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1.
ChemSusChem ; 17(12): e202301921, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38353034

ABSTRACT

To address the growing demand for more sustainable and greener chemistry, mechanochemical methodologies are emerging as key players. However, to date there has been little data highlighting the benefits of these rising mechanochemical technologies with regard to process scale-up activities or implementation in commercial production scale. Herein, we report the first application of bead-mill technology (Dyno®-mill) for the sustainable mechanochemical synthesis of Acetaminophen, known under the brand name Paracetamol. Using the Beckmann rearrangement, the optimized solvent-free methodology delivered a final product on a scale of several tens of grams. In comparison to current production solvent-based process, the proposed process achieves a higher yield while also allowing the removal of solvents in the chemical reaction, hereby reducing one of the extensive drivers to waste generation. The mechanochemical approach was compared to solvent-based process using a combination of green metrics and EcoScale score. The mechanochemical synthesis of paracetamol scores the highest for all the metrics over currently used solution-based processes.

2.
Chemistry ; 28(63): e202202405, 2022 Nov 11.
Article in English | MEDLINE | ID: mdl-35952312

ABSTRACT

Herein we have reported the discovery of a pentacyclic building block comprised of fused indole-quinoline and piperidinone from the natural product perophoramidine as a formidable anticancer agent. The compounds were synthesized in six steps where the key steps involved a blue LED mediated intramolecular cyclopropanation of the indole intermediates and concomitant reduction of the associated aryl nitro moiety to nitroso in the molecule. Cytotoxicity screening of the compounds against an array of cancer cells that is, MCF7, HCT116 and A549 demonstrated 0.6 to 9 µM IC50 s by few of the compounds. γH2AX immunofluorescence assay of the two most potent molecules from the phenotypic screening with anti-γ-H2AX Alexa Fluor 488 antibody revealed extensive DNA damage of the A549 cells which indicated probable PARP inhibition (similar to Perophoramidine). Through molecular docking and molecular dynamic (MD) simulation studies the binding efficiency of our compounds with poly(ADP-ribose)polymerase 1 (PARP 1) enzyme was determined. Chemiluminescent PARP Assay with Histone-coated strips indicated that the most active compounds from the phenotypic screening induced PARP-1 inhibition with IC50 s of 1.3→1.5 µM.


Subject(s)
DNA Breaks, Double-Stranded , Poly(ADP-ribose) Polymerase Inhibitors , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/chemistry , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Molecular Docking Simulation , Poly (ADP-Ribose) Polymerase-1 , DNA , Indoles
3.
Org Biomol Chem ; 19(35): 7627-7632, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34524326

ABSTRACT

Pyrrole and indole derivatives are functionalized via a green initiative with the dimethyl malonate derived phenyl iodonium ylide 4a in the presence of a blue LED via C-H functionalization of the respective heterocycles in methanol to generate the desired compounds 5-7 in moderate to good yields. Control experiments provide insight into the probable reaction mechanism. Finally, the strategy is successfully applied in the generation of azepino[4,5-b]indole 12a/b.

4.
Chimia (Aarau) ; 75(1): 58-63, 2021 Feb 28.
Article in English | MEDLINE | ID: mdl-33637149

ABSTRACT

Remote teaching in the tertiary education sector is a relatively common practice, and the implementation of digital solutions in chemistry teaching offers many new opportunities and tools. A survey was conducted after 3 months of emergency remote teaching linked to the COVID-19 pandemic and showed that half of the students estimated it was difficult to study remotely, and reported they had to invest more time compared to classroom teaching, which led to a drop in motivation. Professors also noted that the time necessary to invest in order to produce digital teaching content was enormous. Massive open online laboratories (MOOLs) and process simulators are interesting tools, but practical lab work and related know-how cannot fully be replaced by digital techniques. Finally, it appeared that the professor-student interaction is very important in the distance-learning process, and that a high level of pedagogical (inter)activity is mandatory to maintain motivation and better quality of teaching and learning.

