- Synthesis and comparative structure-activity study of carbohydrate-based phenolic compounds as α-glucosidase inhibitors and antioxidants
-
Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro -D-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.
- MacHida, Shota,Mukai, Saki,Kono, Rina,Funato, Megumi,Saito, Hiroaki,Uchiyama, Taketo
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-
- Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates
-
It is urgently necessary to develop more effective anti-influenza agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene derivatives are effective inhibitors of influenza virus infection. In the present study, a series of C-28 modified pentacyclic triterpene derivatives via conjugation with a series of polyphenols were synthesized, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK (Madin-Darby canine kidney) cells were evaluated. Four compounds 23m, 23o, 23q and 23s displayed robust anti-influenza potency with averaged IC50 values at the low-micromole level, surpassing the potency of oseltamivir. In addition, the in vitro cytotoxic activity of the four conjugates against MDCK cells showed no toxicity at 100 μM. Further mechanism studies of compound 23s, one of the best representative conjugates with IC50 value of 5.80 μM and a selective index (SI) value of over 17.2, by hemagglutination inhibition (HI), surface plasmon resonance and molecular modeling indicated that this conjugate bound tightly to the viral envelope hemagglutinin (KD = 15.6 μM), thus blocking the invasion of influenza viruses into host cells.
- Li, Haiwei,Li, Man,Xu, Renyang,Wang, Shouxin,Zhang, Yongmin,Zhang, Lihe,Zhou, Demin,Xiao, Sulong
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p. 560 - 568
(2019/01/03)
-
- Dendritic architectures by orthogonal thiol-maleimide "click" and furan-maleimide dynamic covalent chemistries
-
A set of dendrons and dendrimers is synthesized divergently using an orthogonal combination of kinetically-driven thiol-maleimide "click" chemistry and thermodynamically reversible furan-maleimide cycloaddition/retrocycloaddition reactions. Growth is controlled by taking advantage of the selective thiol-ene addition of thiols to the electron withdrawn alkene of maleimide in the presence of electron rich alkene of oxanorbornene. Subsequent activation of growing dendrons/dendrimers requires only heat to induce the dynamic covalent liberation of peripheral furan protecting groups. The methodology introduced provides a new route to multifunctional dendrimers that could, in principle, be synthesized by introducing different branched monomers at any stage of dendrimer growth, allowing dendrimer architectures and properties to be better tailored to their intended applications.
- Frayne, Stephen H.,Stolz, Robert M.,Northrop, Brian H.
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p. 7878 - 7883
(2019/09/06)
-
- Benzoic hydroxamate-based iron complexes as model compounds for humic substances: Synthesis, characterization and algal growth experiments
-
A series of monomeric and dimeric FeIII complexes bearing benzoic hydroxamates as O,O-chelates has been prepared and characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry, EPR spectroscopy and for some examples by X-ray diffraction analysis. The stability of the synthesized complexes in pure water and seawater was monitored over 24 h by means of UV-Vis spectrometry. The ability to release iron from the synthesized model complexes has been investigated with algae growth experiments.
- Orlowska, Ewelina,Roller, Alexander,Wiesinger, Hubert,Pignitter, Marc,Jirsa, Franz,Krachler, Regina,Kandioller, Wolfgang,Keppler, Bernhard K.
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p. 40238 - 40249
(2016/05/24)
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- Visual detection of fluoride ions
-
Dendrimer-hydrazides are coupled to polycyclic aromatic hydrocarbons for use in the visual detection of the presence of low levels of fluoride in a sample. The dendrimers can have a phenyl core, a first generation of aralkyl ethers, and an optional second generation of aralkyl ethers. The compounds form gels with solvents. In the presence of fluoride ion, the gels undergo color changes and/or gel to liquid phase change.
- -
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Page/Page column 23-24
(2015/12/18)
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- Synthesis of Curvulone B Using the 2-Chlorobenzyl Protecting Group
-
A total synthesis of curvulone B has been completed using a Friedel-Crafts reaction and a highly cis-selective intramolecular oxa-Michael addition. The 2-chlorobenzyl protecting group was employed and found to have much greater Lewis acid stability compared to the simple benzyl group.
- Bates, Roderick W.,Wang, Kongchen,Zhou, Guanying,Kang, Dave Zhihong
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p. 751 - 754
(2015/03/30)
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- Biomimetic synthesis of active isorhapontigenin dimers
-
Synthetic isorhapontigenin was treated with several kinds of inorganic reagents and peroxidase so as to prepare active stilbene dimers. Among them, silver acetate in methanol gave two new isorhapontigenin dimers 4 and 5, together with four known natural stilbene dimers 2, 3, 6, and 7. Their structures and relative configurations were determined on the basis of spectral analysis, and their possible formation mechanisms were discussed, respectively. Compounds 2, 6, and 7 were artificially synthesized for the first time. All the products were evaluated for anti-inflammatory activities.
