4521-22-6Relevant academic research and scientific papers
Identification of First-in-Class Inhibitors of Kallikrein-Related Peptidase 6 That Promote Oligodendrocyte Differentiation
A?t Amiri, Sabrina,Deboux, Cyrille,Soualmia, Feryel,Chaaya, Nancy,Louet, Maxime,Duplus, Eric,Betuing, Sandrine,Nait Oumesmar, Brahim,Masurier, Nicolas,El Amri, Chahrazade
, p. 5667 - 5688 (2021/05/29)
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) that causes severe motor, sensory, and cognitive impairments. Kallikrein-related peptidase (KLK)6 is the most abundant serine protease secreted in the CNS, mainly by oligodendrocytes, the myelin-producing cells of the CNS, and KLK6 is assumed to be a robust biomarker of MS, since it is highly increased in the cerebrospinal fluid (CSF) of MS patients. Here, we report the design and biological evaluation of KLK6's low-molecular-weight inhibitors, para-aminobenzyl derivatives. Interestingly, selected hit compounds were selective of the KLK6 proteolytic network encompassing KLK1 and plasmin that also participate in the development of MS physiopathology. Moreover, hits were found noncytotoxic on primary cultures of murine neurons and oligodendrocyte precursor cells (OPCs). Among them, two compounds (32 and 42) were shown to promote the differentiation of OPCs into mature oligodendrocytes in vitro constituting thus emerging leads for the development of regenerative therapies.
Ligand-Controlled Regiodivergence in Nickel-Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids**
Deng, Ruohan,Engle, Keary M.,Fu, Yue,Gao, Yang,Li, Zi-Qi,Liu, Peng,Tran, Van T.
supporting information, p. 23306 - 23312 (2020/10/19)
A nickel-catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand-free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti-Markovnikov products can be accessed with a novel 4,4-disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining step induced by the optimal ligand. DFT calculations reveal that in the anti-Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate- and regioselectivity-determining transmetalation transition state.
Directed palladium(II)-catalyzed intermolecular anti-markovnikov hydroarylation of unactivated alkenes with (hetero)arylsilanes
Lu, Ming-Zhu,Loh, Teck-Peng,Luo, Haiqing,Hu, Zhengsong,Shao, Changdong,Kan, Yuhe
, p. 9022 - 9028 (2020/12/02)
We describe herein a regioselective palladium(II)catalyzed intermolecular hydroarylation of unactivated aliphatic alkenes with electronically and sterically diverse (hetero)arylsilanes under redox-neutral conditions. A removable bidentate 8-amino-quinoline auxiliary was readily employed to dictate the regioselectivity, prevent β-hydride elimination, and facilitate protodepalladation. This silicon-based protocol features a broad substrate scope with excellent functional group compatibility and enables an expeditious route to a variety of γ-aryl butyric acid derivatives in good yields with exclusive anti-Markovnikov selectivity.
Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals
Wu, Fu-Peng,Li, Da,Peng, Jin-Bao,Wu, Xiao-Feng
supporting information, p. 5699 - 5703 (2019/08/01)
In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.
Synthesis of Novel Pterocarpen Analogues via [3?+?2] Coupling-Elimination Cascade of α,α-Dicyanoolefins with Quinone Monoimines
Chen, Hui,Zhao, Sihan,Cheng, Shaobing,Dai, Xingjie,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
, p. 1672 - 1683 (2019/04/08)
By employing triethylamine as a catalyst, [3?+?2] coupling-elimination cascade of α,α-dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.
Cooperative iodine and photoredox catalysis for direct oxidative lactonization of carboxylic acids
Duhamel, Thomas,Mu?iz, Kilian
, p. 933 - 936 (2019/01/23)
A new method for the formation of γ- and δ-lactones from carboxylic acids through direct conversion of benzylic C-H to C-O bonds is described. The reaction is conveniently induced by visible light and relies on a mild cooperative catalysis by the combination of molecular iodine and an organic dye.
Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
, p. 16490 - 16494 (2019/11/03)
Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
An Electrophilic Trifluoromethylthiolation of Silylenol Ethers and β-Naphthols with Diethylaminosulfur Trifluoride and (Trifluoromethyl)trimethylsilane
Saravanan, Perumal,Anbarasan, Pazhamalai
, p. 2894 - 2899 (2018/08/17)
An efficient and general trifluoromethylthiolation of silylenol ethers and β-naphthols have been accomplished employing the combination of diethylaminosulfur trifluoride (DAST) and (trifluoromethyl)trimethylsilane (CF3TMS) as source of electrophilic trifluoromethylthio moiety for the synthesis of α-trifluoromethylthiolated carbonyl compounds and β-naphthols in good yields. Important features of this method include wide functional group tolerance and use of readily available DAST/CF3TMS. Potential of the methodology was demonstrated via the synthesis of α-trifluoromethylthiolated (+)-4-cholesten-3-one and naphthoquinone. (Figure presented.).
Highly enantioselective [3+2] coupling of cyclic enamides with quinone monoimines promoted by a chiral phosphoric acid
Zhang, Minmin,Yu, Shuowen,Hu, Fangzhi,Liao, Yijun,Liao, Lihua,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
, p. 8757 - 8760 (2016/07/15)
Enantioselective [3+2] coupling of cyclic enamides with quinone monoimines was realised using a chiral phosphoric acid as a catalyst. This transformation allowed for the synthesis of highly enantioenriched polycyclic 2,3-dihydrobenzofurans (up to 99.9% ee). The absolute configuration of one product was determined by an X-ray crystal structural analysis. We also found a possible mechanism for this reaction.
Metal-Free Enantioselective Oxidative Arylation of Alkenes: Hypervalent-Iodine-Promoted Oxidative C?C Bond Formation
Shimogaki, Mio,Fujita, Morifumi,Sugimura, Takashi
supporting information, p. 15797 - 15801 (2016/12/16)
The enantioselective oxyarylation of (E)-6-aryl-1-silyloxylhex-3-ene was achieved using a lactate-based chiral hypervalent iodine(III) reagent in the presence of boron trifluoride diethyl etherate. The silyl ether promotes the oxidative cyclization, and enhances the enantioselectivity. In addition, the corresponding aminoarylation was achieved.
