99-76-3Relevant articles and documents
Carboxyl Methyltransferase Catalysed Formation of Mono- and Dimethyl Esters under Aqueous Conditions: Application in Cascade Biocatalysis
Ashbrook, Chloe,Carnell, Andrew J.,Goulding, Ellie,Hatton, Harry,Johnson, James R.,Kershaw, Neil M.,McCue, Hannah V.,Rigden, Daniel J.,Ward, Lucy C.
supporting information, (2022/02/21)
Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5–6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5-hydroxymethylfurfural (HMF).
A Mild Heteroatom (O -, N -, and S -) Methylation Protocol Using Trimethyl Phosphate (TMP)-Ca(OH) 2Combination
Tang, Yu,Yu, Biao
, (2022/03/27)
A mild heteroatom methylation protocol using trimethyl phosphate (TMP)-Ca(OH)2combination has been developed, which proceeds in DMF, or water, or under neat conditions, at 80 °C or at room temperature. A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, are suitable substrates for this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmentally friendly nature of this protocol make it an attractive alternative to the conventional base-promoted heteroatom methylation procedures.
Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
, p. 4567 - 4587 (2021/05/06)
The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
Method for hydrolyzing diarylether compound to generate aryl phenol compound
-
Paragraph 0093-0095, (2021/09/29)
The invention discloses a method for hydrolyzing a diarylether compound to generate an arylphenol compound. According to the method, visible light is utilized to excite a photosensitizer for catalysis. In a reaction solvent, the raw material in the formula (1) breaks a C (sp2)-O bond under the auxiliary action of acid, and hydrolysis is performed to obtain the bimolecular aryl phenol compounds in the formula (3) and the formula (4). The method can catalyze the reaction at room temperature, is green and environment-friendly, and is easy to operate; the universality is wide, the reaction yield is relatively high, and the tolerance of functional groups is strong; the synthesis method not only can realize small-scale hydrolysis conversion of various diarylether compounds, but also can realize hydrolysis of herbicidal ether, triclosan and a lignin template substrate, and even can realize large-scale hydrolysis of triclosan and the lignin template substrate to realize gram-level degradation. A new strategy is provided for recovering phenol derivatives through lignin hydrolysis, degrading pesticides and purifying wastewater containing a degerming agent or herbicide. The method has wide application prospect and use value.
Hydroxyl radical-mediated oxidative cleavage of CC bonds and further esterification reaction by heterogeneous semiconductor photocatalysis
Hong, Mei,Jia, Rui,Miao, Hongyan,Ni, Bangqing,Niu, Tengfei,Wang, Hui
, p. 6591 - 6597 (2021/09/10)
A hydroxyl radical-mediated aerobic cleavage of alkenes and further sequence esterification reaction for the preparation of carbonyl compounds have been developed by using tubular carbon nitride (TCN) as a general heterogeneous photocatalyst under an oxygen atmosphere with visible light irradiation. This protocol has an excellent substrate scope and gives the desired aldehydes, ketones and esters in moderate to high yields. Importantly, this metal-free procedure employed photogenerated hydroxyl radicals in situ as green oxidation active species, avoiding the present additional initiators. The reaction could be carried out under solar light irradiation and was applicable to large-scale reactions. Furthermore, the recyclable TCN catalyst could be used several times without a significant loss of activities.
Site-Selective C-H alkylation of Complex Arenes by a Two-Step Aryl Thianthrenation-Reductive Alkylation Sequence
Granatino, Paola,Lansbergen, Beatrice,Ritter, Tobias
, p. 7909 - 7914 (2021/06/27)
Herein, we present an undirected para-selective two-step C-H alkylation of complex arenes useful for late-stage functionalization. The combination of a site-selective C-H thianthrenation with palladium-catalyzed reductive electrophile cross-coupling grants access to a diverse range of synthetically useful alkylated arenes which cannot be accessed otherwise with comparable selectivity, diversity, and practicality. The robustness of this transformation is further demonstrated by thianthrenium-based reductive coupling of two complex fragments.
