4299-70-1Relevant articles and documents
A novel lead of P-selectin inhibitor: Discovery, synthesis, bioassays and action mechanism
Wu, Jianhui,Zhao, Ming,Wang, Yuji,Wang, Yaonan,Zhu, Haimei,Zhao, Shurui,Peng, Shiqi
, p. 4631 - 4636 (2016)
By docking 126 derivatives of β-carboline-3-carboxylic acid, tetrahydro-β-carboline-3-carboxylic acid and indoloquinolizine into the active pocket of P-selectin (2-(3-(hydroxymethyl)-9H-pyrido[3,4-b]indol-1-yl)ethyl)-L-phenylalanine (HMCEF) was assigned a novel inhibitor. ELISA and flow cytometry experiments showed that HMCEF effectively down-regulated P-selectin expression and supported the rationality of the computer assistant screening, while UV spectrum experiments demonstrated that HMCEF directly bound to P-selectin. In vivo HMCEF dose dependently inhibited the rats and mice to form thrombus and had a minimal effective dose of 20?nmol/kg, dose dependently inhibited inflammatory response of mice and had a minimal effective dose of 20?nmol/kg. The decrease of serum TNFα and IL-8 of the treated mice was proposed to be the action mechanism of HMCEF inhibiting thrombosis and inflammation. All data imply that HMCEF is a novel lead of P-selectin inhibitor.
Stereoselective Synthesis of Functionalized Tetrahydro-β-Carbolines via Pictet-Spengler Reaction
Vavsari, Vaezeh Fathi,Dianati, Vahid,Ramezanpour, Sorour,Balalaie, Saeed
, p. 1955 - 1960 (2015)
A TFA-catalyzed Pictet-Spengler reaction of synthesized tryptophan propargyl ester with aromatic and heteroaromatic aldehydes resulted in cis-tetrahydro-β-carbolines with remarkably high stereocontrol under kinetically controlled conditions. In another approach, a diastereomeric mixture of tetrahydro-β-carboline hydrazides was synthesized. The tetrahydro-β-carboline hydrazides were prepared through the reaction of tryptophan hydrazide with carbonyl compounds via Pictet-Spengler reaction.
Efficient photosensitized splitting of thymine dimer by a covalently linked tryptophan in solvents of high polarity
Song, Qin-Hua,Tang, Wen-Jian,Hei, Xiao-Ming,Wang, Hong-Bo,Guo, Qing-Xiang,Yu, Shu-Qin
, p. 1097 - 1106 (2005)
Tryptophan-thymine dimer model compounds used to mimic the repair reaction of DNA photolyase have been synthesized. The photosensitized cleavage of the dimer by the covalently linked tryptophan is strongly solvent-dependent with the reaction rates increasing in increasingly polar solvents, for example, the quantum yield π = 0.004 in THF/hexane (5:95) and 0.093 in water. The fluorescence of the tryptophan residue is quenched by the dimer moiety by electron transfer from the excited tryptophan to the dimer. Fluorescence- quenching studies indicated that the electron transfer was efficient in polar solvents. The splitting efficiency of the dimer radical anion within the tryptophan.+-dimer.- species is also remarkably solvent-dependent and increases with the polarity of the solvents. The back-electron-transfer reaction in the charge-separated species, which competes with cleavage, was suppressed in polar solvents. These results are in contrast to those of earlier solvent-dependent studies of indole-dimer systems, but they can be rationalized in terms of the differences in the distances between the chromophore unit and the attached dimer. The pH-dependent measurements of the splitting reaction and the deuterium isotope effect showed that the tryptophan radical cation within the charge-separated species does not deprotonate prior to the cleavage of the dimer radical anion. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
1H NMR and theoretical studies on the conformational equilibrium of tryptophan methyl ester
Duarte, Claudimar J.,Cormanich, Rodrigo A.,Ducati, Lucas C.,Rittner, Roberto
, p. 174 - 179 (2013)
Selected 3JHH coupling constants and theoretical calculations were used to explain the conformational equilibrium of L-tryptophan methyl ester (Trp-OMe) in several solvents. The obtained 3J HαHβ values did not exhibit any significant variability and thus indicate that there are no conformational population variations for the side chain of the Trp-O-Me depending on the solvent. Moreover, the potential energy surfaces obtained at the B3LYP/cc-pVDZ theoretical level produced eight energy minima that were analysed by QTAIM and NBO methods. It was possible to conclude that the Trp-OMe conformational preferences were due to hyperconjugative effects involving the nonbonding electron pairs of the main chain nitrogen atom and certain antibonding orbitals (σC4-C13a?? -, σC1-C4a?? - and σC4-H12a?? -) and also to the steric effects from the nonbonding electron pairs of oxygen atoms and the main and side chain of this system.
