An Oxidation Study of Phthalimide-Derived Hydroxylactams

A systematic study of the oxidation of 3-hydroxy-2-substituted isoindolin-1-ones (hydroxylactams) and their conversion to the corresponding phthalimides was undertaken using three oxidants. Of special interest was the introduction of nickel peroxide (NiO2) as an oxidation system for hydroxylactams and comparison of its performance with the commonly used pyridinium chlorochromate (PCC) and iodoxybenzoic acid (IBX) reagents. Using a range of hydroxylactams, optimal conversions of these substrates to the corresponding imides was achieved with 50 equivalents of freshly prepared NiO2 in refluxing toluene over 5–32 h reaction times. By comparison, oxidations of the same substrates using PCC/silica gel (three equivalents) and IBX (three equivalents) required oxidation times of 1–3 h for full conversion but required lengthier purification. While nominal amounts (~25 mg) of substrate hydroxylactams were used to ascertain conversion, scale-up procedures using all three methods gave good to excellent isolated yields of imides.

Comparison of different methods used in drugs of abuse for sample validity testing including pH methods, specific gravity methods, TECO™ Drug Adulteration Test Strip and oxidant assay

Objectives In the absence of sample validity testing, a healthcare provider may fail to identify a patient’s adulteration of their urine sample. This study compared different methods for specific gravity (SG), pH, TECO™ Drug Adulteration Test Strip (dipstick) and oxidant assay to explain the differences and also make an informative decision on method selection. Methods Creatinine, SG and pH measurements are essential in sample validity testing. SG and pH automated chemical methods are compared against pH meter method, SG refractometer and dipstick method. Also, oxidant assay was compared against dipstick method. Results SG chemical method agreement with refractometer is 81.9% and with dipstick method is 64.7%. The refractometer method agreement with dipstick method is 66.1%. pH chemical method agreement with pH Meter method is 74.3% and with dipstick method is 81.4%. pH meter method agreement is 85.7% with dipstick method. Results were analysed using Deming regression analysis and F-test. SG chemical method correlated better with refractometer than the dipstick method. Oxidant assay correlated well with dipstick method in detecting adulterants such as pyridinium chlorochromate, nitrite and bleach. Conclusions Varying degrees of differences were seen in the SG and pH measurements. These differences were both method and instrument dependent. The automated chemical methods are recommended alongside oxidant assay for consistency, accuracy and faster turn-around time as part of sample validity testing for drugs of abuse.

Spectral, Crystalline, Thermal, Morphological characterization and Catalytic Performance of Ruthenium(III) Complexes of Natural Biopolymer Based on Schiff base Ligands

Aims: The aim of this study is to achieve catalytic performance for oxidation of alcohols using Ruthenium(III) metal complexes as a catalyst. Background: The chitosan is a potential candidate which enables synthesis of transition metal complexes from its corresponding bidentate ligands. Method: The chemical modification was performed on chitosan molecule with suitable aldehydes. The oxidation of alcohols was performed using ruthenium metal complexes as catalysts with Pyridinium chlorochromate (PCC) as oxidant and dichloro methane as solvent. To a solution of alcohol (2mmol) in dichloromethane (25mmol), Pyridinium chlorochromate (3 mmol) and Ruthenium(III) complexes (0.01mmol) were added. The solution was stirred for 12 h at room temperature. At the required time, the aldehyde / ketone was extracted with n-hexane. Then hexane was analyzed by GC. Results: The ruthenium(III) complexes derived from modified chitosan Schiff bidentate ligands resulted in good catalytic performance for oxidation of alcohols under optimized conditions. Conclusion: The enhanced catalytic activities of ruthenium(III) complexes were due to the presence of electron donating groups in the Schiff base ligand. : Ruthenium(III) complexes [Ru(CS)4hy3mbd)(H2O)2Cl2] and [Ru(CS)2hybd)(H2O)2Cl2] have been synthesized and characterized by FT-IR, X-ray diffraction, Thermo-gravimetric analysis and SEM with EDX. The ruthenium complexes were derived from chitosan biopolymer based Schiff base ligands. The N and O donor atoms of chitosan Schiff base ligands were involved in complexation reaction with Ruthenium metal ion to form stable coordination complex. This synthesized Ruthenium(III) complexes acted as active catalyst for the oxidation of primary and secondary alcohols which has converted to corresponding aldehydes and ketones at suitable reaction conditions. The oxidation of alcohols was performed using ruthenium metal complexes as catalyst with Pyridinium chlorochromate (PCC) as oxidant and dichloro methane as solvent.

Chemoenzymatic Synthesis of the New 3-((2,3-Diacetoxypropanoyl)oxy)propane-1,2-diyl Diacetate Using Immobilized Lipase B from Candida antarctica and Pyridinium Chlorochromate as an Oxidizing Agent

To exploit the hydrolytic activity and high selectivity of immobilized lipase B from Candida antarctica on octyl agarose (CALB-OC) in the hydrolysis of triacetin and also to produce new value-added compounds from glycerol, this work describes a chemoenzymatic methodology for the synthesis of the new dimeric glycerol ester 3-((2,3-diacetoxypropanoyl)oxy)propane-1,2-diyl diacetate. According to this approach, triacetin was regioselectively hydrolyzed to 1,2-diacetin with CALB-OC. The diglyceride product was subsequently oxidized with pyridinium chlorochromate (PCC) and a dimeric ester was isolated as the only product. It was found that the medium acidity during the PCC treatment and a high 1,2-diacetin concentration favored the formation of the ester. The synthesized compounds were characterized using IR, MS, HR-MS, and NMR techniques. The obtained dimeric ester was evaluated at 100 ppm against seven bacterial strains and two Candida species to identify its antimicrobial activity. The compound has no inhibitory activity against the bacterial strains used but decreased C. albicans and C. parapsilosis growth by 49% and 68%, respectively. Hemolytic activity was evaluated, and the results obtained support the use of the dimeric ester to control C. albicans and C. parapsilosis growth in non-intravenous applications because the compound shows hemolytic activity.

