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• Epoxy alcohols were converted to the corresponding 1,2,3-triacetate derivatives in a one-pot manner using the NaBH4/Ac20 system for the first time and in high yield. • The exact configuration of 2-methyl-1,3-dioxooctahydro-1H-isoindole-4,5,6-triyltriacetate was determined by X-ray diffraction analysis. • Theoretical computations were carried out to explain the regioselectivity in the ring opening reaction of epoxy alcohols. • Theoretical studies and experimental findings are quite compatible with each other. The formation of products occurs under thermodynamic control. Isoindole-1,3‑dione derivatives containing an epoxy alcohol unit were synthesized. Epoxy alcohols were converted to the corresponding 1,2,3-triacetate derivatives in a one-pot manner using the NaBH4/Ac20 system for the first time and in high yield. C-3 selective ring-opening products were obtained with good yield and with stereospecificity with the NaBH 4 /Ac 2 O system at 139–140 °C. The exact configuration of 2-methyl-1,3-dioxooctahydro-1H-isoindole-4,5,6-triyltriacetate was determined by X-ray diffraction analysis which was obtained from the reaction of epoxy alcohol by hydride transferring agent in acetic anhydride. On the other hand, theoretical computations were carried out to explain the regioselectivity in the ring opening reaction of epoxy alcohols. The results showed that the ring-opening reaction of epoxy alcohol proceeds in a thermodynamically controlled manner and regioselectivity occurs depending on the stability of the products. [Display omitted] [ABSTRACT FROM AUTHOR]

We developed a highly versatile transition metal-free Suzuki type cross-coupling protocol. Alkenyl/aryl boronic acids could couple smoothly with propargylic mesylates Csp3 electrophiles in the presence of mild bases. The counterion in the base plays a crucial role for the reactivity. Our metal-free condition is orthogonal towards the classic transition metal catalysed Suzuki reactions. Stereospecific nucleophilic nubstitution of alkenyl boronic acids with bulk sp3-Carbon electrophiles. [Display omitted] • Bulky sp3-carbon electrophiles could couple with alkenyl boronic acids under mild conditions. • Counterion (K+, Na+) assisted nucleophilic substitution is different from conventional nucleophilic substitution. • This metal-free coupling protocol is stereo-specific. [ABSTRACT FROM AUTHOR]

The interaction between chiral drugs and biomimetic membranes is of interest in biophysical research and biotechnological applications. There is a belief that the membrane composition, particularly the presence of cholesterol, could play a pivotal role in determining enantiospecific effects of pharmaceuticals. Our study explores this topic focusing on the interaction of ibuprofen enantiomers (S- and R-IBP) with cholesterol-containing model membranes. The effects of S- and R-IBP at 20 mol% on bilayer mixtures of dipalmitoylphosphatidylcholine (DPPC) with 0, 10, 20 and 50 mol% cholesterol were investigated using circular dichroism and spin-label electron spin resonance. Morphological changes due to IBP enantiomers were studied with atomic force microscopy on supported cholesterol-containing DPPC monolayers. The results reveal that IBP isoforms significantly and equally interact with pure DPPC lipid assemblies. Cholesterol content, besides modifying the structure and the morphology of the membranes, triggers the drug enantioselectivity at 10 and 20 mol%, with the enantiomers differently adsorbing on membranes and perturbing them. The spectroscopic and the microscopic data indicate that IBP stereospecificity is markedly reduced at equimolar content of Chol mixed with DPPC. This study provides new insights into the role of cholesterol in modulating enantiospecific effects of IBP in lipid membranes. [Display omitted] • Bilayers and supported films of DPPC+ 0, 10, 20, and 50 mol% Chol were prepared. • The interaction between biomimetic membranes and IBP enantiomers was investigated. • R- and S-IBP significantly and equally affect DPPC membranes. • Cholesterol at 10 and 20 mol% triggers the drug enantioselectivity. • IBP stereospecificity is markedly reduced in DPPC+50 mol% Chol membranes. [ABSTRACT FROM AUTHOR]

Aldolases catalyze the reversible reactions of aldol condensation and cleavage and have strong potential for the synthesis of chiral compounds, widely used in pharmaceuticals. Here, we investigated a new Class II metal aldolase from the p-hydroxyphenylacetate degradation pathway in Acinetobacter baumannii, 4-hydroxy-2-keto-heptane-1,7-dioate aldolase (AbHpaI), which has various properties suitable for biocatalysis, including stereoselectivity/stereospecificity, broad aldehyde utilization, thermostability, and solvent tolerance. Notably, the use of Zn2+ by AbHpaI as a native cofactor is distinct from other enzymes in this class. AbHpaI can also use other metal ion (M2+) cofactors, except Ca2+, for catalysis. We found that Zn2+ yielded the highest enzyme complex thermostability (Tm of 87 °C) and solvent tolerance. All AbHpaI⋅M2+ complexes demonstrated preferential cleavage of (4R)-2-keto-3-deoxy-D-galactonate ((4R)-KDGal) over (4S)-2-keto-3-deoxy-D-gluconate ((4S)-KDGlu), with AbHpaI⋅Zn2+ displaying the highest R/S stereoselectivity ratio (sixfold higher than other M2+ cofactors). For the aldol condensation reaction, AbHpaI⋅M2+ only specifically forms (4R)-KDGal and not (4S)-KDGlu and preferentially catalyzes condensation rather than cleavage by ~40-fold. Based on 11 X-ray structures of AbHpaI complexed with M2+ and ligands at 1.85 to 2.0 Å resolution, the data clearly indicate that the M2+ cofactors form an octahedral geometry with Glu151 and Asp177, pyruvate, and water molecules. Moreover, Arg72 in the Zn2+-bound form governs the stereoselectivity/stereospecificity of AbHpaI. X-ray structures also show that Ca2+ binds at the trimer interface via interaction with Asp51. Hence, we conclude that AbHpaI⋅Zn2+ is distinctive from its homologues in substrate stereospecificity, preference for aldol formation over cleavage, and protein robustness, and is attractive for biocatalytic applications. [ABSTRACT FROM AUTHOR]

The fatty acid (FA) composition of colostrum (<7 days) and mature milk (>90 days) from cows, goats, camels, donkeys, and mares was analysed. Mare milk had the greatest percentage of polyunsaturated FAs (PUFAs) among all samples and the ratio of saturated FA:monounsaturated FA (MUFA):PUFA (1:0.69:0.84) was nearest to the optimal ratio (1:1:1) formulated by FAO/WHO. Mare milk was composed mainly of C16:0, C18:1c, and C18:3N3. Odd-chain FAs mainly accumulated in mare and donkey milk; cow and goat milk had more short-chain FAs. The distribution of FAs in non-ruminant milk is more reflective of the diet lipid content than that of ruminants. Mare milk had the lowest values of atherogenic index and thrombogenic index, possibly serving as a reference value for the development of anti-cardiovascular function in mare milk. Hence, this result indicates that mare milk could be more suitable for human nourishment than milk from donkey and ruminants. [ABSTRACT FROM AUTHOR]

• P. anantis had higher linalool-producing ability than wild-type E. coli. • Isoprene producing P. ananatis was used as a host strain for linalool production. • The gcd (membrane-bound glucose dehydrogenase) knockout was effective in linalool production. • Two (S)-specific and two (R)-specific linalool synthase genes were found. • 5.6 g/L (S)-linalool and 3.7 g/L (R)-linalool were produced from 60 g/L glucose. Linalool is a monoterpene alcohol, which imparts floral scents to a variety of plants and is extensively used in various kinds of products, such as processed foods and beverages for fragrances and flavors. However, linalool from natural resources is racemate, and production of linalool enantiomers is difficult. To produce stereospecific linalool, we evaluated linalool synthase genes (LINS) from plants, such as Actinidia arguta (AaLINS) and Coriandrum sativum (CsLINS) for (S)-specific LINS and a gram-positive bacterium Streptomyces clavuligerus (ScLINS) for (R)-specific LINS , with Pantoea ananatis strain as the host. Among the 16 LINS examined, AaLINS and ScLINS showed the best (S)-linalool production and (R)-linalool production, respectively, with 100 % enantio excess. Co-expression of the mutated farnesyl diphosphate synthase gene, ispA * (S80 F), from Escherichia coli along with the LINS genes also improved linalool production. In order to prevent volatilization and cell toxicity of linalool, two-phase cultivation with isopropyl myristate was done, which had positive effects on linalool production. The carbon flux to the MVA pathway from glucose was increased by inactivating a membrane-bound glucose dehydrogenase. Overall, 5.60 g/L (S)-linalool and 3.71 g/L (R)-linalool were produced from 60.0 g/L glucose by introduction of AaLINS - ispA * and ScLINS - ispA * in P. ananatis , respectively. [ABSTRACT FROM AUTHOR]

