1159997-91-7Relevant academic research and scientific papers
Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity
Barrios-Rivera, Jonathan,Xu, Yingjian,Wills, Martin
supporting information, p. 6283 - 6287 (2020/09/02)
The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.
Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines
Nie, Huifang,Zhu, Yupu,Hu, Xiaomu,Wei, Zhao,Yao, Lin,Zhou, Gang,Wang, Pingan,Jiang, Ru,Zhang, Shengyong
supporting information, p. 8641 - 8645 (2019/10/17)
Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.
Design, Synthesis, and Biological Evaluation of Tetrahydroisoquinoline-Based Histone Deacetylase 8 Selective Inhibitors
Taha, Taha Y.,Aboukhatwa, Shaimaa M.,Knopp, Rachel C.,Ikegaki, Naohiko,Abdelkarim, Hazem,Neerasa, Jayaprakash,Lu, Yunlong,Neelarapu, Raghupathi,Hanigan, Thomas W.,Thatcher, Gregory R. J.,Petukhov, Pavel A.
supporting information, p. 824 - 829 (2017/08/16)
Histone deacetylase 8 (HDAC8) is a promising drug target for multiple therapeutic applications. Here, we describe the modeling, design, synthesis, and biological evaluation of a novel series of C1-substituted tetrahydroisoquinoline (TIQ)-based HDAC8 inhibitors. Minimization of entropic loss upon ligand binding and use of the unique HDAC8 "open" conformation of the binding site yielded a successful strategy for improvement of both HDAC8 potency and selectivity. The TIQ-based 3g and 3n exhibited the highest 82 and 55 nM HDAC8 potency and 330- and 135-fold selectivity over HDAC1, respectively. Selectivity over other class I isoforms was comparable or better, whereas inhibition of HDAC6, a class II HDAC isoform, was below 50% at 10 μM. The cytotoxicity of 3g and 3n was evaluated in neuroblastoma cell lines, and 3n displayed concentration-dependent cytotoxicity similar to or better than that of PCI-34051. The selectivity of 3g and 3n was confirmed in SH-SY5Y cells as both did not increase the acetylation of histone H3 and α-tubulin. Discovery of the novel TIQ chemotype paves the way for the development of HDAC8 selective inhibitors for therapeutic applications.
Method for solvent accelerated selective dehydrogenation of tetrahydroisoquinoline type compound
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Paragraph 0039; 0040; 0041; 0042; 0043, (2017/07/22)
The invention discloses a method for synthesizing 1-substituted-3,4-dihydroisoquinoline through the solvent accelerated selective partial dehydrogenation of a 1-substituted-1,2,3,4-tetrahydroisoquinoline compound. For a simple and easily obtained cyclic amine type compound such as a tetrahydroisoquinoline compound, a corresponding imine compound can be obtained through selective dehydrogenation; the conversion ratio of the cyclic amine type compound is higher; further, the proportion of a partially dehydrogenated product to a fully dehydrogenated product is more than 20 to 1. The method is simple and convenient to operate, is practical, easy and feasible, and is mild in reaction condition; the actual cost is greatly reduced. In addition, a method for synthesizing 3,4-dihydroisoquinoline through the direct dehydrogenation of tetrahydroisoquinoline has the advantages of atom economy and environmental friendliness.
One-Pot N-Deprotection and Catalytic Intramolecular Asymmetric Reductive Amination for the Synthesis of Tetrahydroisoquinolines
Zhou, Huan,Liu, Yuan,Yang, Suhua,Zhou, Le,Chang, Mingxin
, p. 2725 - 2729 (2017/02/26)
A one-pot N-Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine-bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p-toluenesulfonic acid contributed to the stereocontrol.