- Wang, Xian-Fen,Zhang, Yuan,Lin, Ming-Bao,Hou, Qi,Yao, Chun-Suo,Shi, Jian-Gong
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p. 511 - 521
(2014/06/09)
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- Effect of the bulkiness of the end functional amide groups on the optical, gelation, and morphological properties of oligo(p-phenylenevinylene) π-gelators
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Herein, we describe the role of end functional groups in the self-assembly of amide-functionalized oligo(p-phenylenevinylene) (OPV) gelators with different end-groups. The interplay between hydrogen-bonding and π-stacking interactions was controlled by the bulkiness of the end functional groups, thereby resulting in aggregates of different types, which led to the gelation of a wide range of solvents. The variable-temperature UV/Vis absorption and fluorescence spectroscopic features of gelators with small end-groups revealed the formation of 1D H-type aggregates in CHCl3. However, under fast cooling in toluene, 1D H-type aggregates were formed, whereas slow cooling resulted in 2D H-type aggregates. OPV amide with bulky dendritic end-group formed hydrogen-bonded random aggregates in toluene and a morphology transition from vesicles into fibrous aggregates was observed in THF. Interestingly, the presence of bulky end-group enhanced fluorescence in the xerogel state and aggregation in polar solvents. The difference between the aggregation properties of OPV amides with small and bulky end-groups allowed the preparation of self-assembled structures with distinct morphological and optical features. Buying in bulk: OPV amides with small end-groups self-assemble into 2D/1D aggregates in toluene and 1D aggregates in CHCl3. Bulky end-groups impede fluorescence quenching in the self-assembled state by blocking π-stacking and facilitate morphological transition in THF.
- Babu, Sukumaran Santhosh,Praveen, Vakayil K.,Kartha, Kalathil K.,Mahesh, Sankarapillai,Ajayaghosh, Ayyappanpillai
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p. 1830 - 1840
(2014/07/08)
-
- A detailed investigation of light-harvesting efficiency of blue color emitting divergent iridium dendrimers with peripheral phenylcarbazole units
-
The increase in phosphorescence efficiency was estimated by the energy transfer mechanism for divergent iridium dendrimers with peripheral phenylcarbazole units. A series of Ir-core/phenylcarbazole-end dendrons of the type, Ir(dfppy)2(pic-Czsu
- Cho, Yang-Jin,Wee, Kyung-Ryang,Son, Ho-Jin,Cho, Dae Won,Kang, Sang Ook
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p. 4510 - 4521
(2014/03/21)
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- Structure-activity relationships for vitamin D3-based aromatic a-ring analogues as hedgehog pathway inhibitors
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A structure-activity relationship study for a series of vitamin D3-based (VD3) analogues that incorporate aromatic A-ring mimics with varying functionality has provided key insight into scaffold features that result in potent, selective Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a single substitution at the ortho or para position of the aromatic A-ring, (2) a heteroaryl or biaryl moiety, or (3) multiple substituents on the aromatic A-ring were prepared and evaluated. Aromatic A-ring mimics incorporating either single or multiple hydrophilic moieties on a six-membered ring inhibited the Hh pathway in both Hh-dependent mouse embryonic fibroblasts and cultured cancer cells (IC50 values 0.74-10 μM). Preliminary studies were conducted to probe the cellular mechanisms through which VD3 and 5, the most active analogue, inhibit Hh signaling. These studies suggested that the anti-Hh activity of VD3 is primarily attributed to the vitamin D receptor, whereas 5 affects Hh inhibition through a separate mechanism.
- Deberardinis, Albert M.,Madden, Daniel J.,Banerjee, Upasana,Sail, Vibhavari,Raccuia, Daniel S.,De Carlo, Daniel,Lemieux, Steven M.,Meares, Adam,Hadden, M. Kyle
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p. 3724 - 3736
(2014/05/20)
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- Supramolecular design for two-component hydrogels with intrinsic emission in the visible region
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We report, for the first time, an in situ formation of two-component hydrogels from pyridine derivatives of poly(aryl ether) dendrons and tartaric acid. The two-component system (dendron + acid) undergoes J-type aggregation, leading to fibrillar type self-assembly in THF-water mixture along with blue (470 nm) and green (500 nm) intrinsic emissions. The Royal Society of Chemistry 2013.
- Rajamalli,Atta, Supriya,Maity, Sandeepan,Prasad, Edamana
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supporting information
p. 1744 - 1746
(2013/03/14)
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- A new synthesis of 4′-resveratrol esters and evaluation of the potential for anti-depressant activity
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The 4′-ester analog of the disease preventative resveratrol 1 (RV), 4′-acetyl-RV 2 along with 4′-pivaloate 13 and benzoate 14 RV were synthesized. The previously developed palladium catalyzed decarbonylative Heck coupling was used to assemble the stilbene core together with 3,5-dibenzyl protected phenol intermediates that allowed for efficient coupling and deprotection using boron trifluoride etherate. Studies with Long-Evans rats were performed to establish safety, toxicity, and behavioral parameters. In addition, the Porsalt forced-swim test was used to demonstrate anti-depressant activity.
- Acerson, Mark J.,Fabick, Kimberly M.,Wong, Yong,Blake, Crystal,Lephart, Edwin D.,Andrus, Merritt B.