Allicin is a component of the characteristic smell and flavor of garlic (Allium sativum). A flavin-containing monooxygenase (FMO) produced by A. sativum (AsFMO) was previously proposed to oxidize S-allyl-L-cysteine (SAC) to alliin, an allicin precursor. Here, we present a kinetic and structural characterization of AsFMO that suggests a possible contradiction to this proposal. Results of steady-state kinetic analyses revealed that AsFMO exhibited negligible activity with SAC; however, the enzyme was highly active with L-cysteine, N-acetyl-L-cysteine, and allyl mercaptan. We found that allyl mercaptan with NADPH was the preferred substrate-cofactor combination. Rapid-reaction kinetic analyses showed that NADPH binds tightly (KD of ~2 µm) to AsFMO and that the hydride transfer occurs with pro-R stereospecificity. We detected the formation of a long-wavelength band when AsFMO was reduced by NADPH, probably representing the formation of a charge-transfer complex. In the absence of substrate, the reduced enzyme, in complex with NADP+, reacted with oxygen and formed an intermediate with a spectrum characteristic of C4a-hydroperoxyflavin, which decays several orders of magnitude more slowly than the kcat. The presence of substrate enhanced C4a-hydroperoxyflavin formation and, upon hydroxylation, oxidation occurred with a rate constant similar to the kcat. The structure of AsFMO complexed with FAD at 2.08-Á resolution features two domains for binding of FAD and NADPH, representative of class B flavin monooxygenases. These biochemical and structural results are consistent with AsFMO being an S-monooxygenase involved in allicin biosynthesis through direct formation of sulfenic acid and not SAC oxidation. [ABSTRACT FROM AUTHOR]

The asymmetric reduction of prochiral ketones is a promising process for synthesis of optically active alcohols. The aldo-keto reductase (AKR) is an attractive candidate of biocatalyst, due to its high enantioselectivity and environmentally friendly reaction conditions. In this work, nine putative AKR encoding genes from Corallococcus sp. EGB were cloned and expressed in Escherichia coli. Of these produced enzymes (CoAKRs), CoAKR7 exhibited reductive activity to various ketones and ketoesters, especially very high activity toward ethyl 4-chloro-3-oxobutanoate (COBE) with NADPH as the coenzyme. The CoAKR7 was optimally active at pH 7.0 and 50 °C. The apparent K m and V max for COBE was 14.18 U/mg and 0.269 mM, respectively. Moreover, CoAKR7 catalyzed an anti-Prelog reduction of COBE to (S)-ethyl-4-chloro-3-hydroxybutanoate (CHBE) with e.e. >99%. Enzyme-substrate-cofactor docking analysis elucidated the molecular mechanism of the substrate stereospecificity, providing basis for protein engineering of these enzymes for applications in the synthesis of valuable chemicals. • CoAKR7 for COBE reduction with anti-Prelog stereospecificity was identified from Corallococcus sp. EGB. • CoAKR7 showed high specific activity at 50°C and pH7.0. • CoAKR7 exhibited good thermostability, high substrate affinity and excellent enantioselectivity. • Docking analysis expanded our understanding of the molecular mechanisms of the substrate selectivity of AKRs. [ABSTRACT FROM AUTHOR]

We propose a new model for prochirality that satisfies all known examples: the prochiral plane. This plane contains the prochiral carbon and defines two separate faces for chemical modification. We extend this to enzyme catalysis, replacing the "three point attachment" hypothesis and its variants. Once a prochiral substrate is fixed on an enzyme surface, the asymmetry of the enzyme provides reactants exclusively on one side of the prochiral plane, producing an enantiomerically pure chiral product. The aconitase reaction is detailed as an example, using molecular modeling and its known enzymatic mechanism. We show that the prochiral substrate for this enzyme is not citrate, but rather cis -aconitate. The number of interaction points of cis -aconitate is not relevant to prochirality, but rather to substrate specificity. A second detailed example is the enzyme fumarase; here the substrate fumarate has only two binding sites, but is nonetheless fixed onto the enzyme and has a defined prochiral plane. We also provide a literature survey of more prochiral substrates, all of which have sp2 hybridized carbon and contain a prochiral plane. An example of a prochiral unnatural substrate for sphingosine kinase 2, fingolimod, has an sp3 hybridized prochiral carbon and also contains a prochiral plane. Finally, we provide an intuitive example of a prochiral physical object, a coffee cup, interacting with one hand and lip. • Currently prochirality is defined in terms of a three-point attachment model. • The three-point attachment model cannot explain prochiral conversions by enzymes. • Cis- aconitate, not citrate is the true prochiral substrate for aconitase. • A molecule with one prochiral plane is necessary for prochirality. [ABSTRACT FROM AUTHOR]

• Effect of ID and ED on stereoselective polymerization of isoprene with TiCl 4 /MgCl 2 catalyst was first investigated. • EB had higher catalytic activity than that of DBP. • Alkoxysilanes had activation effect on active species. Two TiCl 4 /MgCl 2 type Ziegler-Natta catalysts containing ethyl benzoate (EB) and dibutyl phthalate (DBP) as internal electron donors (ID) were prepared for isoprene polymerizations using five kinds of external electron donors (ED) (phenyltrimethoxysilane (ED-1), dicyclopentyl(dimethoxy)silane (ED-2), 2-butyl-2-ethyl-1,3-dimethoxypropane (ED-3), 1,3-dimethoxypropane (ED-4) and di(2-ethylhexyl)phthalate (ED-5)). The structure features of TiCl 4 /ID/MgCl 2 catalysts were characterized and the effect of ID and ED on polymerization behaviors was studied. EB had higher adsorption content on catalyst surface, higher catalytic activity and lower trans -1,4 stereoselectivity than DBP. Appropriate introduction of ED-1 and ED-2, expect ED-3, ED-4 and ED-5, caused the enhancement in polymerization activity and trans -1,4 content, while excess addition led to the deactivation. The effect of ED on equilibrium between selective activation and deactivation of active species significantly relied on the electron donor type and concentration. The internal and external electron donors play significant roles in catalytic activity and stereoselectivity of TiCl 4 /MgCl 2 type Ziegler-Natta catalysts for isoprene polymerizations. Internal electron donor EB with small molecular size had higher adsorption ability on support surface and higher catalytic activity than that of DBP which gave polymers with higher trans -1,4 content and M w. Appropriate external electron donors alkoxysilanes, except esters and benzoate, had activation effect on polymerization, thus raising the catalytic activity and polymers trans -1,4 content. Parallelly, excess addition of external electron donors led to the deactivation of active species. The reversible equilibrium effect between selective activation and partial deactivation significantly relied on the concentration and molecular type of external electron donor. [Display omitted] [ABSTRACT FROM AUTHOR]

Pseudopaline and staphylopine are opine metallophores biosynthesized by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The final step in opine metallophore biosynthesis is the condensation of the product of a nicotianamine (NA) synthase reaction (i.e. L-HisNA for pseudopaline and D-HisNA for staphylopine) with anα-keto acid (α-ketoglutarate for pseudopaline and pyruvate for staphylopine), which is performed by an opine dehydrogenase. We hypothesized that the opine dehydrogenase reaction would be reversible only for the opine metallophore product with (R)-stereochemistry at carbon C2 of theα-keto acid (prochiral prior to catalysis).Akinetic analysis using stopped-flow spectrometry with (R)- or (S)-staphylopine and kinetic and structural analysis with (R)- and (S)-pseudopaline confirmed catalysis in the reverse direction for only (R)-staphylopine and (R)-pseudopaline, verifying the stereochemistry of these two opine metallophores. Structural analysis at 1.57-1.85A° resolution captured the hydrolysis of (R)-pseudopaline and allowed identification of a binding pocket for the L-histidine moiety of pseudopaline formed through a repositioning of Phe-340 and Tyr- 289 during the catalytic cycle. Transient-state kinetic analysis revealed an ordered release of NADP+ followed by staphylopine, with staphylopine release being the rate-limiting step in catalysis. Knowledge of the stereochemistry for opine metallophores has implications for future studies involving kinetic analysis, as well as opine metallophore transport, metal coordination, and the generation of chiral amines for pharmaceutical development. [ABSTRACT FROM AUTHOR]

