Optical 2-benzyl-5-hydroxy-4-oxopentanoic acids against carboxypeptidase A:Synthesis,kinetic evaluation and X-ray crystallographic study

2-Benzyl-5-hydroxy-4-oxopentanoic acid 1 and its enantiomers were designed,synthesized and assayed for inhibitory activity against carboxypeptidase A(CPA,EC 3.4.17.1).To verify the role of the terminal hydroxyl group in 1 binding to CPA,2-benzyl-5- benzyloxy-4-oxopentanoic acid 2 was also synthesized and evaluated.The inhibition constants show that both L-1 and D-1 were shown to have strong binding affinity with L-1 being more potent than its enantiomer by 165-fold.On the other hand,the inhibition constant ...

Determination of trans-4-hydroxy-2-alkenals in thermally treated soybean oil by SPE-HPLC

Trans-4-hydroxy-2-hexenal(4-HHE) and trans-4-hydroxy-2-nonenal(4-HNE) are secondary lipid peroxidation products in edible oils, which are cytotoxic and genotoxic. They could covalently bind with protein, phospholipids and DNA, further disrupting the normal function of liver, lung and brain.Derivation process was generally conducted during pretreatment before detection and quantification of 4-HHE and 4-HNE. However, the derivation procedures were time consuming and chemical degradation may occur during the process. Hence, this paper aims to establish a simple solid phase extractionhigh performance liquid chromatography(SPE-HPLC) method to determine the 4-HHE and 4-HNE contents in thermally treated soybean oil. C18 solid phase extraction was applied in the pretreatment process. Firstly, the reliability of the method was evaluated. Good linearity was observed in the range of 0.1–0.5 μg/m L and 0.5–10 μg/m L for 4-HHE and 4-HNE. The limit of detection(LOD) of 4-HHE and 4-HNE were 0.0486 and 0.0129 μg/m L, respectively. And the limit of quantitation(LOQ) of4-HHE and 4-HNE were 0.1458 and 0.0431 μg/m L, respectively. Recovery rate were in the range of89.11%–91.58% and 71.83%–79.40% for 4-HHE and 4-HNE, respectively. The method achieved the extraction, purification and detection of 4-HHE and 4-HNE simultaneously and had the advantages of simple operation, effectiveness, high precision, good repeatability. Then, the method was applied to monitor the concentrations of 4-HHE and 4-HNE in soybean oil heated at 180 °C for 40 h. The contents of 4-HHE and 4-HNE were 0–0.32 μg/g and 0–6.97 μg/g, respectively, which provided guidance for evaluating health risks of thermally treated soybean oil during heating.

A convenient synthesis of methyl 2-hydroxy-4-oxo-4-(substituted phenyl) butanoates from malic acid

A synthesis of methyl 2-hydroxy-4-oxo-4-（substituted phenyl）butanoates has been accomplished using Friedel-Crafts acylation of substituted benzenes with 2-acetoxybutanoyl chloride. The key feature of this strategy is that various 4-arylbutanoates can be obtained conveniently, which are important intermediates for the synthesis of biologically active compounds including ACE inhibitors.？2009 Yong Sup Lee. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

A New Chiral Synthesis of Naturally Occurring (-)-(S)-4-Hydroxy-2-pyrrolidinone

A new and convenient chiral synthesis of naturally occurring (-)-(S)-4-hydroxy-2-pyrrolidinone from (S)-malic acid was reported.

Dietary supplementation with 2-hydroxy-4-methyl(thio)butanoic acid and DL-methionine improves productive performance,egg quality and redox status of commercial laying ducks

This experiment aimed to study the effects of supplemental methionine sources,2-hydroxy-4 methyl(thio)butanoic acid(HMTBa)and DL-Methionine(DL-Met),on productive performance,egg quality,and redox status of laying ducks.A total of 792 healthy 25-wk-old Longyan laying ducks with similar body weights were randomly allotted to 11 treatment groups.Each treatment group had 6 replicates of 12 ducks.The trial lasted for 16 wk.Ducks were fed a basal deficient diet(Met:0.24%;Met+Cys:0.51%)or supplemented with DL-Met or HMTBa at 0.05%,0.12%,0.19%,0.26%,and 0.33%of diet,respectively.Compared with the basal diet,supplementation with either DL-Met or HMTBa increased the average egg weight,egg mass,and decreased feed to egg ratio during the whole trial period(P<0.05).Albumen weight and its ratio to total egg weight were increased,but yolk and shell ratio,albumen height,Haugh unit and shell breaking strength were decreased(P<0.05).Dietary DL-Met or HMTBa supplementation increased taurine,methionine,leucine,tryptophan and arginine content,and decreased serine and lysine content in plasma(P<0.05).The redox status of laying ducks was improved by enhancing the glutathione peroxidase and catalase activities,glutathione content and its ratio relative to glutathione(oxidized)content and decreasing malondialdehyde content and increasing mRNA expression of superoxide dismutase-1,glutathione peroxidase-1,hemeoxygenase-1 and nuclear factor-like 2 in liver and ileum with the supplementation of DL-Met or HMTBa(P<0.05).Liver health status measured by average area proportion lipid droplet was improved with supplementation of DL-Met or HMTBa(P<0.05).Villus height and villus height to crypt depth ratio in the ileum and the ileal gene expression of tight junction protein and occludin were increased with DL-Met or HMTBa supplementation(P<0.05).Taken together,these results suggested that the efficacy of dietary supplementation of HMTBa was similar to DL-Met,and it ranged from 98%to 100%for productive performance and egg albumen ratio in laying ducks(25 to 41 wk).

