3790-45-2Relevant academic research and scientific papers
Metal-Free Access to (Spirocyclic)Tetrahydro-β-carbolines in Water Using an Ion-Pair as a Superacidic Precatalyst
Zhang, Zhenguo,Liu, Xiaoxiao,Ji, Liang,Zhang, Ting,Jia, Zhenhua,Loh, Teck-Peng
, p. 2052 - 2057 (2022/02/10)
The unprecedented triarylcarbonium ion-pair-catalyzed Pictet-Spengler reaction of tryptamines with aromatic aldehydes and cyclic ketones in water was disclosed. Under metal-free conditions, diverse tetrahydro-β-carbolines and spirocyclic tetrahydro-β-carb
Structural simplification of evodiamine: Discovery of novel tetrahydro-β-carboline derivatives as potent antitumor agents
Ma, Zonglin,Huang, Yahui,Wan, Kun,Zhu, Fugui,Sheng, Chunquan,Chen, Shuqiang,Liu, Dan,Dong, Guoqiang
supporting information, (2021/04/02)
Natural products (NPs) have played a crucial role in the discovery and development of antitumor drugs. However, the high structural complexity of NPs generally results in unfavorable physicochemical profiles and poor drug-likeness. A powerful strategy to tackle this obstacle is the structural simplification of NPs by truncating nonessential structures. Herein, a series of tetrahydro-β-carboline derivatives were designed by elimination of the D ring of NP evodiamine. Structure-activity relationship studies led to the discovery of compound 45, which displayed highly potent antitumor activity against all the tested cancer cell lines and excellent in vivo antitumor activity in the HCT116 xenograft model with low toxicity. Further mechanistic research indicated that compound 45 acted by dual Top1/2 inhibition and induced caspase-dependent cell apoptosis coupled with G2/M cell cycle arrest. This proof-of-concept study validated the effectiveness of structural simplification in NP-based drug development, discovered compound 45 as a potent antitumor lead compound and enriched the structure–activity relationships of evodiamine.
Selectivity-tunable oxidation of tetrahydro-β-carboline over an OMS-2 composite catalyst: preparation and catalytic performance
Bi, Xiuru,Tao, Luyao,Yao, Nan,Gou, Mingxia,Chen, Gexin,Meng, Xu,Zhao, Peiqing
supporting information, p. 3682 - 3692 (2021/03/22)
Controlling the reaction selectivity of organic transformations without losing high conversion is always a challenge in catalytic processes. In this work, a H3PO4·12WO3/OMS-2 nanocomposite catalyst ([PW]-OMS-2) was prepared through the oxidation of a Mn(ii) salt with sodium phosphotungstate by KMnO4. Comprehensive characterization indicates that different Mn2+precursors significantly affected the crystalline phase and morphology of the as-synthesized catalysts and only MnSO4·H2O as the precursor could lead to a cryptomelane phase. Moreover, [PW]-OMS-2 demonstrated excellent catalytic activity toward aerobic oxidative dehydrogenation of tetrahydro-β-carbolines due to mixed crystalline phases, enhanced surface areas, rich surface oxygen vacancies and labile lattice oxygen species. In particular, β-carbolines and 3,4-dihydro-β-carbolines could be obtained from tetrahydro-β-carbolines with very high selectivity (up to 99%) over [PW]-OMS-2viatuning the reaction solvent and temperature. Under the present catalytic system, scalable synthesis of a β-carboline was achieved and the composite catalyst showed good stability and recyclability. This work not only clarified the structure-activity relationship of the catalyst, but also provided a practical pathway to achieve flexible, controllable synthesis of functional N-heterocycles.
TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: Facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline
Sathish, Manda,Sakla, Akash P.,Nachtigall, Fabiane M.,Santos, Leonardo S.,Shankaraiah, Nagula
, p. 16537 - 16546 (2021/05/19)
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.
Synthesis of crystalline tetrahydro-beta-carboline
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Paragraph 0085-0089, (2021/03/23)
The present invention relates to a method for preparing a tetrahydro-beta-carboline compound, which comprises a step of preparing a tetrahydro-beta-caboline compound by reacting a tryptamine compound and an aldehyde in an aqueous solution using a reaction accelerator containing a divalent acid. Accordingly, the method for preparing a tetrahydro-beta-carboline compound according to the present invention is an eco-friendly synthetic method that does not use an explosive organic solvent, but uses water as a solvent and tartaric acid which is a natural product as a reaction accelerator, thereby causing no environmental pollution; and requiring no separation process in addition to a simple filtering process since final products are crystals. Therefore, the method for preparing a tetrahydro-beta-carboline compound can be carried out in an industrially very simple and suitable process.