In the present work, the [3 + 2] cycloaddition reaction of 5,5-dimethyl-1-pyrroline N -oxide (Nit-5) and 2-cyclopentenone (CPN-6), experimentally reported by Tamura et al. , was theoretically studied using the newly introduced molecular electron density theory (MEDT). Based on the experimental findings, this reaction takes place in an O3-C4 regio- and an exo -stereospecific fashion to give corresponding [3 + 2] exo cycloadduct as the sole product. The results of the potential energy surface analysis indicated that the experimentally reported product is more favorable both thermodynamically and kinetically relative to other possible adducts. In complete agreement with the experimental outcomes, the conceptual density functional theory reactivity indices explained the reactivity and regioselectivity of the reaction. Calculation of global electron density transfer of the energetically most preferred transition state indicated that the electron density fluxes from Nit-5 as a nucleophilic species toward CPN-6 as an electrophilic species. Analysis of the molecular electrostatic potential map of the most favorable transition state showed that approach of Nit-5 and CPN-6 locates the oppositely charged regions over each other leading to attractive forces between two reagents rationalizing the exo stereoselectivity predominance. The molecular mechanism of the reactions was specified using electron localization function analysis over some relevant points along the intrinsic reaction coordinate profile of the most favorable transition state and the results indicated that this zwitterionic-type [3 + 2] cycloaddition reaction proceeds through a two-stage one-step mechanism. In fact, while the O3-C4 single bond is initialy formed between two fragments through donation of some electron density from the O3 oxygen lone electron-pairs of Nit-5 toward the C4 carbon atom of CPN-6 , the delayed C1-C5 single bond begins to form via C1- to -C5 coupling of pseudodiracal centers created on theses atoms over the course of reaction. Image 1 • We used MEDT to study the [3 + 2] cycloaddition of a nitrone and 2-cyclopentenone. • The results confirm the experimentally observed regio- and stereospecificity. • CDFT reactivity indices explain the reactivity and regioselectivity. • The stereoselectivity can be concluded from comparison of MEP of transition states. • ELF analysis shows that the reaction proceeds via a two-stage one-step mechanism. [ABSTRACT FROM AUTHOR]

Graphical abstract The catalyst active sites produce PP, whose properties - melt flow index (MFI) and molecular-weight distribution (as M w /M n) - depend on internal donors (ID) in the same manner for both methods of catalyst synthesis. Hence, the effect of ID on the catalyst active sites is not related with the effect of ID on the formation of MgCl 2 crystallites with different cuts. Highlights • Polypropylene (PP) catalysts are prepared by two methods introducing internal donors (ID) during or after MgCl 2 formation. • PP properties (melt index, M w /M n) depend on ID but the same manner for both methods of catalyst synthesis. • The effect of ID on the active sites is not related with the effect of ID on the formation of MgCl 2 crystallite cuts. Abstract Propylene polymerization catalysts with different internal donors (ID) are synthesized by two methods: (1) a standard method with ID introduction during formation of MgCl 2 by reacting Mg(OEt) 2 with TiCl 4 , and (2) the introduction of ID on MgCl 2 already formed in the presence of butyl acetate (the substitution method). 1,3-diether, dibutyl phthalate (DBP) and pentane-2,4-diol-dibenzoate (PDDB) are used as ID. Catalysts prepared with the same ID by both methods slightly differ in their composition, activity and stereospecificity (the content of xylene soluble polypropylene (PP) fraction). But the catalyst active sites produce PP, whose properties (melt flow index, MFI, and molecular-weight distribution as M w /M n) depend on ID in the same manner for both methods of catalyst synthesis. Hence, the effect of ID on the catalyst active sites is not related with the effect of ID on the formation of MgCl 2 crystallites with different cuts. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Cyanamides react as nucleophiles with resonance-stabilized carbocation centers. • This S N 1 reaction shows complete stereospecificity to form a single diastereomer. • Cyanamide ring-closure to yohimbine requires 1 min under microwave irradiation. Abstract A highly efficient acid-promoted, stereospecific, transannular ring-closure of medium-ring ether compounds to the indole alkaloid yohimbine is described. Microwave-enhanced acetic acid degradation of cyanamide compounds involves loss of (R)- or (S)- ethers, followed by a stereospecific, nucleophilic ring-closure from the cyanamide to afford yohimbine in up to 74% yield in as little as one minute. This nucleophilic reactivity of the amino moiety of the cyanamide highlights an alternative reactivity profile from its traditional electrophilic properties. Additionally, this reaction pathway highlights a rare case of an S N 1 pathway that proceeds with complete stereospecificity. [ABSTRACT FROM AUTHOR]

Highlights • A series of putative AKR genes were found from GenBank by genome mining approach. • The AKR gene was cloned and functionally expressed in Escherichia coli. • The AKR can catalyze ketopantoyl lactone to optically active (R) -pantolactone. • A putative catalytic mechanism is proposed that Tyr63 acts as a general acid. Abstract (R)-Pantolactone (PL) is a key chiral intermediate for the synthesis of calcium (R)-pantothenate and (R)-panthenol used as food additives. The commercial production of (R)-pantothenate is performed by the resolution of racemic pantothenate, which is synthesized through an aldol condensation and a cyanation reaction. In this study, we investigated another synthetic method of (R)-pantothenate through the stereoselective reduction of ketopantoyl lactone (KPL) by aldo-keto reductase (AKR). A series of conjugated polyketone reductases (CPRs) were discovered from GenBank database by genome mining approach. The putative CPR gene from Candida orthopsilosis Co 90–125 (Cor CPR) was cloned and functionally expressed in Escherichia coli BL21 (DE3). The optimum pH and temperature of recombinant Cor CPR were 6.0–7.0 and 40 ℃, respectively. The K m and v max toward KPL were1.3 mM and 227.3 μ mol/min/mg protein, respectively. The conserved sequences suggest that Cor CPR belongs to AKR3C family of AKR superfamily. Furthermore, a catalytic tetrad was proposed, and the detailed mechanism was clarified by molecular docking. In a batch reaction, 50 mM KPL was reduced to (R)-PL with 99% conversion and > 99% enantiomeric excess within 5 h. The recombinant Cor CPR from C. orthopsilosis shows potential application in the asymmetric synthesis of (R)-pantothenate preparation. [ABSTRACT FROM AUTHOR]

Abstract The formation of O -glycosidic linkage is arguably one of the most important topics in glycoscience due to the prevalence of O -glycosides in nature. Great efforts have been devoted to this field by many carbohydrate chemists to develop stereoselective/stereospecific glycosylation methodologies. Although glycosyl donor- and acceptor-controlled strategies have significantly progressed, the tedious design and pre-synthesis of substrates could not be avoided. On the other hand, reagent-controlled glycosylation can overcome these challenges and produce the desired selectivity by only altering external factors such as concentration, reagents or other reaction conditions. This mini-review discusses selected recent novel methodologies on reagent-mediated stereo-controlled glycosylation in the last decade, classified by the types of glycosyl donors. Graphical abstract Image 1 Highlights • Recent progress on reagent-mediated stereo-controlled glycosylation is reviewed. • Donors include thioglycosides, acetimidates, glycosyl halides, glycals and glycosyl epoxides. • Reagents include additives, solvents and catalysts. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract A nonionic photo-responsive surfactant (NPS) was synthesized for obtaining photo control of foamability, exposed in ultraviolet (UV) light or visible (Vis) light irradiation. The foamability depended on the surface activity of NPS, which possessed low critical micelle concentration (CMC) and high adsorption capacity compared with the similar type of nonionic surfactants. The azobenzene component in NPS as the light-responsive group, showed high sensitive and reversibility, i.e., the trans → cis isomerization occurred only for 1 s and the time to reach reversible isomerization was 85 s. And the fatigue resistance of isomerization was also outstanding, which remained stable for 14 cycles of alternate irradiation. Due to the lack of free volume and increase of barrier for isomerization, the irradiation time and first-order kinetics of isomerization decreased with the increase of NPS concentration. The foaming ratio and foam stability promoted with the NPS concentration increase, however, the stereospecific blockade amongst cis isomers was stronger than that of trans isomers, resulting in the steep decrease of foam half-life. The sustainable foam stability control of NPS applied into foam dyeing to solve the problem of residual foam. [ABSTRACT FROM AUTHOR]

