2-(2-(4-Methoxyphenyl)furo[3,2-h]quinolin-3-yl)acetic Acid

A simple and efficient protocol for the synthesis of the previously unknown 2-(2-(4-methoxyphenyl)furo[3,2-h]quinolin-3-yl)acetic acid was elaborated. The suggested method is based on the telescoped multicomponent reaction of 8-hydroxyquinoline, 4-methylglyoxal, and Meldrum’s acid. The studied process includes the initial interaction of the starting compounds in MeCN followed by intramolecular cyclization to the target product in refluxing acetic acid. The advantage of this approach is the application of readily available starting materials, atom economy, and a simple work-up procedure. The structure of the synthesized furylacetic acid derivative was proven by 1H, 13C, 2D-NMR, IR spectroscopy, and high-resolution mass spectrometry.

Umpolung of Indoles: Triflic Acid-Mediated C3-Regioselective Hy-droarylation of N-H Indoles

The direct dearomative addition of arenes to the C3-position of unprotected indoles is reported under operationally simple conditions with triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to gen-erate an electrophilic indole at the C3-position without the need to introduce a deactivating acetyl group on the indolic nitrogen as in previously reported strategies. This atom economy method delivers biologically relevant 3-aryl indolines and 3,3-spiroindolines in high yields and regioselectivities from both intra and intermolecular processes.

Solvent Screening, Optimization and Kinetic Parameters of The Biocatalytic Epoxidation Reaction of Beta-Pinene Mediated by Novozym®435

Monoterpenes are secondary metabolites widely used in the flavors and fragrance industries and can have their structure altered to enhance their applicability, such as producing epoxides, which are used as synthetic blocks for pharmaceuticals. Epoxides are commonly synthesized by the use of inorganic acids as catalysts, although the acid medium induces epoxide degradation. To overcome these limitations biocatalysis is shown as an alternative, in view that lipases can perform the reaction in a non-acidic medium. Related to, this work aimed to perform the synthesis of beta-Pinene epoxide using Pseudozyma antarctica lipase B (Novozym®435) as biocatalyst and to determine the independent variables that influence the reaction using experimental design tools. Different solvent systems were evaluated for until 72 h, in reactions with molar ratio of 2:2:1 (beta-Pinene, octanoic acid, and urea-hydrogen peroxide - UHP) at 40°C, 250 rpm, and 10%(w/v) of the biocatalyst. Ethyl acetate showed higher conversion (40% in 24 h) into the product without the formation of by-products. The atom economy (AE) was determined using metrics of green chemistry and ethyl acetate proved to have a higher atom economy (67.8%), while the other solvents that used octanoic acid as an acyl donor had 41.3%. In the following reactions, ethyl acetate was maintained as the solvent, while the temperature, molar ratio, and the percentage of the biocatalyst were varied. The increase in the molar ratio (beta-Pinene:UHP, 1:1) and percentage of biocatalyst (20%w/v) resulted in 80% of the product after 3 hof reaction at 40°C. To evaluate the impact of each independent variable, an FFD was performed by varying temperature, molar ratio, stirring, and percentage of enzyme, in one level. All variables were statistically significant, with different rates of impact. Due to this, the same variables were maintained on the CCRD, varying in two levels. The conversion ranged from good to excellent (32 - 93%). The independent variables that influenced the direction were temperature > stirring > molar ratio. In conclusion, the combination of two different tools of experimental design provided the development of an optimized model for beta-Pinene epoxidation, achieving high yields within 3 h.

Ag-TiO2 Nanoparticles-Catalyzed Three-Component Synthesis of 12-Aryl-8,9,10,12-Tetrahydrobenzo[a]-Xanthen-11-Ones in Aqueous Medium

Background: Ag–TiO2 nanoparticles catalyzed synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-ones have been enhanced via a three-component one-pot reaction betweenβ–naphthol, several aldehydes and dimedone in H2O at room temperature. Xanthenes are essential intermediates in chemistry owing to their vast difference in biological activity. Methods: This process offered significant advantages containing appropriate cost efficiency, low amount of the catalyst, application of low-cost available Ag–TiO2 nanoparticles catalyst, purification of the product by non-chromatographic method, easy process, good atom economy, simple isolation and reusability of nanocatalyst. Result: Ag–TiO2 nanoparticles catalyst shows easy access to Xanthenes with appropriate yields in short reaction time and purity. This nanoparticles catalyst was recycled and recovered by easy filtration and was reused up to five times with only an unimportant loss in its catalytic efficacy. Conclusion: This method achieves to have a numerous scope relating to the difference in the aldehydes. Correspondingly, the attractive of this research was that H2O was the only by-products.

6.1 Thiol–Ene/Yne Click Reactions: A Powerful Tool Toward Diversity-Oriented Synthesis

The clickable addition reaction between thiols and unsaturated compounds leading to the generation of (branched/linear) thioethers or (branched/linear) vinyl sulfides is known as the hydrothiolation reaction. Based upon the nature of unsaturation, i.e. double bond or triple bond, hydrothiolation reactions are classified as thiol–ene and thiol–yne click reactions, respectively. These reactions have emerged as a powerful and widely used strategy for the generation of carbon–sulfur bonds due to several associated benefits including versatile synthetic procedures, wide functional-group tolerance, high atom economy with few to no byproducts, and simple purification. The hydrothiolation reactions have numerous trapping applications in the fields of polymer chemistry, nanoengineering, pharmaceuticals, natural products, and perhaps most importantly in medicinal chemistry for the synthesis of many drugs and bioactive molecules.

