共查询到20条相似文献,搜索用时 15 毫秒
1.
Ashit K. Ganguly Sesha S. Alluri Chih-Hung Wang Alyssa Antropow Alex White Danielle Caroccia Dipshikha Biswas Eunhee Kang Li-Kang Zhang Steven S. Carroll Christine Burlein John Fay Peter Orth Corey Strickland 《Tetrahedron》2014
Synthesis and HIV-1 protease inhibitory activity of compound 5 based on the structure of a novel cyclic sulfonamide pharmacophore has been recently disclosed from our group. X-ray crystallographic structure of 5 when bound to the HIV-1 protease defined its binding mode. The importance of the geometry of the substitution at C4–Me (S configuration) was emphasized. In the present paper we wish to disclose the design of novel inhibitors 47 and 48 based on the X-ray structure of compound 5 bound to the HIV-1 protease, their synthesis and activity against HIV-1 protease. By making changes at the C4 position and the carbamate linkage the above compounds 47 and 48 were found to be approximately one hundred fold more active compared to 5 and their Ki values are in the picomolar range. An unusual observation regarding the activity and geometry was made with compounds 51 and 52. X-ray results demonstrate that 48 and 52 bind to the same binding pocket with simultaneous change in the conformation of the cyclic sulfonamide ring. 相似文献
2.
Shiliang He Hang Zhao Xiurong Guo Guang Xin Baozhan Huang Limei Ma Xinglong Zhou Rui Zhang Dan Du Xiaohua Wu Zhihua Xing Wen Huang Qianming Chen Yang He 《Tetrahedron》2013
J-AT nucleoside-based organogelators 1a and 1b were designed and synthesized. They were endowed with unparalleled superiority to natural nucleobase analogues 2–6 to gelate aromatic solvents due to their excellent self-assembly properties. The J-AT nucleoside-based organogelators showed a specific self-complementary base pair recognition characteristic. The gel stabilities of 1a and 1b were drastically influenced by adenine analogue 2, hardly affected by thymine analogue 3, uracil analogue 4, cytosine analogue 5, and mildly interrupted by guanine analogue 6. 相似文献
3.
Amnat Eamvijarn Nelson M. Gomes Tida Dethoup Jamrearn Buaruang Leka Manoch Artur Silva Madalena Pedro Ioulia Marini Vasilios Roussis Anake Kijjoa 《Tetrahedron》2013
Two new metabolites including a new aszonalenin analogue (1c) and a new meroditerpene (3) were isolated, together with aszonalenin (1a), acetylaszonalenin (1b), 13-oxofumitremorgin B (2), aszonapyrone A (4b) and helvolic acid, from the culture of the soil fungus Neosartorya fischeri (KUFC 6344). While the ethyl acetate extract of the culture of the diseased coral-derived fungus Neosartorya laciniosa (KUFC 7896) furnished aszonapyrone B (4a), aszonapyrone A (4b), tryptoquivaline L and 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′-oxolane]-2,2′-dione, the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya tsunodae (KUFC 9213) yielded a new analogue of chevalone C (5) and helvolic acid. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis as well as HR-ESIMS. Compounds 1a–c, 2, 3, 4a, 4b and 5 were evaluated for their in vitro growth inhibitory activity on the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines by the protein binding dye SRB method. 相似文献
4.
Shugo HisamatsuHyuma Masu Masahiro TakahashiKeiki Kishikawa Shigeo Kohmoto 《Tetrahedron letters》2012,53(30):3903-3906
Single crystal X-ray structures of cocrystals, 1·2 and 1·3, derived from U-shaped ureadicarboxylic acid (1) with 2-aminopyrimidine (2) and melamine (3), respectively, were examined. Cocrystals were obtained as a 1:1 mixture of 1 and the corresponding base. Two molecules of 1 and two molecules of the base were combined together via intermolecular H-bonding creating a supramolecularly assembled cyclic heterotetramer motif of rhombus shape. In the case of cocrystal 1·3, the cyclic heterotetramers were connected via H-bonding by utilizing a remaining amino group of melamine resulting in the formation of a tape of cyclic heterotetramer. 相似文献
5.