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p. 2941 - 2944
(2013/06/27)
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- Polycationic ligands in gold catalysis: Synthesis and applications of extremely π-acidic catalysts
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Very often ligands are anionic or neutral species. Cationic ones are rare, and, when used, the positively charged groups are normally appended to the periphery of the ligand. Here, we describe a dicationic phosphine with no spacer between the phosphorus atom and the two positively charged groups. This structural feature makes its donor ability poorer than that of phosphites and only comparable to extremely toxic or pyrophoric compounds such as PF 3 or P(CF3)3. By exploiting these properties, a new Au catalyst has been developed displaying a dramatically enhanced capacity to activate π-systems. This has been used to synthesize very sterically hindered and naturally occurring 4,5-disubstituted phenanthrenes. The present approach is expected to be applicable to the development and improvement of many other transition metal catalyzed transformations that benefit from extremely strong π-acceptor ligands. The mechanism of selected catalytic transformations has been explored by density functional calculations.
- Carreras, Javier,Gopakumar, Gopinadhanpillai,Gu, Liangu,Gimeno, Ana,Linowski, Pawel,Petu?kova, Jekaterina,Thiel, Walter,Alcarazo, Manuel
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supporting information
p. 18815 - 18823
(2014/01/06)
-
- Synthesis and antifungal properties of papulacandin derivatives
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Derivatives of an antifungal agent that targets the β-(1,3)-D-glucan synthase, papulacandin D, were synthesized and tested for activity. The papulacandin D structure contains a challenging benzannulated spiroketal unit, which is introduced in a palladiumcatalyzed cross-coupling reaction of a glycal silanolate and an aryl iodide followed by an oxidative spiroketalization. Four different variants were made, differing in the nature of the acyl side chain with respect to the length, and in the number and stereochemistry of the double bonds. Moderate biological activity was observed for the derivatives with a side chain based on palmitic acid and linoleic acid.
- Van Der Kaaden, Marjolein,Breukink, Eefjan,Pieters, Roland J.
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p. 732 - 737
(2012/07/14)
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- Functionalization of pristine graphene with conjugated polymers through diradical addition and propagation
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Hanging on: Pristine graphene was grafted with conjugated polymers through addition and propagation of diradicals generated from Bergman cyclization of enediyne-containing dendrimers. The surface functionalization was confirmed with TGA, FTIR and Raman spectroscopy, and AFM analysis. The sp2 network of graphene is only slightly destroyed, as revealed by conductivity measurements. Copyright
- Ma, Xiaowei,Li, Fei,Wang, Youfu,Hu, Aiguo
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p. 2547 - 2550,4
(2020/09/02)
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- Low molecular weight fluorescent organogel for fluoride ion detection
-
The design, synthesis, and the photophysical properties of a Low Molecular Weight Gel (LMWG) based on AB3 and AB2 type poly(aryl ether) dendrons with an anthracene chromophore attached through an acylhydrazone linkage are described. The gel is utilized for an efficient 'naked eye' detection of fluoride ions (as low as 0.1 equiv with respect to the gelator concentration), through a reversible gel-sol transition, which is associated with a color change from deep yellow to bright red.
- Rajamalli,Prasad, Edamana
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supporting information; experimental part
p. 3714 - 3717
(2011/09/12)
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- Luminescent micro and nanogel formation from AB3 type poly(aryl ether) dendron derivatives without conventional multi-interactive gelation motifs
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We report the synthesis, gelation and photophysical properties of luminescent AB3 type poly(aryl ether) dendron derivatives in the absence of conventional multi-interactive gelation motifs. The gelation process is controlled through employing partial polar solvent milieu, which significantly enhances the propensity of π-π interaction between the aryl units present in the system. The self-assembly leads to unprecedented gelation through entrapping solvent molecules in the fibrillar arrangement of poly(aryl ether) units. The strategy was further utilized to prepare an excimer based photoluminescent gel through incorporating anthracene units in the dendrons. The close proximity between the anthracene units in the gel renders the formation of anthracene excimers at room temperature, resulting in the emission of bright green light from the gel, upon UV excitation. The study suggests that the size and packing of the self-assembled fibre can be controlled by the generation and functional groups present in the dendron. Furthermore, the strategy envisages an easy approach to generate fluorescent Low Molecular-mass Organic Gelator (LMOG) through incorporating poly cyclic aromatic hydrocarbon units to the poly(aryl ether) dendrons, since the self-assembly is largely guided by π-π interactions. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
- Rajamalli,Prasad, Edamana
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supporting information; experimental part
p. 1541 - 1548
(2011/09/20)
-
- Lanthanide-based coordination polymers assembled from derivatives of 3,5-dihydroxy benzoates: Syntheses, crystal structures, and photophysical properties
-
Two new aromatic carboxylic acids, namely, 3,5-bis(benzyloxy)- benzoic acid (HL1) and 3,5-bis(pyridine-2-ylmethoxy)benzoic acid (HL2), have been prepared by replacing the hydroxyl hydrogens of 3,5-dihydroxy benzoic acid with benzyl and pyridyl moieties, respectively. The anions derived fromHL1 and HL2 have been used for the support of a series of lanthanide coordination compounds [Eu 3+ = 1-2; Tb3+ = 3-4; Gd3+ = 5-6]. The new lanthanide complexes have been characterized on the basis of a variety of spectroscopic techniques in conjunction with an assessment of their photophysical properties. Lanthanide complexes 2, 4, and 6, which were synthesized from 3,5-bis(pyridine- 2-ylmethoxy)benzoic acid, were structurally authenticated by single-crystal X-ray diffraction. All three complexes were found to exist as infinite one-dimensional (1-D) coordination polymers with the general formula {[Ln(L2)3- (H2O)2] xH2O}n Scrutiny of the packing diagrams for 2, 4, and 6 revealed the existence of interesting two-dimensional molecular arrays held together by intermolecular hydrogen-bonding interactions. Furthermore, the coordinated benzoate ligands serve as efficient light harvesting chromophores. In the cases of 1-4, the lowest energy maxima fall in the range 280-340 nm [molar absorption coefficient (ε) = (0.39-1.01) × 104 M-1 cm-1]. Moreover, the Tb3+ complexes 3 and 4 exhibit bright green luminescence efficiencies in the solid state (φoverall = 60% for 3; 27% for 4) and possess longer excited state lifetimes than the other complexes (t = 1.16 ms for 3; 1.38 ms for 4). In contrast to the foregoing, the Eu3+ complexes 1 and 2 feature poor luminescence efficiencies.