Erratum: Site-Selective C-H Alkylation of Complex Arenes by a Two-Step Aryl Thianthrenation-Reductive Alkylation Sequence (J. Am. Chem. Soc. (2021) 143: 21 (7909?7914) DOI: 10.1021/jacs.1c03459)
Granatino, Paola,Lansbergen, Beatrice,Ritter, Tobias
, p. 10477 - 10478 (2021/07/26)
Page 7912. In our previous Communication, we inadvertently drew the substrates derived from the molecule pyriproxyfen with incorrect connectivity of the pyriproxyfen molecule (meta instead of para was drawn), omitted a methylene group from compound 13, and drew an epimer of compound 20 in Scheme 3. These drawing errors have been corrected in the corrected Scheme 3 shown here. As a further clarification, we have commented in the revised Supporting Information about the undefined stereocenter of compound 21. The findings and conclusions of the original communication remain unchanged. We apologize for the errors and for any inconvenience that this may have caused the readers of JACS.
Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes**
Dorian, Andreas,Landgreen, Emily J.,Petras, Hayley R.,Shepherd, James J.,Williams, Florence J.
supporting information, p. 10839 - 10843 (2021/06/21)
The facile production of ArCF2X and ArCX3 from ArCF3 using catalytic iron(III)halides is reported, which constitutes the first iron-catalyzed halogen exchange for non-aromatic C?F bonds. Theoretical calculations suggest direct activation of C?F bonds by iron coordination. ArCX3 and ArCF2X products of the reaction are synthetically valuable due to their diversification potential. In particular, chloro- and bromodifluoromethyl arenes (ArCF2Cl, ArCF2Br respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF2R). To optimize for mono-halogen exchange, a statistical method called Design of Experiments was used. Optimized parameters were successfully applied to electron rich and electron deficient aromatic substrates, and to the late stage diversification of flufenoxuron, a commercial insecticide. These methods are highly practical, being run at convenient temperatures and using inexpensive common reagents.
Photocatalytic Reductive C-O Bond Cleavage of Alkyl Aryl Ethers by Using Carbazole Catalysts with Cesium Carbonate
Yabuta, Tatsushi,Hayashi, Masahiko,Matsubara, Ryosuke
, p. 2545 - 2555 (2021/02/01)
Methods to activate the relatively stable ether C-O bonds and convert them to other functional groups are desirable. One-electron reduction of ethers is a potentially promising route to cleave the C-O bond. However, owing to the highly negative redox potential of alkyl aryl ethers (Ered -2.6 V vs SCE), this mode of ether C-O bond activation is challenging. Herein, we report the visible-light-induced photocatalytic cleavage of the alkyl aryl ether C-O bond using a carbazole-based organic photocatalyst (PC). Both benzylic and non-benzylic aryl ethers underwent C-O bond cleavage to form the corresponding phenol products. Addition of Cs2CO3 was beneficial, especially in reactions using a N-H carbazole PC. The reaction was proposed to occur via single-electron transfer (SET) from the excited-state carbazole to the substrate ether. Interaction of the N-H carbazole PC with Cs2CO3 via hydrogen bonding exists, which enables a deprotonation-assisted electron-transfer mechanism to operate. In addition, the Lewis acidic Cs cation interacts with the substrate alkyl aryl ether to activate it as an electron acceptor. The high reducing ability of the carbazole combined with the beneficial effects of Cs2CO3 made this otherwise formidable SET event possible.
Discovery and characterization of a novel perylenephotoreductant for the activation of aryl halides
Guo, Baodang,Huang, Shuping,Li, Jia,Li, Min,Liu, Xuanzhong,Rao, Yijian,Wu, Yawen,Yin, Huimin,Yuan, Zhenbo,Zhang, Yan
, p. 111 - 120 (2021/06/16)
To develop a photocatalyst with catalytical activity for substrates with low reactivities is always highly desired. Herein, based on the principle of structure–property relationships, we rationally designed the natural product cercosporin, the naturally occurring perylenequinonoid pigment, to develop a novel organic perylenephotoreductant, hexacetyl reduced cercosporin (HARCP), through structural manipulation. Compared with cercosporin, HARCP shows prominent electrochemical and photophysical characteristics with greatly improved photoreductive activity, fluorescence lifetime and fluorescence quantum yield. These properties allowed HARCP as a powerful photoreductant to efficiently realize a series of benchmark reactions, including photoreduction, alkoxylation and hydroxylation to construct C–H and C–O bonds using aryl halides as substrates under mild conditions, all of which have never been achieved by the same photocatalyst. Thus, this study well supports the notion that the principle between structural manipulation and photocatalytic activity is of great significance to design customized photocatalysts for photoredox chemistry.
