- Catalytic Enantioselective Synthesis of Spirooxindoles by Oxidative Rearrangement of Indoles
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Oxidative rearrangement of indoles to access oxindoles has been used as a key step in complex molecule synthesis. We report a catalytic enantioselective variant of this transformation by chiral phosphoric acid catalysis, providing rapid access to a range of enantioenriched spirooxindoles. The high enantioselectivity is controlled by dynamic kinetic resolution.
- Qian, Chenxiao,Li, Pengfei,Sun, Jianwei
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supporting information
p. 5871 - 5875
(2021/02/06)
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- TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: Facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline
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Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.
- Sathish, Manda,Sakla, Akash P.,Nachtigall, Fabiane M.,Santos, Leonardo S.,Shankaraiah, Nagula
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p. 16537 - 16546
(2021/05/19)
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- Aromatic heterocyclic derivative and application thereof in medicine
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The invention provides aromatic heterocyclic derivatives or stereoisomers, tautomers, nitrogen oxides, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, which are used for treating Alzheimer's disease. The invention also discloses pharmaceutical compositions containing the compounds and a method for treating Alzheimer's disease by using the compounds or the pharmaceutical compositions provided by the invention.
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Paragraph 0517; 0519-0520
(2020/02/08)
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- Bifunctional thiosquaramide catalyzed asymmetric reduction of dihydro-β-carbolines and enantioselective synthesis of (-)-coerulescine and (-)-horsfiline by oxidative rearrangement
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Tetrahydro-β-carboline (THBC) is a tricyclic ring system that can be found in a large number of bioactive alkaloids. Herein, we report a simple and efficient method for the synthesis of enantiopure THBCs through a chiral thiosquaramide (11b) catalyzed imine reduction of dihydro-β-carbolines (17a-f). The in situ generated Pd-H employed as hydride source in the reaction of differently substituted chiral THBCs (18a-f) afforded high selectivities (R isomers, up to 96% ee) and good isolated yields (up to 88%). Moreover, the chiral thiosquaramide used also afforded exceptional catalyst activity in the syntheses of (-)-coerulescine (5) and (-)-horsfiline (6) with excellent enantioselectivities up to 98% and 93% ee, respectively, via an enantioselective oxidative rearrangement approach.
- Nachtigall, Fabiane M.,Santos, Leonardo S.,Sathish, Manda
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p. 38672 - 38677
(2020/11/05)
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- Aryl substituted aminotetrahydropyran compound and use thereof
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The invention relates to an aryl substituted aminotetrahydropyran compound and use thereof, and further relates to a pharmaceutical composition comprising the compound. The compound or pharmaceuticalcomposition provided by the invention can be used as a dipeptidyl peptidase-IV (DPP-IV) inhibitor.
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Paragraph 0355; 0359; 0360
(2019/07/04)
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- Light-Driven Intramolecular C?N Cross-Coupling via a Long-Lived Photoactive Photoisomer Complex
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Reported herein is a visible-light-driven intramolecular C?N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.
- Jing, Dong,Lu, Cong,Chen, Zhuo,Jin, Songyang,Xie, Lijuan,Meng, Ziyi,Su, Zhishan,Zheng, Ke
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supporting information
p. 14666 - 14672
(2019/09/06)
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- TETRAHYDROBENZOFURO[2,3-C]PYRIDINE AND BETA-CARBOLINE COMPOUNDS FOR THE TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH TAU AGGREGATES
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The present invention relates to novel compounds of formula (I) that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).
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Page/Page column 46
(2019/12/28)
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- Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors
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Based on perlolyrine (1), a natural alkaloid with weak PDE5 potency from the traditional Chinese aphrodisiac plant Tribulus terrestris L., a series α-substituted tetrahydro-β-carboline (THβC) derivatives were synthesized via T+BF4--mediated oxidative C–H functionalization of N-aryl THβCs with diverse potassium trifluoroborates. Following Winterfeldt oxidation afforded the corresponding furyl/thienyl pyrroloquinolones, of which 5-ethylthiophene/ethylfuran derivatives 20a–b were identified as the most potent and selective PDE5 inhibitors. Among the enantiomers, (S)-20a and (S)-20b (IC50 = 0.52 and 0.39 nM) were found to be more effective than their (R)-antipode, display favorable pharmacokinetic profiles, exert in vitro vasorelaxant effects on the isolated thoracic aorta, and exhibit in vivo efficacy in the anesthetized rabbit erectile model.
- Zheng, Hongbo,Li, Lin,Sun, Bin,Gao, Yun,Song, Wei,Zhao, Xiaoyu,Gao, Yanhui,Xie, Zhiyu,Zhang, Nianzhao,Ji, Jianbo,Yuan, Huiqing,Lou, Hongxiang
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supporting information
p. 30 - 38
(2018/03/08)
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- Dehydrogenation of N-Heterocycles by Superoxide Ion Generated through Single-Electron Transfer
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Nitrogen-containing heteroarene motifs are found in numerous pharmaceuticals, natural products, and synthetic materials. Although several elegant methods for synthesis of these compounds through dehydrogenation of the corresponding saturated heterocycles have been reported, some of the methods are hampered by long reaction times, harsh conditions, and the need for catalysts that are not readily available. This work reports a novel method for dehydrogenation of N-heterocycles. Specifically, O2.? generated in situ acts as the oxidant for N-heterocycle substrates that are susceptible to oxidation through a hydrogen atom transfer mechanism. This method provides a general, green route to N-heteroarenes.