- Sivakumar, Sarika,Reddy,Cowley, Alan H.,Butorac, Rachel R.
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p. 4882 - 4891
(2011/08/03)
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- Synthesis of dendronized polymers through bergman cyclization of enediyne-containing Frechet-type dendrimers
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In this article, dendronized polymers with rigid backbones were synthesized from enediyne-containing Frechet-type dendrimers. Two generations of dendrimers were conically incorporated with 3-(2-(2-(trimethylsilyl)ethynyl)phenyl)prop-2- yn-1-ol. The trimethylsilyl protection groups of enediyne units were subsequently removed, and two types of brush polymers with rigid conjugated backbone were prepared through Bergman cyclization polymerization at elevated temperature under vacuum. The dendronized polymers were characterized with GPC, IR, UV-vis, and NMR spectroscopy. Furthermore, the morphology of the dendronized polymer was revealed by atomic force microscopy.
- Ma, Jianguo,Ma, Xiaowei,Deng, Sheng,Li, Fei,Hu, Aiguo
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experimental part
p. 1368 - 1375
(2012/02/14)
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- Total synthesis of (+)-papulacandin D
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A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side-chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side-chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron-rich and sterically hindered aromatic iodide and (2) a Lewis-base catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.
- Denmark, Scott E.,Kobayashi, Tetsuya,Regens, Christopher S.
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supporting information; experimental part
p. 4745 - 4759
(2010/08/06)
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- Direct functionalization of self-assembled nanotubes overcomes unfavorable self-assembling processes
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Diamides containing alkyne and azido were self-assembled into nanotubes and were reacted under their self-assembled state with small molecules by "click chemistry"; the resulting compounds remain self-assembled into new nanotubes that cannot be formed by
- Nguyen, Thi-Thanh-Tam,Simon, Franois-Xavier,Schmutz, Marc,Mesini, Philippe J.
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supporting information; experimental part
p. 3457 - 3459
(2009/12/26)
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- 1H-INDOLE-2-CARBOXYLIC ACID DERIVATIVES USEFUL AS PPAR MODULATORS
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The present invention relates to certain indole derivatives that are modulators of PPAR, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine.
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Page/Page column 85-86
(2008/06/13)
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- Triazole-linked dendro[60]fullerenes: modular synthesis via a 'click' reaction and acidity-dependent self-assembly on the surface
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A series of Fréchet-type dendron functionalized [60]fullerene derivatives that bear a 1,2,3-triazole linkage group, referred to as triazole-linked dendro[60]fullerenes, were prepared via a modular synthetic protocol based on a Cu-catalyzed [3+2] cycloaddi
- Mahmud, Ilias M.,Zhou, Ningzhang,Wang, Li,Zhao, Yuming
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experimental part
p. 11420 - 11432
(2009/04/11)
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- Hydrogen-bonded dendronized polymers and their self-assembly in solution
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Frechet-type benzyl ether dendrons of second and third generations with a carboxyl group (G2, G3) at the apex site could attach to poly(4-vinylpyridine) (PVP), forming hydrogen-bonded dendronized polymers (HB denpols) in their common solvent, chloroform. The HB denpols show unique self-assembly behavior, forming vesicles in the common solvent under ultrasonic treatment. The structure and morphology of the vesicles were characterized by dynamic light scattering (DLS), static light scattering (SLS), SEM, TEM, and AFM. The size of the vesicles decreases and the thickness of the vascular membrane increases as the molar ratio of Gx/PVP increases. The hydrogen bonding. π-π aromatic stacking of the dendrons. and the considerable difference in architecture between the dendron Gx and PVP are the main factors facilitating the assembly of the HB denpols in the common solvent.
