Acyclic phenylalkanediols as substrates for the study of enzyme recognition. Regioselective acylation by porcine pancreatic lipase: a structural hypothesis for the enzymatic selectivity

The regioselective acylation of phenylalkanediols catalysed by porcine pancreatic lipase (PPL) was the reaction used for modelling different areas in the active site of the enzyme. With this aim, different racemic or prochiral (1,n)-diols, with n ranging from 2 to 6 were resolved via transesterification with vinyl acetate, and the results were explained according to microcrystalline enzyme structure. Thus, we describe a logical model for explaining the enzyme regio and stereoselectivity, based on three residues of the active site (Ser153, Phe216 and His264) which turned out to be crucial for the substrate binding and transformation.     

Products of hydrolysis of C,N-chelated triorganotin(IV) chlorides and use of products as catalysts in transesterification reactions

Triorganotin(IV) chlorides containing one L^CN chelating ligand were hydrolyzed with an excess of sodium hydroxide. The composition of the products is strongly dependent on the nature of the organic groups bound to the tin atom. Di(n-butyl)tin, dimethyltin as well as the diphenyl derivative exhibits an equilibrium between hydroxide and stannoxane forms (oxide), whereas alkyltin species react spontaneously and reversibly with carbon dioxide present in the air to form carbonate species. On the other hand, diphenyl derivatives display virtually no reaction with CO₂ towards carbonates, while the di-t-butyl-substituted tin derivative is stable under the same experimental condition and remains as a tin hydroxide. In the case of the dimethyltin derivative, a methyl group migration was observed with displacement of one L^CN chelating ligand during the reaction on the air. The coordination geometry of the tin central atom(s) of all studied compounds can be described as trigonal bipyramidal with a dative bonded dimethylamino group occupying one coordination site. The catalytic activity of these compounds in transesterification reactions is generally lower compared to the systems reported in the literature, with the exception of the transesterification of ethyl acetate by cyclohexanol which displays a remarkable activity.     

Synthesis of [13]-membered macrocyclic stevastelins via a transesterification reaction as the key step: total synthesis of stevastelin C3

A new synthesis of stevastelin C3 (3), a [13]-membered ring component of the stevastelin family, whose structure was recently revised, is reported. Initially, a macrolactonization approach was attempted to generate the [13]-membered macrolactone but this met with failure, so a translactonization reaction was tried to obtain the targeted stevastelin C3 (3) from the corresponding [15]-membered ring counterpart. Unfortunately, this strategy did not prove successful, and, consequently, we opted to undertake a transesterification reaction from 23, as a means to accommodate the requisite aminoacid moiety at the correct position, to obtain 24. From 24, and through intermediates 25-28, the acyclic precursor of the [13]-membered ring macrolactone, compound 30, was efficiently prepared. By utilizing the synthetic course developed by Chida, we took 30 forward and completed the total synthesis of stevastelin C3 (3).     

Effect of substituent on the enantioselectivity for lipase-catalyzed kinetic resolution of glycerol derivatives

The lipase-catalyzed transesterifications of various substituted diphenyl 1,2-ketals of glycerol have been investigated. Efficient modification of the substrate structure with bis(4-bromophenyl) ketal was found to enhance the enantioselectivity up to E=57 at 0 °C.     

Design and synthesis of useful intermediates for novel lipoxygenase substrates through enzymatic resolution

Unnatural lipoxygenase substrates carrying spacing modifiers with a non-ionic hydroxy terminus and with methylene (flanked by the cis,cis diene moiety) pro-(S)-hydrogen can be synthesized from the intermediates 1a–1c. These intermediates are conveniently synthesized via enzymatic resolution with lipase in organic solvents.     

