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Diels
Kinds of Diels Selected AbstractsFlexible Route to Palmarumycin CP1 and CP2 and CJ-12.371 Methyl EtherEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 23 2010Karsten Krohn Abstract The total synthesis of palmarumycin CP1 (4) and CP2 (5) and racemic CJ-12.371 methyl ether (17) is described using the Diels,Alder reaction of benzoquinone 1,8-dihydroxynaphthalene acetal (10) with 1-methoxy-1,3-butadiene under neat reaction conditions. The stereochemistry of adduct 15 was confirmed by single-crystal X-ray analysis. The transformation of 15 into target products 4, 5, and 17 involved dehydrogenation, methyl ether cleavage, and reduction and oxidation steps. [source] An Efficient Synthesis of Substituted meta -Halophenols and Their Methyl Ethers: Insight into the Reaction MechanismEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2010Faiz Ahmed Khan Abstract An expeditious synthetic methodology leading to substituted meta -halophenols and their corresponding methyl ether derivatives through acid-mediated fragmentation of suitably substituted dihalonorbornyl ketones has been devised. The reaction sequence consists of TBTH-mediated (TBTH is tri- n -butyltin hydride) selective bridgehead halogen reduction of easily accessible Diels,Alder adducts derived from 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene and ,-substituted vinyl acetates, with subsequent conversion into the requisite bicyclic ketones by a two-step hydrolysis/oxidation approach. An extensive mechanistic investigation based on isotope labeling and cross experiments has been carried out and plausible mechanistic pathways based on these results have been proposed. The absence of halogen atoms at the bridgehead positions steers the reaction through a novel pathway involving the incorporation of proton (or deuterium) followed by elimination of HX (or DX), so the described methodology also provides a reliable route to ortho-para dideuteratedphenolic derivatives. [source] Synthesis, Optical Properties, and Crystal Structure of 1,4-DipropyltetraceneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2010Chitoshi Kitamura Abstract We synthesized 1,4-dipropyltetracene on a 200-mg scale, the key step of which involved a Diels,Alder reaction between alkyl-substituted o -quinodimethane, generated in situ, and 1,4-naphthoquinone. The product was obtained as an orange solid, which was soluble in organic solvents including hexane. The optical properties of the product in solution showed no marked differences from those of other 1,4,7,10-tetraalkyltetracenes. Solid-state absorption and fluorescence spectra exhibited 20,30 nm blueshifts compared with those of 1,4,7,10-tetrapropyltetracene. X-ray analysis revealed that two propyl groups were coplanar with the tetracene ring, that there was no , overlap along the stacking direction, and that the molecules formed a herringbone structure. The peripheral alkyl chains were found to be important for controlling the molecular packing and optical properties in the solid state. [source] Chiral Primary Amine,Polyoxometalate Acid Hybrids as Asymmetric Recoverable Iminium-Based CatalystsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 26 2009Jiuyuan Li Abstract A new strategy for the immobilization of iminium organocatalysts through the acid,base assembly of multidentate chiral primary amines and solid polyacids is presented. A suitable structurally distinctive C2 -symmetric chiral primary amine (CPA) was identified in this study and the optimal CPA,POM hybrid obtained catalyzed the Diels,Alder cycloaddition of ,-substituted acroleins in high yields and fair-to-high selectivity under aqueous conditions. The primary amine in the metal,organic-framework (MOF)-like catalyst acted as the catalytic center as well as multidentate basic centers, whereas phosphotungstic acid played dual roles as both catalyst anchors and modulators of the activity and stereoselectivity. Furthermore, the MOF-like catalyst showed both high reactivity and physical stability and thus could be recycled and reused six times with only a small loss of activity and selectivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Stereocontrolled Preparation of Fully Substituted Cyclopentanes: Relevance to Total SynthesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2009Brian Heasley Abstract This Microreview aims to identify important advances in the asymmetric synthesis of fully substituted five-membered carbocyclic ring systems. Recent efforts directed towards the intricate and densely functionalized core substructures of three distinct classes of cyclopentane-based natural products will be examined. Strategies featuring high levels of stereocontrol and/or conciseness in the total number of synthetic steps required to access complex natural product ring fragments are highlighted. Stereoselective Diels,Alder cycloaddition approaches to access functionalized norbornene intermediates as latent chiral cyclopentanes in the tradition of Corey's elegant prostaglandin studies are a recurring theme. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Diels,Alder Reactions of Symmetrically 1,4-Disubstituted Dienes: Theoretical Study on the Influence of the Configuration of the Double Bonds on the Regio- and EndoselectivityEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2008Samira Baki Abstract It was experimentally shown in Diels-Alder reactions that symmetrically 1,4-disubstituted dienes exhibit high regio- and endoselectivity induced by the (E,Z) configuration of the double bonds. In order to understand the origin of this selectivity, the transition states associated with the reaction between a series of such dienes (R = OMe, CH3, NH2, F, CN) on substituted ethylene (R, = CO2Me, CN, F, OMe) were determined by DFT calculations. If the regioselectivity confirmed by a single-point MP2 calculation is predicted to be good in most cases, its direction remains difficult to predict; the R, group of the dienophile can orient itself toward either the (Z) or the (E) side of the diene. Neither primary nor secondary frontier orbital interactions appear to be able to rationalize these results. They are more likely explained by a delicate balance between steric and electrostatic interactions. This hypothesis is further supported by the calculated reactivity of the (E,E) and (Z,Z) corresponding dienes. In any case, a standard DFT calculation, confirmed by a single-point MP2 step, is likely to provide a reliable guideline for a synthesis strategy that allows the control of up to four stereogenic centres in a single reaction step.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] 4-Substituted and 4,5-Disubstituted 3,6-Di(2-pyridyl)pyridazines: Ligands for Supramolecular AssembliesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 9 2008Edwin C. Constable Abstract The syntheses by inverse electron demand Diels,Alder reactions and characterization of 28 members of a family of 3,6-di(2-pyridyl)pyridazines, functionalized in the 4- or 4,5-positions are reported. Single crystal structural data are presented for four representative derivatives. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Highly Regio- and Stereoselective Diels,Alder Cycloaddition of Difluoro(methylene)cyclopropanesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2008Xiao-Chun Hang Abstract The Diels,Alder reactions of difluoro(methylene)cyclopropanes (F2MCPs) with cyclic dienes are described. These cycloaddition reactions exhibited complete regioselectivity and high endo -stereoselectivity. The obtained cycloadducts underwent a retro-Diels,Alder reaction to give the original dienophiles and dienes when heated, reflecting the reversible Diels,Alder reactivity of F2MCPs.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Unexpected Tethering in the Synthesis of Methyl-Substituted Acetyl-1-oxaspiro[4.5]decanes: Novel Woody,Ambery Odorants with Improved Bioavailability,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2008Philip Kraft Abstract To study the olfactory properties of spirocyclic analogs of Iso Gamma (3) with improved water solubility and bioavailability, it was envisaged to spiroannulate 1-acetyl-1,2-dimethylcyclohexanone at the 4-position with a 3,3-dimethyltetrahydrofuran-2-yl moiety that would mimic the polarity of the double bond by its ether function. 