A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the Dötz annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(2′-hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.     

Making Solid‐Phase Peptide Synthesis Greener: A Review of the Literature

To date, the synthesis of peptides is concurrent with the production of enormous amounts of toxic waste. DMF, CH₂Cl₂, and NMP are three of the most toxic organic solvents used in chemical synthesis and are the most common solvents used for peptide synthesis. Additionally, concerns about the hepatotoxicity caused by exposure to DMF and from the toxic and allergenic nature of additives used in peptide synthesis necessitates the need for a green, environmentally friendly, and safer protocol for peptide synthesis. This review summarizes the current literature on green solid‐phase peptide synthesis successes and challenges encountered. The review concludes with suggestions for future research towards a simple and efficient green peptide synthesis protocol.     

A concise and improved synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A concise and improved stereoselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is based on a Dötz benzannulation and an improved oxa-Pictet-Spengler cyclization as the key steps. The synthesis is achieved in six steps in overall yields of 18% for eleutherin and 20% for allo-eleutherin.     

Enantioselective total synthesis of (+)-digitoxigenin

An enantioselective total synthesis of (+)-digitoxigenin is described. This total synthesis is accomplished in a convergent manner using two chiral fragments prepared via the catalytic asymmetric intramolecular cyclopropanation and baker’s yeast mediated reduction developed by us, respectively. This convergent synthesis would be useful for preparing some new derivatives of digitoxigenin for SAR studies and could be applied for the total synthesis of other cardenolides left unprepared.     

Model studies for the synthesis of the antibiotic lactonamycin and the discovery of new reactions and mechanisms for the construction of substituted heterocycles

A new and highly efficient route for the construction of a model for the synthesis of lactonamycin 1 is reported. The chemistry has been utilised for the synthesis of heterocyclic rings, and new reactions for the synthesis of dienes and alkynes are reported.     

A facile synthesis of cyclic bis(3′→5′)diguanylic acid

This paper describes a new method for synthesizing biologically important cyclic bis(3′→5′)diguanylic acid (cGpGp) in a higher yield than that of the existing synthetic method. In the new synthesis, the following two means, in place of those used in the existing synthesis are employed as main strategies to cause the increase in product yield. One of these distinctive strategies in the new synthesis is that the phosphoramidite method is used for the preparation of a key synthetic intermediate of a linear guanylyl(3′→5′)guanylic acid derivative. This method allowed higher-yield formation of the intermediate than that by the triester method used in the existing synthesis. The second distinctive strategy used in the new synthesis is that allyloxycarbonyl and allyl groups are used for the protection of two guanine bases and two internucleotide bonds, respectively. These four allylic protectors can be removed all at once by the organopalladium-catalyzed reaction under neutral conditions. Thus, deprotection of the protected cGpGp precursor was achieved in the present synthesis in a shorter step and under milder conditions than the deprotection achieved in the existing synthesis, which uses diphenylacetyl and o-chlorophenyl groups as protectors for two guanine bases and two internucleotide bonds, respectively, whose full removal requires two different procedures including rather harsh basic treatment. As a result, technical loss and decomposition of the target product in the new synthesis is remarkably reduced.     

Stereoselective Halogenation in Natural Product Synthesis

At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp³‐hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.     

Efficient construction of functionalized 5-carboxymethyl tetramic acids using N-Ac-l-aspartic anhydride as chiral building block

A novel method for the synthesis of densely functionalized optically active 5-carboxymethyl tetramic acids is reported. The proposed strategy is focused on the synthesis of 3,3′-disubstituted pyrrolidine-2,4-diones as useful molecules for the synthesis of natural products. The proposed methodology has been established by X-ray diffraction structure analysis.     

Stereoselective synthesis of anti-1,3-diol units via Prins cyclisation: application to the synthesis of (−)-sedamine

The scope of the Prins cyclisation, the higher stereoselective synthesis of multisubstituted tetrahydropyrans from aldehydes and homoallylic alcohols, is expanded. A new approach for the stereoselective synthesis of polyketide precursors containing anti-1,3-diols, flanked by a variety of alkyl branches and functional groups is described. The approach is successfully exploited for the synthesis of (−)-sedamine.     

An efficient green procedure for the synthesis of chalcones using C-200 as solid support under grinding conditions

Abstract

A simple, rapid, efficient and environmentally benign procedure for the synthesis of chalcones has been achieved by grinding aryl aldehydes and acetophenones with anhydrous barium hydroxide (C-200) in the absence of any solvent. The use of organic solvent for extraction of compound is also avoided. This present method is highly useful for the synthesis of 2′-hydroxy chalcones, required intermediates for the synthesis of flavanoids.     

Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes: a direct synthesis of trisubstituted furans

A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction of terminal alkynes with β-keto α-diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans is operationally simple and applicable to wide substrate scope. Moreover, this synthesis employs cheap Cu(MeCN)₄PF₆ as the catalyst and no additional ligand is needed. Similar reaction has also been applied to ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the synthesis of 2,3,5-trisubstituted N-methoxypyrroles with limited success.     

Optimization of yield in kinetically controlled synthesis of ampicillin with immobilized penicillin acylase in organic media

Immobilized penicillin acylase is a moderately priced versatile enzyme, that is able to catalyze the synthesis of derived penicillins and cephalosporins from the corresponding β-lactam nuclei and proper side-chain precursors. Kinetically controlled synthesis is a better strategy when product yield is a key issue. Yield should increase at reduced water activity by depressing the competing hydrolytic reactions in favor of synthesis; therefore, organic cosolvents can be a suitable reaction media for synthesis. Using response surface methodology and product yield as objective function, temperature and pH were optimized in the kinetically controlled synthesis of ampicillin using previously screened cosolvents and reaction conditions. Optimum pH was 6.0 for ethylene glycol (EG) and glycerol (GL) and 6.6 for 1–2 propanediol (PD); optimum temperature was 30°C for GL and for EG and PD was in the lower extreme of the range studied, optimum lying below 26°C. Maximum molar yields predicted by the model were 58,51, and 46% for EG, GL, and PD, respectively, which were experimentally validated. Highest yield in aqueous buffer was always <40%. Molar yields about 60% compare favorably with values reported for the kinetically and thermodynamically controlled synthesis of ampicillin and other derived penicillins.     