Abstract O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) is a chiral analogous compound of the methamidophos insecticide that induces delayed neuropathy, and the R-(+)-HDCP enantiomer is an inhibitor of neuropathy target esterase (NTE). This enantiomer is not hydrolized by Ca2+-dependent phosphotriesterases in mammal tissues. Our group had reported R-(+)-HDCP hydrolysis in chicken serum enhanced by 30–250 μM copper in ex vivo assays, which we call "antagonistic stereoselectivity". We checked the hypothesis of the role of cupper binding proteins. Two hundred micrograms of human serum ceruloplasmine or horse kidney methallotionein in 1 mL containing 400 μM HDCP for 60 min showed no significant Cu2+-dependent hydrolysis. However under the same conditions, 10 μL of chicken serum or 10 μL of buffer containing 216 μg of chicken serum albumin (CSA) (amount of albumin content in this serum volume) with 100 μM Cu2+ showed the same stereoselectivity and similar levels to the Cu2+-dependent R-(+)-HDCP hydrolysis. About 75% of R-(+)-HDCP were hydrolyzed after 120 min in the presence of 100 μM Cu2+ (inhibited by 5 mM EDTA). No effects was observed by divalent cations Cu2+, Zn2+, Fe2+, Ca2+, Mn2+ and Mg2+. These results confirm that albumin is the protein responsible for "antagonistic stereoselectivity" observed in chicken serum. Highlights • Cupper enhances capacity of chicken albumin for detoxication a phosphoramidate. • The activating effect of cupper is stereo selective. • Albumin is the protein responsible for "antagonistic stereoselectivity" observed in chicken serum. [ABSTRACT FROM AUTHOR]

Abstract A total of nine enantiopure syn -β-substituted-α-amino acids have been synthesised, comprising both syn -β-hydroxy-α-amino acids and syn -β-fluoro-α-amino acids. The key step in the synthetic strategy towards these syn -β-substituted-α-amino acids involves a stereospecific rearrangement, which proceeds via the intermediacy of the corresponding aziridinium ions. The requisite enantiopure syn -α-hydroxy-β-amino esters were prepared via asymmetric aminohydroxylation of the corresponding α,β-unsaturated esters followed by epimerisation of the resultant anti -α-hydroxy-β-amino esters at the C(2)-position. Subsequent activation of the α-hydroxy moiety as a leaving group followed by displacement by the β-amino substituent gave the corresponding aziridinium species. Regioselective in situ ring-opening of the aziridinium intermediates with either water or fluoride gave the corresponding syn -β-hydroxy-α-amino ester or syn -β-fluoro-α-amino ester, respectively, and N -deprotection and ester hydrolysis afforded the target syn -β-substituted-α-amino acids as single diastereoisomers in good overall yield. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A highly selective synthesis of conjugated polyene sulfonyl derivatives is described via the elimination of disulfonyl chloride with readily accessible raw material dihaloalkane. The protocol offers a convenient way to form sulfonamides, sulfonates and even sulfones. Furthermore, this method was manipulated under mild condition with simple operation in high yield to afford only trans products. [ABSTRACT FROM AUTHOR]

An inclusive study towards the stereospecific synthesis of novel cis -3-monosubstituted-β-lactams from cis -3-functionalized 3-phenylsulfonyl/sulfinyl-β-lactams is described. 3-Sulfinyl-β-lactams 5/5ʹ successfully furnished stereospecific cis -3-monosubstituted-β-lactams 6 , however 3-sulfonyl-β-lactams 2 failed to give the desulfurized product 6ʹ . The final stereochemical and structural conformations of novel β-lactams were established by single crystal X-ray crystallographic study ( 5c ). The cis configuration of the β-lactams 5/5ʹ and 6 was assigned in relevance to E and C4-H and C3-H and C4-H respectively. [ABSTRACT FROM AUTHOR]

In the present study, (3a R ,7a S )-1,3,3a,4,7,7a-hexahydroisobenzofuran was submitted to photooxygenation and two isomeric hydroperoxides were successfully obtained. Without any further purification, reduction of the hydroperoxides with titanium tetraisopropoxide catalyzed by dimethyl sulfide gave two alcohol isomers in high yields. After acetylation of alcohol with Ac 2 O in pyridine, epoxidation reaction of formed monoacetates with m -CPBA, then chromatographed and followed by hydrolysis of the acetate groups with NH 3 in CH 3 OH resulted in the formation of epoxy alcohol isomers respectively. These epoxy alcohol isomers were subjected to trans -dihydroxylation reaction with acid (H 2 SO 4 ) in the presence of water to afford triols. Acetylation of the free hydroxyl groups produced benzofuran triacetates in high yields. Ring-opening reaction of furan triacetates with sulfamic acid catalyzed in the presence of acetic acid/acetic anhydrate and subsequently hydrolysis of the acetate groups with ammonia gave the targeted cyclohexane carbasugar-based pentols. All products were separated and purified by chromatographic and crystallographic methods. Structural analyses of all compounds were conducted by spectral techniques including NMR and X-ray analyses. The biological inhibition activity of the target compounds was tested against glycosidase enzymes, α - and β -glucosidase. [ABSTRACT FROM AUTHOR]

Reductive metabolism of strigolactones (SLs) in several plants was investigated. Analysis of aquaculture filtrates of cowpea and sorghum each fed with four stereoisomers of GR24, the most widely used synthetic SL, revealed stereospecific reduction of the double bond at C-3′ and C-4′ in the butenolide D-ring with preference for an unnatural 2′ S configuration. The cowpea metabolite converted from 2′- epi -GR24 and the sorghum metabolite converted from ent -GR24 had the methyl group at C-4′ in the trans configuration with the substituent at C-2′, different from the cis configuration of the synthetic H 2 -GR24 reduced with Pd/C catalyst. The plants also reduced the double bond in the D-ring of 5-deoxystrigol isomers with a similar preference. The metabolites and synthetic H 2 -GR24 stereoisomers were much less active than were the GR24 stereoisomers in inducing seed germination of the root parasitic weeds Striga hermonthica , Orobanche crenata , and O. minor . These results provide additional evidence of the importance of the D-ring for bioactivity of SLs. [ABSTRACT FROM AUTHOR]

Prenylflavonoids are valuable natural products that have diverse biological properties, and are usually generated biologically by multiple metabolic enzymes in nature. In this study, structurally diverse prenylflavonoids were conveniently synthesized by enzymatic catalysis by combining GuILDT, a regiospecific chalcone prenyltransferase, and GuCHI, a stereospecific chalcone isomerase that has promiscuous activity for both chalcones and prenylchalcones as substrates. Our findings provided a new approach for the synthesis of natural/unnatural bioactive prenylflavonoids, including prenylchalcones and optical prenylflavanones with chalcone origins. [ABSTRACT FROM AUTHOR]

A novel strategy for discriminating genuine and adulterated marine oils is proposed. The strategy consists of i ) determining the stereospecific distribution ( sn -1, sn -2 and sn -3) of omega 3 polyunsaturated fatty acids (ω−3 PUFA) on the backbone of triacylglycerols by using liquid chromatography tandem mass spectrometry; ii ) transforming the qualitative stereospecific information into quantitative data by means of a novel strategy; iii ) analyzing the transformed data by principal component analysis. The proposed strategy was tested on pure oils (seal, salmon, cod liver, sandeel, blue whiting, herring), a mixture of blue whiting, herring, sandeel and Norway pout and some intentionally adulterated oils. In addition, some published krill oil data were analyzed to confirm the reliability of the new approach. [ABSTRACT FROM AUTHOR]

