59609-63-1Relevant academic research and scientific papers
Catalyst-Controlled Regiodivergence in Rearrangements of Indole-Based Onium Ylides
Nair, Vaishnavi N.,Kojasoy, Volga,Laconsay, Croix J.,Kong, Wang Yeuk,Tantillo, Dean J.,Tambar, Uttam K.
supporting information, p. 9016 - 9025 (2021/06/30)
We have developed catalyst-controlled regiodivergent rearrangements of onium-ylides derived from indole substrates. Oxonium ylides formed in situ from substituted indoles selectively undergo [2,3]- and [1,2]-rearrangements in the presence of a rhodium and a copper catalyst, respectively. The combined experimental and density functional theory (DFT) computational studies indicate divergent mechanistic pathways involving a metal-free ylide in the rhodium catalyzed reaction favoring [2,3]-rearrangement, and a metal-coordinated ion-pair in the copper catalyzed [1,2]-rearrangement that recombines in the solvent-cage. The application of our methodology was demonstrated in the first total synthesis of the indole alkaloid (±)-sorazolon B, which enabled the stereochemical reassignment of the natural product. Further functional group transformations of the rearrangement products to generate valuable synthetic intermediates were also demonstrated.
Synthesis and Preclinical Evaluation of 6-[18F]Fluorine-α-methyl- l -tryptophan, a Novel PET Tracer for Measuring Tryptophan Uptake
Krasikova, Raisa,Kondrashov, Mikhail,Avagliano, Camilla,Petukhov, Mikhail,Vazquez-Romero, Ana,Revunov, Evgeny,Johnstr?m, Peter,Tari, Lenke,Tóth, Miklós,H?ggkvist, Jenny,Erhardt, Sophie,Cervenka, Simon,Schou, Magnus
, p. 1756 - 1761 (2020/07/04)
The positron emission tomography (PET) radioligand α-[11C]methyl-l-tryptophan ([11C]AMT) has been used to assess tryptophan metabolism in cancer, epilepsy, migraine, and autism. Despite its extensive application, the utility of this tracer is currently hampered by the short half-life of the radionuclide used for its labeling (11C, t1/2 = 20.4 min). We herein report the design, synthesis, radiolabeling, and initial in vivo evaluation of a fluorine-18 (18F, t1/2 = 109.7 min) labeled analogue that is fluorinated in the 6-position of the aromatic ring ([18F]6-F-AMTr). In a head-to-head comparison between [18F]6-F-AMTr and [11C]AMT in mice using PET, peak brain radioactivity, regional brain distribution, and kinetic profiles were similar between the two tracers. [18F]6-F-AMTr was however not a substrate for IDO1 or TPH as determined in in vitro enzymatic assays. The brain uptake of the tracer is thus more likely related to LAT1 transport over the blood-brain barrier than metabolism along the serotonin or kynurenine pathways.
Natural Products for Drug Discovery: Discovery of Gramines as Novel Agents against a Plant Virus
Lu, Aidang,Wang, Tienan,Hui, Hao,Wei, Xiaoye,Cui, Weihao,Zhou, Chunlv,Li, Hongyan,Wang, Ziwen,Guo, Jincheng,Ma, Dejun,Wang, Qingmin
, p. 2148 - 2156 (2019/03/08)
Plant viral diseases seriously affect crop yield and quality. The natural product gramine (1) and its simple structural analogues 2-35 were synthesized from indoles, amines, and aldehydes in one step. The antiviral effects of these alkaloids were evaluated systematically. Most of these compounds were found to have higher antiviral effects than commercial ribavirin for the first time. Especially compounds 22, 30, and 31 exhibited significantly higher effects than ningnanmycin, thereby emerging as novel antiviral leads for further optimization. The preliminary implementation indicated that these compounds likely inhibit the assembly of tobacco mosaic virus (TMV) by cross-linking TMV capsid protein. Gramine analogues were also found to have broad-spectrum fungicidal effects. Although gramine has been reported to have influence on germination and development of Erysiphe graminis, these compounds displayed no fungicidal effects against Blumeria graminis f. sp. tritici on wheat in our test. Some of these compounds also exhibited certain insecticidal activities.
New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity
Soto, Sara,Vaz, Esther,Dell'Aversana, Carmela,Alvarez, Rosana,Altucci, Lucia,De Lera, Angel R.
supporting information; experimental part, p. 2101 - 2112 (2012/04/23)
A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF3, CO2Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.
Total synthesis of (±)-chartelline C
Baran, Phil S.,Shenvi, Ryan A.
, p. 14028 - 14029 (2007/10/03)
The first total synthesis of (±)-chartelline C in a concise 10-step sequence is reported. Highlights of the completion of this decades-old puzzle include (1) chemo- and position-selective installation of the heteroaromatic halogens, (2) halogen-sparing mo
Bromoderivatives of gramines. Preparation and pharmacological properties
Franzone, Jose Sebastian,Cirillo, Rocco,Cravanzola, Carlo
, p. 261 - 268 (2007/10/02)
Bromination of gramine (I), 1-methylgramine (IX), 2-methylgramine (IV) and 1,2-dimethylgramine (XV) with different mole ratios of bromine to substrate was investigated; it was seen that the 5- and 6-position are the normal sites of bromination and 1-methylgramines (IX) and (XV) give better yields of bromoderivatives.Among the compounds submitted the pharmacological screening, 2,6-dibromo-1-methylgramine hydrobromide (Xa) and especially 6-bromo-2-methylgramine (V) showed a clear antiserotoninic antiinflammatory and analgesic activity.Furthermore gramine (V) showed a good anti prostaglandin synthetase activity in vitro.Key-words: Bromogramines. - Antiserotonic activity. - Antiinflammatory activity.