Enantioselective, Copper-Catalyzed Alkynylation of Ketimines to Deliver Isoquinolines with α-Diaryl Tetrasubstituted Stereocenters
Dasgupta, Srimoyee,Liu, Jixin,Shoffler, Clarissa A.,Yap, Glenn P. A.,Watson, Mary P.
supporting information, p. 6006 - 6009 (2016/12/09)
An enantioselective, copper-catalyzed alkynylation of cyclic α,α-diaryl ketiminium ions has been developed to deliver isoquinoline products with diaryl, tetrasubstituted stereocenters. The success of this reaction relied on identification of Ph-PyBox as the optimal ligand, i-Pr2NEt as the base, and CHCl3 as the solvent. A broad scope and functional group tolerance were observed. Notably, the use of both aryl and silyl acetylenes results in high yields and enantioselectivities. Mechanistic experiments are consistent with a dimeric or higher order catalyst.
Palladium carbon catalyzed selective partial dehydrogenation method of tetrahydroisoquinoline
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Paragraph 0044-0047; 0050, (2017/02/09)
The invention relates to a method for synthesis of 1-substituted-3, 4-dihydroisoquinoline by palladium carbon catalyzed selective partial dehydrogenation of a 1-substituted-1, 2, 3, 4-tetrahydroisoquinoline compound. The reaction temperature is 0-80DEG C. For easily available cyclic amine compounds like tetrahydroisoquinoline, a corresponding imine compound can be obtained through selective dehydrogenation, the conversion rate is up to 99%, and the proportion of a partial dehydrogenation product and a complete dehydrogenation product is greater than 20:1. The method provided by the invention has simple and practical operation, the raw materials and catalyst are cheap and easily available, the reaction conditions are mild, and the catalyst can be recycled, thus greatly reducing the actual cost. In addition, the method for synthesis of 3, 4-dihydroisoquinoline through direct dehydrogenation of tetrahydroisoquinoline has the advantages of atom economy and environmental friendliness.
Solvent-promoted highly selective dehydrogenation of tetrahydroisoquinolines without catalyst and hydrogen acceptor
Feng, Guang-Shou,Ji, Yue,Liu, Hui-Fang,Shi, Lei,Zhou, Yong-Gui
supporting information, p. 747 - 749 (2016/02/05)
An unusual solvent DMF-promoted dehydrogenation of 1-substituted 1,2,3,4-tetrahydroisoquinolines to synthesize cyclic imines is described. This environmentally friendly reaction features no requirement of any metal catalysts, oxidants, or hydrogen acceptors. A wide range of structurally varied 3,4-dihydroisoquinolines can be obtained with good yields and excellent chemoselectivities.
Highly selective partial dehydrogenation of tetrahydroisoquinolines using modified Pd/C
Ji, Yue,Chen, Mu-Wang,Shi, Lei,Zhou, Yong-Gui
, p. 33 - 39 (2015/09/28)
A highly selective procedure has been developed for the partial dehydrogenation of 1-substituted-1,2,3,4-tetrahydroisoquinolines over K3PO4·3H2O-modified Pd/C catalyst. This new method provides facile, atom-economical and environmentally friendly access to 1-substituted-3,4-dihydroisoquinolines without the need for stoichiometric amounts of harmful oxidants. The use of standard Pd/C as a catalyst for this process gave poor chemoselectivity. Pleasingly, the use of a K3PO4·3H2O-modified Pd/C catalyst promoted the partial dehydrogenation of 1-substituted-1,2,3,4-tetrahydroisoquinolines with excellent chemoselectivity by suppressing further dehydroaromatization. Furthermore, conducting the reaction under an atmosphere of oxygen led to further improvements in the chemoselectivity of the dehydrogenation, with the ratio of imine to isoquinoline reaching up to 32/1. The heterogenous Pd/C catalyst could also be recycled and reused at least three times with excellent conversion and chemoselectivity, demonstrating the significantly practical potential of this methodology.
New synthetic approach for the preparation of 1-Aryl-3,4-dihydroisoquinolines by liebeskind-srogl reaction
ábrányi-Balogh, Péter,Slégel, Péter,Volk, Balázs,Pongó, László,Milen, Mátyás
, p. 2574 - 2578 (2015/01/09)
An efficient synthetic methodology has been developed to construct 1-aryl-3,4-dihydroisoquinoline derivatives. The reaction was performed under neutral conditions by a palladium-catalyzed desulfitative carbon-carbon cross-coupling protocol.
