- Synthesis and preliminary biological evaluation of antibacterial and antifungal 5-arylidene tetramic acid-cadmium(II) complexes
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The synthesis and biological evaluation of 5-arylidene-N-acetyl-tetramic acids cadmium(II) complexes are reported. Eleven novel compounds were prepared, characterized by nuclear magnetic resonance experiments and screened for their antimicrobial activity
- Matiadis, Dimitris,Stefanou, Valentina,Tsironis, Dimitrios,Panagiotopoulou, Angeliki,Igglessi-Markopoulou, Olga,Markopoulos, John
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- Topology-Based Functionalization of Robust Chiral Zr-Based Metal-Organic Frameworks for Catalytic Enantioselective Hydrogenation
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The design and development of robust and porous supported catalysts with high activity and selectivity is extremely significant but very challenging for eco-friendly synthesis of fine chemicals and pharmaceuticals. We report here the design and synthesis of highly stable chiral Zr(IV)-based MOFs with different topologies to support Ir complexes and demonstrate their network structures-dependent asymmetric catalytic performance. Guided by the modulated synthesis and isoreticular expansion strategy, five chiral Zr-MOFs with a flu or ith topology are constructed from enantiopure 1,1′-biphenol-derived tetracarboxylate linkers and Zr6, Zr9, or Zr12 clusters. The obtained MOFs all show high chemical stability in boiling water, strongly acidic, and weakly basic aqueous solutions. The two flu MOFs featuring the dihydroxyl groups of biphenol in open and large cages, after sequential postsynthetic modification with P(NMe2)3 and [Ir(COD)Cl]2, can be highly efficient and recyclable heterogeneous catalysts for hydrogenation of α-dehydroamino acid esters with up to 98% ee, whereas the three ith MOFs featuring the dihydroxyl groups in small cages cannot be installed with P(NMe2)3 to support the Ir complex. Incorporation of Ir-phosphorus catalysts into Zr-MOFs leads to great enhancement of their chemical stability, durability, and even stereoselectivity. This work therefore not only advances Zr-MOFs as stable supports for labile metal catalysts for heterogeneous asymmetric catalysis but also provides a new insight into how highly active chiral centers can result due to the framework topology.
- Jiang, Hong,Zhang, Wenqiang,Kang, Xing,Cao, Ziping,Chen, Xu,Liu, Yan,Cui, Yong
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supporting information
p. 9642 - 9652
(2020/07/02)
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- Silver-Promoted Direct Phosphorylation of Bulky C(sp2)-H Bond to Build Fully Substituted β-Phosphonodehydroamino Acids
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A general and practical cross-dehydrogenative coupling protocol between readily available trisubstituted α,β-dehydro α-amino carboxylic esters and H-phosphites is described. This C(sp2)-H phosphorylation reaction proceeds with absolute Z-selectivity promoted by silver salt in a radical relay manner. The bulky tetrasubstituted β-phosphonodehydroamino acids were obtained in grams and added new modules to the toolkit for peptide modifications.
- Cao, Hao-Qiang,Liu, Hao-Nan,Liu, Zhe-Yuan,Qiao, Baokun,Zhang, Fa-Guang,Ma, Jun-An
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supporting information
p. 6414 - 6419
(2020/09/02)
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- Chiral bisphosphine ligands based on quinoline oligoamide foldamers: application in asymmetric hydrogenation
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A series of chiral bisphosphine ligands were designed and synthesized based on single-handed quinoline oligoamide foldamers. The bisphosphine ligands can coordinate with Rh(cod)2BF4 in a 1 : 1 stoichiometry and the resulted chiral Rh(i) catalysts were applied in the asymmetric hydrogenation of α-dehydroamino acid esters, in which excellent conversions and promising levels of enantioselectivity were achieved.
- Zheng, Lu,Zheng, Dan,Wang, Yanru,Yu, Chengyuan,Zhang, Kun,Jiang, Hua
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supporting information
p. 9573 - 9577
(2019/11/20)
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- Structure activity relationship studies on rhodanines and derived enethiol inhibitors of metallo-β-lactamases
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Metallo-β-lactamases (MBLs) enable bacterial resistance to almost all classes of β-lactam antibiotics. We report studies on enethiol containing MBL inhibitors, which were prepared by rhodanine hydrolysis. The enethiols inhibit MBLs from different subclasses. Crystallographic analyses reveal that the enethiol sulphur displaces the di-Zn(II) ion bridging ‘hydrolytic’ water. In some, but not all, cases biophysical analyses provide evidence that rhodanine/enethiol inhibition involves formation of a ternary MBL enethiol rhodanine complex. The results demonstrate how low molecular weight active site Zn(II) chelating compounds can inhibit a range of clinically relevant MBLs and provide additional evidence for the potential of rhodanines to be hydrolysed to potent inhibitors of MBL protein fold and, maybe, other metallo-enzymes, perhaps contributing to the complex biological effects of rhodanines. The results imply that any medicinal chemistry studies employing rhodanines (and related scaffolds) as inhibitors should as a matter of course include testing of their hydrolysis products.