A New Sesquiterpene-substituted Benzoic Acid from the Brown Alga Dictyopteris divaricata

A new sesquiterpene-substituted benzoic acid has been isolated from the brown Alga Dictyopteris divaricata Okam.. Its structure was elucidated as 3-[(2-hydroxy-2,5,5,8a-tetra- methyldecahydro-1-naphthalenyl)methyl]-4-hydroxybenzoic acid, named dictyvaric acid on the basis of spectroscopic methods including IR, HRFABMS, 1D and 2D NMR techniques.

野鸦椿的植物化学成分研究

从野鸦椿 (EuscaphisjaponecaKantiz)枝叶的甲醇提取物分离得到 6个化合物 ,通过波谱分析鉴定为 5 ,7 dihydroxy 2 methyl benzopyran 4 one(Ⅰ ) ,3,4 ,5 trihydroxy benzoicacidmethylester(Ⅱ ) ,3,7 dihydroxy 5 octanolide(Ⅲ ) ,methyl 5 ,7 dihydroxy 2 (Z) octenoate(Ⅳ ) ,7 hydroxy 2 octen 5 olide(Ⅴ )和vomifoliol(Ⅵ )。

A new pyrrolidone derivative from Pistacia chinensis

A new N-phenyl-pyrrolidone derivative had been isolated from Pistacia chinesis Bunge. Its structure was elucidated as 4-hydroxy-5-（2-oxo-1-pyrrolidinyl）-benzoic acid, named pistaciamide on the basis of the 1D-NMR, DEPT, HMQC and HMBC spectroscopic techniques. 2007 Xi Kui Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Indole Alkaloids from the Roots of Ervatamia hainanensis

Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy （2-oxopropyl）-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.

Pharmacokinetics of oxiracetam and its degraded substance (HOPAA) after oral and intravenous administration in rats

The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.

4-(Succinimido)-1-butane sulfonic acid as a Bronsted acid catalyst for synthesis of pyrano[4,3-b]pyran derivatives under solvent-free conditions

4-（Succinimido）-1-butane sulfonic acid as an efficient and reusable Bronsted acid catalyzed the synthesis of pyrano[4,3-b]pyran derivatives under solvent-free conditions.The catalyst can be prepared by mixing succinimide and 1,4-butanesultone that is more simple and safer than the preparation of succinimide sulfonic acid.This method has the advantages of high yield,clean reaction,simple methodology and short reaction time.The catalyst could be recycled without significant loss of activity.

Absorption of methionine sources in animals-is there more to know?

This literature review evaluates the absorption of methionine (Met) sources such as 2-hydroxy-4-methylthiobutyric acid (HMTBa), its calcium salts (HMTBa-Ca), and DL-methionine (DL-Met) by focusing on the state of knowledge regarding the absorption mechanism, experimental methodology, and factors affecting their absorption. The 2 Met sources differ in mechanism and site of absorption due to differences in their chemical characteristics and enzymatic conversion. This review addresses diffusion- and transport-mediated absorption systems for amino acids and carboxylic compounds, best elucidated by in vitro, ex vivo, and in vivo experimental models. Opportunities and limitations in the use of radioisotopes to depict absorption sites as well as host and microbial metabolism are described. Physiological and environmental conditions that lead to changes in gut absorptive capacity and the impact of Met source absorption are also evaluated. This review concludes that any comparison between HMTBa and DL-Met should consider their different behaviors during the absorption phase. Hence, the chemical characteristics of these 2 molecules entail different absorption sites and mechanisms, from passive absorption in the case of HMTBa and HMTBa-Ca to active transporters for DL-Met, HMTBa, and HMTBa-Ca. In addition, the different conversion modes of these 2 molecules further differentiate their absorption modes. Considering these important differences, it is easier to understand the apparent divergence between the conclusions of existing publications. When comparing these 2 molecules, it is recommended to properly adapt to the conditions under which the absorption of Met sources is evaluated.

