A green bromination process for synthesis of a novel drug candidate

A bromination process has been developed using a salt-based brominating reagent and a non-chlorinated solvent system. The process affords enhanced selectivity and enables product isolation by simple filtration of the reaction mixture, resulting in a substantially reduced waste stream.     

A process for preparation of anticancer drug 9-nitro camptothecin

Camptothecin and some of its semisythetic derivatives such as topotecan, irinotecan and 9-nitrocamptothecin, have exhibited strong antitumor activity against various experimental tumor model. The water insoluble 9-nitrocamptothecin demonstrated very potent antitumor activity against many different types of human cancers and HIV. Literature procedures for preparing 9-nitrocamptothecin are direct nitration of camptothecin using a concentrated nitric/concentrated sulfuric acid system or a combin…     

Efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe

An efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe through chiral Evans auxiliary (S)-4-phenyl-2-oxazolidinone is described. The key steps in this process are the condensation of (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one and N-(4-((tert-butyldimethylsilyl)oxy)benzylidene)-4-fluoroaniline, and the stereoselective reduction of ezetimibe-ketone with NaBH₄/I₂, which is first applied in the synthesis of ezetimibe. The process is concise, mild, easy to operate, and highly stereoselective (99.6% of de value of ezetimibe). In addition, three diastereomers of ezetimibe are synthesized and served as the references in quality control of the product.     

Promising anticancer drug thapsigargin: A perspective toward the total synthesis

The guaianolide ring containing sesquiterpene thapsigargin is found in the roots and fruits of Mediterranean plant Thapsia garganica L. It is known for its activity as a potent antagonist for Ca²⁺-ATPase (sarco–endoplasmic reticulum Ca²⁺-ATPase) inhibition. Recently, a prodrug mipsagargin is being investigated to target the blood vessel of the cancer cells for the treatment of tumors. The limited natural supply (low isolation and only localized growth (Mediterranean area)) from the natural sources strongly urges for the development of chemical synthetic strategies to access these natural products. This review pertain the various strategies used so far in the thapsigargin’s synthesis, focusing on major contributions in the total synthesis till date.     

An efficient and green process for the synthesis of 5-methyl-2-nitrobenzoic acid

Research on Chemical Intermediates - A new and environmental friendly nitration process of methyl 3-methylbenzoate by mixtures of HNO3/Ac2O for the synthesis of 5-methyl-2-nitrobenzoic acid has...     

A crystallization-induced stereoselective glycosidation reaction in the synthesis of the anticancer drug etoposide

The anticancer drug etoposide, 1, is prepared in 79% overall yield from readily available 4'-demethyl-4-epipodophyllotoxin, 3, and 4, 6-O-ethylidene-2,3-O-dibenzyl-D-glucose, 4, via a crystallization-induced stereoselective glycosidation reaction followed by catalytic hydrogenation.     

Scalable synthesis of cladosporin

Cladosporin, a secondary metabolite isolated from fungal sources like Cladosporium cladosporioides and Aspergillus flavus was found to exhibit selective nano-molar activity against malarial parasite Plasmodium falciparum by inhibiting parasitic protein biosynthesis. In addition, this natural product has a broad range of bioactivities including, antiparasitic, antifungal, antibacterial as well as plant growth inhibition. However, it has limited availability from the natural sources for further development. Herein, we report a modified and improved synthetic route which led us to produce this potent natural product in a gram scale. Conversion of the undesired diastereomer to desired one via Mitsunobu inversion of secondary alcohol and carbon monoxide insertion reaction towards the construction of isocoumarin unit are the key features of the present synthesis.     

Hydrolysis process of the second generation platinum-based anticancer drug cis-amminedichlorocyclohexylamineplatinum(II)