- Xie, Dang,Jiang, Ming,Zhang, Guangzhao,Chen, Daoyong
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p. 3346 - 3353
(2008/02/08)
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- Total synthesis of papulacandin D
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A total synthesis of the antifungal agent papulacandin D is reported. The molecule is representative of a large class of C-aryl glycosides that exhibit significant antifungal activity. The synthetic strategy bifurcates the molecule into two nearly equal subunits, the arylglycoside and 18-carbon fatty acid side chain. The key strategic transformations are (1) the palladium catalyzed, organosilanolate-based cross-coupling of a protected glucal silanol and (2) a catalytic enantioselective allylation of a dienal using allyltrichlorosilane. The synthesis was accomplished in 31 steps overall from commercial starting materials to afford over 50 mg of the natural product. Copyright
- Denmark, Scott E.,Regens, Christopher S.,Kobayashi, Tetsuya
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p. 2774 - 2776
(2008/02/02)
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- Optical switching and antenna effect of dendrimers with an anthracene core
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Dendrimers 6Gi (i=1-4) consisting of an anthracene core and Frechet dendrons which are attached via a CH2OCH2 chain in the 9-position undergo quantitative and completely reversible intramolecular [4π+4π] cycloaddition. The
- Cao, Derong,Dobis, Silvia,Gao, Chunmei,Hillmann, Sabine,Meier, Herbert
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p. 9317 - 9323
(2008/12/20)
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- Synthesis and retrostructural analysis of libraries of AB3 and constitutional isomeric AB2 phenylpropyl ether-based supramolecular dendrimers
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We report the synthesis of methyl esters of 3-(4-hydroxyphenyl)propionic, 3-(3,4-dihydroxyphenyl)propionic, 3-(3,5-dihydroxyphenyl)propionic, and 3-(3,4,5-trihydroxyphenyl)propionic acids and their use in a convergent iterative strategy to prepare up to four generations of three libraries, one of 3,4,5- and two of constitutional isomeric 3,4- and 3,5-substituted 3-phenylpropyl dendrons. Each library contains 3-[3,4,5-tris(dodecyl-1-oxy) phenyl]propyl-, 3-[3,4-bis(dodecyl-1-oxy)phenyl]propyl-, 3-{3,4-bis[3-(4- dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl-, and 3-{3,4,5-tris[3-(4-dodecyl- 1-oxyphenyl)propyl-1-oxy]phenyl}propyl ether first-generation dendrons on their periphery and -CO2CH3, -COOH, and -CH2OH groups at their apex. Regardless of their generation number and their periphery, internal, and apex structures, these dendrons self-assemble into supramolecular dendrimers that self-organize into all periodic and quasi-periodic assemblies encountered previously and in several unencountered with architecturally related benzyl ether-based supramolecular dendrimers. A variety of porous columnar lattices that were previously obtained only from dendritic dipeptides and hollow supramolecular spheres were also discovered from these building blocks. The more flexible and less compact 3-phenylpropyl ether repeat units are stable under acidic conditions, facilitate a simpler synthetic strategy, provide faster dynamics of self-assembly into higher-order supramolecular structures of larger dimensions, exhibit lower transition temperatures than the corresponding benzyl ether homologues, and demonstrate the generality of the self-assembly concept based on amphiphilic dendrons.
- Percec, Virgil,Peterca, Mihai,Sienkowska, Monika J.,Ilies, Marc A.,Aqad, Emad,Smidrkal, Jan,Heiney, Paul A.
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p. 3324 - 3334
(2007/10/03)
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- Total synthesis of (±)-quadrangularin A
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The key to successful coupling in the synthesis of (±)- quadrangularin A (1) was the introduction of tert-butyl groups in the precursor to block two reactive positions. Thus, the oxidative coupling of 3,5-di-(tert-butyl) resveratrol was carried out regioselectively in an efficient total synthesis of the natural product. (Chemical Equation Presented)
- Li, Wenling,Li, Hao,Li, Ying,Hou, Zijie
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p. 7609 - 7611
(2008/02/12)
-
- Self-assembly of chiral depsipeptide dendrimers
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The self-assembly of chiral depsipeptide dendrons 4, which contain a cyanuric acid building block at their focal point, with the homotritopic Hamilton receptor 1 is reported. The 1:3 compositions of the resulting chiral supramolecular dendrimers, the association constants Kn, and the cooperativity of binding expressed by Scatchard plots and the Hill coefficients nH was determined by NMR titration experiments. The most pronounced positive cooperativity was found for the complexes 1L3 with L being the second-generation dendrons 4c-e. The least stable complexes are formed with the bulky third-generation dendrons 4f-h. Similar results are obtained by the corresponding complexation of the achiral Frechet-type first- to third-generation dendrons 3 with 1. Chiroptical investigations of 1:3 complexes of 1 and 4 reveal chirality transfer from the dendron to the Hamilton receptor as demonstrated by the appearance of new CD absorption bands at 310 nm.
- Hager, Kristine,Franz, Alexander,Hirsch, Andreas
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p. 2663 - 2679
(2008/02/03)
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- Structural and thermodynamic studies on cation-II interactions in lectin-ligand complexes: High-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction
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The high-resolution X-ray crystal structures of the carbohydrate recognition domain of human galectin-3 were solved in complex with N-acetyllactosamine (LacNAc) and the high-affinity inhibitor, methyl 2-acetamido-2-deoxy-4-O-(3-deoxy-3-[4-methoxy-2,3,5,6-tetrafluorobenzamido] -β-D-galactopyranose)-β-D-glucopyranoside, to gain insight into the basis for the affinity-enhancing effect of the 4-methoxy-2,3,5,6- tetrafluorobenzamido moiety. The structures show that the side chain of Arg144 stacks against the aromatic moiety of the inhibitor, an interaction made possible by a reorientation of the side chain relative to that seen in the LacNAc complex. Based on these structures, synthesis of second generation LacNAc derivatives carrying aromatic amides at 3′-C, followed by screening with a novel fluorescence polarization assay, has led to the identification of inhibitors with further enhanced affinity for galectin-3 (Kd ≥ 320 nM). The thermodynamic parameters describing the binding of the galectin-3 C-terminal to selected inhibitors were determined by isothermal titration calorimetry and showed that the affinity enhancements were due to favorable enthalpic contributions. These enhancements could be rationalized by the combined effects of the inhibitor aromatic structure on a cation-Π interaction and of direct interactions between the aromatic substituents and the protein. The results demonstrate that protein-ligand interactions can be significantly enhanced by the fine-tuning of arginine-arene interactions.