A systematic review of metabolism of methionine sources in animals:One parameter does not convey a comprehensive story

The goal of this review article,based on a systematic literature search,is to critically assess the state of knowledge and experimental methodologies used to delineate the conversion and metabolism of the 2 methionine(Met)sources DL-methionine(DL-Met)and DL-2-hydroxy-4-(methylthio)butanoic acid(HMTBa).The difference in the chemical structures of HMTBa and DL-Met indicates that these molecules are absorbed and metabolized differently in animals.This review explores the methodologies used to describe the 2-step enzymatic conversion of the 3 enantiomers(D-HMTBa,L-HMTBa and D-Met)to L-Met,as well as the site of conversion at the organ and tissue levels.Extensive work was published documenting the conversion of HMTBa and D-Met into L-Met and,consequently,the incorporation into protein using a variety of in vitro techniques,such as tissue homogenates,cell lines,primary cell lines,and everted gut sacs of individual tissues.These studies illustrated the role of the liver,kidney,and intestine in the con-version of Met precursors into L-Met.A combination of in vivo studies using stable isotopes and infusions provided evidence of the wide conversion of HMTBa to L-Met by all tissues and how some tissues are net users of HMTBa,whereas others are net secreters of L-Met derived from HMTBa.Conversion of D-Met to L-Met in organs other than the liver and kidney is poorly documented.The methodology cited in the literature to determine conversion efficiency ranged from measurements of urinary,fecal,and respiratory excretion to plasma concentration and tissue incorporation of isotopes after intraperitoneal and oral in-fusions.Differences observed between these methodologies reflect differences in the metabolism of Met sources rather than differences in conversion efficiency.The factors affecting conversion efficiency are explored in this paper and are mostly associated with extreme dietary conditions,such as noncommercial crystalline diets that are very deficient in total sulfur amino acids with respect to requirements.Impli-cations in the diversion of the 2 Met sources toward transsulfuration over transmethylation pathways are discussed.The strengths and weaknesses of some methodologies used are discussed in this review.From this review,it can be concluded that due to the inherent differences in conversion and metabolism of the 2 Met sources,the experimental methodologies(e.g.,selecting different organs at different time points or using diets severely deficient in Met and cysteine)can impact the conclusions of the study and may explain the apparent divergences of conclusion found in the literature.It is recommended when con-ducting studies or reviewing the literature to properly select the experimental models that allow for differences in how the 2 Met precursors are converted to L-Met and metabolized by the animal to enable a proper comparison of their bioefficacy.

Dietary methionine sources and levels modulate the intestinal health status of broiler chickens

Given the key role of methionine in biological processes,adequate methionine should be provided to meet the nutritional requirements.DL-2-hydroxy-4-(methylthio)-butanoic acid(DL-HMTBA)has been considered as an important source of methionine.However,the effects of different sources and levels of methionine on the intestinal health status have not been clarified yet.An experiment was carried out to investigate the effects of different dietary sources and levels of methionine on the intestinal epithelial barrier,inflammatory cytokines expression,ileal morphology,microbiota composition,and cecal short chain fatty acids(SCFA)profiles.For this purpose,720 male Arbor Acre broiler chicks at 1 d old were randomly assigned to a 2×3 factorial arrangement with 2 methionine sources(DL-methionine and DLHMTBA)and 3 total sulfur amino acids(TSAA)levels(80%,100%,and 120%of Arbor Acre recommendation).The results showed that DL-HMTBA supplementation promoted intestinal physical barrier at both gene expression level of claudin-1 and serum diamine oxidase level(P<0.05),and the inflammatory cytokine IL-6 m RNA expression was down-regulated by dietary DL-HMTBA supplementation compared with the DL-methionine group(P<0.05).Meanwhile,an upregulated gene expression of claudin-1 and zonula occluden-1(ZO-1)were observed in the low-TSAA treatment on d 14(P<0.05),whereas this treatment increased the expression of IL-1βand IL-6(P<0.05).Villus height to crypt depth ratio was high(P<0.05)in the middle-level TSAA group.Furthermore,DL-HMTBA supplementation optimized the microbiota of the ileum especially the relative abundance of Lactobacillus,where the digestion and absorption were completed,and elevated the concentrations of SCFA(acetate,propionate,and butyrate)in the cecal content on d 21(P<0.01).In conclusion,dietary DL-HMTBA supplementation improved the intestinal barrier function,immune homeostasis and optimized the microbiota to promote intestinal health status in broiler chickens.