The hydrolysis process of the anticancer drug cis-amminedichlorocyclohexylamineplatinum(II) (JM118 or cis-[PtCl2(NH3)cyclohexylamine]) and the influence of solvent models therein have been studied using hybrid density functional theory (B3LYP). The aquation reactions leading to the activated drug forms a key step for the reaction with the target DNA. In this study, the stepwise hydrolysis, cis-[PtCl2(NH3)cyclohexylamine] + 2 H2O --> cis-[Pt(NH3)cyclohexylamine(OH2)2]2+ + 2 Cl- was explored, using three different models. Implicit solvent effects were incorporated through polarized continuum models. The stationary points on the potential energy surfaces for the first and second hydrolysis steps, proceeding via a general S(N)2 pathway, were fully optimized and characterized. It was found that the explicit solvent effects originating from the inclusion of extra water molecules into the system are significantly stronger than those arising from the bulk aqueous medium, especially for the second aquation step, emphasizing the use of appropriate models for these types of problems. In comparison with previous work on the parent compound cisplatin, a slower rate of hydrolysis is determined for the first (rate determining) reaction. The results furthermore imply that the doubly aquated form of JM118 will be the main DNA binding form of the drug. The results provide detailed energy profiles for the mechanism of hydrolysis of JM118, which may assist in understanding the reaction mechanism of the drug with the DNA target and in the design of novel Pt-containing anticancer drugs.     

Improved and large-scale synthesis of 10-methyl-aplog-1, a potential lead for an anticancer drug

10-Methyl-aplog-1 (1), a simplified analog of tumor-promoting aplysiatoxin, is a potential lead for cancer therapy that exhibits marked and selective growth inhibitory effects against several human cancer cell lines and negligible tumor-promoting activity in vivo. However, more detailed evaluations of its toxicity and anticancer activity in vivo are hampered by supply problems associated with a non-optimal synthetic method. We here addressed this issue through a more practical and reliable synthetic method that afforded several hundred milligrams of 1 with high purity (>98%) in 23 steps from commercially available m-hydroxycinnamic acid with an overall yield of 1.1%. The utilization of two key reactions, substrate-controlled epoxidation and the oxidative cleavage of alkene with a free hydroxyl group, successfully reduced the existing five synthetic steps and markedly improved the handling of large amounts of intermediates. We also demonstrated for the first time that such an analog was synthetically accessible in reliable quantities and also that this large supply could advance in vivo trials for the treatment of cancer.     

Scalable and efficient synthesis of the mycolactone core

A highly efficient, scalable, and stereoselective synthesis of the mycolactone core is reported. The synthesis consists of 14 longest linear steps, with 19% overall yield.     

Waste-grass-mediated green synthesis of silver nanoparticles and evaluation of their anticancer,antifungal and antibacterial activity

Grass waste was used for transform an inexpensive waste into health. Silver nanoparticles (AgNPs) have been synthesized using waste material (dried grass). The average size of silver nanoparticles observed in transmission electron images was estimated to be about 15?nm. The anticancer, antifungal and antibacterial effect of AgNPs were studied in vitro. The minimum inhibitory concentration of AgNPs against Pseudomonas aeruginosa and Acinetobacter baumannii was calculated about 3?µg/ml. The highest level of inhibitory effect of AgNPs against Fusarium solani was close to 90% at a concentration of 20?μg/ml of AgNPs. An inhibitory effect on the cancer cell growth is reach, by increasing the concentration of AgNPs to 5?µg/ml; the cancer cells’ survival decreases about 30%. Western results showed that the expression of Cyclin D1 protein of MCF-7 cell line decreased after treatment with the effective concentration of AgNPs.     

Nucleophilic aromatic substitution of methacrylamide anion and its application to the synthesis of the anticancer drug bicalutamide

The anticancer drug (R,S)-biscaltamide was prepared in three steps in >90% overall yield. A key step in the new synthesis involved a new nucleophilic aromatic substitution reaction of methacrylamide anion.     

Scalable strategies for the synthesis of well-defined copper metal and oxide nanocrystals

This tutorial review highlights the most promising methods for the preparation of well-defined copper metal and oxide nanocrystals. These methodologies could be applied to other metals. We present the main synthetic strategies and associated mechanisms to control monodispersity, size, morphology and structure of metal and oxide nanomaterials which can adopt spherical, polyhedral, cubic, rod, wire, plate shapes and possibly hollow structures. We also consider the scale-up of the production of these nanocrystals, which is crucial for a wide range of potential applications such as catalysis, photovoltaics, electronics, optics and electrocatalysis.     

