4383-06-6Relevant articles and documents
Highly efficient Meerwein-Ponndorf-Verley reductions over a robust zirconium-organoboronic acid hybrid
Song, Jinliang,Hua, Manli,Huang, Xin,Visa, Aurelia,Wu, Tianbin,Fan, Honglei,Hou, Minqiang,Zhang, Zhaofu,Han, Buxing
, p. 1259 - 1265 (2021/02/26)
The Meerwein-Ponndorf-Verley (MPV) reaction is an attractive approach to selectively reduce carbonyl groups, and the design of advanced catalysts is the key for these kinds of interesting reactions. Herein, we fabricated a novel zirconium organoborate using 1,4-benzenediboronic acid (BDB) as the precursor for MPV reduction. The prepared Zr-BDB had excellent catalytic performance for the MPV reduction of various biomass-derived carbonyl compounds (i.e., levulinate esters, aldehydes and ketones). More importantly, the number of borate groups on the ligands significantly affected the catalytic activity of the Zr-organic ligand hybrids, owing to the activation role of borate groups on hydroxyl groups in the hydrogen source. Detailed investigations revealed that the excellent performance of Zr-BDB was contributed by the synergetic effect of Zr4+and borate. Notably, this is the first work to enhance the activity of Zr-based catalysts in MPV reactions using borate groups.
Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol- O-demethylase
Grimm, Christopher,Lazzarotto, Mattia,Pompei, Simona,Schichler, Johanna,Richter, Nina,Farnberger, Judith E.,Fuchs, Michael,Kroutil, Wolfgang
, p. 10375 - 10380 (2020/10/02)
The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O-demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical compounds by deprotecting reactive hydroxyl moieties. Various oxidative enzymes are known to catalyze this reaction at the expense of molecular oxygen, which may lead in the case of phenols/catechols to undesired side reactions (e.g., oxidation, polymerization). Here an oxygen-independent demethylation via methyl transfer is presented employing a cobalamin-dependent veratrol-O-demethylase (vdmB). The biocatalytic demethylation transforms a variety of aryl methyl ethers with two functional methoxy moieties either in 1,2-position or in 1,3-position. Biocatalytic reactions enabled, for instance, the regioselective monodemethylation of substituted 3,4-dimethoxy phenol as well as the monodemethylation of 1,3,5-trimethoxybenzene. The methyltransferase vdmB was also successfully applied for the regioselective demethylation of natural compounds such as papaverine and rac-yatein. The approach presented here represents an alternative to chemical and enzymatic demethylation concepts and allows performing regioselective demethylation in the absence of oxygen under mild conditions, representing a valuable extension of the synthetic repertoire to modify pharmaceuticals and diversify natural products.
Regioselectivity of Cobalamin-Dependent Methyltransferase Can Be Tuned by Reaction Conditions and Substrate
Pompei, Simona,Grimm, Christopher,Farnberger, Judith E.,Schober, Lukas,Kroutil, Wolfgang
, p. 5977 - 5983 (2020/10/06)
Regioselective reactions represent a significant challenge for organic chemistry. Here the regioselective methylation of a single hydroxy group of 4-substituted catechols was investigated employing the cobalamin-dependent methyltransferase from Desulfitobacterium hafniense. Catechols substituted in position four were methylated either in meta- or para-position to the substituent depending whether the substituent was polar or apolar. While the biocatalytic cobalamin dependent methylation was meta-selective with 4-substituted catechols bearing hydrophilic groups, it was para-selective for hydrophobic substituents. Furthermore, the presence of water miscible co-solvents had a clear improving influence, whereby THF turned out to enable the formation of a single regioisomer in selected cases. Finally, it was found that also the pH led to an enhancement of regioselectivity for the cases investigated.
Understanding the cytotoxic effects of new isovanillin derivatives through phospholipid Langmuir monolayers
de Carvalho, Ana C.,Girola, Natália,de Figueiredo, Carlos R.,Machado, André C.,de Medeiros, Lívia S.,Guadagnin, Rafael C.,Caseli, Luciano,Veiga, Thiago A.M.
, p. 205 - 213 (2018/11/01)
Twenty-one isovanillin derivatives were prepared in order to evaluate their cytotoxic properties against the cancer cell lines B16F10-Nex2, HL-60, MCF-7, A2058 and HeLa. Among them, seven derivatives exhibited cytotoxic activity. We observed that for obtaining smaller IC50 values and for increasing the index of selectivity, two structural features are very important when compared with isovanillin (1); a hydroxymethyl group at C-1 and the replacement of the hydroxyl group at C-3 by different alkyl groups. As the lipophilicity of the compounds was changed, we decided to investigate the interaction of the cytotoxic isovallinin derivatives on cell membrane models through Langmuir monolayers by employing the lipids DPPC (1,2-diplamitoyl-sn-glycero-3-phosphocoline) and DPPS (1,2-diplamitoyl-sn-glycero-3-phosphoserine). The structural changes on the scaffold of the compounds modulated the interaction with the phospholipids at the air-water interface. These results were very important to understand the biophysical aspects related to the interaction of the cytotoxic compounds with the cancer cell membranes.
