323-87-5Relevant articles and documents
Synthesis of the tricyclic core structure of vindoline
Guo, Zihong,Schultz, Arthur G.
, p. 919 - 921 (2004)
An efficient synthesis of the core tricyclic structure (18) of vindoline has been achieved using the strategy, which features an intramolecular 1,3-dipolar cycloaddition of the azido dienone (12) to give aziridine (13) with complete region- and stereocontrol.
Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway
Yang, Yu,Borel, Timothy,De Azambuja, Francisco,Johnson, David,Sorrentino, Jacob P.,Udokwu, Chinedum,Davis, Ian,Liu, Aimin,Altman, Ryan A.
, p. 797 - 811 (2021/01/13)
In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, α-amino-β-carboxymuconate-?-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD+ levels. In this study, an Food and Drug Administration (FDA)-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with the results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed half-maximal inhibitory concentration (IC50) values 1 order of magnitude better than diflunisal at 1.32 ± 0.07 μM (22) and 3.10 ± 0.11 μM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD+ levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD.
Synthesis of zwitterionic palladium complexes and their application as catalysts in cross-coupling reactions of aryl, heteroaryl and benzyl bromides with organoboron reagents in neat water
Ramakrishna,Dastagiri Reddy
supporting information, p. 8598 - 8610 (2017/07/12)
N-(3-Chloro-2-quinoxalinyl)-N′-arylimidazolium salts (aryl = 2,6-diisopropylphenyl [HL1Cl]Cl, aryl = mesityl [HL2Cl]Cl) have been synthesized by treating 2,3-dichloroquinoxaline with the corresponding N′-arylimidazole in neat water. Facile reactions of these imidazolium salts with Pd(PPh3)4 and Pd2(dba)3/PPh3 (dba = dibenzyledene acetone) at 50 °C have afforded zwitterionic palladium(ii) complexes [Pd(HL1)(PPh3)Cl2] (I) and [Pd(HL2)(PPh3)Cl2] (II) in excellent yields. I and II have been tested for their ability to catalyze Suzuki-Miyaura cross coupling (SMC) reactions in neat water/K2CO3 and are found to be highly active for carrying out these reactions between aryl bromides and organoboron reagents. Furthermore, the scope of the catalyst I was also examined by employing (hetero)aryl bromides, hydrophilic aryl bromides, benzyl bromides and various organoboron reagents. More than 80 aryl/benzyl bromide-arylboronic acid combinations were screened in neat water/K2CO3 and it was found that I was a versatile catalyst, which produced biaryls/diarylmethanes in excellent yields. A TON of 82 000 was achieved by using I. Studies on the mechanism have also been carried out to investigate the involvement of carbene complexes in the catalytic path. Poison tests and a two-phase test were also conducted and the results are reported.