- Soerme, Pernilla,Arnoux, Pascal,Kahl-Knutsson, Barbro,Leffler, Hakon,Rini, James M.,Nilsson, Ulf J.
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p. 1737 - 1743
(2007/10/03)
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- Synthesis of versatile intermediates of the ferrocene series: Reductive amination of ferrocenecarbaldehyde
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Reductive amination of ferrocenecarbaldehyde with several primary and secondary amines in the presence of sodium triacetoxyborohydride was studied. This method was used for the synthesis of new ferrocenylmethylamines, viz., N-(ferrocenylmethyl)isoleucine methyl ester, N,N-bis(ferrocenylmethyl)glycine ethyl ester, and N-(3,5-dibenzyloxybenzyl)-N-(ferrocenylmethyl)methylamine. The latter is a potential precursor of a dendrimer with the chiral ferrocenyl plane in the core.
- Khrushcheva,Sokolov
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p. 830 - 833
(2007/10/03)
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- Dendronized protein polymers: Synthesis and self-assembly of monodisperse cylindrical macromolecules
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Monodisperse dendronized protein polymers (DPPs), cylindrical dendrimers containing protein core, can be efficiently produced through a combined modular biosynthetic strategy. These DPP materials possess predictable size, shape, and solubility. In organic
- Zhuravel, Michael A.,Davis, Nicolynn E.,Nguyen, SonBinh T.,Koltover, Ilya
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p. 9882 - 9883
(2007/10/03)
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- A new convergent approach to dendritic macromolecules
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The novel convergent growth approach to dendritic macromolecules is described. Polyether dendritic sectors [G-na]-OH from the first to the fourth generations, respectively, were prepared by this approach from readily available starting material.
- Cao, Xiaoping,Wang, Feng,Guo, Shu
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p. 3149 - 3158
(2007/10/03)
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- Mechanistic studies on the biomimetic reduction of tetrahydroxynaphthalene, a key intermediate in melanin biosynthesis
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1,3,6,8-Tetrahydroxynaphthalene (T4HN) is an aromatic polyketide, serving as a general precursor of fungal melanin. Melanin biosynthesis involves two consecutive deoxygenations of T4HN, consisting of the reduction of a phenolic carbon followed by dehydrat
- Ichinose,Ebizuka,Sankawa
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p. 192 - 196
(2007/10/03)
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- Development of a novel hapten for radioimmunoassay of the lignan, enterolactone in plasma (Serum). Total synthesis of (±)-trans-5- carboxymethoxyenterolactone and several analogues
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A recently developed method for the analysis of the mammalian lignan, enterolactone 1, is based on time-resolved fluoroimmunoassay (TR-FIA) using an europium chelate as a label. This RIA utilizes enterolactone derivatives carrying a carboxylic acid appendage for the production of antiserum and tracer. The synthesis of 5-carboxymethoxyenterolactone 6 and analogues 5, 7 and 8 is described, and their suitability for the method are discussed. (C) 2000 Elsevier Science Ltd.
- M?kel?, Taru,Matikainen, Jorma,W?h?l?, Kristiina,Hase, Tapio
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p. 1873 - 1882
(2007/10/03)
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- A simple method for controlling dendritic architecture and diversity: A parallel monomer combination approach
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A novel parallel monomer combination approach to manipulating the architectural disposition of dendritic macromolecules is described. It harnesses the synthetic speed and power of the double-stage convergent growth approach and classical parallel synthesi
- Freeman,Chrisstoffels,Frechet
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p. 7612 - 7617
(2007/10/03)
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- Phenylglycine derivatives useful for treating disorders of the central nervous system
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A pharmaceutical compound of the formula: STR1 in which R1 is hydrogen, hydroxy or C1-6 alkoxy, R2 is hydrogen, carboxy, tetrazolyl, --SO2 H, --SO3 H, --OSO3 H, --CONHOH, or --P(OH)OR', --PO(OH)OR', --OP(OH)OR' or --OPO(OH)OR' where R' is hydrogen, C1-6 alkyl, C2-6 alkenyl or aryl C1-6 alkyl, R3 is hydrogen, hydroxy or C1-4 alkoxy, and R4 is fluoro, trifluoromethyl, nitro, C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, heteroaryl, optionally substituted aryl, optionally substituted aryl C1-6 alkyl, optionally substituted aryl C2-6 alkenyl, optionally substituted aryl C2-6 alkynyl, optionally substituted aryloxy, optionally substituted aryl C1-6 alkoxy, optionally substituted arylthio, optionally substituted aryl C1-6 alkylthio or --CONR"R'", --SO2 NR"R"", --NR"R'", --OCONR"R"' or --SONR"R'" where R" and R'" are each hydrogen, C1-6 alkyl or aryl C1-6 alkyl, or R" and R'" together form a C3-7 alkylene ring; provided that (i) R1, R2 and R3 are not all hydrogen,and (ii) when R2 and R3 are hydrogen and R1 is hydroxy, R4 is not fluoro; or a salt or ester thereof.