5.
Org Lett ; 22(11): 4537-4541, 2020 06 05.
Article in English | MEDLINE | ID: mdl-32453580

ABSTRACT

We report a novel blue LED mediated intramolecular C-H functionalization of tryptamine derivatives to generate azepino[4, 5-b]indoles (4) in moderate to good yields. By altering the substitution at the tryptamine nitrogen, intramolecular cyclopropanation is achieved in high yields under the same reactions condition to provide natural product inspired polycyclic indoles (6), which are further transformed to spiropiperidino (5 and 8) indoles in decent yields. The mechanism of formation of the compounds was investigated through DFT studies.

7.
Chimia (Aarau) ; 66(4): 196-200, 2012.
Article in English | MEDLINE | ID: mdl-22613148

ABSTRACT

We report herein the enantioselective Cu-catalyzed conjugate addition of organometallic reagents to sensitive Michael acceptors and their application to the synthesis of relevant target molecules. This is one of the most important methodologies to form a C-C bond in an enantioselective manner. A wide range of α,ß-unsaturated aldehydes and ß,γ-unsaturated-α-ketoesters has been successfully used. Reactivity, regio- and enantioselectivities were strongly dependent on the reaction conditions, therefore moderate to very good results were obtained. Furthermore, γ-substituted-α-ketoesters were used as chiral building blocks for further derivatization with complete retention of the chiral information to obtain key compounds.

10.
J Am Chem Soc ; 130(13): 4347-51, 2008 Apr 02.
Article in English | MEDLINE | ID: mdl-18327940

ABSTRACT

Synthetic ion channels and pores attract current attention as multicomponent sensors in complex matrixes. This application requires the availability of reactive signal amplifiers that covalently capture analytes and drag them into the pore. pi-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers because aromatic electron donor-acceptor (AEDA) interactions account for their recognition within pi-acidic naphthalenediimide (NDI) rich synthetic pores. Focusing on amplifier design, we report here the synthesis of a complete collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation potentials by cyclic voltammetry, and calculate their quadrupole moments. Blockage experiments reveal that subtle structural changes in regioisomeric DAN amplifiers can be registered within NDI pores. Frontier orbital overlap in AEDA complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are shown to contribute to isomer recognition by synthetic pores. Particularly important with regard to practical applications of synthetic pores as multianalyte sensors, we further demonstrate that application of the lessons learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides access to privileged amplifiers with submicromolar activity.


Subject(s)
2-Naphthylamine/analogs & derivatives , Anthracenes/chemistry , Naphthalenes/chemistry , Phenanthrolines/chemistry , 2-Naphthylamine/chemical synthesis , 2-Naphthylamine/chemistry , Amplifiers, Electronic , Electrodes , Hydrogen Bonding , Imides , Molecular Structure , Oxidation-Reduction , Quantum Theory , Sensitivity and Specificity , Stereoisomerism
11.
Dalton Trans ; (3): 407-12, 2004 Feb 07.
Article in English | MEDLINE | ID: mdl-15252547

ABSTRACT

The chemistry of the ligand 1, 2,6-bis(imidazol-2-yl)pyridine with manganese, cobalt, nickel and ruthenium has been investigated. The ligand binds as a meridional tridentate ligand as shown by the crystal structures of [Mn(1)2](CF3SO3)2 x Et2O and [Ru(1)2](PF6)2 x 2CH3CN x H2O. The coordinated ligand is deprotonated in mildly basic solution, and this leads to a drop in the metal M(III)/M(II) reduction potential for cobalt and ruthenium of roughly 1.3 V. The crystal structure of Na2(PPN)[Co(1 - 2H)2]2(OH) x MeOH x 2H2O confirms the deprotonation and shows sodium to bind to the deprotonated nitrogen atoms. No stabilisation of the M(III) oxidation state was observed for nickel and manganese.


Subject(s)
Imidazoles/chemistry , Organometallic Compounds/chemical synthesis , Pyridines/chemistry , Transition Elements/chemistry , Crystallography, X-Ray , Ligands , Models, Molecular , Molecular Structure , Organometallic Compounds/chemistry , Oxidation-Reduction
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