Polymer-supported titanate as catalyst for the transesterification of acrylic monomers

Transesterification of (meth)acrylic esters catalysed by alkyl titanates is an important industrial reaction. The current processes are homogeneous but heterogeneous alternatives are attractive for cost and environmental reasons. We have developed a straightforward and cost-effective synthesis of a polymer-supported titanium alkoxide catalyst involving cheap, readily available and relatively non-toxic chemicals, solvents and workup procedures. Efficiency and stability of the catalyst were tested in a laboratory-scale continuous flow reactor under equilibrium conditions for the preparation of N,N-dimethylaminoethylacrylate, a chemical of industrial interest. The results obtained indicate a good stability of the system to metal leaching on the long term.     

Activities of octoate salts as novel catalysts for the transesterification of flexible polyurethane foams with diethylene glycol

Polyurethane foams are disposed of not only at the end of their use but also as scrap during slabstock manufacturing, leading to an environmental and economic problem. Flexible polyurethane foams can be advantageously treated by two-phase glycolysis in order to recover their constituent polyols with an improved quality compared to the single phase processes. The glycolysis comprises a transesterification, which has been traditionally catalyzed by alkanolamines, titanium compounds and acetates. In this work, the performance evaluation of new catalysts based on alkaline, alkaline-earth and transition metal octoate salts has been carried out. The carboxylates have showed different catalytic activities according to their basicity and coordination ability. A reaction mechanism for the polyurethane glycolysis in the presence of the carboxylate catalysts studied has also been proposed. The mechanism involves several steps, including the formation of a metal alkoxylate, coordination-insertion of the alkoxide into the urethane group and transfer from recovered polyol to glycol. Among the octoates studied, lithium and stannous octoates showed a remarkable catalytic activity. They yielded the greatest quality for the recovered polyol as well as the highest decomposition rates.     

别苏氨酸的合成与酶拆分方法的研究

设计了一种新颖实用的制备L-别苏氨酸和D-别苏氨酸的方法。以α-C消旋的N-乙酰化苏氨酸为原料,用L-(或D-)氨基酰化酶拆分相应的底物得到了高光学纯度的L-别苏氨酸(或D-别苏氨酸)。为了获得较高收率,考查p H,温度,Co2+浓度对拆分反应的影响。确定最优条件为:p H 7.5,温度37℃,Co2+浓度0.1 g·L-1。反应产率达到93.8%(L-allo-Thr)、89.8%(D-allo-Thr),de99%。该方法具有立体选择性高,操作简单,反应条件温和的优点。     

Boric acid: an efficient and environmentally benign catalyst for transesterification of ethyl acetoacetate

An efficient and environmentally benign boric acid catalyzed protocol for the transesterification of ethyl acetoacetate with a variety of primary and secondary alcohols in good to excellent yields is described. The versatility of this transformation is demonstrated with problematic substrates such as propargyl alcohol and allyl alcohol, which are known to undergo Carroll rearrangement during transesterification.     

A green and expedient synthesis of enantiopure diketopiperazines via enzymatic resolution of unnatural amino acids

Dipeptides comprising a d-phenylglycyl moiety coupled to the l-enantiomer of 2-amino butyric acid, norvaline, norleucine, and homocysteine were successfully synthesized from d-phenylglycine amide and the racemate of the corresponding unnatural amino acid. The reaction is catalyzed by an immobilized form of penicillin G acylase in an aqueous medium. The dipeptides were subsequently converted into the corresponding enantiopure diketopiperazines in overall isolated yields of 22–33%.     

Niobium(V) oxide: a new and efficient catalyst for the transesterification of β-keto esters

Niobium(V) oxide is an efficient catalyst for the transesterification of β-keto esters with several kinds of alcohols, leading to good conversions. Moderate to good isolated product yields have been obtained at faster rates than those recently reported for various catalysts.     

Semicarbazones and thiosemicarbazones,XIII: Study of the hydrolysis of coordinated thiosemicarbazones

Summary The hydrolysis of coordinated thiosemicarbazones was studied. It was found that the nickel(II) ion promotes the reaction. Steric and electronic influences were found. The hydrolysis ofATSC in the trigonal bipyramid compounds [M(ATSC)₂Cl]Cl [M=Fe(II), Co(II), Ni(II)], is higher with the Ni(II) complex, the compound with the shorterM-N distance.

