22537-07-1Relevant articles and documents
Formation of Self-Templated 2,6-Bis(1,2,3-triazol-4-yl)pyridine [2]Catenanes by Triazolyl Hydrogen Bonding: Selective Anion Hosts for Phosphate
Byrne, Joseph P.,Blasco, Salvador,Aletti, Anna B.,Hessman, Gary,Gunnlaugsson, Thorfinnur
, p. 8938 - 8943 (2016)
We report the remarkable ability of 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) compounds 2 with appended olefin amide arms to self-template the formation of interlocked [2]catenane structures 3 in up to 50 % yield when subjected to olefin ring-closing metathesis in CH2Cl2. X-ray diffraction crystallography enabled the structural characterization of both the [2]catenane 3 a and the non-interlocked macrocycle 4 a. These [2]catenanes showed selective triazolyl hydrogen-bonding interactions with the tetrahedral phosphate anion when screened against a range of ions; 3 a,b are the first examples of selective [2]catenane hosts for phosphate.
Acetyl Coenzyme A Analogues as Rationally Designed Inhibitors of Citrate Synthase
Bello, Davide,Rubanu, Maria Grazia,Bandaranayaka, Nouchali,G?tze, Jan P.,Bühl, Michael,O'Hagan, David
, p. 1174 - 1182 (2019)
In this study, we probed the inhibition of pig heart citrate synthase (E.C. 4.1.3.7) by synthesising seven analogues either designed to mimic the proposed enolate intermediate in this enzyme reaction or developed from historical inhibitors. The most potent inhibitor was fluorovinyl thioether 9 (Ki=4.3 μm), in which a fluorine replaces the oxygen atom of the enolate. A comparison of the potency of 9 with that of its non-fluorinated vinyl thioether analogue 10 (Ki=68.3 μm) revealed a clear “fluorine effect” favouring 9 by an order of magnitude. The dethia analogues of 9 and 10 proved to be poor inhibitors. A methyl sulfoxide analogue was a moderate inhibitor (Ki=11.1 μm), thus suggesting hydrogen bonding interactions in the enolate site. Finally, E and Z propenoate thioether isomers were explored as conformationally constrained carboxylates, but these were not inhibitors. All compounds were prepared by the synthesis of the appropriate pantetheinyl diol and then assembly of the coenzyme A structure according to a three-enzyme biotransformation protocol. A quantum mechanical study, modelling both inhibitors 9 and 10 into the active site indicated short CF???H contacts of ≈2.0 ?, consistent with fluorine making two stabilising hydrogen bonds, and mimicking an enolate rather than an enol intermediate. Computation also indicated that binding of 9 to citrate synthase increases the basicity of a key aspartic acid carboxylate, which becomes protonated.
Palladium(II)-Catalyzed Aminotrifluoromethoxylation of Alkenes: Mechanistic Insight into the Effect of N-Protecting Groups
Chen, Chaohuang,Chen, Pinhong,Hou, Chuanqi,Liu, Guosheng
supporting information, p. 346 - 350 (2020/05/25)
An efficient palladium-catalyzed regioselective 5-exo aminotrifluoromethoxylation of alkenes has been established herein, which provides a practical route towards the synthesis of OCF3-containing pyrrolidines. tert-Butyloxycarbonyl (Boc) as an amino protecting group plays a significant role in both the chemo- and regioselectivities. In addition, preliminary mechanistic studies reveal that the amino protecting group of substrates and the counter anion of palladium catalyst play critical roles in reaction efficiency presumably due to an isomerization of alkyl- Pd(II) intermediates. Moreover, the asymmetric 5-exo aminotrifluoromethoxylation reaction has also been achieved by introducing a sterically bulky pyridinyl-oxazoline ligand.
Cross-Module Enoylreduction in the Azalomycin F Polyketide Synthase
Zhai, Guifa,Wang, Wenyan,Xu, Wei,Sun, Guo,Hu, Chaoqun,Wu, Xiangming,Cong, Zisong,Deng, Liang,Shi, Yanrong,Leadlay, Peter F.,Song, Heng,Hong, Kui,Deng, Zixin,Sun, Yuhui
, p. 22738 - 22742 (2020/10/12)
The colinearity of canonical modular polyketide synthases, which creates a direct link between multienzyme structure and the chemical structure of the biosynthetic end-product, has become a cornerstone of knowledge-based genome mining. Herein, we report genetic and enzymatic evidence for the remarkable role of an enoylreductase in the polyketide synthase for azalomycin F biosynthesis. This internal enoylreductase domain, previously identified as acting only in the second of two chain extension cycles on an initial iterative module, is shown to also catalyze enoylreduction in trans within the next module. The mechanism for this rare deviation from colinearity appears to involve direct cross-modular interaction of the reductase with the longer acyl chain, rather than back transfer of the substrate into the iterative module, suggesting an additional and surprising plasticity in natural PKS assembly-line catalysis.