The wild-type OPAA enzyme has relatively high levels of catalytic activity against several organophosphate G-type nerve agents. A series of mutants containing replacement amino acids at the OPAA Y212, V342, and I215 sites showed several fold enhanced catalytic efficiency on sarin, soman, and GP. One mutant, Y212F/V342L, showed enhanced stereospecificity on sarin and that enzyme along with a phosphotriesterase mutant, GWT, which had the opposite stereospecificity, were used to generate enriched preparations of each sarin enantiomer. Inhibition of acetylcholinesterase by the respective enantioenriched sarin solutions subsequently provided identification of the sarin enantiomers as separated by normal phase enantioselective liquid chromatography coupled with atmospheric pressure chemical ionization–mass spectrometry. [ABSTRACT FROM AUTHOR]

In order to understand the trans -1,4 stereospecific polymerization mechanism of conjugated dienes with the heterogeneous Ziegler-Natta catalyst, isoprene polymerization kinetics at different polymerization temperature in the initial polymerization stage and the microstructures of polymers and its fractions were studied in this work. Both polymerization temperature and time influenced the polymerization behavior greatly. The nascent polyisoprene (30s) with unusual high cis -1,4-units was observed and then the trans -1,4/ cis -1,4 ratio of the polymers increased obviously to finally trans -1,4-dominated (96 mol%) with the increase in polymerization time. Fractions of the products based on the different crystallizability at different temperature were isolated and characterized by 1 H-NMR, 13 C-NMR, GPC and DSC. The nascent polyisoprene under 30s polymerization time was mainly composed by fractions A and G with 30–60 mol% trans -1,4-units and 2–26 mol % trans - cis dyad linkages. Active species with low stereoregularity may contribute to theses fractions. While fractions D and E with high trans -1,4 unit (>96 mol%) from active species with high stereoregularity were growing to the predominated components with increased conversion. At least two kinds of active species with different stereospecificity and lifetime were proposed to explain the isoprene polymerization with heterogeneous TiCl 4 /MgCl 2 -Al(i-Bu) 3 catalyst. Effects of temperature on cis / trans -1,4 structure were discussed. Hopely, this research would provide a further understanding about trans -1,4 stereospecific polymerization of conjugated dienes with heterogeneous Ziegler-Natta type catalysts. [ABSTRACT FROM AUTHOR]

The first committed step of the shikimate pathway is catalyzed by a metalloenzyme 3-deoxy- d -arabino-heptulosonate-7-phosphate synthase (DAH7PS), which exhibits vulnerability to the oxidative stress. DAH7PS undergoes inactivation in multiple ways in the presence of redox metal, H 2 O 2 , and superoxide. The molecular mechanism and susceptibility of its inactivation might differ in different organisms and are presently unclear. In the present work, we have cloned, expressed and purified a DAH7PS from Providencia alcalifaciens (PaDAH7PS). The oligomeric state and effect of redox metal treatment on its stability were analyzed through the size exclusion chromatography. The FTIR, MALDI-TOF/TOF-MS studies revealed that methionine residues were modified to methionine sulfoxide in PaDAH7PS. During oxidation, PaDAH7PS is altered into partially folded protein and unfolded states as determined by CD and Fluorescence studies. A significant loss in enzymatic activity of PaDAH7PS was determined and the formation of amorphous aggregates was visualized using AFM imaging and also confirmed by ThT binding based assay. This is the first report where we have shown a hexameric DAH7PS and the methionine residues of PaDAH7PS get oxidize in the presence of oxidative stress. The partially folded and unfolded oligomeric states with high β-content of PaDAH7PS might be the critical precursors for aggregation. [ABSTRACT FROM AUTHOR]

Fructose-1,6-bisphosphate (FBP) aldolase, a glycolytic enzyme, catalyzes the reversible and stereospecific aldol addition of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (D-G3P) by an unresolved mechanism. To afford insight into the molecular determinants of FBP aldolase stereospecificity during aldol addition, a key ternary complex formed by DHAP and D-G3P, comprising 2% of the equilibrium population at physiological pH, was cryotrapped in the active site of Toxoplasma gondii aldolase crystals to high resolution. The growth of T. gondii aldolase crystals in acidic conditions enabled trapping of the ternary complex as a dominant population. The obligate 3(S)-4(R) stereochemistry at the nascent C3-C4 bond of FBP requires a si-face attack by the covalent DHAP nucleophile on the D-G3P aldehyde si-face in the active site. The cis-isomer of the D-G3P aldehyde, representing the dominant population trapped in the ternary complex, would lead to re-face attack on the aldehyde and yield tagatose 1,6- bisphosphate, a competitive inhibitor of the enzyme. We propose that unhindered rotational isomerization by the D-G3P aldehyde moiety in the ternary complex generates the active trans-isomer competent for carbonyl bond activation by activesite residues, thereby enabling si-face attack by the DHAP enamine. C-C bond formation by the cis-isomer is suppressed by hydrogen bonding of the cis-aldehyde carbonyl with the DHAP enamine phosphate dianion through a tetrahedrally coordinated water molecule. The active site geometry further suppresses C-C bond formation with the L-G3P enantiomer of D-G3P. UnderstandingC-Cformation is of fundamental importance in biological reactions and has considerable relevance to biosynthetic reactions in organic chemistry. [ABSTRACT FROM AUTHOR]

In coordination polymerization chemistry, the most active species are cationic transition metals which bear vacant sites for monomer coordination. The steric and electronic properties around the metal center are strongly related to the polymerization behavior. Thus, the development of the catalyst system mainly represents the design of neutral metal complex precursors, especially the structure of the ligand. On the other hand, the choice of counteranions derived from the cocatalysts sometimes plays a crucial role in the controlled coordination polymerization. Some unusual polymerization behaviors on stereospecificity, activity, and monomer reactivity ratios have been reported by designing the structure of these cocatalysts. The review summarizes these examples of polymerization controlled by cocatalysts. Various cocatalysts, such as methylaluminoxane (MAO), fluoroarylboranes, and borates with different activation mechanisms, are introduced based on their structural analysis and molecular design. Heterogeneous cocatalysts, important for industrial applications, are also mentioned with their various characterization methods. The application of these cocatalysts is discussed, along with the introduction of several techniques evaluating the relationship between cocatalysts and polymerization behavior. Moreover, the counter-anionic effect in the late-transition metal-catalyzed polymerization chemistry, which recently attracted many researchers for its versatile applicability for polar monomers, is reviewed. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of 1-substituted 3-( t -butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for h TRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S -configuration, providing exceptionally potent antagonists 13 S and 16 S with K i(CAP) = 0.1 nM. Particularly significant, 13 S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for r TRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13 S and 16 S in our h TRPV1 homology model indicated that the binding modes differed somewhat, with that of 13 S more closely resembling that of GRT12360 . [ABSTRACT FROM AUTHOR]

The stereospecifically labeled 6-monodeuterio methyl 2,6-diamino-2,6-dideoxy-α- and β- d -glucopyranosides were synthesized with a view to determining their side chain conformations. NMR studies in D 2 O at pH 5 and pH 11 reveal both anomers to adopt very predominantly the gt conformation consistent with the gauche conformation of 2-aminoethanol and its acetate salt. In contrast, as also revealed with the help of stereospecifically-labelled monodeuterio isotopomers, the methyl 2-amino-2-deoxy-α- and β- d -glucopyranosides are an approximately 1:1 mixture of gg and gt conformers as is found in glucopyranose itself. [ABSTRACT FROM AUTHOR]

The stereostructure of β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters synthesized by Bellassoued et al. [J. Org. Chem . 2001 , 66 , 5054–5057 ] using Mukaiyama aldol reaction has been reassigned using density functional theory NMR 1 H chemical shifts calculations. It is now concluded that the major diastereoisomer is syn and the minor is anti . Within this assignment, for all silyl esters, δ Ha ( anti ) > δ Ha ( syn ), δ Hb ( anti ) < δ Hb ( syn ), and 3 J Ha-Hb ( anti ) > 3 J Ha-Hb ( syn ). Since the experimental assignment was based on the stereostructure ( E / Z ) of the cinnamic acid obtained by elimination of trimethylsilyl 3-phenyl-3-(trimethylsiloxy)-2-(trimethylsilyl)propanoate in the presence of TiCl 4 and on the assumption that this elimination is anti stereospecific in acidic medium, one arrives at the conclusion that the elimination of syn and anti β -trimethylsiloxy- α -trimethylsilyl alkanoic acid silyl esters is not anti stereospecific. [ABSTRACT FROM AUTHOR]