Ruthenium Catalyzed Tandem Pictet-Spengler Reaction
Cherepakhin, Valeriy,Nalikezhathu, Anju,Williams, Travis J.
supporting information, (2020/07/15)
We report a pyridyl-phosphine ruthenium(II) catalyzed tandem alcohol amination/Pictet-Spengler reaction sequence to synthesize tetrahydro-β-carbolines from an alcohol and tryptamine. Our conditions use a Lewis acid cocatalyst, In(OTf)3, that is compatible with typically base catalyzed amination and an acid catalyzed Pictet-Spengler cyclization. This method proceeds well with benzylic alcohols, heterocyclic carbinols, and aliphatic alcohols. We also show how combining this reaction with a subsequent cycloamination enables a direct synthesis of tetracyclic alkaloids like harmicine.
Selective construction of alkaloid scaffolds by alcohol-based direct and mild aerobic oxidative Pictet-Spengler reactions
Han, Feng,Li, Huan,Liu, Haicheng,Liu, Jianping,Xu, Qing
, p. 7079 - 7085 (2020/10/02)
Employing TBN/TEMPO as the catalysts and oxygen as the oxidant, the biologically and pharmaceutically significant tetrahydro-β-carboline and β-carboline alkaloid scaffolds that used to be obtained by multi-step processes can now be selectively obtained in only one-stepviadirect aerobic oxidative Pictet-Spengler reactions of tryptamines with alcohols under mild conditions, with water generated as the byproduct. In this reaction, TBN/TEMPO was interestingly found to be able to facilitate the cyclization step of the whole reaction. This method tolerates a variety ofC- andN-substituted tryptamines, and both the more reactive benzylic and allylic alcohols and the less reactive aliphatic alcohols. This method can also be extended to dihydro-β-carboline synthesis and applied to the more available and more economical tryptophan for β-carboline synthesis, revealing its broad substrate scope and potential in synthetic applications.
Discovery of 3,3′-pyrrolidinyl-spirooxindoles as cardioprotectant prohibitin ligands
Elderwish, Sabria,Audebrand, Ana?s,Nebigil, Canan G.,Désaubry, Laurent
supporting information, (2019/11/26)
The scaffold proteins prohibitins-1 and 2 (PHB1/2) play many important roles in coordinating many cell signaling pathways and represent emerging targets in cardiology and oncology. We previously reported that a family of natural products derivatives, flavaglines, binds to PHB1/2 to exert cardioprotectant and anti-cancer effects. However, flavaglines also target the initiation factor of translation eIF4A, which doesn't contribute to cardioprotection and may even induce some adverse effects. Herein, we report the development of a convenient and robust synthesis of the new PHB2 ligand 2′-phenylpyrrolidinyl-spirooxindole, and its analogues. We discovered that these compounds displays cardioprotective effect against doxorubicin mediated cardiotoxicity and uncovered the structural requirement for this activity. We identified in particular some analogues that are more cardioprotectant than flavaglines. Pull-down experiments demonstrated that these compounds bind not only to PHB2 but also PHB1. These novel PHB ligands may provide the basis for the development of new drugs candidates to protect the heart against the adverse effects of anticancer treatments.
Asymmetric Biocatalytic Synthesis of 1-Aryltetrahydro-β-carbolines Enabled by “Substrate Walking”
Eger, Elisabeth,Iding, Hans,Kroutil, Wolfgang,Kuhn, Bernd,Schrittwieser, Joerg H.,Wetzl, Dennis
, p. 16281 - 16285 (2020/11/30)
Stereoselective catalysts for the Pictet–Spengler reaction of tryptamines and aldehydes may allow a simple and fast approach to chiral 1-substituted tetrahydro-β-carbolines. Although biocatalysts have previously been employed for the Pictet–Spengler react
Organic light-emitting compound, preparation and application thereof and light-emitting device containing organic light-emitting compound
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Paragraph 0113; 0115; 0116; 0117, (2019/04/26)
The invention discloses an organic light-emitting compound. The organic light-emitting compound has a structural formula represented in a following figure. The organic light-emitting compound has chemical stability, and a material containing the organic light-emitting compound has high glass transition temperature and high decomposition temperature, and is an OLED material with excellent performance. The synthetic route of the material has simple and easy operation and high reaction yield, the preparation cost of the OLED material can be reduced, and therefore the material has a good industrialization prospect. The OLED material can be used as a dopant of a light-emitting layer in an organic light-emitting device, effects of high brightness, high efficiency and low voltage can be achievedthrough an organic light-emitting diode prepared by using the OLED material, and screen dark spots can be avoided effectively; and superior performance is achieved.
