3233-32-7Relevant academic research and scientific papers
Fluorine-containing substituents: Metabolism of the α,α-difluoroethyl thioether motif
Rodil, Andrea,Slawin, Alexandra M.Z.,Al-Maharik, Nawaf,Tomita, Ren,O'Hagan, David
, p. 1441 - 1447 (2019)
We report the metabolism of the recently introduced α,α-difluoroethyl thioether motif to explore further its potential as a substituent for bioactives discovery chemistry. Incubation of two aryl-SCF2CH3 ethers with the model yeast organism Cunninghamella elegans, indicates that the sulfur of the thioether is rapidly converted to the corresponding sulfoxide, and then significantly more slowly to the sulfone. When the substrate was (p-OMe)PhSCF2CH3, then the resultant (demethylated) phenol sulfoxide had an enantiomeric excess of 60%, and when the substrate was the β-substituted-SCF2CH3 naphthalene, then the enantiomeric excess of the resultant sulfoxide was 54%. There was no evidence of defluorination, unlike the corresponding oxygen ether (p-OMe)PhOCF2CH3, which was converted to the (demethylated) phenol acetate ester during C. elegans incubation. We conclude that the aryl-S-CF2CH3 motif is metabolised in a similar manner to aryl-SCF3, a motif that is being widely explored in discovery chemistry. It is however, significantly less lipophilic than aryl-SCF3 which may offer a practical advantage in tuning overall phar-macokinetic profiles of molecules in development.
Synthetic approach to the functionalized tricyclic core of atropurpuran
Chen, Huan,Li, Xiao-Huan,Gong, Jing,Song, Hao,Liu, Xiao-Yu,Qin, Yong
, p. 347 - 353 (2016)
A strategy for synthesizing the tricyclic fragment 5 of atropurpuran 1 is reported. Rings A and C of atropurpuran were assembled stereoselectively via two intramolecular Michael additions. The advanced tricyclic skeleton 5 shows the correct functionality and stereochemistry for atropurpuran 1, so the skeleton may serve as a key intermediate in its total synthesis.
Direct Acetoxylation of Arenes
Hong Nguyen, Thi Anh,Hou, Duen-Ren
supporting information, p. 8127 - 8131 (2021/08/23)
Acetoxylation of arenes is an important reaction and an unmet need in chemistry. We report a metal-free, direct acetoxylation reaction using sodium nitrate under an anhydrous environment of trifluoroacetic acid, acetic acid, and acetic anhydride. Arenes (31 examples), with oxidation potentials (Eox, in V vs SCE) lower than benzene (2.48 V), were acetoxylated with good yields and regioselectivity. A stepwise, single electron-transfer mechanism is proposed.
carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis
D?ring, Manuel,Sieber, Volker,Simon, Robert C.,Tafertshofer, Georg,Zachos, Ioannis
supporting information, p. 14701 - 14706 (2021/05/13)
Here we report a new robust nicotinamide dinucleotide phosphate cofactor analog (carba-NADP+) and its acceptance by many enzymes in the class of oxidoreductases. Replacing one ribose oxygen with a methylene group of the natural NADP+ was found to enhance stability dramatically. Decomposition experiments at moderate and high temperatures with the cofactors showed a drastic increase in half-life time at elevated temperatures since it significantly disfavors hydrolysis of the pyridinium-N?glycoside bond. Overall, more than 27 different oxidoreductases were successfully tested, and a thorough analytical characterization and comparison is given. The cofactor carba-NADP+ opens up the field of redox-biocatalysis under harsh conditions.
Stereoselective synthesis of selenium-containing glycoconjugates via the mitsunobu reaction
Cermola, Flavio,De Nisco, Mauro,Manfra, Michele,Pedatella, Silvana,Serpico, Luigia
, (2021/05/26)
A simple and efficient route for the synthesis of new glycoconjugates has been developed. The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joined to a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontrol detected in the Mitsunobu key reaction led to the most attractive product showing a natural Dconfiguration. Thus, we were able to obtain the target molecules from the commercially available D-ribose via a shorter and convenient sequence of reactions.
Aqueous microdroplets containing only ketones or aldehydes undergo Dakin and Baeyer-Villiger reactions
Gao, Dan,Jin, Feng,Lee, Jae Kyoo,Zare, Richard N.
, p. 10974 - 10978 (2019/12/28)
The Dakin and Baeyer-Villiger (BV) oxidation reactions require addition of peroxides as oxidants and an acid or a base as a catalyst. Reaction times range from hours to days to obtain target products. Previously, we reported that hydrogen peroxide (H2O2) is spontaneously generated in water microdroplets without any added chemicals or applied electrical potential. Here, we report that the Dakin and BV reactions occur in modest yields within milliseconds in aqueous microdroplets at room-temperature without the addition of external peroxides and catalysts. H2O2 generation is the result of the special environment of the microdroplet surface, which promotes water autoionization. We find that increasing the content of water and decreasing the droplet size improve the product yield of the Dakin and BV reactions, supporting the contention that the amount of H2O2 generated in aqueous microdroplets could induce the two reactions and the reactions occur at or near the air-water interface of the microdroplet surface.