Avian species contain low levels of enzymes that hydrolyze organophosphorus compounds (OPs), and chickens are used as a model of OPs delayed neurotoxicity. For both reasons, we studied the ability of chicken tissue for OP detoxication. A significant activating effect of Cu 2+ on the hydrolysis of O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) was observed in hen plasma and the microsomal fractions of the liver, brain, and mainly in hen serum, by spectrophotometric and chiral chromatography methods. The concentration of 1 mM of Cu 2+ or Zn 2+ showed 200% and 168% activation, respectively, in hen plasma compared with the Ca 2+ -dependent hydrolysis, whereas these cations had an inhibitory effect on soluble liver and brain fractions. An increase of 1.5 to 19.5 fold in HDCP hydrolyzing activity was obtained for the 30–250 μM Cu 2+ range when using chicken serum instead of hen plasma. This Cu 2+ -dependent hydrolysis in chicken serum was stereoselective for the R-(+)-HDCP isomer, which proved the opposite to the Ca 2+ -dependent stereoselective hydrolysis of the S-(–)-HDCP isomer reported in rat and rabbit serum. The level of copper needed to exert this effect should be further evaluated for its suitability for potential therapeutic and biotechnological applications. [ABSTRACT FROM AUTHOR]

The inhibition kinetics and stereospecificity of the chiral nerve agent derivative O , S -diethylphenylphosphonothioate (DEPP) were examined for two forms of acetylcholinesterase (human and eel) and equine butyrylcholinesterase. Both S- and R-DEPP are poor inhibitors of eel AChE (IC 50 150 μM), consistent with a large, nondiscriminatory binding interaction in the active site of this enzyme. However, S-DEPP is active against human and equine AChE with low μM IC 50 s. DEPP stereospecificities (S/R) toward these enzymes are moderate (20) relative to other cholinesterase-organophosphate (OP) systems. Pralidoxime, a common rescue agent, affects a modest recovery of both hAChE and eqBChE from treatment with S-DEPP. This result is consistent with expected chemical modification by DEPP and indicates that a measurable amount of the enzyme-phosphonate adduct does not undergo aging. Kinetic analysis of inhibition of both hAChE and eqBChE by S-DEPP yields K I values near 8 μM and k 2 values of about 0.10 min −1 . In both cases, the reaction is practically irreversible. Second order rate constants calculated from these values are similar to those obtained previously using other thio-substituted OPs with bulky groups. Since BChE has a more accommodating acyl pocket than AChE, the similar behaviors of both enzymes toward S-DEPP is notable and is likely a reflection of the weakened potency of DEPP relative to chemical warfare agents. [ABSTRACT FROM AUTHOR]

Polypropylene with special properties can be obtained using two supported metallocene catalysts of different stereospecificities: rac-Me 2 Si(2-Me-benz[e]Ind) 2 ZrCl 2 [CAT-B] as an isotactic catalyst precursor and Ph 2 C(Cp)(9-Flu)ZrCl 2 [CAT-C] as a syndiospecific catalyst precursor supported on silica/MAO. These catalysts were evaluated either isolated or as a binary system. Catalysts physical mixtures and hybrid catalysts were prepared at three proportions, and tested in propylene polymerization. The effect to the activity and presence of hydrogen in the structural and mechanical properties of resultant polypropylenes were investigated. The influence of the binary systems containing more than half of the syndiotactic fraction on the molecular and mechanical properties respect to the isotactic polypropylene was evaluated. The great contribution of the sPP was observed in the polypropylene synthesized with the catalysts physical mixtures in absence of hydrogen. These samples showed a reduction of the crystallinity leading to an increase in the stress at break, because the flexion resistance is reduced. Polymers obtained with hybrid catalysts have an average molecular weight and crystallinity nearly to isotactic polypropylene with a break at very low strains, and high modulus. [ABSTRACT FROM AUTHOR]

The stereospecificity of aminoacyl-tRNA synthetases helps exclude d -amino acids from protein synthesis and could perhaps be engineered to allow controlled d -amino acylation of tRNA. We use molecular dynamics simulations to probe the stereospecificity of the class I tyrosyl- and glutaminyl-tRNA synthetases (TyrRS, GlnRS), including wildtype enzymes and three point mutants suggested by three different protein design methods. l / d binding free energy differences are obtained by alchemically and reversibly transforming the ligand from L to D in simulations of the protein–ligand complex. The D81Q mutation in Escherichia coli TyrRS is homologous to the D81R mutant shown earlier to have inverted stereospecificity. D81Q is predicted to lead to a rotated ligand backbone and an increased, not a decreased l -Tyr preference. The E36Q mutation in Methanococcus jannaschii TyrRS has a predicted l / d binding free energy difference ΔΔ G of just 0.5 ± 0.9 kcal/mol, compared to 3.1 ± 0.8 kcal/mol for the wildtype enzyme (favoring l -Tyr). The ligand ammonium position is preserved in the d -Tyr complex, while the carboxylate is shifted. Wildtype GlnRS has a similar preference for l -glutaminyl adenylate; the R260Q mutant has an increased preference, even though Arg260 makes a large contribution to the wildtype ΔΔ G value. [ABSTRACT FROM AUTHOR]

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant eicosanoid generated by cytochrome P450 (CYP) enzymes in C. elegans , is a potential signaling molecule in the regulation of pharyngeal pumping activity of this nematode. As a chiral molecule, 17,18-EEQ can exist in two stereoisomers, the 17(R),18(S)- and 17(S),18(R)-EEQ enantiomers. Here we tested the hypothesis that 17,18-EEQ may function as a second messenger of the feeding-promoting neurotransmitter serotonin and stimulates pharyngeal pumping and food uptake in a stereospecific manner. Serotonin treatment of wildtype worms induced a more than twofold increase of free 17,18-EEQ levels. As revealed by chiral lipidomics analysis, this increase was almost exclusively due to an enhanced release of the (R , S)-enantiomer of 17,18-EEQ. In contrast to the wildtype strain, serotonin failed to induce 17,18-EEQ formation as well as to accelerate pharyngeal pumping in mutant strains defective in the serotonin SER-7 receptor. However, the pharyngeal activity of the ser-7 mutant remained fully responsive to exogenous 17,18-EEQ administration. Short term incubations of well-fed and starved wildtype nematodes showed that both racemic 17,18-EEQ and 17(R),18(S)-EEQ were able to increase pharyngeal pumping frequency and the uptake of fluorescence-labeled microspheres, while 17(S),18(R)-EEQ and also 17,18-dihydroxyeicosatetraenoic acid (17,18-DHEQ, the hydrolysis product of 17,18-EEQ) were ineffective. Taken together, these results show that serotonin induces 17,18-EEQ formation in C. elegans via the SER-7 receptor and that both the formation of this epoxyeicosanoid and its subsequent stimulatory effect on pharyngeal activity proceed with high stereospecificity confined to the (R , S)-enantiomer. • 17,18-EEQ is the most abundant eicosanoid generated by cytochromes P450 in C. elegans. • Only its (R , S)-enantiomer stimulates pharyngeal pumping in a stereospecific manner. • Serotonin induces 17,18-EEQ formation via the SER-7 receptor. • The pharyngeal activity of the ser-7 mutant remained fully responsive to 17,18-EEQ. • 17,18-EEQ functions as a second messenger of this feeding-promoting neurotransmitter. [ABSTRACT FROM AUTHOR]

