about 28 kcal/kg/day.After 6 months,the Kt/V(where K is the dialyzer clearance of urea,t is the dialysis time,and V is the volume of the distribution of urea)was 1.33±0.25 in KA group,and 1.34±0.25 in the control group.The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group.In addition,the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group.There were no significant differences between the groups with respect to the anthropometry parameters,dialysis adequacy,serum calcium and phosphorus levels,inflammatory markers,and amino-acid profiles,or in relation to the parameters determined by BIA.Both groups achieved dialysis adequacy and maintained nutritional status during the study.Conclusions:In this cohort of Chinese patients with MHD,the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day,maintained well nutritional status during study period.The KA supplement(0.1 g/kg/day)did not improve the essential amino acid/non-essential amino acid ratio,nor did it change the patients5 mineral metabolism,inflammatory parameters,or body compositions.展开更多
An unprecedented decarboxylative alkylation reaction of fl-keto acids with isochromans has been developed under oxidative conditions. A range of β-keto acids smoothly undergo decarboxylative alkylation with isochroma...An unprecedented decarboxylative alkylation reaction of fl-keto acids with isochromans has been developed under oxidative conditions. A range of β-keto acids smoothly undergo decarboxylative alkylation with isochromans in the presence of 2,2,6,6-tetramethylpiperdine-1-oxoammonium hexafluorophosphate to give structurally diverse 1-acylmethylisochromans in moderate to excellent yields with extremely high regioselectivity.展开更多
The reaction of benzhnidazole methiodide with ethyl malonate in the existence of base was studied,and a new convenient synthetic method of the β-keto acid was provided.
Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may pro...Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 （p-ERK1/2） in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 （2.5 μL/mL）, the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.展开更多
β-Keto acids are unstable to heat,acids,and bases,and have rarely been employed as carbon nucleophiles for the formation of carbon-carbon bonds.In this context,an efficient decarboxylative alkylation reaction of β-k...β-Keto acids are unstable to heat,acids,and bases,and have rarely been employed as carbon nucleophiles for the formation of carbon-carbon bonds.In this context,an efficient decarboxylative alkylation reaction of β-keto acids with benzylic alcohols has been developed,for the first time,through sequential cleavage of carbon-oxygen and carbon-carbon bonds.In the presence of 10 mol% of ferric chloride,a range of β-keto acids smoothly undergo decarboxylative alkylation with benzylic alcohols to give structurally diverse unsymmetric ketones in moderate to excellent yields and with extremely high regioselectivity.Preliminary mechanistic studies indicate that the reaction proceeds through an SN1 alkylation followed by decarboxylation.展开更多
Oxalic acid was found to be an efficient catalyst for Pechmann condensation, which includes the reaction between phenols and β-keto esters leading to formation of coumarin derivatives. The advantages of present metho...Oxalic acid was found to be an efficient catalyst for Pechmann condensation, which includes the reaction between phenols and β-keto esters leading to formation of coumarin derivatives. The advantages of present methods are the use of cheap and easy available catalyst, solvent-free reaction conditions, better yields and shorter reaction time.展开更多
Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and...Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.展开更多
Silica-bonded S-sulfonic acid （SBSSA） was prepared by the reaction of 3-mercaptopropylsilica （MPS） and chlorosulfonic acid in chloroform. This solid acid has been employed as a recyclable catalyst for the synthesi...Silica-bonded S-sulfonic acid （SBSSA） was prepared by the reaction of 3-mercaptopropylsilica （MPS） and chlorosulfonic acid in chloroform. This solid acid has been employed as a recyclable catalyst for the synthesis of coumarins from phenols and β-keto- esters at 80 ℃ under solvent-free conditions.展开更多
基金financially sponsored by the National Key Research and Development Program of China (2016YFA0204300, 2019YFA09005000)the National Natural Science Foundation of China (21536004, 21776085, 21871085)+2 种基金the Natural Science Foundation of Shanghai (18ZR1409900)Key Project of the Shanghai Science and Technology Committee (18DZ1112703)the Fundamental Research Funds for the Central Universities (WF1714026)。
文摘Optically pure(R)-γ-and(R)-δ-lactones can be prepared by intramolecular cyclization of chiral hydroxy acids/esters reduced asymmetrically from γ-and δ-keto acids/esters using Saccharomyces cerevisiae(S.cerevisiae) as a whole-cell biocatalyst.However,some of the enzymes catalyzing these reactions in S.cerevisiae are still unknown up to date.In this report,two carbonyl reductases,OdCRl and OdCR2,were successfully discovered,and cloned from S.cerevisiae using a genome-mining approach,and overexpressed in Escherichia coli(E.coli).Compared with OdCR1,OdCR2 can reduce 4-oxodecanoic acid and 5-oxodecanoic acid asymmetrically with higher stereoselectivity,generating(R)-γ-decalactone(99% ee) and(R)-δ-decalactone(98% ee) in 85% and 92%yields,respectively.This is the first report of native enzymes from S.cerevisiae for the enzymatic synthesis of chiral γ-and δ-lactones which is of wide uses in food and cosmetic industries.