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- Asymmetric Synthesis of a Series of Chiral AB2 Monomers for Dendrimer Construction
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Efficient preparation of a series of four chiral, nonracemic AB2 monomers suitable for the construction of dendrimers is presented. Monomers 1-4 possess the common structural features of a diphenolic moiety and a benzylic or aliphatic hydroxyl which render these molecules suitable for convergent dendrimer synthesis. The same basic, high-yielding, five-step sequence is employed for 1-4. Stilbene derivatives 13 and 14 are prepared by a Horner-Wadsworth-Emmons modified Wittig reaction between 3,5- or 3,4-bis(benzyloxy)benzaldehyde (8 and 10) and an ester-substituted benzylphosphonate (11 or 12). Cinnamate derivatives 21 and 22 are prepared similarly from 8 and 10 and triethyl phosphonoacetate. Chirality is introduced in the form of a 1,2-diol unit by Sharpless asymmetric dihydroxylation (AD) (>97% ee in all cases). Protection of the 1,2-diols as their acetonide derivatives provides dioxolane intermediates 17, 18, 25, and 26. Reduction of the ester groups followed by hydrogenolysis of the benzyl ethers yields AB2 monomers 1-4 in 57-67% overall yield from 8 and 10.
- McElhanon, James R.,Wu, Mu-Jen,Escobar, Maya,Chaudhry, Umer,Hu, Chun-Ling,McGrath, Dominic V.
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p. 908 - 915
(2007/10/03)
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- Induction of liquid crystallinity by host-guest interactions
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A molecular clip is described which binds aromatic guests by an induced fit mechanism. It contains twelve long aliphatic chains and can evoke liquid-crystalline properties in a variety of molecules, including polymers and porphyrins, by a process of molecular recognition.
- Van Nunen, Johanna L. M.,Folmer, Brigitte F. B.,Nolte, Roeland J. M.
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p. 283 - 291
(2007/10/03)
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- Selective endothelin A receptor ligands. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives
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This paper describes the discovery of a new non-peptide endothelin A (ET(A)) selective ligand, 2,4-dibenzyloxybenzoic acid 3, which inhibits the binding of [125I]ET-1 to ET(A) receptors with an IC50 of 9 μM (ET-1 = endothelin-1). Optimisation of 3 resulted in compound 52 which had an IC50 of 1 μM. One of the analogues of 3, compound 15, was examined in a functional assay and shown to antagonise ET-1-induced contraction of rat aorta. The identification of 3 was made through the application of ChemDBS-3D searching of our corporate database. The 3D query, using an aromatic ring to a carboxylic acid group separated by 10.2 ± 1.1 A, was derived from an examination of common pharmacophoric distances found in the low energy conformations of two known ET(A) antagonists, the cyclic pentapeptide BQ 123 1 and myriceron caffeoyl ester 2.
- Astles,Brown,Handscombe,Harper,Harris,Lewis,Lockey,McCarthy,McLay,Porter,Roach,Smith,Walsh
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p. 409 - 423
(2007/10/03)
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- A urinary metabolite of Δ1-tetrahydrocannabinol. The first synthesis of 4''-hydroxy-Δ1-tetrahydrocannabinol-7-oic acid labelled with deuterium
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The first synthesis of 4''-hydroxy-Δ1-THC-7-oic acid, one of the three major metabolites of Δ1-THC identified in human urine is discussed. Methyl 4-(3,5-dihydroxyphenyl)butanoate (8) was prepared from 3,5-dihydroxybenzoic acid in an overall yield of 15%. 8 was condensed with a terpene synthon (9) under acidic conditions followed by hydrolysis and conversion of the 4''-carboxylic acid function to the corresponding methyl ketone using methyllithium. Reduction with NaBH4 afforded the secondary alcohol in the side-chain. Acetylation and removal of the 1,3-dithiane masking group gave the aldehyde in C-7-position which was further oxidized using NaClO2 followed by deacetylation to give the desired metabolite 14. The same procedure may be used for the synthesis of unlabelled 4''-hydroxy-Δ1-THC-7-oic acid.