In the biosynthetic pathway of bacteriochlorophyll(BChl)- a / b / c / d / e molecules, BchF and BchV enzymes catalyze the hydration of a C3-vinyl to C3-1-hydroxyethyl group. In this study, the in vitro reactions catalyzed by BchF and BchV partially afforded a C31-epimeric mixture of the hydrated products (secondary alcohols), with the primary recovery of the C3-vinylated substrate. The stereoselectivity and substrate specificity for the in vitro reverse enzymatic dehydration were examined using zinc chlorophyll analogs as model substrates by BchF and BchV, which were obtained from extracts of Escherichia coli overexpressing the respective genes from Chlorobaculum tepidum and used without further purification. Both BchF and BchV preferred dehydration of the (31 R)-epimers over the (31 S)-epimers. The (31 R)-epimer was directly dehydrated by BchF and BchV to give the C3-vinylated product. By contrast, two reaction pathways for BchF and BchV dehydrations of the (31 S)-epimer were proposed: (1) the (31 S)-epimer would be directly dehydrated to C3-vinyl group. (2) the (31 S)-epimer would be epimerized to the (31 R)-epimer, and the resulting epimer was dehydrated. The results indicated that both BchF and BchV did function as a hydratase/dehydratase and could play a role in the C31-epimerization. An increase in the alkyl size at the C8-position gradually suppressed the BchF and BchV-catalyzed dehydration in vitro , while the C121- and C20-methylation only slightly affected the reaction. Using the BchF dehydration, a large amount of 3-vinyl-bacteriochlorophyllide- a was successfully prepared, with the retention of the chemically labile, central magnesium atom. [Display omitted] • BchF and BchV are hydrases in C3-vinyl group of chlorophylls in vivo. • BchF/V have high catalytic abilities of dehydration over hydration in vitro. • BchF/V (de)hydrases might be related to the epimerization in C3-1-hydroxyethyl group. • BchF/V dehydration was suppressed by terminal methylations in C8-ethyl group. • BchF dehydration was applied to efficient preparation of a chlorophyll derivative. [ABSTRACT FROM AUTHOR]

We have developed a Triangular Spatial Relationship (TSR)-based computational method for protein structure comparison and motif discovery that is both sequence and structure alignment-free. A protein 3D structure is modeled by all possible triangles that are constructed with every three C α atoms of amino acids as vertices. Every triangle is represented using an integer (a key). The keys are calculated by a rule-based formula which is a function of a representative length, a representative angle, and the vertex labels associated with amino acids. A 3D structure is thereby represented by a vector of integers (TSR keys). Global or local structure comparisons are achieved by computing all keys or a set of keys, respectively. Many enzymatic reactions and notable marketed drugs are highly stereospecific. Thus, in this paper, we propose a modified key calculation formula by including a mechanism for discriminating mirror-image keys to capture stereo geometry. We assign a positive or a negative sign to the integers representing mirror-image keys. Applying the new key calculation function provides the ability to further discriminate mirror-image keys that were previously considered identical. As the result, applying the mirror-image discrimination capability (i) significantly increases the number of distinct keys; (ii) decreases the number of common keys; (iii) decreases structural similarity; (iv) increases the opportunity to identify specific keys for each type of the receptors. The specific keys identified in this study for the cases of without (not applying) and with (applying) mirror-image discrimination can be considered as the structure signatures that exclusively belong to a certain type of receptors. Applying mirror-image discrimination introduces stereospecificity to keys for allowing more precise modeling of ligand - target interactions. The development of mirror-image TSR keys of C α atom, in conjunction with the integration of C α TSR keys with all-atom TSR keys for amino acids and drugs, will lead to a new and promising computational method for aiding drug design and discovery. [Display omitted] • Mirror-image discrimination capability is introduced into the Triangular Spatial Relationship (TSR)-based key generation formula to capture stereo geometry. • Applying mirror images decreases structural similarity which can be partially explained by the observation of a decrease in common keys. • For a hierarchically organized structure dataset, applying mirror images enhances the opportunity to discover specific keys that exclusively belong to certain types of proteins. • Different types of receptors share little sequence similarity and are functionally diverse. However, similar substructures are identified within each protein of a receptor family. • Unique substructures are identified for the majority of the receptor types, which build a foundation for designing new inhibitors specifically for certain types of receptors. • The TSR-based method has its advantage in studying protein sequence, structure and function relationships. [ABSTRACT FROM AUTHOR]

[Display omitted] Chiral borates can undergo various transformations that occur with high stereospecificity, so they are of great significance in asymmetric synthesis. Herein we described a new catalytic system for copper-catalyzed asymmetric conjugate hydroboration of α,β-unsaturated amides. Under the optimal conditions, the reactions proceeded smoothly to afford the corresponding chiral β-hydroxyl amides with up to 96% yield and 84% ee by employing chiral N,P-ligand. The reaction conditions are mild, the operation is simple, and it has good substrate generality. [ABSTRACT FROM AUTHOR]

Some volatile aromatic solvents have similar or opposite effects to anesthetics in the central nervous system. Like for anesthetics, the mechanisms of action involved are currently the subject of debate. This paper presents an in vivo study to determine whether direct binding or effects on membrane fluidity best explain how solvents counterbalance anesthesia’s depression of the middle-ear reflex (MER). Rats were anesthetized with a mixture of ketamine and xylazine while also exposed to solvent vapors (toluene, ethylbenzene, or one of the three xylene isomers) and the amplitude of their MER was monitored. The depth of anesthesia was standardized based on the magnitude of the contraction of the muscles involved in the MER, determined by measuring cubic distortion product oto-acoustic emissions (DPOAEs) while triggering the bilateral reflex with contralateral acoustic stimulation. The effects of the aromatic solvents were quantified based on variations in the amplitude of the DPOAEs. The amplitude of the alteration to the MER measured in anesthetized rats did not correlate with solvent lipophilocity (as indicated by logKow values). Results obtained with the three xylene isomers indicated that the positions of two methyl groups around the benzene ring played a determinant role in solvent/neuronal cell interaction. Additionally, Solid-state Nuclear Magnetic Resonance (NMR) spectra for brain microsomes confirmed that brain lipid fluidity was unaffected by solvent exposure, even after three days (6 h/day) at an extremely high concentration (3000 ppm). Therefore, aromatic solvents appear to act directly on the neuroreceptors involved in the acoustic reflex circuit, rather than on membrane fluidity. The affinity of this interaction is determined by stereospecific parameters rather than lipophilocity. [ABSTRACT FROM AUTHOR]

In human, Tyrosinase enzyme (TyH) is involved in the key steps of protective pigments biosynthesis (in skin, eyes and hair). The use of molecules targeting its binuclear copper active site represents a relevant strategy to regulate TyH activities. In this work, we targeted 2-Hydroxypyridine- N -oxide analogs (HOPNO, an established chelating group for the tyrosinase dicopper active site) with the aim to combine effects induced by combination with a reference inhibitor (kojic acid) or natural substrate (tyrosine). The HOPNO–MeOH (3) and the racemic amino acid HOPNO-AA compounds (11) were tested on purified tyrosinases from different sources (fungal, bacterial and human) for comparison purposes. Both compounds have more potent inhibitory activities than the parent HOPNO moiety and display strictly competitive inhibition constant, in particular with human tyrosinase. Furthermore, 11 appears to be the most active on the B16–F1 mammal melanoma cells. The investigations were completed by stereospecificity analysis. Racemic mixture of the fully protected amino acid 10 was separated by chiral HPLC into the corresponding enantiomers. Assignment of the absolute configuration of the deprotected compounds was completed, based on X-ray crystallography. The inhibition activities on melanin production were tested on lysates and whole human melanoma MNT-1 cells. Results showed significant enhancement of the inhibitory effects for the (S) enantiomer compared to the (R) enantiomer. Computational studies led to an explanation of this difference of activity based for both enantiomers on the respective position of the amino acid group versus the HOPNO plane. [Display omitted] • Hydroxypyridine- N -oxide analogs prepared including a non-canonic amino acid. • Inhibition on tyrosinase enzymes from mushroom, bacterial and human sources tested. • Inhibition stereoselectivity demonstrated (enzymes and cell-based assays). [ABSTRACT FROM AUTHOR]