Facile Synthesis of Propranolol and Novel Derivatives

Propranolol is one of the first medications of the beta-blocker used for antihypertensive drugs. This study reports the facile route for the synthesis of propranolol and its novel derivatives. Herein, propranolol synthesis proceeded from 1-naphthol and isopropylamine under mild and less toxic conditions. Novel propranolol derivatives were designed by reactions of propranolol with benzoyl chloride, pyridinium chlorochromate, and n-butyl bromide through esterification, oxidation reduction, and alkylation, respectively. The isolation and purity of compounds were conducted using column chromatography and thin-layer chromatography. Mass spectrometry and 1H-NMR spectroscopy were applied to identify new compounds structure. Propranolol derivatives from 2-chlorobenzoyl chloride (compound 3), 2-fluorobenzoyl chloride (compound 5), and especially acetic anhydride (compound 6) manifested high yields and significantly increased water solubility. Six semisynthetic propranolol derivatives promise to improve antioxidative and biological activities.

Oxidation of Isodrimeninol with PCC Yields Drimane Derivatives with Activity against Candida Yeast by Inhibition of Lanosterol 14-Alpha Demethylase

Candida species cause an opportunistic yeast infection called Candidiasis, which is responsible for more than 50,000 deaths every year around the world. Effective treatments against candidiasis caused by non-albicans Candida species such as C. glabrata, C. parapsilosis, C. aureus, and C. krusei are limited due to severe resistance to conventional antifungal drugs. Natural drimane sesquiterpenoids have shown promising antifungal properties against Candida yeast and have emerged as valuable candidates for developing new candidiasis therapies. In this work, we isolated isodrimeninol (C1) from barks of Drimys winteri and used it as starting material for the hemi-synthesis of four sesquiterpenoids by oxidation with pyridinium chlorochromate (PCC). The structure of the products (C2, C3, C4, and C5) was elucidated by 1D and 2D NMR spectroscopy resulting in C4 being a novel compound. Antifungal activity assays against C. albicans, C. glabrata, and C. krusei revealed that C4 exhibited an increased activity (IC50 of 75 μg/mL) compared to C1 (IC50 of 125 μg/mL) in all yeast strains. The antifungal activity of C1 and C4 was rationalized in terms of their capability to inhibit lanosterol 14-alpha demethylase using molecular docking, molecular dynamics simulations, and MM/GBSA binding free energy calculations. In silico analysis revealed that C1 and C4 bind to the outermost region of the catalytic site of 14-alpha demethylase and block the entrance of lanosterol (LAN) to the catalytic pocket. Binding free energy estimates suggested that C4 forms a more stable complex with the enzyme than C1, in agreement with the experimental evidence. Based on this new approach it is possible to design new drimane-type sesquiterpenoids for the control of Candida species as inhibitors of 14-alpha demethylase.

Photocatalytic Cleavage of β-O-4 Ether Bonds in Lignin over Ni/TiO2

It is of great importance to explore the selective hydrogenolysis of β-O-4 linkages, which account for 45–60% of all linkages in native lignin, to produce valued-added chemicals and fuels from biomass employing UV light as catalyst. TiO2 exhibited satisfactory catalytic performances in various photochemical reactions, due to its versatile advantages involving high catalytic activity, low cost and non-toxicity. In this work, 20 wt.% Ni/TiO2 and oxidant PCC (Pyridinium chlorochromate) were employed to promote the cleavage of β-O-4 alcohol to obtain high value chemicals under UV irradiation at room temperature. The Ni/TiO2 photocatalyst can be magnetically recovered and efficiently reused in the following four consecutive recycling tests in the cleavage of β-O-4 ether bond in lignin. Mechanism studies suggested that the oxidation of β-O-4 alcohol to β-O-4 ketone by oxidant PCC first occurred during the reaction, and was followed by the photocatalysis of the obtained β-O-4 ketone to corresponding acetophenone and phenol derivates. Furthermore, the system was tested on a variety of lignin model substrates containing β-O-4 linkage for the generation of fragmentation products in good to excellent results.

Synthesis of Natural (−)-Antrocin and Its Enantiomer via Stereoselective Aldol Reaction

The total synthesis of (−)-antrocin and its enantiomer are presented. Antrocin (−)-1 is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC50: 0.6 μM). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to α,β-unsaturated ketone; (b) resolution of (±)-7 using chiral auxiliary L-dimethyl tartrate through formation of cyclic ketal diastereomers followed by simple column chromatography separation and acid hydrolysis; (c) substrate-controlled stereoselective aldol condensation of (+)-12 with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (−)-14; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (−)-antrocin. In addition, (+)-9 cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.