Design, synthesis and biological evaluation of curcumin analogues as novel LSD1 inhibitors
Wang, Jiming,Zhang, Xiangyu,Yan, Jiangkun,Li, Wei,Jiang, Qinwen,Wang, Xinran,Zhao, Dongmei,Cheng, Maosheng
supporting information, (2019/10/22)
Histone lysine-specific demethylase 1 (LSD1) was the first discovered histone demethylase. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development, and thus, it is an attractive molecular target for the development of novel cancer therapeutics. In this study, we worked on the structural optimization of natural products and identified 30 novel LSD1 inhibitors. Utilizing a structure-based drug design strategy, we designed and synthesized a series of curcumin analogues that were shown to be potent LSD1 inhibitors in the enzyme assay. Compound WB07 displayed the most potent LSD1 inhibitory activity, with an IC50 value of 0.8 μM. Moreover, WA20 showed an anticlonogenic effect on A549 cells with an IC50 value of 4.4 μM. Molecular docking simulations were also carried out, and the results indicated that the inhibitors bound to the protein active site located around the key residues of Asp555 and Asp556. These findings suggested that compounds WA20 and WB07 are the first curcumin analogue-based LSD1 inhibitors with remarkable A549 suppressive activity, providing a novel scaffold for the development of LSD1 inhibitors.
C70 Fullerene-Catalyzed Metal-Free Photocatalytic ipso-Hydroxylation of Aryl Boronic Acids: Synthesis of Phenols
Kumar, Inder,Sharma, Ritika,Kumar, Rakesh,Kumar, Rakesh,Sharma, Upendra
supporting information, p. 2013 - 2019 (2018/04/02)
A metal-free C70 fullerene-catalyzed method has been developed for the ipso-hydroxylation of aryl and heteroaryl boronic acids to corresponding phenols under photocatalytic conditions. The reaction proceeds under oxygen atmosphere and the mechanistic study revealed that C70 plays a critical role in the generation of reactive oxygen species in the presence of blue light. Reactions in the presence of 18O-labelled water and oxygen confirmed the generation of reactive oxygen species from oxygen molecule. Amine used as a reductant could be recovered in the form of imine. The current method is also applicable to the synthesis of aryl ethers in one-pot two-step process. (Figure presented.).
Total Synthesis of Divergolides E and H
Caplan, Scott M.,Floreancig, Paul E.
, p. 15866 - 15870 (2018/11/10)
This manuscript describes the first total syntheses of divergolides E and H. The route employs a telescoped hetero-Diels–Alder and oxidative carbon–hydrogen bond cleavage as an entry into the central bridged bicyclic acetal unit. Additional key steps of the highly convergent route include a desymmetrizing epoxidation, a chelation-controlled alkenylzinc addition, an amide formation between a hindered aniline and an acylating agent that is prone to ketene formation, and a challenging macrolactonization.
KHF2: A mild and selective desilylating agent for phenol tert-butyldimethylsilyl (TBDMS) ethers
Lakshman, Mahesh K.,Tine, Fatou A.,Khandaker, Tashrique A.,Basava, Vikram,Agyemang, Nana B.,Benavidez, Michael S.A.,Ga?i, Marikone,Guerrera, Lisa,Zajc, Barbara
, p. 381 - 385 (2017/02/10)
TBDMS (t-BuMe2Si, tert-butyldimethylsilyl) ethers of a variety of phenols have been deprotected with KHF2 in MeOH, at room temperature. Carboxylic ester and labile phenolic acetate were unaffected under these conditions. In competition reactions between TBDMS ethers of a phenol and two primary benzylic alcohols, the phenolic ether underwent cleavage whereas the alcohol ethers remained intact. From a substrate containing both a phenolic hydroxyl group and a secondary, doubly benzylic hydroxyl group protected as TBDMS ethers, the phenol was rapidly and selectively released. Cleavage of TBDMS, TBDPS, and TIPS ethers of a phenol was also compared. TBDMS and TBDPS ethers underwent cleavage at room temperature within 30 minutes, whereas removal of the TIPS ether required 2.5 hours. Ease of cleavage appears to be TBDMS ≈ TBDPS > TIPS. At 60°C, TBDMS ethers of primary benzylic, allylic, and unactivated alcohols can be efficiently desilylated over a prolonged period (13-17 h). Thus, KHF2 proves to be a mild and effective reagent for the selective desilylation of phenol TBDMS ethers at room temperature.
