39987-25-2Relevant articles and documents
Synthesis and Unprecedented Complexation Properties of β-Cyclodextrin-Based Ligand for Lanthanide Ions
Champagne, Pier-Luc,Barbot, Cécile,Zhang, Ping,Han, Xuekun,Gaamoussi, Issam,Hubert-Roux, Marie,Bertolesi, Gabriel E.,Gouhier, Géraldine,Ling, Chang-Chun
, p. 8964 - 8977 (2018)
Here, we report the synthesis and detailed studies on the coordination chemistry of a novel chemically modified polyaminocarboxylate (5) based on β-cyclodextrin (CD) scaffold for lanthanides. The target ligand is prepared in a highly efficient manner (seven total steps) from β-CD using the readily available iminodiacetic acid as a starting material. A propargyl group is attached to the iminodiacetate via N-alkylation, and the obtained derivative is efficiently conjugated to the β-CD scaffold via the copper(I)-mediated 1,3-dipolar cycloaddition. The generated 1,2,3-triazolmethyl residues advantageously provide a competent chelating group while displacing the metal coordination center away from the primary rim of β-CD, to afford the required conformational flexibility. The functional groups from each of the two adjacent glucopyranosyl units of β-CD complete a uniquely created octavalent coordination sphere for lanthanides while still sparing one site for dynamic water coordination. To help study the coordination chemistry of CD ligand 5, we also design a relevant maltoside ligand 6, which faithfully represents one submetal-binding section of ligand 5. Thanks to HRMS and NMR studies, we successfully elucidate the coordination chemistries of synthesized ligands. The octavalent coordination sphere of ligand 5 shows strong binding affinity to lanthanides. By potentiometric titration experiments, ligand 5 is found to bind gadolinium(III), forming 1:1, 1:2, and 1:3 multinuclear complexes with lanthanides, thus possessing great capacity for catalyzing the dynamic water-exchange. Further NMR studies also reveal that the formed ligand 5/Gd(III) complexes show significantly better abilities to alter T1 relaxivities of coordinated water than DOTA-Gd(III) and also some of the synthetic CD probes reported in the literature.
Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors
Li, Guangzhe,Dong, Huijuan,Ma, Yao,Shao, Kun,Li, Yueqing,Wu, Xiaodan,Wang, Shisheng,Shao,Zhao, Weijie
supporting information, p. 2327 - 2331 (2019/07/09)
The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MTT assay, respectively. The results showed that neolamellarin A 1 (IC50 = 10.8 ± 1.0 μM) and derivative 2b (IC50 = 11.9 ± 3.6 μM) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.
Large-Scale Synthesis of Piperazine-2,6-dione and Its Use in the Synthesis of Dexrazoxane Analogues
Roh, Jaroslav,Karabanovich, Galina,Novakova, Veronika,?im?nek, Tomá?,Vávrová, Kate?ina
, p. 4580 - 4588 (2016/12/14)
An efficient, large-scale synthesis of piperazine-2,6-dione was developed. The advantages of this procedure include the use of inexpensive starting materials, satisfactory yields, and a convenient workup without the need for chromatographic techniques. Furthermore, this procedure can be easily modified for the preparation of 1-substituted piperazine-2,6-dione hydrobromides. The utility of the prepared piperazine-2,6-dione was demonstrated in the synthesis of a novel analogue of the only drug used in clinical practice to prevent anthracycline-induced cardiotoxicity, dexrazoxane.