Adamantane acid esters with alkoxyaryl alcohols: Synthesis, antiproliferative activity, and influence on microtubule network of tumor cells
Zefirov,Nurieva,Pikulina, Yu. A.,Ogon′kov,Wobith,Kuznetsov,Zefirova
, p. 1503 - 1509 (2017/12/15)
Adamantaneacetic and adamantanecarboxylic acid esters containing 3-hydroxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, or 5-(hydroxymethyl)-2-methoxyphenyl groups were synthesized as unusual analogs of natural antitumor and anti-tubulin agents combretastatin A-4 and 2-methoxyestradiol. The compounds were found to possess noticeable cytotoxicity to epithelial human carcinoma cell line A549 (EC50 = 4.3—81 μmol L–1). An ability to cause complete depolymerization of microtubule network of A549 cells was demonstrated for 5-(hydroxymethyl)-2-methoxyphenyl adamantan-1-ylacetate (6a) at a concentration of 100 μmol L–1. Ester 6a belongs to a new structural type, which is unusual for the ligands of the tubulin colchicine domain, and is an interesting lead compound for further structural optimization.
Design, synthesis and biological evaluation of novel macrocyclic bisbibenzyl analogues as tubulin polymerization inhibitors
Sun, Bin,Li, Lin,Hu, Qing-Wen,Xie, Fei,Zheng, Hong-Bo,Niu, Huan-Min,Yuan, Hui-Qing,Lou, Hong-Xiang
, p. 484 - 499 (2016/07/06)
A series of novel macrocyclic bisbibenzyl analogues was designed, synthesized, and evaluated for their antiproliferative activity in vitro. All of the compounds were tested in five anthropic cancer cell lines, including a multidrug-resistant phenotype. Among these novel molecules, compounds 88, 92 and 94 displayed excellent anticancer activity against Hela, k562, HCC1428, HT29, and PC-3/Doc cell lines, with average IC50 values ranging from 2.23 μM to 3.86 μM, and were more potent than the parental compound marchantin C and much more potent than the positive control Adriamycin. In addition, the mechanism of action of compound 88 was investigated by cell cycle analysis and a tubulin polymerization assay in HCC1482 cells. The binding mode of compound 88 to tubulin was also investigated utilizing a molecular docking study. In conclusion, the present study improves our understanding of the action of bisbibenzylbased tubulin polymerization inhibitors and provides a new molecular scaffold for the further development of antitumor agents that target tubulin.
CSJ acting as a versatile highly efficient greener resource for organic transformations
Maity, Himadri Sekhar,Misra, Kaushik,Mahata, Tanushree,Nag, Ahindra
, p. 24446 - 24450 (2016/03/15)
Simple, new, greener and efficient alternatives to the existing protocols have been developed for the reduction of aromatic aldehydes to their corresponding alcohols, decarboxylation of substituted benzoic acids (C6-C1) and substituted cinnamic acids (C6-C3) with a hydroxyl group at the para position with respect to the acid group to corresponding phenolic compounds and vinyl phenols respectively by using a natural feedstock, cucumber juice (CSJ), which acts as a greener solvent system, performing a substrate-selective reaction. Additionally, the hydrolysis of the acetyl as well as the benzoyl group of aromatic compounds has been carried out to afford excellent yield by CSJ.
Synthesis and Biological Evaluation of 1,2,3-triazole tethered Pyrazoline and Chalcone Derivatives
Hussaini, Syed Mohammed Ali,Yedla, Poornachandra,Babu, Korrapati Suresh,Shaik, Thokhir B.,Chityal, Ganesh Kumar,Kamal, Ahmed
, p. 97 - 109 (2016/07/09)
A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin-A4(CA-4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 μm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 μm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis.
Anti-tubercular agents. Part 8: Synthesis, antibacterial and antitubercular activity of 5-nitrofuran based 1,2,3-triazoles
Kamal, Ahmed,Hussaini, Syed Mohammed Ali,Faazil, Shaikh,Poornachandra,Narender Reddy,Kumar, C. Ganesh,Rajput, Vikrant Singh,Rani, Chitra,Sharma, Rashmi,Khan, Inshad Ali,Jagadeesh Babu
, p. 6842 - 6846 (2014/01/06)
A series of 5-nitrofuran-triazole conjugates were synthesized and evaluated for their antimicrobial activity against both Gram-positive and Gram-negative bacterial strains. All the compounds exhibited promising inhibition towards Gram-positive pathogenic strains, while mild inhibitory effects were observed towards Gram-negative bacterial strains. Some of the compounds 8a, 8b, 8e, 8f, 8h are most active among the series exhibiting MIC value of 1.17 μg/ml against different bacterial strains. The bactericidal activity is found to be in accordance with the bacterial growth inhibition data. Compound 8e was found to be equipotent to the standard drug Ciprofloxacin displaying MBC value of 1.17 μg/ml against the bacterial strain Bacillus subtilis. The compounds have also demonstrated promising antibacterial activity against the resistant strain MRSA and were found to be effective inhibitors of biofilm formation. The compound 8b exhibited excellent anti-biofilm activity with IC50 value as low as 0.8 μg/ml. These conjugates were also screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Compound 8e showed promising antitubercular activity with MIC value of 0.25 μg/ml. Most of these compounds are less toxic to normal mammalian cells than the widely used antibacterial drug Ciprofloxacin.
New greener alternatives for bioreduction of aromatic aldehydes and decarboxylation of aromatic acids using juice of fruits
Misra, Kaushik,Maity, Himadri Sekhar,Chanda, Subhankar,Nag, Ahindra
experimental part, p. 92 - 95 (2012/09/22)
Cocos nucifera L. and Borassus flabellifer L. juices act as bio catalytic system for the reduction of aromatic aldehydes to alcohols and selective decarboxylation of substituted cinnamic acid to styrene and substituted benzoic acid to polyphenolic compound. Both juices exhibit good activity when aromatic aldehydes and aromatic acids contain electron-donating groups at specific positions. Moreover, C. nucifera juice exhibits good result for the reduction and decarboxylation properties than B. flabellifer juice under the same reaction condition.