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Semicarbazone und Thiosemicarbazone, 13. Mitt.: Untersuchungen zur Hydrolyse koordinierter Thiosemicarbazone

Zusammenfassung Bei der Hydrolyse von koordinierten Thiosemicarbazonen wurde festgestellet, daß das Nickel(II)-Ion die Reaktion begünstigt. Es wurden sterische und elektronische Einflüsse gefunden. Die Hydrolysengeschwindigkeit desATSC im trigonal bipyramidalen Komplex [M(ATSC)₂Cl]Cl [M=Fe(II), Co(II), Ni(II)] ist höher mit dem Ni(II)-Komplex, der Verbindung mit der kürzerenM-N-Distanz.

     

On the chemistry of pyrrole pigments,LXXXVII: The apomyoglobin heme pocket as a reaction vessel in bile pigment chemistry

Summary An apomyoglobin biliverdin complex was reduced to a bilirubin apomyoglobin complex with retention of the helix chirality of the chromophore. Chelation of the mesobiliverdin-XIII apomyoglobin complex with zinc ions in aqueous solution yielded an enantiomer of the corresponding derivative. These two systems document the possibility of using the heme pocket of apomyoglobin to execute stereospecific reactions. The chiroptical properties of the two product systems are discussed.

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Zur Chemie von Pyrrolpigmenten, 87. Mitt.: Die Häm-Tasche des Apomyoglobins als Reaktionsgefäß für die Chemie von Gallenfarbstoffen

Zusammenfassung Der Apomyoglobin-Biliverdin-Komplex wurde zum entsprechenden Apomyoglobin-Bilirubin-Komplex unter Retention der Helixkonfiguration des Chromophors reduziert. Chelierung des Apomyoglobin-Mesobiliverdin-XIII-Komplexes mit Zinkionen in wäßriger Lösung lieferte ein Enantiomer des entsprechenden Derivates. Diese beiden Systeme dokumentieren die Verwendbarkeit der Häm-Tasche des Apomyoglobins um stereospezifische Reaktionen durchzuführen. Die chiroptischen Eigenschaften der beiden Produktsysteme werden diskutiert.

     

Preparation and characterisation of amorphous mesoporous aluminophosphate and metal aluminophosphate as an efficient heterogeneous catalyst for transesterification reaction

Preparation, characterisation of pure aluminophosphate and aluminophosphate modified with different transition metals (V, Fe, Co Ni & Cu) and their catalytic activity in mono/dibenzyl substituted malonates synthesis are explained. The materials were prepared by the coprecipitation method in the absence of any structure-directing species and characterized for their composition, crystalline nature, total surface acidity, specific surface area pore diameter and pore volume by different techniques. Catalytic activity of the materials was investigated in transesterification of diethylmalonate with benzyl alcohol in liquid phase. Pure aluminophosphate resulted only in benzyl ethylmalonate whereas the incorporation of transition metals favored the formation of both benzyl ethylmalonate and dibenzylmalonate. Catalytic activity parallels the surface acidity and mesoporosity of the catalysts. The effect of the molar ratio of reactants, amount of catalyst, and reaction time on the conversion of diethyl malonate and transester yield has been studied. The highest activity of iron aluminophosphate is attributed to its mesoporous nature with uniform pore size distribution, higher surface acidity and surface area. Further, the scope and generality of iron aluminophosphate as a catalyst in the transesterification was studied using various aliphatic, alicyclic and aromatic alcohols. The catalysts could be recycled by retaining most of its initial activity.     

Catalysts/cosolvents and general acid catalysts for acceleration of the hydrolysis of osmate(VI) esters

New catalysts/cosolvents as hydrolysis aids and the properties of the catalyst/cosolvent that effect the efficiency of the hydrolysis aid for the hydrolysis of osmate(VI) esters of aliphatic olefins are presented. Also, the effect of pH of the reaction media on the specific and general acid-catalysed hydrolysis of osmate(VI) esters of conjugated aromatic olefins is presented.     

