14473-91-7Relevant academic research and scientific papers
Photochemical regulation of an artificial hydrolase by a backbone incorporated tertiary structure switch
Lindgren, N. Johan V.,Varedian, Miranda,Gogoll, Adolf
, p. 501 - 505 (2009)
A stilbene chromophore has been incorporated into the turn region of a 42 amino acid peptide, linking two helical peptide sections. Spatial proximity between these sections, as well as aggregation into dimers, is required to facilitate the catalytic function of this artificial hydrolase. Photomodulation of the hydrolase activity results in an increase of the activity of 42% upon switching from the trans to the cis isomer of the chromophore. This is rationalized by a change in the aggregation state of the peptidomimetic, which is supported by diffusion coefficients obtained from PFG-NMR experiments. The results show that incorporation of a small, relatively flexible chromophore into a large peptide is capable of inducing a considerable change in tertiary structure and thus, functionality.
Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives
Liu, Yue,Li, Peng-Xiao,Mu, Wen-Wen,Sun, Ya-Lei,Liu, Ren-Min,Yang, Jie,Liu, Guo-Yun
, (2022/01/13)
This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.
Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation
Gong, Pei-Xue,Xu, Fangning,Cheng, Lu,Gong, Xu,Zhang, Jie,Gu, Wei-Jin,Han, Wei
supporting information, p. 5905 - 5908 (2021/06/18)
A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.
Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,β-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters
Gao, Ang,Jiang, Run-Chuang,Liu, Chuang-Chuang,Liu, Qi-Le,Lu, Xiao-Yu,Xia, Ze-Jie
supporting information, p. 8829 - 8842 (2021/06/30)
Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.
Metal-Free Hydropyridylation of Thioester-Activated Alkenes via Electroreductive Radical Coupling
Xu, Hehuan,Liu, Jiayu,Nie, Feiyun,Zhao, Xiaowei,Jiang, Zhiyong
, p. 16204 - 16212 (2021/10/25)
An electrochemical hydropyridylation of thioester-activated alkenes with 4-cyanopyridines has been developed. The reactions experience a tandem electroreduction of both substrates on the cathode surface, protonation, and radical cross-coupling process, resulting in a variety of valuable pyridine variants, which contain a tertiary and even a quaternary carbon at the α-position of pyridines, in high yields. The employment of thioesters to the conjugated alkenes enables no requirement of catalyst and high temperature, representing a highly sustainable synthetic method.
Toward a Scalable Synthesis and Process for EMA401, Part II: Development and Scale-Up of a Pyridine- A nd Piperidine-Free Knoevenagel-Doebner Condensation
Hardegger, Leo A.,Humair, Roger,Sidler, Eric
, p. 1756 - 1762 (2020/10/26)
During route scouting for EMA401 (1), an angiotensin II type 2 antagonist, we identified the synthesis of key amino acid intermediate 2 via its cinnamic acid derivative 3 as a streamlined option. In general, cinnamic acids can be synthesized from the corresponding aldehydes by a Knoevenagel-Doebner condensation in pyridine with piperidine as an organocatalyst. We aimed to replace both of these reagents and found novel conditions involving toluene as the solvent and morpholine as the organocatalyst. Scale-up of the process allowed the production of 25 kg of cinnamic acid 3 that was of the quality required for process development of the subsequent phenylalanine ammonia lyase-catalyzed step. The modified conditions were found to be widely applicable to alternative aldehydes and thus are of relevance to practitioners of chemical scale-up.
Design, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents
Atmaram Upare, Abhay,Gadekar, Pradip K.,Sivaramakrishnan,Naik, Nishigandha,Khedkar, Vijay M.,Sarkar, Dhiman,Choudhari, Amit,Mohana Roopan
supporting information, p. 507 - 512 (2019/02/19)
Cinnamic acid and its derivatives are known for anti-tubercular activity. The present study reports the synthesis of cinnamic acid derivatives via bioisosteric replacement of terminal carboxylic acid with “oxadiazole”. A series of cinnamic acid derivatives (styryl oxadiazoles) were designed and synthesized in good yields by reaction of substituted cinnamic acids (2, 15a-15s) with amidoximes. The synthesized styryl oxadiazoles were evaluated in vitro for anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Ra strain. The structure-activity relationship (SAR) study has identified several compounds with mixed anti-tubercular profiles. The compound 32 displayed potent anti-tubercular activity (IC50 = 0.045 μg/mL). Molecular docking studies on mycobacterial enoyl-ACP reductase enzyme corroborated well with the experimental findings providing a platform for structure based hit-to-lead development.
Tandem IBX-Promoted Primary Alcohol Oxidation/Opening of Intermediate β,γ-Diolcarbonate Aldehydes to (E)-γ-Hydroxy-α,β-enals
Kumari, Anupama,Gholap, Sachin P.,Fernandes, Rodney A.
, p. 2278 - 2290 (2019/06/17)
A tandem IBX-promoted oxidation of primary alcohol to aldehyde and opening of intermediate β,γ-diolcarbonate aldehyde to (E)-γ-hydroxy-α,β-enal has been developed. Remarkably, the carbonate opening delivered exclusively (E)-olefin and no over-oxidation of γ-hydroxy was observed. The method developed has been extended to complete the stereoselective total synthesis of both (S)- and (R)-coriolides and d-xylo- and d-arabino-C-20 guggultetrols.
Iodine-Catalyzed Facile Approach to Sulfones Employing TosMIC as a Sulfonylating Agent
Kadari, Lingaswamy,Palakodety, Radha Krishna,Yallapragada, Lakshmi Prapurna
supporting information, p. 2580 - 2583 (2017/05/24)
A novel iodine-catalyzed functionalization of a variety of olefins and alkynes and direct decarboxylative functionalization of cinnamic and propiolic acids with TosMIC to provide access to various vinyl, allyl, and β-iodo vinylsulfones is described. This simple, efficient, and environmentally benign approach employing inexpensive molecular iodine as a catalyst demonstrates a versatile protocol for the synthesis of highly valuable sulfones, rendering it attractive to both synthetic and medicinal chemistry.
Kinetic Resolution of Aromatic β-Amino Acids Using a Combination of Phenylalanine Ammonia Lyase and Aminomutase Biocatalysts
Weise, Nicholas J.,Ahmed, Syed T.,Parmeggiani, Fabio,Turner, Nicholas J.
supporting information, p. 1570 - 1576 (2017/05/05)
An enzymatic strategy for the preparation of (R)-β-arylalanines employing phenylalanine aminomutase and ammonia lyase (PAM and PAL) enzymes has been demonstrated. Candidate PAMs with the desired (S)-selectivity from Streptomyces maritimus (EncP) and Bacillus sp. (PabH) were identified via sequence analysis using a well-studied template sequence. The newly discovered PabH could be linked to the first ever proposed biosynthesis of pyloricidin-like secondary metabolites and was shown to display better β-lyase activity in many cases. In spite of this, a method combining the higher conversion of EncP with a strict α-lyase from Anabaena variabilis (AvPAL) was found to be more amenable, allowing kinetic resolution of five racemic substrates and a preparative-scale reaction with >98% (R) enantiomeric excess. This work represents an improved and enantiocomplementary method to existing biocatalytic strategies, allowing simple product separation and modular telescopic combination with a preceding chemical step using an achiral aldehyde as starting material. (Figure presented.).