In this paper, an environmentally benign silica-supported perchloric acid (HClO 4 –SiO 2) catalyzed green FCDR strategy has been developed for the synthesis of (Z)-THIs (6) with high stereospecificity via an intramolecular hydrogen bond (IHB) directed approach, involving the reaction of methyl ketones (1), N-bromosuccinimide (NBS) (2), isatins (4) and thiosemicarbazide (5) in ethanol at reflux temperature for 45–60 min in one-pot. The reaction proceeds through the construction of C–Br (α-bromination), C–S & C–N (heterocyclization), and C N (condensation) bonds in one pot. The absolute structure of the compound (Z)-3-(2-(4-(4-bromophenyl)thiazol-2-yl)hydrazono)indolin-2-one (6e) has been confirmed by single-crystal XRD analysis. Further, the role of IHB on Z -configuration of the synthesized (Z)-THIs is proved by single-crystal XRD and 1H NMR studies. Wide substrate scope, good functional group tolerance, scalability, improved safety since the method circumvents the use of highly lachrymatric α-bromoketones as starting materials, high product yields (up to 98%), short reaction times, reusable solid Brønsted acid catalyst (HClO 4 –SiO 2), and products that do not require column chromatography purification are all attractive features of this FCDR strategy. Electrochemical properties of THIs (6) are examined by cyclic voltammetry. The HOMO and LUMO energy level of THIs, 6a, 6c, 6d, 6j, 6o-6v, 6y, and 6aa are comparable with the reported ambipolar materials, and the HOMO levels of other THIs, 6b, 6e-6i, 6n, 6w, 6x, 6z and 6 ab-6ae are similar with the most commonly used hole transporting materials (HTMs). A practical, straightforward and green FCDR strategy has been demonstrated for the synthesis of (Z)-THIs (6) in the presence of HClO 4 –SiO 2 via an IHB directed approach. The reaction proceeds through the formation of C–Br, C–S, C–N & C N bonds in one-pot. The role of IHB on (Z)-configuration of the synthesized (Z)-THIs was confirmed by single crystal XRD and 1H NMR studies. The HOMO and LUMO energy level of (Z)-THIs are comparable with the most commonly used ambipolar and hole transporting materials. [Display omitted] • Environmentally benign HClO 4 –SiO 2 catalyzed FCDR strategy for synthesis of (Z)-THIs. • Z -configuration of THIs confirmed by single crystal XRD and 1HNMR studies. • Construction of C–Br, C–N, C–S and C N bonds in a single-step operation. • (Z)-THIs could be promising ambipolar materials for efficient OLEDs. [ABSTRACT FROM AUTHOR]

Background Semi-synthetic oleanane triterpenoid antioxidant inflammation modulators (tpAIMs) are small molecules that interact with KEAP1 cysteine residue 151 (C151) and activate NRF2. Exploration of the structure-activity relationship between the tpAIMs and KEAP1 is limited by the predominantly hydrocarbon nature of the oleanane triterpenoid pentacyclic ring structure. Therefore, we used novel, chemically-tractable, synthetic antioxidant inflammation modulators (sAIMs) to probe the stereoselectivity of the ligand-protein interaction. Methods We measured several parameters of NRF2 activation to assess the potency of sAIM enantiomers with natural (tpAIM-like) 4( S ),5( S ),10( R ) or unnatural 4( R ),5( R ),10( S ) configurations. Additionally, we determined the crystal structure of the KEAP1 BTB domain in complex with two different sAIMs. Results We found that the potencies of sAIM enantiomers in the natural configuration were similar to those of the tpAIM, RTA 405. Strikingly, sAIM enantiomers in the unnatural configuration were 10- to 40-fold less potent than their natural counterparts. Crystallographic studies of sAIMs in complex with the KEAP1 BTB domain demonstrated that these ligands form a covalent bond with C151 and revealed the presence of additional hydrogen bonds, Van der Waals interactions, and pi-stacking interactions. Conclusions Although KEAP1 C151 is required for NRF2 activation by tpAIMs and sAIMs, interactions with other KEAP1 residues are critical for the stereospecific recognition and potency of these ligands. General significance This work demonstrates that reversible cyanoenone Michael acceptors, such as the tpAIMs and sAIMs, can be specifically tuned to regulate redox sensitive cysteine residues on key signaling molecules, an approach with significant promise for innovative drug development. [ABSTRACT FROM AUTHOR]

Pentacyclic pyrrolo[3,4- a ]carbazole-1,3(2 H )-diones are accessed via two key synthetic steps, an intermolecular Diels–Alder (D–A) reaction between an N -protected 3-vinyl-1 H -indole and N -methyl-maleimide, and a Lewis acid-catalysed intramolecular carbonyl-ene cyclisation reaction. Cyclopentyl- or cyclohexyl-containing scaffolds can be formed through variation in the length of the alkyl tether, whilst the observed stereospecificity of carbonyl-ene cyclisation supports a concerted mechanism. [ABSTRACT FROM AUTHOR]

Density functional theory has been used to study the mechanism and stereospecificity of the catalytic reaction of human glyoxalase I. We used the quantum mechanical cluster method to model the enzyme active site. Glyoxalase I accepts both enantiomers of the hemithioacetal between methylglyoxal and glutathione and converts them to the S -D enantiomer of lactoylglutathione. We have compared several previously suggested or alternative reaction mechanisms for both substrates on an equal footing. The results show that the coordination shell of the Zn ion in the optimized geometries is more symmetric than in some inhibitor crystal structures, which we assign to differences in the electronic structure and the protonation states of the substrate. The symmetry of the active site model indicates that the enzyme can use the same reaction mechanism for the S and the R enantiomers of the substrate, but with exchanged roles of the two active-site glutamate residues. However, the calculations show some asymmetry (0–4 kcal mol −1 differences in reaction energies and activation barriers), caused by the different coordination states of the glutamate residues in the starting crystal structure. Our results indicate that the only possibility for the stereospecificity of glyoxalase I is differences in the electrostatic surroundings and flexibility of the glutamate residues in the active site owing to their neighboring residues in the protein. [ABSTRACT FROM AUTHOR]

Assemblies between the pseudo-enantiomers with different π electronic systems, [Pt(bpy){Co( d -pen) 2 }] + (bpy = 2,2′-bipyridine, pen = penicillaminate) and [M(phen){Co( l -pen) 2 }] + (M = Pt or Pd, phen = 1,10-phenanthroline), or [Pt(bpy){Co( l -pen) 2 }] + and [M(phen){Co( d -pen) 2 }] + , have been examined from stereo- and spectrochemical aspects. As a result, a mixture of equimolar amounts of optically active sulfur-bridged dinuclear complex, [Pt(bpy){Co( d -pen) 2 }]Cl, and its pseudo-enantiomer, [M(phen){Co( l -pen) 2 }]Cl, in H 2 O crystallizes as [Pt(bpy){Co( d -pen) 2 }][M(phen){Co( l -pen) 2 }]Cl 2 ·14H 2 O, in which two complex cations with imperfect enantiomorphisms form a 1:1 π–π stacked unit. In the crystal, such a 1:1 π–π stacked unit develops into a linear-chain through further π–π stacking contacts with adjacent 1:1 π–π stacked units. [ABSTRACT FROM AUTHOR]

Oxidative aminoaziridination is a general, functional group tolerant, stereospecific, and in many cases stereoselective synthetic method for the preparation of diverse N -aminoaziridine derivatives. This focused review begins with a short historical sketch of the field, continues with its recent accomplishments and presents an outlook for the areas where this methodology can successfully be applied. [ABSTRACT FROM AUTHOR]

Aporphine alkaloids were transformed into the corresponding stereospecific 4 R -hydroxyaporphine alkaloids through the solid-state fermentation of Stephania epigaea with Clonostachys rogersoniana . This process was validated by both solid- and liquid-state fermentations with aporphine alkaloids as substrates. Cytochrome P450 enzymes were confirmed to participate in the catalysis of this biotransformation. 4 R -Hydroxyaporphine alkaloids exhibit the same levels of acetylcholinesterase (AChE) inhibitory and cytotoxic activities as aporphine alkaloids and are considerably more water soluble than aporphine alkaloids, indicating their potential as water-soluble AChE inhibitors and antitumor agents. This paper suggests that C. rogersoniana fermentation can facilitate a novel biotransformation of aporphine alkaloids in S. epigaea to 4 R -hydroxyaporphine alkaloids. [ABSTRACT FROM AUTHOR]