103678-74-6Relevant articles and documents
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo
Ju, Yuan,He, Lihui,Zhou, Yuanzheng,Yang, Tao,Sun, Ke,Song, Rao,Yang, Yang,Li, Chengwei,Sang, Zitai,Bao, Rui,Luo, Youfu
, p. 3104 - 3119 (2020)
Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of Staphylococcus aureus infections. In an unbiased screen of 2632 molecules, a peptidomimetic boronate, MLN9708, was found to be a potent suppressor of SaClpP function. A time-saving and cost-efficient strategy integrating in silico position scanning, multistep miniaturized synthesis, and bioactivity testing was deployed for optimization of this hit compound and led to fast exploration of structure-activity relationships. Five of 150 compounds from the miniaturized synthesis exhibited improved inhibitory activity. Compound 43Hf was the most active inhibitor and showed reversible covalent binding to SaClpP while did not destabilize the tetradecameric structure of SaClpP. The crystal structure of 43Hf-SaClpP complex provided mechanistic insight into the covalent binding mode of peptidomimetic boronate and SaClpP. Furthermore, 43Hf could bind endogenous ClpP in S. aureus cells and exhibited significant efficacy in attenuating S. aureus virulence in vitro and in vivo.
Hybrids of aurantiamide acetate and isopropylated genipin as potential anti-inflammatory agents: The design, synthesis, and biological evaluation
Wang, Hongwei,Gao, Sufan,Li, Jiaming,Ma, Xiaodong,Liu, Wandong,Qian, Shihu
, p. 797 - 808 (2020/12/03)
A novel series of hybrids designed on the basis of aurantiamide acetate and isopropylated genipin were synthesized and biologically evaluated as anti-inflammatory agents. Among them, compound 7o exhibited the best inhibitory activity against TNF-α secretion (IC50?=?16.90?μM) and was selected for further in vitro and in vivo functional study. The results demonstrated that 7o was capable of suppressing the expression of LPS-induced iNOS and COX-2, as well as reducing the production of NO at the concentration of 5?μM, which may be resulted from its regulation of NF-κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable in vivo anti-inflammatory activity with an inhibition rate of 53.32% against xylene-induced ear swelling in mice at the dose of 5?mg/kg.
Organocatalytic asymmetric [4+2] cyclization of 2-benzothiazolimines with azlactones: Access to chiral benzothiazolopyrimidine derivatives
Ni, Qijian,Wang, Xuyang,Xu, Fangfang,Chen, Xiaoyun,Song, Xiaoxiao
supporting information, p. 3155 - 3158 (2020/03/23)
An organocatalytic asymmetric domino Mannich/cyclization reaction between 2-benzothiazolimines with azlactones has been successfully developed. With the bifunctional squaramide catalyst, this formal [4+2] cyclization occurs with good to high yields and excellent stereoselectivities (up to 99% ee, >20?:?1 dr), providing an efficient and mild access to chiral benzothiazolopyrimidines bearing adjacent tertiary and quaternary stereogenic centers.
Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis
Alemán, José,Bernardi, Luca,Borello, Fabio,Cano, Rafael,Capaccio, Vito,Díaz-Tendero, Sergio,De Riccardis, Francesco,Della Sala, Giorgio,Rodríguez, Ricardo I.,Sicignano, Marina
supporting information, p. 2914 - 2920 (2020/04/28)
The first enantioselective method for the installation of the SCF3 group at the C-4 position of azlactones is described in the present communication under quinidinium phase transfer catalysis. The higher performance of substrates containing electron-rich 2-aryl groups at the azlactone was rationalized using DFT calculations.