- Huang, Yuan-Qiong,Song, Hong-Jian,Liu, Yu-Xiu,Wang, Qing-Min
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supporting information
p. 2065 - 2069
(2018/01/27)
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- Oxidative Rearrangement Coupling Reaction for the Functionalization of Tetrahydro-β-carbolines with Aromatic Amines
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The observation of an unexpected oxidative rearrangement coupling reaction led to the development of a novel method for the efficient functionalization of tetrahydro-β-carbolines (THβCs). The treatment of THβCs with photogenerated singlet oxygen (1O2) afforded unstable dioxetanes, which underwent further transformation to form new bonds in the presence of trifluoroacetic acid. This operationally simple protocol exhibits broad functional-group tolerance and is suitable for the late-stage functionalization of complex druglike molecules.
- Ye, Jinxiang,Wu, Jianlei,Lv, Tingting,Wu, Guolin,Gao, Yu,Chen, Haijun
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supporting information
p. 14968 - 14972
(2017/11/20)
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- 6-Hydroxy- and 6-methoxy-β-carbolines as acetyl- and butyrylcholinesterase inhibitors
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In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on β-carbolines (BCs). 6-Oxygenated β-carboline and β-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine.
- Schott, Yvonne,Decker, Michael,Rommelspacher, Hans,Lehmann, Jochen
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p. 5840 - 5843
(2007/10/03)
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- Binding of β-carbolines at 5-HT2 serotonin receptors
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A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4-tetrahydro-β-carbolines was examined at 5-HT2A and 5-HT2C serotonin receptors. Whereas most of the methoxy-substituted derivatives typically displayed affinities similar to their unsubstituted parents, certain (particularly 8-substituted) bromo derivatives displayed enhanced affinity. A binding profile was obtained for selected β-carbolines.
- Grella, Brian,Teitler, Milt,Smith, Carol,Herrick-Davis, Katharine,Glennon
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p. 4421 - 4425
(2007/10/03)
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- Potassium superoxide as an alternative reagent for Winterfeldt oxidation of beta-carbolines.
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Potassium superoxide was examined as an alternative oxidation reagent for the Winterfeldt reaction. KO(2) was found to be superior to the original Winterfeldt protocol for base-sensitive substrates. [reaction--see text]
- Jiang, Weiqin,Zhang, Xuqing,Sui, Zhihua
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- Use of derivatives of tetrahydro-beta-carbolines as antimetastatic agents
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PCT No. PCT/EP97/01582 Sec. 371 Date Nov. 12, 1998 Sec. 102(e) Date Nov. 12, 1998 PCT Filed Mar. 27, 1997 PCT Pub. No. WO97/37658 PCT Pub. Date Oct. 16, 1997The present invention concerns the use of beta-carboline derivatives of formula I bearing at least a free or esterified carboxylic group on the piperidine ring, for the preparation of pharmaceutical compositions having antimetastatic properties.
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- Synthesis of the oxindole alkaloid (-)-Horsfiline
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A synthesis of (-)-horsfiline ((-)-1), a metabolite isolated recently from Horsfieldia syperba, is described. The diastereoface selectivity of the crucial oxidative rearrangement of chiral tetrahydro-β-carboline precursors into the corresponding oxindoles was investigated in some detail and found to depend critically on the substitution pattern of the aliphatic amino group. These findings were exploited for the preparation of(-)-1, as well as of the unnatural optical antipode (+)-1, starting from 5-hydroxy-L-tryptophan as the single source from the chiral pool.
- Pellegrini,Strassler,Weber,Borschberg
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p. 1979 - 1992
(2007/10/02)
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- Method of suppressing appetite by administration of tetrahydro-beta-carboline derivatives
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Compounds of formula I are useful for suppressing appetite, and for altering macronutrient preferences, STR1 where the R2 -R9 substituents are so selected as to meet a defined quantitative structure activity relationship (QSAR) quantity relating to the partition coefficient of the compound, the net charge on the ring nitrogen, and the radical superfdelocalizability at the position-8 ring carbon.
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- Electron Impact and Chemical Ionization Fragmentation of 5-Methoxytryptamine and Some 6-Methoxy-β-carbolines
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Electron impact (EI) and chemical ionization (CI) mass spectra of 5-methoxytryptamine (5-MT) and seven 6-methoxy-β-carbolines have been recorded and interpreted.Proposed fragmentation pathways are depicted on the basis of spectra of deuterium labelled analogs of 5-MT, 6-methoxy-1,2,3,4-tetrahydro-β-carboline (6-MeO-THBC) and 6-Methoxy-1-methyl-1,2,3,4-tetrahydro-β-carboline (6-MeO-1-Me-THBC).In the EI mass spectrum of 5-MT, the base peak m/z 160 is formed by the expulsion of CH4N.The positive ion so formed is suggested to have a quinolinium structure.In chemical ionization with CH4 as the reaction gas, the most abundant ion is produced by cleavage of NH3.The ion m/z 173 yields the base peak in the EI mass spectrum of 6-MeO-THBC.This ion is formed by a retro Diels-Alder reaction, an important fragmentation pathway of 6-MeO-1-Me-THBC, too. 6-MeO-harmalan easily loses one hydrogen atom in EI fragmentation followed by methyl loss from the methoxy group, this latter process yielding the base peak, m/z 197 in the EI mass spectrum of 6-MeO-harman.M+1 is the base peak in the CI mass spectra of all 6-MeO-β-carbolines.
- Gynther, Jukka,Peura, Pekka,Salmi, Seija
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p. 849 - 860
(2007/10/02)
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