60676-77-9Relevant academic research and scientific papers
Design and synthesis of β-carboline and combretastatin derivatives as anti-neutrophilic inflammatory agents
Kumar, Sunil,Wang, Yi-Hsuan,Chen, Po-Jen,Chang, Yu-Chia,Kashyap, Hemant K.,Shen, Ya-Ching,Yu, Huang-Ping,Hwang, Tsong-Long
, (2021/04/09)
A series of β-carboline derivatives was synthesized by the Pictet-Spengler reaction with or without the combretastatin skeleton. The structures of these derivatives were elucidated by spectroscopic techniques. All synthesized compounds were evaluated for
Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines
Cozzi, Nicholas V.,Daley, Paul F.
, p. 959 - 964 (2016/05/24)
N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20 mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted-DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1Aand 5-HT2Breceptors, while the affinity of DALT itself at 5-HT1Areceptors was slightly lower at 100 nM. Among the 5-HT2subtypes, the weakest affinity was at 5-HT2Areceptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5Asubtypes and little or no affinity for the 5-HT3subtype. These compounds also had generally nanomolar affinities for adrenergic α2A, α2B, and α2Creceptors, sigma receptors σ1and σ2, histamine H1receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several nonserotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated correlations among physicochemical properties of the congeneric 5-substituted-DALT compounds. The descriptors included electronic (σp), hydrophobic (π), and steric (CMR) parameters. The binding affinity at 5-HT1A, 5-HT1D, 5-HT7, and κ opioid receptors was positively correlated with the steric volume parameter CMR. At α2A, α2B, and α2Creceptors, and at the histamine H1receptor, binding affinity was correlated with the Hammett substituent parameter σp; higher affinity was associated with larger σpvalues. At the σ2receptor, higher affinity was correlated with increasing π. These correlations should aid in the development of more potent and selective drugs within this family of compounds.
Synthesis of tetrahydro-β-carbolines via isomerization of N-allyltryptamines: A metal-catalyzed variation on the Pictet-Spengler theme
Ascic, Erhad,Hansen, Casper L.,Le Quement, Sebastian T.,Nielsen, Thomas E.
supporting information; experimental part, p. 3345 - 3347 (2012/05/04)
An efficient and broadly applicable alternative to the classical Pictet-Spengler synthesis of tetrahydro-β-carbolines is presented. The method relies on metal-catalyzed isomerization of allylic amines to form reactive iminium intermediates which can be trapped by a tethered indole nucleophile. The Royal Society of Chemistry 2012.
General strategy for the syntheses of corynanthe, tacaman, and oxindole alkaloids
Deiters, Alexander,Pettersson, Martin,Martin, Stephen F.
, p. 6547 - 6561 (2007/10/03)
We report herein the total synthesis of the corynanthe alkaloid dihydrocorynantheol and the formal syntheses of the indole alkaloids tacamonine, rhynchophylline, and hirsutine. The strategies for assembling the corynanthe and tacaman skeletal frameworks comprised of both the classical ABD → ABCD and ABC → ABCD approaches wherein the variously substituted piperidinone D-rings were formed via ring-closing metathesis (RCM) followed by a 1,4-addition to introduce the requisite side chain at C(15). Since 1,4-additions to α,β-unsaturated lactams represent an underdeveloped field, we conducted a series of studies with two unsaturated lactams employing organocuprates and metal enolates as the nucleophiles. These studies revealed that organocuprates derived from Grignard reagents and either stoichiometric amounts of CuCN or catalytic amounts of CuBr·DMS complex are excellent nucleophiles for such additions; TMSC1 was a crucial additive for optimizing these reactions. The anion derived from ethyl 1,3-dithiolane-2-carboxylate was also an excellent nucleophile in these 1,4-additions, although the stereochemistry of such 1,4-additions to carboline-derived, unsaturated lactams was sensitive to substitution on the indole nitrogen atom. The ABD → ABCD approach to these alkaloids featured a novel one-pot sequence of an RCM reaction and a zirconocene-catalyzed carbomagnesation followed by a second RCM to generate the D-ring.