Synthesis of diastereoisomeric pairs of novel analogues of d4T having an isochroman glycon moiety; their enzymatic kinetic resolution, their enantiopure synthesis, molecular modeling and NMR structural study

An efficient route, starting from 2-bromobenzaldehyde, is described to synthesize racemic diastereoisomeric thymine derivatives of isochroman, which are aromatic analogues of Stavudine, an approved anti-HIV drug. The relative configurations were determined by NOE proton NMR experiments in connection with molecular modeling. Following the separation of the latter diastereoisomers, kinetic resolution was achieved via a transesterification reaction catalyzed by lipases. Using this method, moderate ee's were obtained (0.74-0.98). Thus, an alternative strategy starting from d-mannitol was proposed to provide pure enantiomers. The attribution of absolute configurations was made by chemical filiation on the basis of the configurations obtained from d-mannitol. The structural attributions were confirmed by studying the behavior of proton NMR shifts of the corresponding isochroman Mosher's esters.     

Multi-functionalized chiral crown ethers as enzyme models for the synthesis of peptides. Multiple chiral recognition in the enzyme model

A novel approach to the enzyme model for the synthesis of peptides has been established by using multi-functionalized chiral crown ethers as hosts. The new strategy consists of three key steps as follows. (1) Guest assembly: the host having one free thiol and one thioester withN-protected-amino acid or peptide proceeds via rapid intra-complex thiolysis of-amino acid ester salts to form the dithioester, and assembles two guests. (2) Amide formation: the intramolecular aminolysis occurs between the bound guests to form the amide bond. (3) Peptide chain elongation: as the thiol reactive group is regenerated, the above two reactions are repeated to elongate the peptide chain. In the present paper, we describe the multiple chiral recognition that could be achieved by the chiral crown ether in both the intra-complex thiolysis and the intramolecular aminolysis. For explanation of the chiral recognition, we propose a likely structure for the intermediate of the aminolysis.     

Novel reaction systems for the synthesis of O-glucosides by enzymatic reverse hydrolysis

Our studies are presented to replace alcohols as solvents in reverse hydrolytic reactions catalyzed by immobilized β-glucosidase to synthesize O-substituted β-d-glucopyranosides in preparative-scale. We found that 1,2-diacetoxyethane is a suitable solvent and O-alkyl or aryl β-d-glucosides were synthesized in moderate yields (after isolation 12-19%). In these reactions proportion of glucose and glucosyl acceptor hydroxy compounds was 1:20. We suggest that 1,2-diacetoxyethane can be useful not only for alcohols but for other glucosyl donor compounds unsuitable for the role of solvent (e.g., phenols) in the synthesis of O-β-d-glucosides by reverse hydrolysis.     

Analytical and kinetic study of the aqueous hydrolysis of four organophosphorus and two carbamate pesticides

The hydrolysis of six selected pesticides has been studied in aqueous solution. Four organophosphorus pesticides (disulfoton, isofenfos, isazofos and profenfos) and two N-methylcarbamate derivatives (oxamyl and ethiofencarb) were selected. Hydrolysis was performed in purified buffered water at different pH in the range 7.0–10.0 (ionic strength?=?2.5?mM, T?=?25°C). At pH?=?8.0, isofenfos and disulfoton (t _1/2?≈?4 years, t _1/2?≈?1 year, resp.) were found to be far more stable than isazofos (t _1/2?≈?5 months), ethiofencarb and profenofos (t _1/2<1 month), themselves more stable than oxamyl (t _1/2?≈?1 day). As expected, a strong dependence on pH was observed for all pesticides: the rate of degradation increased when the pH increased. Degradation products were identified by GC–MS and/or LC–MS. Possible structures are presented in the article.     