碳一化工路线制备乙二醇研究进展

乙二醇(EG)是一种重要的化工原料,主要用来生产新型聚酯纤维.近年来由于我国聚酯产业发展迅速,极大的推动了对乙二醇的需求.碳一化工路线以资源丰富、价格便宜的天然气或煤为原料合成乙二醇,有着诱人的工业化前景.综述了以合成气为原料合成乙二醇的研究进展,包括合成气直接合成法、甲醛羰化法、CO偶联法、甲醛氢甲酰化法以及甲醛缩合法等.     

Mechanistic Insights into a Sustainable Mechanochemical Synthesis of Ettringite

Mechanochemistry offers an environmentally benign and facile synthesis method for a variety of cement paste constituents. In addition, these methods can be used to selectively tune the properties of cement components. The mineral ettringite is an important component of cementitious materials and has additional technological potential due to its ion exchange properties. Synthesis of ettringite via mechanochemistry is an environmentally friendly alternative to conventional wet-chemical synthesis established in industry. This contribution explores the mechanism of a two-step mechanochemical synthesis of ettringite, which was previously found to greatly improve the reaction conversion as compared with one-pot synthesis. The crystallinity of Al(OH)₃ was found to decrease during the first stage of this mechanochemical synthesis. This was correlated to a significant decrease in the particle size of Al(OH)₃ in this stage. No other significant changes were found for the other components, suggesting that mechanochemical activation of Al(OH)₃ is responsible for the enhanced formation of ettringite by the two-step approach. The environmentally friendly approach developed for ettringite synthesis offers a versatile synthetic strategy, which can be applied to synthesise further cementitious materials.     

Study of the kinetic parameters for synthesis and hydrolysis of pharmacologically active salicin isomer catalyzed by baker’s yeast maltase

One of the key elements for understanding enzyme reactions is determination of its kinetic parameters. Since transglucosylation is kinetically controlled reaction, besides the reaction of synthesis, very important is the reaction of enzymatic hydrolysis of created product. Therefore, in this study, kinetic parameters for synthesis and secondary hydrolysis of pharmacologically active α isosalicin by baker’s yeast maltase were calculated, and it was shown that specifity of maltase for hydrolysis is approximately 150 times higher then for synthesis.     

Technological aspects of fructose conversion to high-purity 5-hydroxymethylfurfural,a versatile platform chemical

Two improved methods for the synthesis of 5-hydroxymethylfurfural by acid-catalyzed dehydration of fructose have been developed. The first one is the synthesis in ionic liquids with continuous removal of water under reduced pressure, and the second is the synthesis in the two-phase system consisting of aqueous NaHSO₄ and methyl isobutyl ketone under atmospheric pressure. Both methods ensure isolation of crystalline 5-hydroxymethylfurfural with high purity and multiple recycling of the catalytic system. The synthesis in ionic liquid is convenient on a laboratory scale. Despite relatively low yield, the two-phase synthesis is preferred for industrial scale-up due to simple isolation and purification procedures combined with efficient regeneration of extractant and the catalytic system.     

生物催化不对称合成beta-羟基酸衍生物

手性β-羟基酸及其衍生物是应用化工和有机合成的关键中间体, 生物催化的不对称合成方法以其绿色环保, 简洁高效及高立体选择性已然成为一个新兴的研究热点。本文较系统的总结了生物催化的β-羟基酸及其衍生物不对称合成研究工作,重点介绍了脂肪酶,腈代谢酶及还原酶在合成手性β-羟基酸衍生物中的应用。最后,对今后生物催化不对称合成β-羟基酸的发展方向做一展望。     

A total synthesis of the ammonium ionophore, (−)-enniatin B

A nine-step (longest linear) batch total synthesis of the cyclic hexadepsipeptide (−)-enniatin B is described. The synthesis minimizes precipitation during reaction conditions for adaptability to flow synthesis. The route was used to prepare >100 mg of the natural product.     

Intermediacy of silylene and germylene in direct synthesis of organosilanes and organogermanes

In the direct synthesis of silicon compounds by reactions of elemental silicon with methyl chloride, methanol and hydrogen chloride, silylene formed on surface of silicon grains during the reaction is an intermediate. The reaction of surface silylene with a variety of unsaturated hydrocarbons provides new direct synthesis of organosilanes. In the direct synthesis of methylchlorogermanes from elemental germanium, surface germylene is not an intermediate, while tetrachlorogermane is synthesized by the direct reaction of germanium with hydrogen chloride via dichlorogermylene intermediate. Various unsaturated hydrocarbons or organic chlorides added to the system of tetrachlorogermane synthesis give new methods for the synthesis of organogermanes.     

A novel methodology for the synthesis of 1-desoxy-Δ-tetrahydrocannabinol (THC) analogues

A versatile and efficient sequence was developed for the synthesis of 1-desoxy-Δ⁸-THC analogues and is demonstrated by the synthesis of sulfonamide analogues with an acetylene group at the C-2^′ position in the side chain. In this procedure the 1-desoxy-Δ⁸- THC ring structure is built first and the synthesis of the side chain is then developed.