616-75-1Relevant academic research and scientific papers
Cleavage of Carboxylic Esters by Aluminum and Iodine
Sang, Dayong,Yue, Huaxin,Fu, Yang,Tian, Juan
, p. 4254 - 4261 (2021/03/09)
A one-pot procedure for deprotecting carboxylic esters under nonhydrolytic conditions is described. Typical alkyl carboxylates are readily deblocked to the carboxylic acids by the action of aluminum powder and iodine in anhydrous acetonitrile. Cleavage of lactones affords the corresponding ω-iodoalkylcarboxylic acids. Aryl acetylates undergo deacetylation with the participation of the neighboring group. This method enables the selective cleavage of alkyl carboxylic esters in the presence of aryl esters.
Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)
Condon, Sylvie,Le Gall, Erwan,Pichon, Christophe,Presset, Marc,Xavier, Tania
supporting information, p. 2085 - 2094 (2021/09/02)
The use of mono-substituted malonic acid half oxyesters (SMAHOs) has been hampered by the sporadic references describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials.
Exploration of New Biomass-Derived Solvents: Application to Carboxylation Reactions
Gevorgyan, Ashot,Hopmann, Kathrin H.,Bayer, Annette
, p. 2080 - 2088 (2020/02/20)
A range of hitherto unexplored biomass-derived chemicals have been evaluated as new sustainable solvents for a large variety of CO2-based carboxylation reactions. Known biomass-derived solvents (biosolvents) are also included in the study and the results are compared with commonly used solvents for the reactions. Biosolvents can be efficiently applied in a variety of carboxylation reactions, such as Cu-catalyzed carboxylation of organoboranes and organoboronates, metal-catalyzed hydrocarboxylation, borocarboxylation, and other related reactions. For many of these reactions, the use of biosolvents provides comparable or better yields than the commonly used solvents. The best biosolvents identified are the so far unexplored candidates isosorbide dimethyl ether, acetaldehyde diethyl acetal, rose oxide, and eucalyptol, alongside the known biosolvent 2-methyltetrahydrofuran. This strategy was used for the synthesis of the commercial drugs Fenoprofen and Flurbiprofen.
Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors
Schade, Markus,Merla, Beatrix,Lesch, Bernhard,Wagener, Markus,Timmermanns, Simone,Pletinckx, Katrien,Hertrampf, Torsten
supporting information, p. 11801 - 11808 (2020/11/26)
Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.
Exploring the Promiscuous Enzymatic Activation of Unnatural Polyketide Extender Units in Vitro and in Vivo for Monensin Biosynthesis
Grote, Marius,Schulz, Frank
, p. 1183 - 1189 (2019/03/11)
The incorporation of new-to-nature extender units into polyketide synthesis is an important source for diversity yet is restricted by limited availability of suitably activated building blocks in vivo. We here describe a straightforward workflow for the biogenic activation of commercially available new-to-nature extender units. Firstly, the substrate scope of a highly flexible malonyl co-enzyme A synthetase from Streptomyces cinnamonensis was characterized. The results were matched by in vivo experiments in which the said extender units were accepted by both the polyketide synthase and the accessory enzymes of the monensin biosynthetic pathway. The experiments gave rise to a series of predictable monensin derivatives by the exploitation of the innate substrate promiscuity of an acyltransferase and downstream enzyme functions.
Synthesis and insecticidal activity of mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety
Pan, Jianke,Yu, Lu,Liu, Dengyue,Hu, Deyu
, (2018/05/30)
Mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety were designed, synthesized, and evaluated for their insecticidal activity. Some of the title compounds showed remarkable insecticidal properties against Aphis craccivora. Compound I13 exhibited satisfactory insecticidal activity against A. craccivora. Meanwhile, label-free proteomics analysis of compound I13 treatment identified a total of 821 proteins. Of these, 35 proteins were up-regulated, whereas 108 proteins were down-regulated. Differential expressions of these proteins reflected a change in cellular structure and metabolism.
Design and synthesis of malonamide derivatives as antibiotics against methicillin-resistant staphylococcus aureus
Su, Jung-Chen,Huang, Yu-Ting,Chen, Chang-Shi,Chiu, Hao-Chieh,Shiau, Chung-Wai
, (2018/01/03)
Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to humans. Most existing antimicrobial drugs, including the β-lactam and quinoxiline classes, are not effective against MRSA. In this study, we synthesized 24 derivatives of malonamide, a new class of antibacterial agents and potentiators of classic antimicrobials. A derivative that increases bacterial killing and biofilm eradication with low cell toxicity was created.
Ni-Catalyzed Enantioselective Reductive Diarylation of Activated Alkenes by Domino Cyclization/Cross-Coupling
Wang, Kuai,DIng, Zhengtian,Zhou, Zhijun,Kong, Wangqing
supporting information, p. 12364 - 12368 (2018/10/05)
A Ni-catalyzed enantioselective reductive diarylation of activated alkenes by domino cyclizative/cross-coupling of two aryl bromides is developed. This reaction proceeds under very mild conditions and shows broad substrate scope, without requiring the use of preformed organometallic reagents. Moreover, this approach provides direct access to various bis-heterocycles bearing all-carbon quaternary centers in synthetically useful yields (up to 81%) with excellent enantioselectivity (>30 examples, 90-99% ee).
Copper-catalyzed carboxylation of hydroborated disubstituted alkenes and terminal alkynes with cesium fluoride
Juhl, Martin,Laursen, Simon L. R.,Huang, Yuxing,Nielsen, Dennis U.,Daasbjerg, Kim,Skrydstrup, Troels
, p. 1392 - 1396 (2017/05/24)
A protocol for the hydrocarboxylation of disubstituted alkenes and terminal alkynes providing access to different secondary carboxylic acids and malonic acid derivatives has been developed. This methodology relies on an initial hydroboration using 9-BBN followed by carboxylation with carbon dioxide in the presence of a copper catalyst and the additive, cesium fluoride. Different cyclohexene, styrene, and stilbene derivatives could be utilized, and alkynes could be transformed into their corresponding dicarboxylic acids in good yields. Finally, six different terpenoids were carboxylated using the developed procedure. (Chemical Equation Presented).
Copper-catalyzed intermolecular chloro- and bromotrifluoromethylation of alkenes
Fu, Mingyang,Chen, Long,Jiang, Yongpeng,Jiang, Zhong-Xing,Yang, Zhigang
supporting information, p. 348 - 351 (2016/02/19)
A highly practical copper-catalyzed intermolecular halotrifluoromethylation of alkenes has been developed under mild reaction conditions. A variety of Cl/Br-containing trifluoromethyl derivatives were directly synthesized from a wide range of alkenes, including electron-deficient and unactivated alkenes.