有机-无机复合型固体酸催化剂的制备及其催化甘油乙酸甲酯酯交换反应

酸性催化剂在传统的炼化工艺和最近的生物炼制技术中均起着十分重要的作用.相较于传统的液体酸,固体酸催化剂由于具有易分离、可重复使用、无腐蚀性和环保等优点而引起了广泛的研究兴趣.在过去的几十年中,研究者们成功研制出多种不同类型的固体酸,如沸石、杂多酸、金属氧化物和磺化的碳基材料等.但是,传统的固体酸仍存在一些不足,如酸中心类型和酸强度不确定、表面酸位点分布不均以及活性位点易流失、稳定性较差等.甘油是生物柴油生产过程中的主要副产物.据统计,2022年全球生物柴油的年产量将达到1410亿升,这意味着甘油的产量也将增加.因此,将过剩的甘油催化转化制备高附加值产品具有重要的意义.甘油在酸催化的作用下可以制备得到丙酮缩甘油、甘油酯、丙烯醛和甘油醚等高附加值产品.其中,乙酸甘油酯(包括单乙酸甘油酯(MAG)、二乙酸甘油酯(DAG)和三乙酸甘油酯)在工业中具有广泛的应用,它们既可用于医药、食品和化妆品行业,又可作为燃料添加剂改善生物柴油的性能.目前乙酸甘油酯的主要合成路径为甘油与乙酸或乙酸酐酯化法,但乙酸和乙酸酐对反应设备有腐蚀性,限制了其在工业上的大规模应用.乙酸甲酯是聚乙烯醇生产过程中的主要副产物,具有来源广泛、安全、无味、易分离(沸点低)等优点,因此,以乙酸甲酯为乙酰化试剂与甘油进行酯交换反应制备乙酸甘油酯这一新的合成路径引起了关注.然而固体酸催化剂在该反应中的应用鲜有文献报道.对羟基苯磺酸(PSA)是一种有机液体强酸,可用于缩醛化、酯化、酯交换等酸催化反应中,但它不可分离、无法重复使用而且对环境污染严重.因此,本文采用一锅法,将均相PSA固载在经硅烷偶联剂KH560改性的磷酸锆载体(K-ZrP)上,制备得到一系列不同PSA含量的无机-有机复合型固体酸催化剂(PSA/K-ZrP-x).通过X射线衍射、红外光谱、固体核磁共振碳谱(13C SSNMR)表征方法研究了催化剂的精细结构,吡啶吸附红外(Py-IR)光谱结果表明催化剂的酸性中心主要是布朗斯特酸,通过热重、X射线光电子能谱表征结果计算催化剂中活性组分([H+],S)的整体与表面含量,结果表明PSA/K-ZrP-2中PSA的含量已饱和,且PSA在K-ZrP载体表面分散均匀,从而增加了表面酸位点的可接触性,通过氮气吸脱附和扫描电镜研究了PSA/K-ZrP-x的形成过程,线扫描元素分析表明PSA/K-ZrP-2具有蒲公英状结构.以甘油乙酸甲酯酯交换反应为模型反应,考察了所制备催化剂的活性,结果表明PSA/K-ZrP-2催化剂的稳定性明显高于H3PW12O40,Amberlyst-45,HBEA和HZSM-5等常见的商业化固体酸和AlCl3,FeCl3等路易斯酸.在2.2％[H+]含量的PSA/K-ZrP-2催化剂作用下,10 mmol甘油与100 mmol乙酸甲酯于100℃反应4h,甘油转化率可达81.3％,MAG和DAG的选择性之和达97.7％.在反应初期(0.17 h),该催化剂的比活性可达24028.2 mg-glycerol/g-cat/h,且五次循环使用后活性无明显降低.结合本文表征结果,偶联剂KH560可增强对羟基苯磺酸和磷酸锆之间的相互作用,从而提高催化剂的稳定性.同时,该催化剂在甘油与其它酯类的酯交换反应中也表现出优异的反应活性,表明PSA/K-ZrP-2固体酸催化剂具有较好的普适性.