Self-Assembled Lipid Cubic Phase and Cubosomes for the Delivery of Aspirin as a Model Drug

Three-dimensionally organized lipid cubic self-assemblies and derived oil-in-water emulsions called “cubosomes” are attractive for various biotechnological applications due to their ability to be loaded with functional molecules and their associated sustained release properties. Here, we employed both of these lipid-based systems for the delivery of a model drug, aspirin, under comparable conditions. Studies were performed by varying drug-to-lipid ratio and the type of release medium, water and phosphate buffer saline (PBS). Release rates were determined using UV−vis spectroscopy, and small-angle X-ray scattering was used to confirm the type of self-assembled nanostructures formed in these lipid systems. The release from the bulk lipid cubic phase was sustained as compared to that of dispersed cubosomes, and the release in PBS was more efficient than in water. The tortuosity of the architecture, length of the diffusion pathway, type of nanostructure, and physicochemical interaction with the release media evidently contribute to these observations. This work is particularly important as it is the first report where both of these nanostructured lipid systems have been studied together under similar conditions. This work provides important insights into understanding and therefore controlling the release behavior of lipid-based drug nanocarriers

The Nano-Based Catalyst for the Synthesis of Benzimidazoles

The properties of benzimidazole and its derivatives have been studied over more than one hundred years. The benzimidazole ring is an important pharmacophore in modern drug discovery. Benzimidazole-based compounds possess potential application as medicinal drugs, presently; more than 20 drugs are available for the treatment of different diseases. Also, this motif is considered as privileged structure in medicinal chemistry because of its wide range of biological activities viz., antibacterial, antifungal, anticonvulsant, anti-tubercular, anti-HIV, anti-diabetic, anti-oxidant, anticancer, anti-inflammatory, analgesic antileishmanial, and antihistaminic agents etc. Owing to the diverse therapeutic applications, the incorporation of benzimidazole nucleus has become a field of high interest to organic and medicinal chemists. The various key starting materials (KSMs) utilized includes, aromatic and heteroaromatic 2-nitro-amines, phenylenediamine, carboxylic acids or its derivatives. However, these classical methods suffer from demerits such as, low atom economy, the formation of by-products, harsh reaction conditions, extended reaction period, expensive catalysts, and unsatisfactory yield of products as well as toxic solvents. Hence, the chemists have their attention towards developing synthetic processes primarily based on the set of principles of green chemistry. In this context, many efficient methods were developed for the synthesis of benzimidazole using the nanocatalyst or nanostructures. In this review, special emphasis has been given to discuss the “green” synthetic techniques adopted for the preparation of functionalized benzimidazole congeners as well as key mechanistic considerations and future outlook in this area. In this review, the literature up to the November 2021 in which very recently reported synthetic routes to access benzimidazole scaffolds are discussed. We are focused on, in particular, the synthetic methodologies/routes to construct 2-substituted/1,2-disubstituted benzimidazole or benzimidalones via various protocols involving condensation, cyclization, metal-free conditions, solvent-free conditions, and using nanocatalyst. This review will further aid the researcher to in developing more efficient and facile methods for the synthesis of benzimidazoles and associated hybrids

L-Pyrrolidine-2-Carboxylic Acid Sulfate: A New Ionic Liquid for the Synthesis of Bioactive Tetrahydrobenzo[b]pyrans

Published ArticleMulticomponent reactions (MCRs), a significant subclass of reac tions, are one-pot processes in which three or four easily-approachable components react to form a single product. The methodology is a powerful synthetic tool for the preparation of important drugs and other biologically active compounds. 1 MCRs have been useful in the development of environ- mentally-friendly and less expensive procedure s for the generation of libraries of heterocy- clic compounds 2 and the development of MCRs can le ad to new, efficient, synthetic methodologies. Tetrahydrobenzo[b]pyrans an d their derivatives are an important class of heterocyclic compounds with antic oagulant, antitumor, spasmoly tic, antibacterial, diuretic, potassium channel activating and insulin-sensitizing activities. 3–6 4H-Benzo[b]pyrans are usually synthesized from a -cyano cinnamonitrile derivatives with dimedone catalyzed by acid or base. 7 Recently MCRs have been used for their preparation. As compared to the conventional linear step synthesis, they can make the process easier, reduce time, save money, energy, and raw materials, resulting in both economic and environmental bene- fits. 8–9 A number of methods have been reported using dimedone, aromatic aldehydes and malononitrile in the presence of catalysts, such as CeCl 3 ¢ 7H 2 O, 10 N-methylimidazole, 11 tet- ramethyl ammonium hydroxide, 12 MgO, 13 amines, 14 2,2,2-trifluoroethanol, 15 and TiO 2 . 16 Other methods have involved microwave heating, 17 ultrasonic irradiation, 18 electrosynthe- sis, 19 hexadecyldimethylbenzylammonium bromide (HDMBAB), 20 Na 2 SeO 4 , 21 DABCO, 2

Concise and Scalable Synthesis of Aspalathin, a Powerful Plasma Sugar-Lowering Natural Product

Aspalathin (<b>1</b>), a dihydrochalcone <i>C</i>-glucoside, exhibits powerful plasma sugar-lowering properties and thus potentially could be used to treat diabetes. Small quantities occur in rooibos tea, manufactured via fermentation of the leaves of <i>Aspalathus linearis</i>, hence necessitating the need for an efficient and concise synthesis. Efforts to synthesize aspalathin (<b>1</b>) via coupling of a glucose donor to the nucleophilic phloroglucinol ring of the dihydrochalcone moiety have invariably failed, presumably because of ring deactivation by the electron-withdrawing carbonyl group. Reduction of the carbonyl group of a chalcone (<b>15</b>) and coupling of the resulting 1,3-diarylpropane (<b>16</b>) to tetra-<i>O</i>-benzyl-β-d-glucopyranose afforded the <i>C</i>-glucosyl-1,3-diarylpropane (<b>17</b>). Regiospecific benzylic oxidation regenerated the carbonyl group and afforded the per-<i>O</i>-methylaspalathin (<b>1a</b>) quantitatively. This method was not successful with the per-<i>O</i>-benzyl-protected dihydrochalcone. However, the nucleophilicity of the phenolic hydroxy groups of the dihydrochalcone or its acetophenone precursor is not diminished by the carbonyl group. Thus, glucosylation of the di-<i>O</i>-benzylacetophenone (<b>5c</b>) at −40 °C afforded the α-<i>O</i>-glucoside (<b>19</b>) in 86% yield. Raising the temperature allowed facile BF₃-catalyzed rearrangement to the β-<i>C</i>-glucoside (<b>6b</b>), which upon hydrogenation, afforded aspalathin (<b>1</b>) in 80% overall yield [based on the usage of di-<i>O</i>-benzylphloroacetophenone (<b>5c</b>) and tetra-<i>O</i>-benzyl-1α-fluoro-β-d-glucose (<b>2e</b>)]