- Selective hydroboration of equilibrating allylic azides
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The iridium(i)-catalyzed hydroboration of equilibrating allylic azides is reported to provide only the anti-Markovnikov product of alk-1-ene isomers in good yields and with good functional group tolerance.
- Liu, Ruzhang,Zhang, Yuanyuan,Xu, Jun
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p. 8913 - 8916
(2021/09/13)
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- Supramolecular phenoxy-alkyl maleate-based hydrogels and their enzyme/pH-responsive curcumin release
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Low-molecular-weight gelators that self-assemble via non-covalent interactions have been attracting significant attention due to their good biocompatibility, low toxicity, inherent biodegradability as well as their convenience of design. Enzymatically dig
- Kumar, Bijari Anil,Nayak, Rati Ranjan
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p. 5559 - 5567
(2019/04/04)
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- Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis
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The ligands of certain G-protein-coupled receptors (GPCRs) have been identified as endogenous lipids, such as lysophosphatidylserine (LysoPS). Here, we analyzed the molecular basis of the structure-activity relationship of ligands of GPR34, one of the LysoPS receptor subtypes, focusing on recognition of the long-chain fatty acid moiety by the hydrophobic pocket. By introducing benzene ring(s) into the fatty acid moiety of 2-deoxy-LysoPS, we explored the binding site's preference for the hydrophobic shape. A tribenzene-containing fatty acid surrogate with modifications of the terminal aromatic moiety showed potent agonistic activity toward GPR34. Computational docking of these derivatives with a homology modeling/molecular dynamics-based virtual binding site of GPR34 indicated that a kink in the benzene-based lipid surrogates matches the L-shaped hydrophobic pocket of GPR34. A tetrabenzene-based lipid analogue bearing a bulky tert-butyl group at the 4-position of the terminal benzene ring exhibited potent GPR34 agonistic activity, validating the present hydrophobic binding pocket model.
- Sayama, Misa,Inoue, Asuka,Nakamura, Sho,Jung, Sejin,Ikubo, Masaya,Otani, Yuko,Uwamizu, Akiharu,Kishi, Takayuki,Makide, Kumiko,Aoki, Junken,Hirokawa, Takatsugu,Ohwada, Tomohiko
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supporting information
p. 6384 - 6399
(2017/08/02)
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- Zirconium complexes with pendant aryloxy groups attached to the metallocene moiety by ethyl or hexyl spacers
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Four zirconium complexes with pendant aryloxy groups attached to the metallocene moiety by ethyl or hexyl spacers have been synthesized and characterized by spectroscopic methods and HR-MS or elemental analysis. The solid state structure of bis[{6-(2,6-dimethylphenoxy)hexyl}cyclopentadienyl] zirconium dichloride was determined by single crystal X-ray diffraction. The prepared complexes were tested as catalyst precursors in the polymerization of ethylene upon activation with MAO. The results showed a marked effect of the spacer length on the catalytic activity, while only a minor effect of the substitution on the aryl group, which affected its steric properties.
- Cho, Won Seok,Kim, So Han,Kim, Da Jung,Mun, Sang-Deok,Kim, Ran,Go, Min Jeong,Park, Myung Hwan,Kim, Min,Lee, Junseong,Kim, Youngjo
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p. 205 - 212
(2013/10/22)
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- Design, synthesis, and biological evaluation of N-Alkylated deoxynojirimycin (DNJ) derivatives for the treatment of dengue virus infection
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We recently described the discovery of oxygenated N-alkyl deoxynojirimycin (DNJ) derivative 7 (CM-10-18) with antiviral activity against dengue virus (DENV) infection both in vitro and in vivo. This imino sugar was promising but had an EC50 against DENV in BHK cells of 6.5 μM, which limited its use in in vivo. Compound 7 presented structural opportunities for activity relationship analysis, which we exploited and report here. These structure-activity relationship studies led to analogues 2h, 2l, 3j, 3l, 3v, and 4b-4c with nanomolar antiviral activity (EC50 = 0.3-0.5 μM) against DENV infection, while maintaining low cytotoxicity (CC50 > 500 μM, SI > 1000). In male Sprague-Dawley rats, compound 3l was well tolerated at a dose up to 200 mg/kg and displayed desirable PK profiles, with significantly improved bioavailability (F = 92 α 4%).