Solubility enhancement of decitabine as anticancer drug via green chemistry solvent: Novel computational prediction and optimization

Nowadays, supercritical fluid technology (SFT) has been an interesting scientific subject in disparate industrial-based activities such as drug delivery, chromatography, and purification. In this technology, solubility plays an incontrovertible role. Therefore, achieving more knowledge about the development of promising numerical/computational methods of solubility prediction to validate the experimental data may be advantageous for increasing the quality of research and therefore, the efficacy of novel drugs. Decitabine with the chemical formula C₈H₁₂N₄O₄ is a chemotherapeutic agent applied for the treatment of disparate bone-marrow-related malignancies such as acute myeloid leukemia (AML) by preventing DNA methyltransferase and activation of silent genes. This study aims to predict the optimum value of decitabine solubility in CO₂SCF by employing different machine learning-based mathematical models. In this investigation, we used AdaBoost (Adaptive Boosting) to boost three base models such as Linear Regression (LR), Decision Tree (DT), and GRNN. We used a dataset that has 32 sample points to make solubility models. One of the two input features is P (bar) and the other is T (k). ADA-DT (Adaboost Algorithm-Decision Tree), ADA-LR (Adaboost Algorithm-Linear Regresion), and ADA-GRNN (Generative Regression Neural Network) models showed MAE of 6.54 × 10^?5, 4.66 × 10^?5, and 8.35 × 10^?5, respectively. Also, in terms of R-squared score, these models have 0.986, 0.983, and 0.911 scores, respectively. ADA-LR was selected as the primary model according to numerical and visual analysis. Finally, the optimal values are (P = 400 bar, T = 3.38 K × 102, Y = 1.064 × 10^?3 mol fraction) using this model.     

Carrier polymers for cisplatin-type anticancer drug models

Following a brief discussion of the concept of polymer–drug conjugation and the use of platinum drugs in cancer therapy, the paper presents recent results in the synthesis of water-soluble polymeric carriers designed for the binding of antineoplastic coordination compounds of the cisplatin type. The target polymers, specifically, are linear aliphatic polyamides comprising the ethylenediamine ligand system in the main chain as the potential metal binding site. With solubility in aqueous media a key requirement for intravenously injectable conjugates, the polymers also contain hydrosolubilizing oligo(ethylene oxide) units in the chain, which serve the additional purpose of imparting resistance to serum protein binding and capture by the reticuloendothelial system. The synthesis methods include interfacial polymerization, high-temperature solution polycondensation in polyphosphoric acid and Michael addition polymerization, with 1,2-bis(2-aminoethylamino)ethane and 1,2-bis(3-aminopropylamino)ethane used as the amine comonomers providing the ethylenediamine ligand segment. The target polymers, crudely fractionated by dialysis in 25,000 molecular-mass cult-off tubing, are isolated by freeze-drying as water-soluble solids possessing inherent viscosities of 10–20 ml/g. A selected carrier polymer is converted to the corresponding water-soluble cis-diaminedichloroplatinum(II) conjugate by treatment with tetrachloroplatinate(II) anion in aqueous solution.     

Microwave-assisted solid phase synthesis of Imatinib, a blockbuster anticancer drug

An expeditious, high yield and convenient synthesis of Imatinib was carried out on an aldehydic, super acid-sensitive resin, through an efficient, microwave-assisted synthetic protocol. The high versatility of the reaction scheme may enable the straightforward preparation of libraries of potential protein kinase inhibitors endowed with large molecular diversity.     

Scalable total synthesis of horsfiequinone A

Starting from two commercially available substrates, methoxyhydroquinone and piperonyl alcohol, a scalable four-step total synthesis of horsfiequinone A was developed. The notable feature of the synthesis is the application of two continuous sequential transformations. Namely, the key aldehyde 9 and horsfiequinone A were prepared via scalable Wittig/hydrolysis and Wittig/catalytic hydrogenation/oxidation sequences, respectively. Importantly, the synthetic route required only three recrystallizations and one column chromatography purification step.     

Cationic supramolecular nanoparticles for co-delivery of gene and anticancer drug

Self-assembly supramolecular nanoparticles (SNPs) are synthesized using polyethylenimine (PEI) crosslinked by cyclodextrins (CyDs), adamantyl doxorubicin and plasmid DNA. SNPs successfully conduct the cooperative co-delivery of chemotherapeutic anticancer drug and plasmid DNA in vitro and in vivo.