3-Phenoxypropanoic acid (1), 3-(phenylthio)propanoic acid (2), and 4-phenylbutanoic acid (3) were pyrolysed between 520 and 682 K. Analysis of the pyrolysates showed the elimination products to be acrylic acid and the corresponding arene. Pyrolysis of ethyl 3-phenoxypropanoate (4) and its methyl analogue (5), ethyl 3-(phenylthio)propanoate (6) and its methyl counterpart (7), and 3-phenoxypropane nitrile (8) were also investigated between 617 and 737 K. The thermal gas-phase elimination kinetics and product analysis are compatible with a thermal retro-Michael reaction pathway involving a four-membered cyclic transition state. 相似文献
6.
Boris-Marko Kukovec Zora Popović Gordana Pavlović Marijana Vinković Dražen Vikić-Topić 《Polyhedron》2008
Cadmium(II) complexes of 3-hydroxypicolinic acid, namely [CdI(3-OHpic)(3-OHpicH)(H2O)]2 (1), [Cd(3-OHpic)2(H2O)2] (2) and [Cd(3-OHpic)2]n (3) were prepared and characterized by spectroscopic methods (IR, NMR) and their molecular and crystal structures were determined by X-ray crystal structure analysis. Complexes 1 and 2 were prepared in similar reaction conditions using different cadmium(II) salts: cadmium(II) iodide and cadmium(II) acetate dihydrate, respectively, while 3 was prepared by recrystallization of 2 from N,N-dimethylformamide solution. Various coordination modes of 3-OHpicH in 1–3 were established in the solid state: bidentate N,O-chelated mode in 1 and 2, monodentate mode through the carboxylate O atom from zwitterionic ligand in 1 and bidentate N,O-chelated and bridging mode in 3. In the DMF solution of all prepared complexes, only monodentate mode of 3-OHpicH binding to cadmium(II) through the carboxylate O atom was established by 1H, 13C, 15N and 113Cd NMR spectroscopy. 相似文献
7.
Takuya Tashiro Takatsugu Hirokawa Hiroshi Watarai Kenji Mori 《Tetrahedron letters》2007,48(19):3343-3347
RCAI-56 (3), a carbocyclic analogue of KRN7000 (1) was synthesized through an efficient coupling of a carba-α-d-galactose derivative 11 with cyclic sulfamidate derivative 13 of phytosphingosine to give 15. Carbasugar derivative 11 was prepared by starting from methyl α-d-galactopyranoside (4), employing Pd(II)-catalyzed Ferrier rearrangement as the key step. RCAI-56 (3) is a potent stimulant of NKT cells in vivo to induce the production of Th1 biased cytokines such as interferon-γ in mice. According to the docking model of CD1d-3 complex, its stabilization energy is approximately at the same level as that of the CD1d-1 complex. 相似文献
8.
Maria Letizia Ciavatta M. Pilar Lopez-Gresa Rosario Nicoletti Ernesto Mollo Guido Cimino 《Tetrahedron》2008,64(22):5365-5369
Chemical investigation of the culture broth of the fungus Eutypella scoparia ICB-OBX, isolated from the marine pulmonate mollusc Onchidium sp., led to the finding of novel compounds 1 and 2, structurally related to angiotensin II binding inhibitors cytosporins, along with unrelated known nitrogen metabolites (compounds 3-5). The structure and the relative stereochemistry of the novel metabolites were assigned mainly by a detailed analysis of two-dimensional NMR techniques whereas the absolute stereochemistry was proposed by modified Mosher's method. Compound 2 contains an unusual cyclic carbonate functionality that is rare among natural products. 相似文献
9.