- Yu, Wenquan,Gill, Tina,Wang, Lijuan,Du, Yanming,Ye, Hong,Qu, Xiaowang,Guo, Ju-Tao,Cuconati, Andrea,Zhao, Kang,Block, Timothy M.,Xu, Xiaodong,Chang, Jinhong
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supporting information; experimental part
p. 6061 - 6075
(2012/08/14)
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- Synthesis of acceptor substrate analogs for the study of glycosyltransferases involved in the second step of the biosynthesis of O-antigen repeating units
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O-antigens of Gram negative bacteria are polysaccharides covalently attached to lipopolysaccharides (LPS) that have roles as virulence factors. Due to the lack of defined substrates for in vitro assays only a few of the enzymes involved in the biosynthesis of O-antigens have been studied. Many O-antigens have GlcNAc at the reducing end of the oligosaccharide chain linked to pyrophosphate-lipid. We therefore designed and synthesized a series of GlcNAc-pyrophosphate-lipid analogs of the natural GlcNAc-pyrophosphate-undecaprenol acceptor substrate for studies of the acceptor specificities of O-antigen biosynthetic enzymes. We synthesized analogs with modifications of the pyrophosphate bond as well as the lipid chain. These compounds will be useful for the specificity studies of many bacterial glycosyltransferases. Knowledge of the substrate specificities is the basis for the development of specific glycosyltransferase inhibitors that could block O-antigen biosynthesis.
- Riley, John G.,Xu, Changchang,Brockhausen, Inka
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scheme or table
p. 586 - 597
(2010/10/04)
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- Synthesis and evaluation of verticipyrone analogues as mitochondrial complex I inhibitors
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Verticipyrone has recently been isolated from the culture broth of Verticillium sp. and shown to inhibit NADH fumarate reductase, as well as NADH oxidoreductase (complex I) of the mitochondrial electron transport chain. In order to assess the structural elements in verticipyrone essential for complex I inhibitor, 15 structural analogues were prepared and analyzed for their effects on mitochondrial NADH oxidoreductase and NADH oxidase activities. Also measured were the abilities of several of the analogues to inhibit respiration as judged by a shift to glycolysis, and to inhibit the growth of several mammalian cell lines. The nature of the pyrone ring was shown to be important to potency of inhibition, as was the length and nature of substituents in the side chain of the analogues.
- Leiris, Simon J.,Khdour, Omar M.,Segerman, Zachary J.,Tsosie, Krystal S.,Chapuis, Jean-Charles,Hecht, Sidney M.
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experimental part
p. 3481 - 3493
(2010/10/20)
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- End-quenching of TiCl4-catalyzed quasiliving polyisobutylene with alkoxybenzenes for direct chain end functionalization
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Alkoxybenzenes were used to end-quench TiCl4-catalyzed quasiliving isobutylene polymerizations initiated from 2-chloro-2,2,4- trimethylpentane or 5-tert-butyl-1,3-di(1-chloro-1-methylethyl)benzene at -70 °C in 40/60 (v/v) hexane/methyl chloride. The alkoxybenzene/chain end molar ratios were in the range 2.5-4. Effective alkoxybenzene quenchers included those with simple alkyl groups, such as anisole and isopropoxybenzene, haloalkyl tethers, such as (3-bromopropoxy)benzene and (2-chloroethoxy)benzene, and even those with hydroxyl and amine functionality, such as 4-phenoxy-1-butanol and 6-phenoxyhexylamine. Alkylation was generally quantitative and occurred exclusively in the para position; multiple alkylations on the same alkoxybenzene were not observed. The alkylation reactions were tolerant of temperatures ranging from -70 to -30 °C and were unimpeded by the presence of endo- or exo-olefin termini. In situ cleavage of the ether linkage of anisole and isopropoxybenzene termini allowed single pot syntheses of phenol-terminated polyisobutylenes.
- Morgan, David L.,Martinez-Castro, Nemesio,Storey, Robson F.
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experimental part
p. 8724 - 8740
(2011/12/02)
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- Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates
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To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21WAF1/CIP1 by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.
- Suzuki, Takayoshi,Nagano, Yuki,Kouketsu, Akiyasu,Matsuura, Azusa,Maruyama, Sakiko,Kurotaki, Mineko,Nakagawa, Hidehiko,Miyata, Naoki
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p. 1019 - 1032
(2007/10/03)
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- Thiol-based SAHA analogues as potent histone deacetylase inhibitors
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In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a series of thiol-based compounds modeled after suberoylanilide hydroxamic acid (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated. Compound 6, in which t
- Suzuki, Takayoshi,Kouketsu, Akiyasu,Matsuura, Azusa,Kohara, Arihiro,Ninomiya, Shin-Ichi,Kohda, Kohfuku,Miyata, Naoki
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p. 3313 - 3317
(2007/10/03)
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- Self-assembly and dynamics of [2]- and [3]rotaxanes with a dinuclear macrocycle containing reversible Os-N coordinate bonds
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With a dinuclear macrocycle 2 that contains weak reversible OsVI-N coordinate bonds, self-assembly and equilibrium dynamics of [2]- and [3]rotaxanes have been investigated. When the macrocycle 2 was mixed together with threads 4a-e, which all contain an adipamide station but different sizes of end groups, [2]pseudorotaxane- and rotaxane-like complexes were immediately formed with large association constants > of 7 × 103M-1 in CDCl3 at 298 K. Exchange dynamics, explored by 2D-EXSY experiments, suggest that assembly and disassembly of complexes occur through two distinct pathways, slipping or clipping, and this depends on the size of the end groups. The slipping pathway is predominant with smaller end groups that give pseudorotaxane-like complexes, while the clipping pathway is observed with larger end groups that yield rotaxane-like complexes. Under the same conditions, exchange barriers (ΔG≠) were 14.3 kcal mol-1 for 4a and 16.7 kcal mol-1 for 4d, and indicate that the slipping process is at least one order of magnitude faster than the clipping process. Using threads 13a and 13b that contain two adipamide groups, more complicated systems have been investigated in which [2]rotaxane, [3]rotaxane, and free components are in equilibrium. Concentration- and temperature-dependent 1H NMR spectroscopic studies allowed the identification of all possible elements and the determination of their relative distributions in solution. For example, the relative distribution of the free components, [2]rotaxane, and [3]rotaxane are 30, 45, and 25%, respectively, in a mixture of 2 (2mM) and 13a (2mM) in CDCl3, at 10°C. However, [3]rotaxane exists nearly quantitatively in a mixture of 2 (4mM) and 13a (2mM) in CDCl3 at a low temperature - 10°C.
