Current Organic Synthesis - Volume 18, Issue 4, 2021

Latest progress in the liquid crystal (LC) field related to azo molecules incorporated into natural product- based moieties for the improvement of LC texture and mesomeric phases has received great interest among researchers. A LC containing natural product-based moieties i.e. menthol, kojic acid, cholesterol and chalcone with stable azo and azobenzene scaffolds with specific optical tunability, has been widely used in photo-active materials such as Liquid Crystal Display (LCD), LC films, smart windows and other devices. This review discusses the influence of azobenzene, a renowned photo-responsive and stable LC scaffold, in mesogenic phases due to photo-isomerization and optical switching. The incorporation of mesomeric phases of natural product moieties to azo molecules has improved the properties of LC, i.e, from the nematic phase to the smectic phase with proper magnetic field alignment. Natural product-based LC can be useful in numerous applications, especially practical electronic or optic devices such as optical image storage, display devices, solar cells, optical switching.

The role of amino acids and peptides has found remarkable usage in both living systems and nonliving materials, which have enabled its utility by virtue of crafting molecular architectures through covalent bonds and non-covalent interactions. In material chemistry, the role of peptides in Liquid Crystals (LCs) is profound, especially in the rapid construction of supramolecular hierarchical networks. The importance of LCs for a variety of societal needs leads to the synthesis of innumerable LCs by conventional mesogenic strategy and nonconventional molecular design principles. For example, electronic appliances, including flat panel TV displays, electronic notebooks, digital cameras, domestic devices, use LCs as an integral component for such applications. In addition, LCs are useful in biological systems, including stem cell research, sensors for bacteria, virus, and proteins. These accomplishments are possible mostly due to the non-conventional molecular design principles for crafting LCs using smaller molecular motifs. The usage of amino acids and peptides in LCs facilitates many intrinsic characteristics, including side-chain diversity, chirality, directionality, reversibility, electro-optical, columnar axis, stimuli-responsive complex molecular architectures. The next essential criteria for any LCs design for useful applications are room temperature LC (RT-LC); therefore, the quest for such LCs system remains highly significant. Evidently, there are around half a million liquid crystalline molecules; only a handful of RTLCs has been found, as there is no simple, precise strategy or molecular design principles to obtain RT-LC systems. The smaller molecular motifs of amino acids and linear peptides as a structural part of mesogenic molecules led to many LC phases with properties, including lyotropic, thermotropic, and its applications in different realms. Therefore, this review serves as a compilation of Small Peptide-based LCs (SPLCs) exhibiting lyotropic and thermotropic phases with applications in the recent advancements.

Introduction: This is the first report on chiral polymorphic hydrazine-based asymmetric liquid crystal trimers, 1-[4'-(4''-(5-Cholesteryloxy)carbonyl)butyloxy]-3-[N-benzylideneoxy-N'-(4'''-decyloxybenzylidene) hydrazine] butyloxybenzenes, and 1-[4'-(4''-(10-cholesteryloxy)carbonyl)nonyloxy]-3-[N-benzylideneoxy-N'-(4'''- decyloxybenzylidene)hydrazine]butyloxybenzenes., in which the hydrazine and cholesterol arms were connected via two flexible methylene spacers (n = 3-12 units and m = 4 or 9, respectively) to the central resorcinol core. Materials and Methods: FT-IR, 1D and 2D NMR spectroscopy, and CHN microanalysis were used to elucidate the structures of the trimers. Differential scanning calorimetry, polarizing optical microscopy and X-ray diffraction were used to study the transitional and phase properties of the trimers, which were length and spacer parity dependent. Trimers with short spacer length in the cholesteryl arm, m = 4 showed an interesting phase sequence of BP/N*-TGBA*-SmA*. Results and Discussion: The TGBA* phase was sensitive to spacer length as it was only observed in trimers with short ester linkage. For the long analogues, m = 9, characteristic visible reflection and a much simpler phase sequence with only N* and SmA* phases were observed. Conclusion: The X-ray diffraction measurements revealed that layer periodicities of the SmA* phase were approximately half the estimated all-trans molecular length (d/L ≈ 0.44-0.52), thus suggesting that the molecules are either strongly intercalated or bent.