- Szirmai,Odqvist,Halldin
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p. 309 - 324
(2007/10/03)
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- N-SUBSTTTUTED ANILINES, INHIBITORS OF PHOSPHOLIPASES A2
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Compounds of the formula wherein R1, R2, R3, R4, Rs, Re, R7, R8, n, m, o, p and q are as hereinafter set forth, and, when R2 is hydrogen, pharmaceutically acceptable salts thereof with bases,are described. The compounds of formula 1 are potent inhibitors of phospholipases A2 (PLA2's) and are therefore useful in the treatment of inflammatory diseases, such as psosiasis, inflammatory bowel disease, asthma, allergy, arthritis, dermatitis, gout, pulmonary disease, myocardial ischemia/reperfusion, and trauma induced inflammation, such as spinal cord injury
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- Synthesis and Protein-Tyrosine Kinase Inhibitory Activity of Polyhydroxylated Stilbene Analogues of Piceatannol
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A series of hydroxylated trans-stilbene related to the antileukemic natural product trans-3,3',4,5'-tetrahydroxy stilbene (piceatannol) (1) has been prepared and tested for inhibition of the lymphoid cell lineage-specific protein-tyrosine kinase p56lck, which plays an important role in lymphocyte proliferation and immune function.A number of the analogues displayed enhanced enzyme inhibitory activity relative to the natural product.Reduction of the double bond bridging the two aromatic rings and benzylation of the phenolic hydroxyl groups was found to decrease activity significantly.The most potent compounds in the series proved to be trans-3,3',5,5'-tetrahydroxystilbene, trans-3,3',5-trihydroxystilbene, and trans-3,4,4'-trihydroxystilbene.
- Thakkar, Kshitij,Geahlen, Robert L.,Cushman, Mark
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p. 2950 - 2955
(2007/10/02)
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- DEOXYGENATION IN THE BIOSYNTHESIS OF POLYKETIDES: MECHANISM OF BIOMIMETIC REDUCTION OF TETRAHYDROXYNAPHTHALENE
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A biomimetic synthesis of scytalone, a simple derivative of tetralone, was reinvestigeted using NMR spectroscopy.Scytalone was formed from 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) by sodium borohydride reduction only in the presence of sodium methoxi
- Ichinose, Koji,Ebizuka, Yutaka,Sankawa, Ushio
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p. 2873 - 2875
(2007/10/02)
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- A FULLY SYNTHETIC ROUTE TO THE PAPULACANDINS. STEREOSPECIFIC SPIROACETALIZATION OF A C-1-ARYLATED METHYLGLYCOSIDE
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Lewis acid-catalyzed, hetero Diels-Alder reaction of (E)-1-methoxy-3-trimethylsilyloxy-1,3-butadiene, with 6-benzoyloxymethyl-2,4-dibenzyloxy benzaldehyde afforded 2-(6-benzoyloxymethyl-2,4-dibenzyloxyphenyl)-2,3-dihydro-4H-pyran-4-one.This was converted into a derivative of papulacandin D by a stereospecific, spiroacetalization of a C-1 methoxylated aryl glycoside, methyl benzoate.
- Danishefsky, Samuel,Phillips, Gary,Ciufolini, Marco
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p. 317 - 328
(2007/10/02)
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- Biosynthesis of Fungal Metabolites. Terrein, a Metabolite of Aspergillus terreus Thom
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Terrein, a metabolite of Aspergillus terreus Thom, is biosynthesised from 3,4-dihydro-6,8-dihydroxy-3-methylisocoumarin by contraction of an aryl ring.The direction of the ring contraction has been investigated using acetate as precursor.
- Hill, Robert A.,Carter, Rachel H.,Staunton, James
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p. 2570 - 2576
(2007/10/02)
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- Drugs derived from Cannabinoids. Part 8. The Synthesis of Side-chain Analogues of Δ6a,10a-Tetrahydrocannabinol
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The continuation of studies on the synthesis of side-chain analogues of Δ6a,10a-tetrahydrocannabinol as potential therapeutic agents has led to the syntheses of a possible metabolite 1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzopyran-3-ylacetic acid (1) and 2-(1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzopyran-3-yl)pent-4-ynoic acid (17c).The Pechmann condensation of ethyl 4-methyl-2-oxocyclohexane-1-carboxylate with methyl 3,5-dihydroxyphenylacetate (11), followed by Grignard reaction, was utilized to produce the pyran (1).The key step in the synthesis of the propargylacetic acid (17c) was propargylation of the malonate (15) under phase-transfer catalysis.
- Meltzer, Peter C.,Dalzell, Haldean C.,Razdan, Raj K.
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p. 2825 - 2829
(2007/10/02)
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- Synthesis of Cannabinoid Model Compounds. Part 2): (3R,4R)-δ1(6)-Tetrahydrocannabinol-5"-oic Acid and 4"(R,S)-Methyl-(3R,4R)-δ1(6)-Tetrahydrocannabinol-5"-oic Acid
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Two novel cannabinoid model compounds, (3R,4R)-Δ1(6)-tetrahydrocannabinol-5"-oic acid (22) and 4"(R,S)-methyl-(3R,4R)-Δ1(6)-tetrahydrocannabinol-5"-oic acid (23) were synthesized by acid-catalyzed condensation of (+)-trans-p-mentha-2,8-dien-1-ol (1) with the substituted resorcinols 18 and 19 obtained by a Wittig reaction between 3,5-bis(benzyloxy)benzaldehyde (7) and methyl 4-bromobutanoate (10) or methyl 4-bromo-2(R,S)-methylbutanoate (11) resp. with subsequent hydrogenation.The resulting methyl esters 20 and 21 were hydrolyzed to give acids 22 and 23.
- Franke, Ingo,Binder, Michael
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p. 2508 - 2514
(2007/10/02)
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