- Chang, Sung-Youn,Choi, Jeung Soon,Jeong, Kyu-Sung
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p. 2687 - 2697
(2007/10/03)
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- Ortho-directed lithiation of ω-phenoxy alcohols
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ω-Phenoxy alcohols, PhO(CH2)(n)OH (n = 2-7), have been subjected to metalation with 2 equiv of n-butyllithium in tetrahydrofuran/methylcyclohexane solvent. Reaction of the resulting lithiated compounds with carbon dioxide (n = 2-7), benzaldehyde (n = 2-6), benzophenone (n = 2, 3), dimethylformamide (n = 2), ethyl formate (n = 2), and chlorodiphenylphosphine (n = 3) afforded the corresponding ortho- substituted hydroxyalkoxybenzenes in yields ranging from 45 to 83%. The synthesis is also reported of five new bis[o-(ω-hydroxyalkoxy)phenyl]mercury compounds (n = 2-6), four crystal structures of which have been determined.
- Salteris, Constantinos S.,Kostas, Ioannis D.,Micha-Screttas, Maria,Heropoulos, George A.,Screttas, Constantinos G.,Terzis, Aris
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p. 5589 - 5592
(2007/10/03)
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- Aryloxy alkanols as anti-retrovirus agents
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Aryloxyalkanol derivatives having the formula wherein n is an integer from 3 to 8 and Ar is (1) 1- or 2-naphthylenyl, (2) phenyl optionally substituted by from 1 to 3 C1-4 lower alkyl groups, or (3) a diphenyl moiety of structure STR1 wherein Y
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- Conversion of One Hydroxy Group in a Diol to a Phenyl Ether with Triphenylbismuth Diacetate, a New Glycol Reaction Showing Strong Axial Preference in Six-Membered Rings
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After being refluxed for a few hours, a dichloromethane solution of a diol with triphenylbismuth diacetate gave in most cases excellent yields of a monophenyl ether.No diphenylated products were found.Tertiary hydroxy groups were only phenylated in bis tertiary diols, and then in poor yield.Increasing the distance between the hydroxy groups up to six carbon atoms decreased the speed of the reaction which nevertheless was still preparatively useful.Diols in flexible rings behaved like their acyclic counterparts.The course of the reaction was also examined with someconformationally rigid molecules: trans-4-tert-butyl-cis-2-hydroxycyclohexanol, trans-4-tert-butyl-trans-2-hydroxycyclohexanol, cholestane-2α,3α-diol, cholestane-2α,3β-diol, and pyranoside derivatives with the α-D-gluco, α-D-manno, α-D-galacto, and α-D-allo configurations.The phenylations of cis-diols were strongly regioselective for axial epimers, while those of trans, bis equatorial diols were undiscriminate and often much slower.A feasible general mechanism is proposed to explain these results.
- David, Serge,Thieffry, Annie
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p. 441 - 447
(2007/10/02)
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- SELECTIVE PHENYLATION IN MILD CONDITIONS OF ONE HYDROXY GROUP IN GLYCOLS WITH TRIPHENYLBISMUTH DIACETATE: A NEW SPECIFIC GLYCOL REACTION.
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Refluxing for 4-5 h a dichloromethane solution of diol in the presence of an equimolecular quantity of triphenylbismuth diacetate gave the monophenyl ether in good to excellent yield.
- David, Serge,Thieffry, Annie
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p. 5063 - 5066
(2007/10/02)
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- Method of treating lipidemia with aryloxyalkylaminobenzoic acids and esters
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Aryloxyalkylaminobenzoic acids and esters as hypolipemic compounds.
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