Francis E. Appoh 《Journal of organometallic chemistry》2005,690(5):1209-1217
The interaction of six ferrocene-amino acid conjugates (Fc-CO-Gly-OH (2a), Fc-CO-Asp-OH (3a), Fc-CO-Glu-OH (4a), 1,1′-Fc(CO-Gly-OH) (2b), 1,1′-Fc(CO-Asp-OH) (3b), and 1,1′-Fc(CO-Glu-OH) (4b)) with Mg2+, Ca2+, Zn2+, La3+, and Tb3+ was investigated in aqueous solutions using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Addition of metal ions to solutions caused, in some cases, large changes in the half-wave potential, E1/2. Our electrochemical results show that the Gly systems, 2a and 2b, show a preference for binding Mg2+, whereas the Asp and Glu conjugates prefer binding Ln3+. 相似文献
10.
Lewis acid-catalyzed condensation of 1,2- and 1,3-dimethoxybenzenes with paraformaldehyde afforded an ortho-bridged cyclic trimer (1) and a meta-bridged cyclic tetramer (2), respectively. Furthermore, condensation of 1,3,5-trimethoxybenzene with paraformaldehyde in the presence of Lewis acid catalyst successfully rendered the first dodecamethoxy-substituted calix[4]arene (3) with high yield. From X-ray crystallography, it was found that 3 formed the partial cone conformation. The conformational behavior of 3 in the solution was investigated by variable temperature 1H NMR measurements. The partial cone structure observed in the solid state was retained in the solution at low temperatures. Furthermore, because of the slow conformational exchanges of 3 on the NMR time scale, bimodal conformational exchanges were found. The host-guest property of 3 with the electron accepting guest, tetracyanoethylene (TCNE) was examined by UV-Vis measurements, and the ability to associate with the 3-TCNE complex was three times higher than that of the 2-TCNE complex. The observation is due to the superior electron donating property and slow conformational exchanges of 3 compared with those of analogous 2. 相似文献
11.
Xiao-Qiang Li 《Tetrahedron》2004,60(37):8275-8284
The donor-acceptor interaction-driven supramolecular arrangement of a new series of quadruply hydrogen-bonded homo- and heterodimers have been investigated in chloroform with 1H NMR and UV-Vis spectroscopy. Two kinds of structurally complementary monomers have been prepared. Monomers 3 and 4 are incorporated with one ureidopyrimidone unit and one electron deficient pyromellitic diimide (PDI) or naphthalene diimide (NDI) unit, respectively, monomers 5 and 6 are incorporated with two ureidopyrimidone units and one PDI or NDI unit, respectively, whereas monomers 7 and 8 consist of one electron rich bis-p-phenylene[34]crown-10 unit and one or two 2,7-diamido-1,6-naphthyridine units, respectively. Compounds 3 and 4 exist exclusively as homodimers, respectively. Adding 1 equiv. of 7 to the solution of 3·3 and 4·4 induced them to partially or fully dissociate to produce heterodimers 3·7 and 4·7 due to intermolecular donor-acceptor interaction and the formation of a new binding mode between the ureidopyrimidone of 3 or 4 and the 2,7-diamido-1,6-naphthyridine unit of 7. Both 5 and 6 exist as cyclic monomer and dimer in chloroform. Adding 1 equiv. of 8 to the solution of 5 or 6 in chloroform caused all the cyclic dimer and most of the cyclic monomer to de-cyclize to form new heterodimers 5·8 and 6·8, respectively. 1H NMR and UV-vis study revealed that heterodimer 5·8 has a structure in which the PDI of 5 is not threaded through the cavity of the bis-p-phenylene[34]crown-10 unit of 8. In contrast, in addition to the heterodimer similar to 5·8, about 40% of heterodimer 6·8 is generated, in which the PDI of 6 is threaded through the cavity of the bis-p-phenylene[3]crown-10 unit of 8 due to the increased donor-acceptor interaction between NDI and bis-p-phenylene[34]crown-10. Steric hindrance and mismatching of the hydrogen bonding moiety play important roles in the arrangement of the new homo- and heterodimers. 相似文献
12.