Catalytic Aerobic Cross-Dehydrogenative Coupling of Azlactones en Route to α,α-Disubstituted α-Amino Acids
Tsuji, Taro,Tanaka, Takafumi,Tanaka, Tsukushi,Yazaki, Ryo,Ohshima, Takashi
supporting information, p. 4164 - 4170 (2020/06/04)
We developed a catalytic aerobic method to synthesize α,α-disubstituted α-amino acids through cross-dehydrogenative coupling of azlactones. Combining an iron catalyst with a bisoxazolidine ligand resulted in high catalytic performance, and cross-coupling with an indole proceeded smoothly under aerobic conditions. A wide variety of α-aryl and aliphatic amino acid derived azlactones were applied to the present catalysis. In addition, a quaternary carbon could be constructed using oxindole and benzofuranone under aerobic conditions.
Palladium-catalyzed asymmetric decarboxylative allylation of azlactone enol carbonates: Fast access to enantioenriched α-allyl quaternary amino acids
Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,De Lorenzi, Ersilia,Colombo, Lino
, p. 732 - 741 (2019/01/09)
We report a fast protocol for the synthesis of enantioenriched quaternary 4-allyl oxazol-5-ones. The key step is a Pd-catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α-amino acids. The use of (R,R)-DACH-phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4-allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step.
Catalytic, Enantioselective α-Alkylation of Azlactones with Nonconjugated Alkenes by Directed Nucleopalladation
Nimmagadda, Sri Krishna,Liu, Mingyu,Karunananda, Malkanthi K.,Gao, De-Wei,Apolinar, Omar,Chen, Jason S.,Liu, Peng,Engle, Keary M.
supporting information, p. 3923 - 3927 (2019/03/07)
A palladium(II)-catalyzed enantioselective α-alkylation of azlactones with nonconjugated alkenes is described. The reaction employs a chiral BINOL-derived phosphoric acid as the source of stereoinduction, and a cleavable bidentate directing group appended to the alkene to control the regioselectivity and stabilize the nucleopalladated alkylpalladium(II) intermediate in the catalytic cycle. A wide range of azlactones were found to be compatible under the optimal reaction conditions to afford products bearing α,α-disubstituted α-amino-acid derivatives with high yields and high enantioselectivity.
Enantioselective synthesis of pyrano[2,3-: C] pyrrole via an organocatalytic [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones
Wang, Yichen,Chen, Yuzhen,Li, Xiaoping,Mao, Yukang,Chen, Weiwen,Zhan, Ruoting,Huang, Huicai
supporting information, p. 3945 - 3950 (2019/04/30)
An enantioselective [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones has been successfully developed through a squaramide catalysis strategy. This protocol provides an efficient and mild access to obtain pyrano[2,3-c]pyrrole scaffolds containing contiguous quaternary and tertiary stereogenic centers in excellent yields (up to 99%) with high levels of diastereo- and enantioselectivities (up to 99% ee). Two possible pathways were proposed to explain the observed stereoselectivity.
Asymmetric construction of dihydrobenzofuran-2,5-dione derivatives via desymmetrization of p-quinols with azlactones
Xie, Lihua,Dong, Shunxi,Zhang, Qian,Feng, Xiaoming,Liu, Xiaohua
supporting information, p. 87 - 90 (2019/01/03)
The desymmetrization of p-quinols through a chiral bisguanidinium hemisalt catalyzed enantioselective Michael addition/lactonization cascade reaction with azlactones was reported. 3-Amino-benzofuran-2,5-diones containing a chiral amino acid residue were achieved with up to 99% ee and >19?:?1 dr. An exploration of the structure of the catalyst bisguanidinium was undertaken, revealing a bifunctional catalytic model.
Bifunctional squaramide-catalyzed synthesis of chiral dihydrocoumarins via ortho-quinone methides generated from 2-(1-tosylalkyl)phenols
Zhou, Ji,Wang, Mao-Lin,Gao, Xiang,Jiang, Guo-Fang,Zhou, Yong-Gui
supporting information, p. 3531 - 3534 (2017/03/30)
A bifunctional squaramide-catalyzed reaction of azlactones with o-quinone methides in situ generated from 2-(1-tosylalkyl)-phenols has been successfully developed under basic conditions, providing an efficient and mild access to chiral dihydrocoumarins bearing adjacent tertiary and quaternary stereogenic centers in high yields with excellent diastereo- and enantioselectivities.