The present protocol is a simple and eco-friendly approach for the one-pot procedure for the synthesis of substituted imidazopyridines ranging from important feedstock’s like styrene promoted by NBS. Through sonicator and microwave commercially available styrene with NBS in water followed by reaction with 2- aminopyridines afforded important heterocyclic scaffolds in an one-pot procedure.

Synthesis of levothyroxine sodium, the sodium salt of a synthetic levoisomer of thyroxine, revolutionized the management of hypothyroidism and related symptoms. However, the primary synthetic route to this active pharmaceutical ingredient (API) is more than 70+ years old with low-yielding steps and obsolete reagents. It lacks experimental data on intermediates, making laboratory and large-scale synthesis of this API difficult and time-consuming. Here, we describe an improved synthesis of levothyroxine using commonly available modern reagents. By modifying and replacing low yielding and/or unproductive steps of Chalmers synthesis, we were able to achieve higher overall yields (39-51%) consistently. Key modifications include an alternative path to the selective N-acetylation step that yielded 5 in a pure and consistent fashion. Our improved methodology, coupled with detailed experimental data, provides a practical alternative to existing methods that can be conveniently implemented to synthesize Levothyroxine sodium in fine chemical settings.

The phosphorus-containing heterocycles are an important class of compounds in organic chemistry. Because of their potential application in many fields, especially, the synthetic pesticides, medicine and catalyst, the phosphorus-containing heterocycles have attracted continuous attention from organic synthesis scientists. The development of efficient and low-cost catalytic systems is of great interest for the construction of heterocycles C-P bond. Usually, the phosphorus-containing heterocycles is prepared via direct carbon–hydrogen (C-H) bond activation or pre-functionalized of heterocycles with phosphorus-hydrogen (P-H) bond of phosphorus compounds reaction by metal-catalyzed. This review summarizes recent progress in the heterocycles C-P bond formation reactions by metal-catalyzed, which mainly focus on the discussion of the reaction mechanism. It aims to provide efficient methods for the future synthesis and application in this field.

Aim and Objective: To explore the impact of synthesis conditions (temperature and time) on the properties of developed Graphene Oxide (GO). Background: A highly promising approach has been used for the synthesis of graphene oxide (GO) from graphite flakes using the modified Hummers method. Concentrated sulfuric acid was used as an intercalating agent and the oxidation was done with the help of potassium permanganate and hydrogen peroxide. Methods: The present method does not need expensive membranes for the filtration of Carbon and metalcontaining residues. The pre-cooling method is used to eradicate the explosive behavior of intermediate steps. The high quality of synthesized graphene oxides was confirmed by a series of characterization techniques, including Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, energy-dispersive X-ray spectroscopy, and atomic force microscopy. Results: The results indicated the presence of Oxygen-containing functional groups, and a rise in the Oxygen content confirmed the synthesis of high-quality graphene oxide. Conclusion: As per obtained experimental findings and subsequent analysis, the synthesized high-quality graphene oxide could be used in the design of membranes for water treatment applications.

Aim: To develop anti-cancer active pharmaceutical intermediates. Background: Acridone derivatives possess a wide range of pharmacological activities: 1) they intercalate DNA and 2) form a covalent bond with DNA. Objective: To screen in vitro anti-cancer activity against Cdc25b and SHP1 of new acridone derivatives and preliminary study on the structure-activity relationship. Materials and Methods: The synthesis of new acridone derivatives and in vitro evaluation of their anti-cancer activity on Cdc25b and SHP1 was achieved. Natural products that contain acridine structures, such as cystodytin A and acronycine, are isolated from certain marine (tunicates & ascidians, sponges, sea anemones) and plant (bark of Australian scrub ash tree) species. Herein, we report the efficient one-pot green synthesis of twelve novel 3,4-dihydro-1 (2H) acridone derivatives, using montmorillonite K10 as the catalyst and iron/citric acid in water. Also, their inhibitory activity against Cdc25B and SHP1 is examined, in which specific derivatives show enhanced inhibitory activity compared to others. Results and Discussion: Twelve new acridone derivatives were prepared, starting from 2-nitrobenzaldehyde derivatives and 1, 3-cyclohexanedione derivatives, which exhibited substantial anti-cancer activity against Cdc25b and SHP1 cells. Conclusion: Preliminary studies on the structure-activity relationship have shown the influence of the structural parameters and, in particular, the nature of the substituent on aromatic ring structure and cyclohexanone. Other: Further study on the structure-activity relationship is required.