Boron Accumulation in Brain Tumor Cells through Boc-Protected Tryptophan as a Carrier for Boron Neutron Capture Therapy
Chio, Chun-Ming,Chou, You-Cheng,Hsu, Fu-Chun,Huang, Ying-Cheng,Lai, Yen-Buo,Yu, Chung-Shan
, p. 589 - 596 (2020)
Boron neutron capture therapy (BNCT) is a binary therapeutic approach. Nonradioactive boron-10 atoms accumulated in tumor cells combining with the neutron beams produce two highly energetic particles that could eradicate the cell that takes it and the neighboring cells. Small molecules that carry boron atom, e.g. 5- and 6-boronated and 2,7-diboronated tryptophans, were assessed for their boron accumulation in U87-MG, LN229, and 3T3 for BNCT. TriBoc tryptophan, TB-6-BT, shows boron-10 at 300 ppm in both types of tumor cells with a tumor to normal ratio (T/N) of 5.19-5.25 (4 h). TB-5-BT and DBA-5-BT show boron-10 at 300 ppm (2 h) in U87-MG cells. TB-5-BT exerts a T/N of >9.66 (1 h) in LN229 compared with the current clinical boronophenyl alanine with a highest T/N of 2.3 (1 h) and accumulation concentration of 50 ppm. TB-5-BT and TB-6-BT warrant further animal study.
Design, synthesis of novel tryptophan derivatives for antiplatelet aggregation activity based on tripeptide pENW (pGlu-Asn-Trp)
Xie, Zhouling,Feng, Sen,Wang, Ying,Cao, Chen,Huang, Jing,Chen, Yahui,Kong, Yi,Li, Zhiyu
, p. 363 - 374 (2015)
pENW, a three mer peptide derived from Agkistrodon acutus Guenther venom, has been found to be an antagonist of the GPIIb/IIIa receptor and shows antiplatelet aggregation activity. Based on pENW and a GPIIb/IIIa inhibitor Tirofiban, a series of tryptophan derivatives were designed, synthesized and evaluated for their antiplatelet aggregation activity induced by ADP. The most potent compound 87 was also tested for the bleeding time and antithrombotic activity in vivo in comparison with Tirofiban. The results indicated that 87 shows similar antiplatelet aggregation activity as Tirofiban to the aggregation of platelet induced by all of the four agonists, but has lower bleeding risk than Tirofiban, representing a promising lead compound for further study.
TOTAL SYNTHESIS OF Na-METHYL-Δ18-ISOKOUMIDINE, A POSSIBLE PRECURSOR OF THE KOUMINE TYPE INDOLE ALKALOIDS
LIU, Zhujin,XU, Feng
, p. 3457 - 3460 (1989)
A novel total synthesis of title compound 3 is described.
Indole Alkaloids from a Soil-Derived Clonostachys rosea
Fang, Jianguo,Jiang, Chun-Xiao,Miao, Ya-Mei,Ren, Hao,Tian, Li-Li,Wang, Xiaolei,Wu, Quan-Xiang,Xu, Qianhe,Yu, Bo,Yu, Zhen-Qing,Zhang, Jin Z.,Zhang, Jiwen,Zhao, Chun,Zhou, Pan-Pan
supporting information, p. 2468 - 2474 (2021/09/13)
Clonorosins A ( 1 ) and B ( 2 ), two novel indole alkaloids featuring unprecedented 6/5/6/6/5 and 6/5/5 cores, together with seven known indole-linked 2,5-diketopiperazine alkaloids ( 3 - 9 ), were isolated from the soil-derived fungusClonostachys roseaYRS-06. The new structures were proposed through HR-MS, NMR, and ECD spectroscopic data. They were established by comparing the calculated NMR, ECD, and specific rotation data with the experimental. To assist in determining the absolute configuration of the chiral carbon in the side chain of 2,5-diketopiperazine derivatives, flexible analogues 3i - 3iv were synthesized and analyzed. 1 was active againstFusarium oxysporumwith an MIC value of 50 μg/mL. 7 and 8 showed excellent activity against human HeLa and HepG2 cells with IC50values of 0.12-0.60 μM.
The benzyl can be selectively removed by visible light or near visible light. Method for protecting allyl and propargyl group
-
Paragraph 0034, (2021/10/16)
The invention provides a method for selectively removing benzyl, allyl and propargyl protecting groups by visible light or near visible light, namely a substrate containing benzyl, allyl or propargyl protecting groups. The method has the advantages of simple operation, safe and clean visible light or near visible light as excitation conditions, cheap and easily available reagents, high reaction yield, high reaction chemistry and regional selectivity, and is suitable for selective removal of benzyl, allyl and propargyl protecting groups in various substrates.
Method for preparing pharmaceutical intermediate of tryptophan derivative
-
Paragraph 0043-0051; 0086-0090, (2021/09/21)
The synthesis method comprises the following steps: L - tryptophan derivatives are taken as starting materials, and esterification is carried out in sequence. The amidation, Boc protection, hydrolysis, amidation or sequential esterification, amidation, Boc protection, hydrogenation, hydrolysis, amidation yields a target product, a tryptophan derivative pharmaceutical intermediate. The preparation method has the advantages of cheap and easily available raw materials, environment friendliness, less process three wastes, accords with the idea of green pharmacy, mild reaction conditions, simple process, simple and convenient operation, high yield and purity and easy amplification and production.