Oxidase enzymes as sustainable oxidation catalysts

Oxidation is one of the most important processes used by the chemical industry. However, many of the methods that are used pose significant sustainability and environmental issues. Biocatalytic oxidation offers an alternative to these methods, with a now significant enzymatic oxidation toolbox on offer to chemists. Oxidases are one of these options, and as they only depend on molecular oxygen as a terminal oxidant offer perfect atom economy alongside the selectivity benefits afforded by enzymes. This review will focus on examples of oxidase biocatalysts that have been used for the sustainable production of important molecules and highlight some important processes that have been significantly improved through the use of oxidases. It will also consider emerging classes of oxidases, and how they might fit in a future biorefinery approach for the sustainable production of important chemicals.

Diels–Alder Cycloadditions of Bio-Derived Furans with Maleimides as a Sustainable «Click» Approach towards Molecular, Macromolecular and Hybrid Systems

This mini-review highlights the recent research trends in designing organic or organic-inorganic hybrid molecular, biomolecular and macromolecular systems employing intermolecular Diels–Alder cycloadditions of biobased, furan-containing substrates and maleimide dienophiles. The furan/maleimide Diels–Alder reaction is a well-known process that may proceed with high efficiency under non-catalytic and solvent-free conditions. Due to the simplicity, 100% atom economy and biobased nature of many furanic substrates, this type of [4+2]-cycloaddition may be recognized as a sustainable “click” approach with high potential for application in many fields, such as fine organic synthesis, bioorganic chemistry, material sciences and smart polymers development.

Facile Synthesis of the Dicyanophosphide Anion via Electrochemical Activation of White Phosphorus: An Avenue to Organophosphorus Compounds

Organophosphorus compounds (OPCs) have gained tremendous interest in the past decades due to their wide applications ranging from synthetic chemistry to materials and biological sciences. We describe herein a practical and versatile approach for the transformation of white phosphorus (P4) into useful OPCs with high P atom economy via a key bridging anion [P(CN)2]–. This anion can be prepared on a gram scale directly from P4 through an unprecedented electrochemical process. A variety of OPCs involving phosphinidenes, cyclophosphanes and phospholides have been made readily accessible from P4 in a two-step manner. Our approach has a significant impact on the future preparation of OPCs in laboratory and industrial settings.

The Efficient Synthesis of Azasugars from Pentoses

<p>Azasugars [e.g., 1-deoxy-aza-xylopyranose (1) Figure 1] are structural analogues of sugars [e.g., α-D-xylopyranose (2)] where the ring oxygen is substituted by a nitrogen atom. The resemblance of azasugars to their carbohydrate counterparts gives them various biological properties, such as the inhibition of glycosidase and glycosyltransferase enzymes, and as such, these compounds have been in clinical trials for the treatment of AIDS, diabetes,and cancer. Synthetic routes to azasugars have often involved the use of protecting groups, and therefore have generally reduced efficiency by requiring additional steps to apply or remove protecting groups or requiring adjustment of stereochemistry during the synthesis. This thesis presents the first example of a synthesis of four sterochemically different piperidine triols through a four-step methodology minimising the use of protecting groups starting from pentoses. The synthesis of D-xylose derived (3R,4r,5S)-piperidine triol was previously obtained in 40% yield over five steps, but was afforded in 45% overall yield over four steps using the methodology described within this thesis. Next, D-ribose derived (3R,4s,5S)-piperidine triol was obtained in 40% overall yield over four steps, which afforded a vast improvement on the previous most efficient synthetic route obtaining the azasugar in 24% yield over four steps. This four-step three-pot methodology has thus allowed for the synthesis of these piperidine triols in overall yields ranging from 4-69%, surpassing previous total syntheses in efficiency and improving overall atom economy. To further probe the applicability of the methodology, N-alkyl analogues (such as butyl-, phenylethyl-, and hydroxyethyl-analogues) of all four different piperidine triols were synthesised in comparable or greater overall yields compared to literature reports without any required adaptation to the original procedure. Included in these N-alkyl analogues are seven novel azasugars which were obtained in overall yields ranging from 6-35%.</p>

The Efficient Synthesis of Azasugars from Pentoses

<p>Azasugars [e.g., 1-deoxy-aza-xylopyranose (1) Figure 1] are structural analogues of sugars [e.g., α-D-xylopyranose (2)] where the ring oxygen is substituted by a nitrogen atom. The resemblance of azasugars to their carbohydrate counterparts gives them various biological properties, such as the inhibition of glycosidase and glycosyltransferase enzymes, and as such, these compounds have been in clinical trials for the treatment of AIDS, diabetes,and cancer. Synthetic routes to azasugars have often involved the use of protecting groups, and therefore have generally reduced efficiency by requiring additional steps to apply or remove protecting groups or requiring adjustment of stereochemistry during the synthesis. This thesis presents the first example of a synthesis of four sterochemically different piperidine triols through a four-step methodology minimising the use of protecting groups starting from pentoses. The synthesis of D-xylose derived (3R,4r,5S)-piperidine triol was previously obtained in 40% yield over five steps, but was afforded in 45% overall yield over four steps using the methodology described within this thesis. Next, D-ribose derived (3R,4s,5S)-piperidine triol was obtained in 40% overall yield over four steps, which afforded a vast improvement on the previous most efficient synthetic route obtaining the azasugar in 24% yield over four steps. This four-step three-pot methodology has thus allowed for the synthesis of these piperidine triols in overall yields ranging from 4-69%, surpassing previous total syntheses in efficiency and improving overall atom economy. To further probe the applicability of the methodology, N-alkyl analogues (such as butyl-, phenylethyl-, and hydroxyethyl-analogues) of all four different piperidine triols were synthesised in comparable or greater overall yields compared to literature reports without any required adaptation to the original procedure. Included in these N-alkyl analogues are seven novel azasugars which were obtained in overall yields ranging from 6-35%.</p>