The mechanism for the 1,3-dipolar cycloaddition between the hindered thiocarbonyl ylide 1 and tetracyanoethylene 2 has been studied at the B3LYP/6-31G∗ level. Formation of the [3+2] cycloadduct 4 takes place through a stepwise mechanism that is initiated by the nucleophilic attack of the thiocarbonyl ylide 1 to the ethylene derivative 2 to give a zwitterionic intermediate IN. The subsequent cyclization of IN yields a seven-membered cyclic ketene imine 6, which equilibrates with the thermodynamically more stable [3+2] cycloadduct 4. The computed free energies are in agreement with the experimental outcomes. 相似文献
13.
New conformationally restricted analogues of tumor promoter (−)-indolactam-V (1), indolinelactam-Vs (8, 11) and their hexyl derivatives at position 1 or 7 (9, 10, 12, 13), were synthesized from 1. (3R)-Indolinelactam-V (8) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3S)-indolinelactam-V (11) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 (10, 13) showed binding affinities for C1 domains of protein kinase C (PKC) isozymes compared to 1, but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3S)-1-hexylindolinelactam-V (12) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes. 相似文献
14.
Cyclic prodrug 1 was derived from RGD peptidomimetic 2 by linking the amino and carboxylic acid groups via an (acyloxy)alkoxy linker. The formation of a cyclic prodrug can transiently alter the physicochemical properties of the RGD peptidomimetic. Cyclic prodrug 1 was synthesized via the key intermediate 8, and the synthesis of this key intermediate was accomplished using two different routes. Cyclic prodrug 1 has a smaller hydrodynamic radius and higher membrane interaction potential than those of the parent RGD peptidomimetic 2. The cell membrane permeation of cyclic prodrug 1 is twice that of the parent peptidomimetic 2. The prodrug-to-drug conversion can be carried out in isolated porcine esterase as well as human plasma. The cyclic prodrug is more stable at pH 4 than pH 7, and is very unstable at pH 10. The cyclic prodrug has antithrombic activity, suggesting that it can be converted to the RGD peptidomimetic in platelet-rich plasma (PRP). 相似文献
15.
Synthesis of the structure claimed for puetuberosanol 1 (using the Juliá-Colonna oxidation in a key step) showed that the natural product was a different material. The isomeric epoxy alcohols 16-18 can be discounted from the alternatives. An analogue 19 of marshrin 2 was prepared but the synthesis of the natural product was thwarted by failure of a Juliá-Colonna oxidation in the key step. The epoxy ketone 29 was prepared by Darzens condensation and was converted into (±)-phebalosin 3. 相似文献
16.
Yasutake Takahashi Takurou Sakakibara Hideo Tomioka Kazuyoshi Fujimoto 《Tetrahedron letters》2006,47(24):3995-3999
Steady state and laser flash photolytic experiments with precursors 6 and 11 revealed that diphenyl substitution affects the lifetime and reaction mode of cyclobutylidene. 2,2-Diphenylcyclobutylidene 3 (τ <0.1 ns) produces methylenecyclopropane 1 via 1,2-carbon in significant preference to the positional isomer 2 or cyclobutene 4. On the other hand, 3,3-diphenylcyclobutylidene 5 (τ = ca. 4 ns) gives 1,2-hydrogen shift product 4 more favorably than 1,2-carbon shift product 2 together with formal carbene dimer 14. MRMP2//MP2 calculations afford useful results to understand the interrelationship among substitution, structure, and reactivity. 相似文献
17.
