- Stereoselective Total Synthesis of KAE609 via Direct Catalytic Asymmetric Alkynylation to Ketimine
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A direct catalytic asymmetric alkynylation protocol is applied to provide the requisite enantioenriched propargylic α-tertiary amine, allowing for the stereoselective total synthesis of KAE609 (formerly NITD609 or cipargamin).
- Takada, Hisashi,Kumagai, Naoya,Shibasaki, Masakatsu
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Read Online
- Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to N-Unprotected Ketimines: Efficient Synthesis of Cipargamin
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Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-unprotected ketimines is realized for the first time by employing chiral BIBOP-type ligands with a Rh loading as low as 1 mol %. A range of chiral α-trifluoromethyl-α,α-diaryl α-tertiary amines or 3-amino-3-aryloxindoles were formed with excellent ee values and yields by employing either WingPhos or PFBO-BIBOP as the ligand. The method has enabled an efficient enantioselective synthesis of cipargamin.
- Zhu, Jinbin,Huang, Linwei,Dong, Wei,Li, Naikai,Yu, Xingxin,Deng, Wei-Ping,Tang, Wenjun
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p. 16119 - 16123
(2019/11/03)
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- Tertiary amine compound, bisphosphine ligand, and intermediate and preparation method of tertiary amine compound
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The invention discloses a tertiary amine compound, a bisphosphine ligand, and an intermediate and a preparation method of the tertiary amine compound, and provides a tertiary amine compound preparation method, which comprises: under the protection of a ga
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- Synthesis of Chiral Tryptamines via a Regioselective Indole Alkylation
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A practical synthesis of chiral tryptamines from simple, unprotected indoles has been developed. Indole nucleophiles prepared with MeMgCl in the presence of CuCl reacted with chiral cyclic sulfamidates almost exclusively at the C3-position of i
- Wolfard, Jens,Xu, Jie,Zhang, Haiming,Chung, Cheol K.
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supporting information
p. 5431 - 5434
(2018/09/12)
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- A asymmetric catalytic synthesis volute four hydrogens[...] compounds
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The invention discloses a method for asymmetric catalytic synthesis of a spirocyclic tetrahydrocarbazoline compound, comprising the steps: by taking 3-alkenyl indole and isatin derived ketimine as raw materials, a complex formed by chiral amine oxide and nickel trifluoromethane sulfonate as a catalyst and dichloromethane as a solvent, performing reaction on the raw materials at (-30) DEG C to (-10) DEG C at the normal pressure for 96-192h; then adding 6.0M HCl(solution) and performing reaction at 30 DEG C for 4-48h to obtain the chiral spirocyclic tetrahydro carbazoline compound, wherein the yield of the chiral spirocyclic tetrahydro carbazoline compound can reach up to 95%, and the enantioselectivity can reach up to 99%. According to the method provided by the invention, the catalytic reaction conforms with the green chemistry atom economy and has a good prospect in industrial application, thereby providing a new path for asymmetric synthesis of compounds with high anti-malarial activity (NITD609).
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Paragraph 0080; 0081; 0084
(2017/03/14)
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- CHEMICAL PROCESS FOR PREPARING SPIROINDOLONES AND INTERMEDIATES THEREOF
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The present invention relates to processes and intermediates useful for the manufacture of spiroindolone compounds such as (1'R,3'S)-5,7'-dichloro-6'-fluoro-3'-methyl-2',3',4',9'-tetrahydrospiro[indoline-3,1'-pyrido[3, 4-b]indol]-2-one and salts and hydrates and solvates thereof.
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- Spirotetrahydro β-carbolines (spiroindolones): A new class of potent and orally efficacious compounds for the treatment of malaria
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The antiplasmodial activity of a series of spirotetrahydro β-carbolines is described. Racemic spiroazepineindole (1) was identified from a phenotypic screen on wild type Plasmodium falciparum with an in vitro IC50 of 90 nM. Structure-activity relationships for the optimization of 1 to compound 20a (IC50 = 0.2 nM) including the identification of the active 1R,3S enantiomer and elimination of metabolic liabilities is presented. Improvement of the pharmacokinetic profile of the series translated to exceptional oral efficacy in the P. berghei infected malaria mouse model where full cure was achieved in four of five mice with three daily doses of 30 mg/kg.
- Yeung, Bryan K. S.,Zou, Bin,Rottmann, Matthias,Lakshminarayana, Suresh B.,Ang, Shi Hua,Leong, Seh Yong,Tan, Jocelyn,Wong, Josephine,Keller-Maerki, Sonja,Fischli, Christoph,Goh, Anne,Schmitt, Esther K.,Krastel, Philipp,Francotte, Eric,Kuhen, Kelli,Plouffe, David,Henson, Kerstin,Wagner, Trixie,Winzeler, Elizabeth A.,Petersen, Frank,Brun, Reto,Dartois, Veronique,Diagana, Thierry T.,Keller, Thomas H.
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experimental part
p. 5155 - 5164
(2010/09/05)
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- ORGANIC COMPOUNDS
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The invention relates to organic compounds which have interesting pharmaceutical properties. In particular, the compounds are useful in the treatment and/or prevention of infections such as those caused by Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Trypanosoma cruzi and parasites of the Leishmania genus such as, for example, Leishmania donovani. The invention also relates to pharmaceutical compositions containing the compounds, as well as processes for their preparation.
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Page/Page column 26-27
(2009/12/02)
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