Aims: We have developed this work to recommend an original route for the preparation of triazole derivatives. Background: Carbohydrates containing 1,2,3-triazole derivatives have various biological activities. Due to their advantageous and biological property, they are eye-catching synthetic targets in the arsenal of organic chemistry. Thus, finding green and efficient methods, as well as using the ball milling procedure for the synthesis of these heterocycles, is of interest to organic chemistry researchers. Objective: The objective of this study was to synthesize carbohydrate-derived triazoles under high-speed vibration milling conditions and investigate their properties. Materials and Methods: A mixture of glycoside azide derivatives (1 mmol) and prop-2-yn-1-ol (1.5 mmol) in the presence of copper (I) was vigorously shaken under vibration milling conditions at 650 rpm with three balls for 15 min. The deprotection of the resulting triazole derivatives was affected by treatment with 4M hydrochloric acid in methanol under reflux. Results and Discussion: A short and convenient route to synthesize carbohydrate-derived triazoles, based on a ball-mill via 1,3-dipolar cycloaddition reactions to prop-2-yn-1-ol, was developed. Cleavage of the isopropylidene protecting group provided water-soluble triazoles, evaluated as glycogen phosphorylase inhibitors. 1-[6- (4-Hydroxymethyl-[1,2,3]triazol-1-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-ethane-1,2-diol was the best inhibitor of rabbit muscle glycogen phosphorylase b (IC50 = 60 μM). Conclusion: In summary, we developed new, short and convenient routes to glucose-derived 1,2,3-triazole based on 1,3-dipolar cycloaddition reactions flowed by ball milling. The use of isopropylidene protective groups gave access to the analogous deprotected water-soluble motifs, analogous to known inhibitors of glycogen phosphorylase.

Background: Corticosteroids are an important group of polycyclic compounds having a wide range of pharmacological and physiological properties. Thiopyran derivatives are important building blocks of many biologically active compounds. Objective: Keeping in mind the wide range of applications of corticosteroids and thiopyran, herein we intend to develop a simple and efficient strategy to synthesize steroidal thiopyran derivatives starting with different commercially available corticosteroids and study their biological properties. Materials and Methods: To achieve our aim, we employed a one-pot multi-component synthesis of steroidal thiopyran derivatives by the reaction of corticosteroids, malononitrile, and carbon disulphide in the presence of triethylamine as a catalyst. Results and Discussion: An array of novel thiopyran compounds was obtained with the highest product yield using Et3N. Scanning electron microscopy analysis manifested agglomeration pertaining to brick-shaped crystals of corticosteroid thiopyran. Synthesized compounds were also found to be active as anti-bacterial agents. Conclusion: We describe a facile one-pot multi-component synthesis of corticosteroid thiopyran derivatives, which are found to possess anti-bacterial activity. Excellent yields of the products, simple work-up, easily available starting materials, and non-chromatographic purification are some of the main advantages of this protocol.

Introduction: Miuraenamides belong to natural marine compounds with interesting biological properties. Materials and Methods: Miuraenamides initiate polymerization of monomeric actin and therefore show high cytotoxicity by influencing the cytoskeleton. New derivatives of the miuraenamides have been synthesized containing an N-methylated amide bond instead of the more easily hydrolysable ester in the natural products. Results: Incorporation of an aromatic side chain onto the C-terminal amino acid of the tripeptide fragment also led to highly active new miuraenamides. Conclusion: In this study, we showed that the ester bond of the natural product miuraenamide can be replaced by an N-methyl amide. The yields in the cyclization step were high and generally much better than with the corresponding esters. On the other hand, the biological activity of the new amide analogs was lower compared to the natural products, but the activity could significantly be increased by incorporation of a p-nitrophenyl group at the C-terminus of the peptide fragment.