文摘High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.
文摘Background:The effects of keto acid(KA)supplements on Chinese patients receiving maintenance hemodialysis(MHD)are unclear.This study aimed to evaluate the effects of KA supplementation on nutritional status,inflammatory markers,and bioelectric impedance analysis(BIA)parameters in a cohort of Chinese patients with MHD without malnutrition.Methods:This was a prospective,randomized,controlled,single-center clinical study conducted in 2011 till 2014.Twenty-nine patients with MHD were randomly assigned to a control(n=14)or a KA(n=15)group.The control group maintained a dietary protein intake of 0.9 g/kg/day.The KA group received additional KA supplement(0.1 g/kg/day).BIA was used to determine the lean tissue mass,adipose tissue mass,and body cell mass.The patients,nutritional status,dialysis adequacy,and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.Results:The daily total energy intake for both groups was about 28 kcal/kg/day.After 6 months,the Kt/V(where K is the dialyzer clearance of urea,t is the dialysis time,and V is the volume of the distribution of urea)was 1.33±0.25 in KA group,and 1.34±0.25 in the control group.The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group.In addition,the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group.There were no significant differences between the groups with respect to the anthropometry parameters,dialysis adequacy,serum calcium and phosphorus levels,inflammatory markers,and amino-acid profiles,or in relation to the parameters determined by BIA.Both groups achieved dialysis adequacy and maintained nutritional status during the study.Conclusions:In this cohort of Chinese patients with MHD,the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day,maintained well nutritional status during study period.The KA supplement(0.1 g/kg/day)did not improve the essential amino acid/non-essential amino acid ratio,nor did it change the patients5 mineral metabolism,inflammatory parameters,or body compositions.
基金Acknowledgement We are grateful for the financial support from the National Natural Science Foundation of China （21232007 and 21172206）, the National Basic Research Program of China （973 Program 2010CB833300）, and the Program for Changjiang Scholars and Innovative Research Team in University （IRT1189）.
文摘An unprecedented decarboxylative alkylation reaction of fl-keto acids with isochromans has been developed under oxidative conditions. A range of β-keto acids smoothly undergo decarboxylative alkylation with isochromans in the presence of 2,2,6,6-tetramethylpiperdine-1-oxoammonium hexafluorophosphate to give structurally diverse 1-acylmethylisochromans in moderate to excellent yields with extremely high regioselectivity.
基金Project (No. 29872032) supported by the National Natural Science Foundation of Chinathe Provincial Natural Science Foundation of Shanxi Province
文摘The reaction of benzhnidazole methiodide with ethyl malonate in the existence of base was studied,and a new convenient synthetic method of the β-keto acid was provided.
文摘Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid （AKBA） is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 （p-ERK1/2） in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 （2.5 μL/mL）, the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.
基金supported by the National Natural Science Foundation of China (21172206,20972147,and J1030412)the National Basic Research Program of China (2010CB833300)the Program for Changjiang Scholars and Innovative Research Team in University (IRT1189)
文摘β-Keto acids are unstable to heat,acids,and bases,and have rarely been employed as carbon nucleophiles for the formation of carbon-carbon bonds.In this context,an efficient decarboxylative alkylation reaction of β-keto acids with benzylic alcohols has been developed,for the first time,through sequential cleavage of carbon-oxygen and carbon-carbon bonds.In the presence of 10 mol% of ferric chloride,a range of β-keto acids smoothly undergo decarboxylative alkylation with benzylic alcohols to give structurally diverse unsymmetric ketones in moderate to excellent yields and with extremely high regioselectivity.Preliminary mechanistic studies indicate that the reaction proceeds through an SN1 alkylation followed by decarboxylation.
文摘Oxalic acid was found to be an efficient catalyst for Pechmann condensation, which includes the reaction between phenols and β-keto esters leading to formation of coumarin derivatives. The advantages of present methods are the use of cheap and easy available catalyst, solvent-free reaction conditions, better yields and shorter reaction time.
基金the Guangdong Medical Research Foundation,No.A2018550
文摘Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.
文摘Silica-bonded S-sulfonic acid （SBSSA） was prepared by the reaction of 3-mercaptopropylsilica （MPS） and chlorosulfonic acid in chloroform. This solid acid has been employed as a recyclable catalyst for the synthesis of coumarins from phenols and β-keto- esters at 80 ℃ under solvent-free conditions.