- Zhang, Dong,Markoulides, Marios S.,Stepanovs, Dmitrijs,Rydzik, Anna M.,El-Hussein, Ahmed,Bon, Corentin,Kamps, Jos J.A.G.,Umland, Klaus-Daniel,Collins, Patrick M.,Cahill, Samuel T.,Wang, David Y.,von Delft, Frank,Brem, Jürgen,McDonough, Michael A.,Schofield, Christopher J.
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supporting information
p. 2928 - 2936
(2018/04/19)
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- An Atropos Biphenyl Bisphosphine Ligand with 2,2′-tert-Butylmethylphosphino Groups for the Rhodium-Catalyzed Asymmetric Hydrogenation of Enol Esters
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This is an update of our previous work concerning the development of Atropos biphenyl bisphosphine ligands. An unexpected Atropos structural property was confirmed by single crystal X-ray diffraction and this result is consistent with the computational calculations described in our previous work. This P-stereogenic bisphosphine ligand possessing a biphenyl backbone and 2,2′-tert-butylmethylphosphino groups has been applied to the Rh-catalyzed asymmetric hydrogenation of enol esters, which has not been widely studied and can be used for the synthesis of several important bioactive compounds. Although there is room for further improvement in enantioselectivity, the results reported herein provide a further understanding of such types of ligands. (Figure presented.).
- Jia, Jia,Fan, Dongyang,Zhang, Jian,Zhang, Zhenfeng,Zhang, Wanbin
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supporting information
p. 3793 - 3800
(2018/09/20)
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- Construction of Chiral-Fused Tricyclic γ-Lactams via a trans-Perhydroindolic Acid-Catalyzed Asymmetric Domino Reaction
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An asymmetric domino reaction was developed utilizing readily available cyclic α-dehydroamino ketones and aldehydes, which when subjected a 2-iodoxybenzoic acid (IBX)-mediated oxidation gives pyrrolidinone-containing tricyclic derivatives. trans-Perhydroi
- An, Qianjin,Shen, Jiefeng,Liu, Delong,Liu, Yangang,Zhang, Wanbin
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supporting information
p. 2925 - 2928
(2017/06/07)
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- Single-Biocatalyst Synthesis of Enantiopure d-Arylalanines Exploiting an Engineered d-Amino Acid Dehydrogenase
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A practical and efficient biocatalytic synthesis of aromatic d-amino acids has been developed, based on the reductive amination of the corresponding α-keto acids via a recombinant whole cell system composed of an engineered dehydrogenase and cofactor recycling apparatus. The reaction was shown to give excellent enantioselectivity (≥98%) and good yields at the preparative scale across a broad range of substrates. Additionally, the structure of the variant enzyme was solved to allow rationalisation of the observed reaction rates. The engineered whole cell catalyst was also used to mediate the production of d-phenylalanine derivatives from racemic mixtures and cheaper l-amino acids by combining it with an enantiocomplementary deaminase. (Figure presented.).
- Parmeggiani, Fabio,Ahmed, Syed T.,Thompson, Matthew P.,Weise, Nicholas J.,Galman, James L.,Gahloth, Deepankar,Dunstan, Mark S.,Leys, David,Turner, Nicholas J.
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supporting information
p. 3298 - 3306
(2016/10/20)
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- Cation-triggered switchable asymmetric catalysis with chiral aza-crownphos
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An aza-crown ether, modified phosphoramidite ligand, has been designed and synthesized. The ON/OFF reversible switch of catalytic activity for its rhodium catalyst was thoroughly investigated in the asymmetric hydrogenation of dehydroamino acid esters modulated by host-guest interactions. In the OFF state, the catalyst is almost inactive (less than 1% conversion) because of the formation of an intermolecular sandwich complex by two aza-crown ether moities and the cationic rhodium metal center. In using alkali-metal-cations as the trigger, the catalytic activity was turned ON and consequently resulted in full conversions and excellent enantioselectivities (up to 98% ee).
