3574-01-4Relevant academic research and scientific papers
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
supporting information, 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
Microwave-Assisted Synthesis of Tetrahydro-β-carbolines and β-Carbolines
Eagon, Scott,Anderson, Marc O.
, p. 1653 - 1665 (2015/10/05)
A microwave-mediated Pictet-Spengler procedure utilizing 1,2-dichloroethane (DCE) and trifluoroacetic acid (TFA) was developed to provide tetrahydro-β-carboline salts in high yields. Reactions are complete in 20 minutes or less and the product precipitates from solution in high yields and purity, negating the need for liquid-liquid extraction or column chromatography. This method tolerates a wide range of functionality and can be performed on milligram to gram scales. A subsequent microwave-mediated aromatization of the synthesized tetrahydro-β-carbolines to β-carbolines was also developed utilizing catalytic Pd/C. The aromatization is complete in 60 min or less with most substrates requiring minimal purification. A microwave-assisted Pictet-Spengler procedure was developed to afford tetrahydro-β-carboline salts in high yields with no liquid-liquid extraction or chromatography required. A subsequent microwave-assisted aromatization procedure was also developed to provide β-carbolines in high yields requiring limited purification.
Monoamine oxidase (MAO-N) catalyzed deracemization of tetrahydro-β- carbolines: Substrate dependent switch in enantioselectivity
Ghislieri, Diego,Houghton, Deborah,Green, Anthony P.,Willies, Simon C.,Turner, Nicholas J.
, p. 2869 - 2872 (2014/01/06)
The tetrahydro-β-carboline (THBC) ring system is an important structural motif found in a large number of bioactive alkaloid natural products. Herein we report a broadly applicable method for the synthesis of enantiomerically pure β-carbolines via a deracemization procedure employing the D9 and D11 variants of monoamine oxidase from Aspergillus niger (MAO-N) in combination with a nonselective chemical reducing agent. Biotransformations were performed on a preparative scale, leading to the synthesis of optically enriched products in excellent enantiomeric excess (e.e.; up to 99%) and isolated yield (up to 93%). Interestingly, a switch in enantioselectivity associated with the MAO-N variants is observed as the nature of the C-1 substituent of the THBC is varied. Molecular modeling provided an explanation for this observation and highlighted key active site residues which were modified, resulting in an increase in (R)-selectivity associated with the enzyme. These results provide insight into the factors which influence the selectivity of the MAO-N variants, and may offer a platform for future directed evolution projects aimed toward the challenge of engineering (R)-selective amine oxidase biocatalysts.
Application of chlorotrimethylsilane in Pictet-Spengler reaction
Ryabukhin, Sergey V.,Panov, Dmitriy M.,Plaskon, Andrey S.,Tolmachev, Andrey A.,Smaliy, Radomyr V.
, p. 1507 - 1517 (2013/02/21)
Chlorotrimethylsilane has been found to be an efficient condensing agent in the Pictet-Spengler reaction, affording an extremely straightforward synthetic route to tetrahydro-β-carboline derivatives and their analogs. The applicability of the method has b
Microwave-assisted one-pot preparation of tetrahydro-β-carboline hydrochlorides under solvent-free conditions
Liu, Fei,You, Qi-Dong
, p. 3933 - 3938 (2008/03/13)
An efficient and environmentally friendly synthesis of tetrahydro-β- carboline hydrochlorides via Pictet-Spengler reaction was described. Tryptamine hydrochlorides were used as the reactant and no additional acid catalyst was needed. This reaction was com
Synthesis of 1-aryl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indoles (1,2,3,4-tetrahydro-β-carbolines) under high pressures
Agafonov,Dudin,Preobrazhenskii,Zhulin
, p. 560 - 562 (2007/10/03)
The reactions of aromatic aldehydes with tryptamine (1) in solvents of different polarity were studied. The yields of carbolines in the chosen media decrease with an increase in the donating properties of the aryl substituent, but they markedly increase a
Carboxyl-Mediated Pictet-Spengler Reaction. Direct Synthesis of 1,2,3,4-Tetrahydro-β-carbolines from Tryptamine-2-carboxylic Acids
Narayanan, Krishnaswamy,Schindler, Liesl,Cook, James M.
, p. 359 - 365 (2007/10/02)
The Pictet-Spengler condensation of various tryptamine-2-carboxylic acids 9a-f with carbonyl compounds in benzene/dioxane/trifluoroacetic acid (Table I) with simultaneous loss of carbon dioxide afforded directly the corresponding 1,2,3,4-tetrahydro-β-carb
1-METHYL-, 1-PHENYL, AND 1-(2-(2-DIMETHYLAMINOETHOXY)PHENYL)-2,3,4,9-TETRAHYDRO-1H-PYRIDOINDOLE AND THEIR 2-SUBSTITUTED DERIVATIVES: SYNTHESIS AND PHARMACOLOGICAL SCREENING
Hulinska, Hana,Taufmann, Petr,Frycova, Hana,Protiva, Miroslav
, p. 373 - 380 (2007/10/02)
1-Methyl- and 1-phenyl-2,3,4,9-tetrahydro-1H-pyridoindole (I and IV) were transformed via the chloroacetyl derivatives II and V to the 4-methylpiperazinoacetyl compounds III and VI; compound VI inhibits effectively the formation of the indomethacin-induced gastric ulcers in rats but is devoid of anticholinergic activity and does not inhibit the gastric secretion in rats.Reaction of tryptamine with 2-(2-dimethylaminoethoxy)benzaldehyde afforded compound IX which proved inactive in tests for antidepressant activity.Compounds IV and IX were treated with ethyl chloroformate and gave carbamates VII and X; compound VII does not show anticonvulsant activity.