We developed a new protecting group, the cyclic sulfite for the protection of the 3′,5′-dihydroxy group of nucleosides. Seven cyclic sulfites, 4a-c, 5a-b, and 6a-b were prepared in high yields from the corresponding xylo-uridines 1 and 2, and xylo-adenosines 3 with thionyl chloride, respectively. Synthesis of the puromycin intermediate 8 was carried out by deprotection of the sulfite moiety through an intramolecular cyclization of the 2′-α-carbamate 7. 相似文献
18.
[1-Phenyl-2-[(E)-3-phenylprop-2-en-1-oyl-κO]ethenyl-κC1]tetracarbonylmanganese (1a) reacts with PhCCH in CCl4 at room temperature to form [2,4-diphenyl-6-(2-phenylethenyl)pyranyl-η5]tricarbonylmanganese (2a), whose X-ray crystal structure is reported to complement that of its isomer [6-oxo-2,4,7-triphenylcyclohepta-1,4-dienyl-1,2,3,4,5-η]tricarbonylmanganese (3a), previously obtained from the reaction under reflux; but for 1a and PhCCPh the pyranyl complex cannot be isolated before rearrangement to the 3a analogue occurs. More forcing reaction conditions for 1a with Me3SiCCH and for [1-(2-trifluoromethylphenyl)-2-[(E)-3-(2-trifluoromethylphenyl)prop-2-en-1-oyl-κO]ethenyl-κC1]tetracarbonylmanganese (1b) with Me3SiCCH and PhCCH give new analogues of 3a where previously only 2a analogues had been isolated.The reaction in CCl4 under reflux of PhCCH and the β-deuterio analogue of 1a, [1-phenyl-2-[(E)-3-phenylprop-2-en-1-oyl-3d-κO]ethenyl-κC1]tetracarbonylmanganese, gave deuteriated 3a with exo-D at the α-carbon, C7. This is inconsistent with the Mn-mediated Ph migration mechanism originally proposed to accommodate the endo position of Ph in 3a, and instead it implicates a cyclopropyl carbonyl-addition intermediate or a cyclopropyl acyl-substitution transition state in the key rearrangement step for 2a → 3a. 相似文献
19.
Yingquan Song Hondamuni I. De SilvaWilliam P. Henry Guozhong YeSabornie Chatterjee Charles U. Pittman Jr. 《Tetrahedron letters》2011,52(35):4507-4511
The five-membered cyclic ketene-N,O-acetal, 2-oxazolidin-2-ylidene-1-phenylethanone 1, and its anion 2, formed on deprotonation, are ambident nucleophiles. Compound 1 was synthesized by benzoylation of 2-methyl-2-oxazoline to give a ring-opened N,C,O-trisbenzoylation product, 9, followed by N,O-double debenzoylation using methanolic KOH. Compound 1 reacted with benzoyl chloride to give N,C,O-trisbenzoylated 9, and reacted with phenyl chloroformate to give the similar ring-opened carbonic acid 3-[(2-chloro-ethyl)-phenoxycarbonyl-amino]-3-oxo-1-phenyl-propenyl ester phenyl ester, 13. In contrast, ambident anion 2 reacted with benzoyl chloride to give the β,β-bisbenzoylated cyclic ketene-N,O-acetal, 16, and reacted with phenyl chloroformate to give the novel heterocycle 3-(2-hydroxy-ethyl)-6-phenyl-[1,3]oxazine-2,4-dione, 17. 相似文献
20.
Synthesis, photophysical, and complexation properties of fluorescent chemosensors, L1 and L2, with ‘receptor-spacer-fluorophore’ motif (L1: NS2O2-cyclic receptor, L2: acyclic analogue receptor) are described. Maximum chelation-enhanced fluorescence effect (TURN-ON type) was observed in the presence of Ag+ for both fluoroionophores in a 1:1 (v/v) aqueous ethanol solution: remarkably superior selectivity of L1 (150-fold) with cyclic receptor than that of the L2 (50-fold) with acyclic analogue was found. According to the fluorescence and NMR titrations, the excellent selectivity of L1 is attributed to its topology-based higher affinity in complexation. 相似文献