- Ouyang, Guang-Hui,He, Yan-Mei,Li, Yong,Xiang, Jun-Feng,Fan, Qing-Hua
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supporting information
p. 4334 - 4337
(2015/04/14)
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- Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors
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Abstract Protein-protein interactions are critical for regulating the activity of translation initiation factors and multitude of other cellular process, and form the largest block of untapped albeit most challenging targets for drug development. 4EGI-1, (E/Z)-2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl) hydrazono)-3-(2-nitrophenyl)propanoic acid, is a hit compound discovered in a screening campaign of small molecule libraries as an inhibitor of translation initiation factors eIF4E and eIF4G protein-protein interaction; it inhibits translation initiation in vitro and in vivo. A series of 4EGI-1-derived thiazol-2-yl hydrazones have been designed and synthesized in order to delineate the structural latitude and improve its binding affinity to eIF4E, and increase its potency in inhibiting the eIF4E/eIF4G interaction. Probing a wide range of substituents on both phenyl rings comprising the 3-phenylpropionic acid and 4-phenylthiazolidine moieties in the context of both E- and Z-isomers of 4EGI-1 led to analogs with enhanced binding affinity and translation initiation inhibitory activities.
- Takrouri, Khuloud,Chen, Ting,Papadopoulos, Evangelos,Sahoo, Rupam,Kabha, Eihab,Chen, Han,Cantel, Sonia,Wagner, Gerhard,Halperin, Jose A.,Aktas, Bertal H.,Chorev, Michael
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p. 361 - 377
(2014/04/17)
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- Microwave-assisted synthesis and antimicrobial screening of new imidazole derivatives bearing 4-thiazolidinone nucleus
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A new series of compounds 2-((1-(4-(4-arylidene-2-methyl-5-oxo-4,5-dihydro- 1H-imidazol-1-yl)phenyl)ethylidene)hydrazono)thiazolidin-4-ones (4a-o) have been synthesized under conventional and microwave irradiation method. All compounds were characterized by IR, 1H NMR, 13C NMR and mass spectra. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus by bioassays, namely serial broth dilution. The synthesized compounds showed potent antimicrobial activity against tested microorganisms. Compounds 4h, 4j, 4m and 4n were the most potent amongst tested compounds.
- Desai,Joshi,Rajpara,Vaghani,Satodiya
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p. 1893 - 1908
(2013/07/26)
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- Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets
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Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotoxicity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.
- Baud, Matthias G. J.,Leiser, Thomas,Haus, Patricia,Samlal, Sharon,Wong, Ai Ching,Wood, Robert J.,Petrucci, Vanessa,Gunaratnam, Mekala,Hughes, Siobhan M.,Buluwela, Lakjaya,Turlais, Fabrice,Neidle, Stephen,Meyer-Almes, Franz-Josef,White, Andrew J. P.,Fuchter, Matthew J.
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scheme or table
p. 1731 - 1750
(2012/04/23)
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- Synthesis and anti-inflammatory activity of imidazo[1,2-a] pyridinyl/pyrazinyl benzamides and acetamides
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The present study involves synthesis and determination of anti-inflammatory activity of a series of imidazo[1,2-a]pyridinyl/pyrazinyl benzamides and acetamides. Sixteen new imidazo[1,2-a]pyridinyl/pyrazinyl benzamides and acetamides have been prepared by the ring opening of 4-arylidene-2-methyl/ phenyloxazolones with 2-amino azaheterocycles. All the compounds show significant anti-inflammatory activity. The anti-inflammatory activity studies reveal that both acetamide and benzamide derivatives are equally active. Among the two classes of compounds, i.e., imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazines, the latter show better activity.
- Hemasrilatha,Sruthi,Manjula,Harinadha Babu,Vittal Rao
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scheme or table
p. 981 - 987
(2012/09/22)
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- Complexes of Ca2+ and Mg2+ with N-acetyl-α,β-dehydrodipeptides: The state in an alcoholic solution and its relationship with asymmetric induction upon diastereoselective hydrogenation
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In an alcoholic solution, N-acetyl-α,β-dehydrodipeptides interact with Ca2+ and Mg2+ ions to form complex particles containing several dehydrodipeptide molecules per metal ion. The composition of these particles and steric interactions in them determine the acidity of the carboxyl groups and the degree of asymmetric induction upon diastereoselective hydrogenation.
- Lisichkina,Larina,Peregudov,Vasil'era,Belikov
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p. 895 - 898
(2007/10/03)
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