3,3-Dimethyl-4-methylenehex-5-en-1-ol (9) was prepared by copper(I)-mediated 1,4-conjugate addition of the Grignard reagent of chloroprene (7) to 3-methylbut-2-enal with subsequent LAH reduction. However, the Diels,Alder reaction of diene 9 with (E)-3-methylpent-3-en-2-one in the presence of Me2AlCl unexpectedly provided exclusively the undesired meta adduct 10, as was discovered after cyclization to 11 with MeSO3H. The wrong selectivity was due to a tethering effect of the Lewis acid, and this could be evaded by changing the carbonyl function of the dienophile to a hydroxy group. Thereby the (5,R*,7,S*,8,S*)-configured 1-(4,,4,,7,,8,-tetramethyl-1,-oxaspiro[4.5]decan-7,/8,-yl)ethan-1-ones 11 and 14, as well as the like -configured 1-(4,,4,,7,-trimethyl-1,-oxaspiro[4.5]decan-7,/8,-yl)ethan-1-ones 16 and 19, were prepared selectively and studied for their odor characters, threshold values, and octanol/water partition coefficients. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Synthesis of Highly Functionalized Anthraquinones and Evaluation of Their Antitumor Activity,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 27 2007Lutz F. Tietze Abstract Highly functionalized anthraquinones which derive from the natural products mensacarcin, islandicin, and chrysophanol have been efficiently synthesized using a Diels,Alder reaction as key step. The introduction of the proposed pharmacophoric side chain unit has been achieved by an addition of an aryllithium species onto different aldehydes. Furthermore, the antitumor activity of these novel compounds has been studied by the in vitro growth inhibition of human lung carcinoma cells of line A549.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Enantio- and Diastereomerically Pure Decalins by Deslongchamps-Type Annulation of Dienolates Containing a Chiral Lactone SubstituentEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 7 2007Thomas Tricotet Abstract A conceptionally novel 1,3-asymmetric induction has been established. It controls the relative and absolute configuration of up to 5 stereocenters. They emerge from the anionic Diels,Alder reactions ("Deslongchamps annulations") between oxocyclohexenecarboxylates 25, 29 and dienolates 26, 30. The latter contain a ,-lactone. A Ph3Si,CH2 substituent therein controls the asymmetry of C,C bond formation with ds , 10:1. Strangely, the preferred sense of attack of the dienophile is contrasteric. Cycloadduct 31 was processed by an unprecedented fluoride-induced ambient-temperature tandem fragmentation. It turned the lactone moiety into an allyl group and the ,-oxo (trimethylsilyl)ethyl ester into a ketone. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] WTDWTR: What To Do With This Reaction?EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2006A New Program in the Field of Computer-Aided Synthesis Design, Alder Reaction, Application to the Diels Abstract We present WTDWTR (What To Do With This Reaction?), which is a new program in the field of computer-aided organic synthesis. WTDWTR tries to answer the question: what kind of structures can be obtained from a given reaction? We present the results that were obtained for the Diels,Alder reaction of structures that possess four fused rings of size 6, 6, 6 and 5 ("isomers" of the steroidal skeleton) for which WTDWTR generated 590 solutions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Thermal Behaviour of Selected C10H16 MonoterpenesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2006Achim Stolle Abstract The presented work investigates the thermal behaviour of selected monoterpenes under various reactor temperatures and residence times (carrier gas, reactor inserts). In addition to the analysis of the liquid products by capillary GC and GC-MS, chemical derivatisation techniques (Diels,Alder reaction, hydrogenation) were used to identify the liquid-phase products. A thermal conversion of ,-pinene (1), myrcene (2) and limonene (4) in a reaction network is presented and the experimental evidence for the formation of pyrolysis products by a biradical pathway is discussed. The reaction network was modified based on the identification of additional C10H16 terpene isomers. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Diels,Alder Reactions of 2,-Hydroxychalcones with ortho -Benzoquino-dimethane: A New Synthesis of 3-Aryl-2-naphthyl 2-Hydroxyphenyl KetonesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2006Cristela M. Brito Abstract Diels,Alder reactions of the 2,-hydroxychalcones 1a,e with ortho -benzoquinodimethane (3) yielded the 3-aryl-1,2,3,4-tetrahydro-2-naphthyl 2-hydroxyphenyl ketones 4a,e in good yields. The dehydrogenation of the cycloadducts 4a,e to 3-aryl-2-naphthyl 2-hydroxyphenyl ketones 5a,e was studied. Good results were obtained when DDQ was used as oxidant and microwave irradiation as energy source. Several benzoxanthone derivatives were also obtained as minor products. Structures of all new compounds were established by extensive NMR studies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Why do Electron-Deficient Dienes React Rapidly in Diels,Alder Reactions with Electron-Deficient Ethylenes?EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 23 2004A Density Functional Theory Analysis Abstract The Diels,Alder reaction of the electron-deficient (ED) dimethyl 2,3-dimethylenesuccinate with two electron-rich (ER) and two ED ethylenes has been studied at the B3LYP/6-31G* level of theory. The analysis of the geometry and electronic structure of the transition state of the reaction with the ED dimethyl 2-methylenemalonate along with the analysis of the global and local electrophilicity indices of the reagents provide an explanation of the participation of this ED diene as nucleophile against powerful electrophiles in polar Diels,Alder reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] An Efficient Route to 4/5/6 Polycyclic ,-LactamsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 23 2004Nicolas Desroy Abstract The synthesis of 4/5/6 polycyclic ,-lactams by enyne metathesis and Diels,Alder reactions is described. Compared to the synthesis of 4/6/6 and 4/7/6 polycyclic ,-lactams previously reported by our laboratory, formation of the strained 4/5/6 compounds requires alternative reaction conditions. Indeed, the synthesis of the 4/5 bicyclic diene 12 was more difficult than those of the 4/6 (13) and 4/7 (14) dienes. The strain of the 4/5 system could be observed by NMR spectroscopy and molecular modelling. Moreover, the reactivity of 4/5 diene 12 towards Diels,Alder cycloaddition was also different from that of the 4/6 (13) and 4/7 (14) dienes. Cycloadditions with 4/5 diene 12 therefore had to be performed in lithium perchlorate/diethyl ether (LPDE) or in an ionic liquid in order to proceed in good yields with various dienophiles. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] 3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles: Synthesis and Diels,Alder TransformationsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 21 2004Vera L. M. Silva Abstract Reactions between cinnamoyl(2-hydroxybenzoyl)methanes and hydrazine hydrate in acetic acid gave 3-(2-hydroxyphenyl)-5-styrylpyrazoles, while the corresponding reactions with phenylhydrazine yielded 5-(2-hydroxyphenyl)-1-phenyl-3-styrylpyrazoles as the major products and 3-(2-hydroxyphenyl)-1-phenyl-5-styrylpyrazoles as by-products. The reaction mechanism of this transformation is discussed. The first cycloaddition reactions between ortho -benzoquinodimethane and either 3-(2-hydroxyphenyl)-5-styrylpyrazoles or 5-(2-hydroxyphenyl)-1-phenyl-3-styrylpyrazoles afforded 5-[2-(3-aryl-1,2,3,4-tetrahydronaphthyl)]-3-(2-hydroxyphenyl)pyrazoles or 3-[2-(3-aryl-1,2,3,4-tetrahydronaphthyl)]-1-phenyl-5-(2-hydroxyphenyl)pyrazoles, respectively. These cycloadducts were converted into the corresponding naphthylpyrazoles by oxidation with DDQ in dry 1,4-dioxane. The structures of all new derivatives have been established by NMR spectroscopy. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Synergistic Effect of Pybox Substituents and Lanthanide Cations in Reversing the Asymmetric Induction in the Catalysed Diels,Alder Reaction between 3-Acryloyl-1,3-oxazolidin-2-one and CyclopentadieneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 14 2004Giovanni Desimoni Abstract The enantioselectivity in the pybox/lanthanide(III) triflate catalysed Diels,Alder reaction between cyclopentadiene and 3-acryloyl-1,3-oxazolidin-2-one is profoundly influenced by the presence of a phenyl group in the 5,-position of the ligand, since it sometimes amplifies, and sometimes reverses the enantioselectivity induced by the 4,-substituent. The results can be summarised in three points. Of the catalysts derived from (4,R,5,R)-4-Me-5-Ph-pybox (6), the ScIII -based one is both strongly endo -selective and strongly enantioselective. Several catalysts derived from (4,R,5,R)- trans -diphenyl-pybox (9) give up to 50% yields of exo - 4 and, at least with PrIII and LaIII, induce excellent ee values in both endo and exo adducts. The (4,R,5,S)- cis -diphenyl-pybox (8) is a novel and valuable ligand, since opposite enantiomers can be obtained with good selectivity simply by changing the cation from ScIII to LaIII. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Toward Diels,Alder Reactions on a Solid Support Using Polymer Bound N -Substituted 3-Hydroxy-4,4-dimethyl-2-pyrrolidinone Acrylate DerivativesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2004Rhalid Akkari Abstract Several N -substituted 3-hydroxy-4,4-dimethyl-2-pyrrolidinone acrylate derivatives, selected to allow their attachment to a polymer, have been prepared and tested as dienophiles in the Diels,Alder reaction. The experiments, performed under TiCl4 catalysis in solution or the solid phase with isoprene and cyclopentadiene as dienes, pointed out the difficulties associated with some of these compounds that failed to give the corresponding cycloadduct. 13C NMR studies provided some evidence regarding the nature of the interactions between the acrylate compounds and TiCl4. It appears that the outcome of the reaction is dependent on the acrylate structure and that the 4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)benzoic acid acrylate derivatives are highly efficient to give the cycloadduct in good yield and with high regio- or endoselectivity in both solution and solid-phase reaction conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Synthesis and Some Chemical Transformations of (Z)- and (E)-2-Acetyl-1-ferrocenyl-3-methylbuta-1,3-dienes , A New Type of Cationic CycloadditionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2004Elena I. Klimova Abstract Dehydration of (E)- and (Z)-2-acetyl-1-ferrocenyl-3-methylbut-1-en-3-ols gave the corresponding (E)- and (Z)-2-acetyl-1-ferrocenyl-3-methylbuta-1,3-dienes, which have a cross-conjugated system of three double bonds. These heterotrienes readily afford the products of linear and cyclodimerization by following a cationic cyclodimerization mechanism; they also form Diels,Alder adducts with azodicarboxylic and maleic acid N -phenylimides. The spatial structures of (E)-2-acetyl-1-ferrocenyl-3-methylbuta-1,3-diene, (E,E)-1,5-diferrocenyl-2-isopropenyl-6-isopropylidene-3-methyl-1,3-octadiene-7-one, and 7-ferrocenyl-4-(ferrocenylmethylidene)-8-isopropylidene-1,3,5-trimethyl-9-oxabicyclo[3.3.1]non-2-ene were elucidated by X-ray diffraction analyses of single crystals. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Novel DNA-Damaging Tropolone Derivatives from Goupia glabraEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 21 2003Dulce Mesa-Siverio Abstract Two novel tropolone derivatives 1 and 2 have been isolated from Goupia glabra. Their structures were determined by extensive 1D and 2D NMR spectroscopic studies. Compound 2 constitutes the first example isolated from a natural source of a Diels,Alder adduct between a tropolone and a naphthalene derivative. Compounds 1 and 2 exhibit significant toxicity towards a panel of DNA damage checkpoint defective yeast mutants, and behave as genotoxins, which highlights their potential to be used as anticancer drugs. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Cycloaddition Behavior of 1,2-Thiaphospholes: Reactions with Diazocumulenes and with CyclopentadieneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2003Jochen Kerth Abstract 1,2-Thiaphospholes 3a,b react with (1-diazo-2-oxoalkyl)silanes 1a,c to form [1,2]thiaphospholo[2,,3,:3,4][1,3]diphospholo[1,5- b][1,2]thiaphosphole systems 4 with cis - anti - cis configuration of the tricyclic framework. They are accompanied by small amounts of compounds 5 that are presumably the cis - syn - cis isomers of 4, and 6-alkylidene-1-phospha-2-thiabicyclo[3.1.0]hex-3-enes 6. It is likely that these reactions proceed by [3+2] cycloaddition of diazocumulenes, which coexist with diazo compounds as minor equilibrium components, at the P=C bond of the heterophospholes, followed by N2 elimination and formation of short-lived 2-alkylidene-1,2(,5)thiaphospholes. The latter can either add to excess thiaphosphole to form the tricyclic products or undergo electrocyclization to form bicyclic alkylidenephosphiranes. Thiaphosphole 3a does not seem to react directly with cyclopentadiene in a [4+2] or [2+4] cycloaddition. Reaction with excess cyclopentadiene at 120 °C yields the polycyclic compounds 15 and 16, which are likely to arise from a Diels,Alder reaction of 3a, reacting as a heterodiene, with the cyclopentadiene dimer. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] A C2 -Chiral Bis(amidinium) Catalyst for a Diels,Alder Reaction Constituting the Key Step of the Quinkert,Dane Estrone SynthesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 9 2003Svetlana B. Tsogoeva Abstract A novel C2 -chiral bis(amidinium) salt 12 has been synthesised from 5-(tert -butyl)isophthalic acid. The hydrogen-bond-mediated association of dienophiles 3a and 3b with the chiral host molecule 12 accelerates the Diels,Alder reactions with diene 2 by more than three orders of magnitude. In addition, enantioselective formation of the desired adducts is observed under catalysis with 12. Good ratios of 4a(b) + ent - 4a(b)/5a(b) + ent - 5a(b) from 1:10 to 1:22 were found in all reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Doxorubicin-Conjugated Immuno-Nanoparticles for Intracellular Anticancer Drug DeliveryADVANCED FUNCTIONAL MATERIALS, Issue 11 2009Meng Shi Abstract A polymeric nanoparticle comprised of surface furan groups is used to bind, by Diels,Alder (DA) coupling chemistry, both targeting anti-human epidermal growth factor receptor 2 (anti-HER2) antibodies and chemotherapeutic doxorubicin (DOX) for targeted, intracellular delivery of DOX. In this new approach for delivery, where both chemotherapeutic and targeting ligand are attached, for the first time, to the surface of the delivery vehicle, the nuclear localization of DOX in HER2-overexpressing breast cancer SKBR-3 cells is demonstrated, as determined by confocal laser scanning microscopy. Flow cytometric analysis shows that the conjugated DOX maintains its biological function and induces similar apoptotic progression in SKBR-3 cells as free DOX. The viable cell counts of SKBR-3 cancer cells following incubation with different nanoparticle formulations demonstrates that the combined DOX and anti-HER2 nanoparticle is more efficacious than the nanoparticle formulation with either DOX or anti-HER2 alone. While free DOX shows similar cytotoxicity against both cancerous SKBR-3 cells and healthy HMEC-1 cells, the combined DOX-anti-HER2 nanoparticle is significantly more cytotoxic against SKBR-3 cells than HMEC-1 cells, suggesting the benefit of nanoparticle-conjugated DOX for cell type-specific targeting. The DOX-conjugated immuno-nanoparticle represents an entirely new method for localized co-delivery of chemotherapeutics and antibodies. [source] Exploiting Chemical Switching in a Diels,Alder Polymer for Nanoscale Probe Lithography and Data Storage,ADVANCED FUNCTIONAL MATERIALS, Issue 11 2006B. Gotsmann Abstract Reversibly crosslinked polymer films have properties that are beneficial to scanned-probe data storage and lithographic applications that use thermomechanical nanoindentation as a write or expose mechanism. The novel polymer under study contains linkages based on thermally reversible Diels,Alder crosslinking. Thermomechanical properties on the nanometer scale are analyzed by indentation experiments on polymer thin films using heated tips. The underlying indentation mechanism is studied at varying tip temperatures and indentation times, revealing Arrhenius kinetics. This is in contrast to the Williams,Landau,Ferry kinetics usually observed for polymer systems. The discrepancy is explained by the reversible crosslinking incorporated into the structure of the polymer that allows switching between two different states: a rigid, highly crosslinked, low-temperature state, and a deformable, fragmented, high-temperature state. An individual indentation volume of less than 10,20,L (10,000,molecule pairs) is estimated. These kinetics experiments demonstrate that a chemical reaction of only a few thousand molecules can be transduced into a mechanically measurable action. The ability to cycle between two sets of properties in these materials opens up new perspectives in lithography and data storage. Examples of data storage with densities up to 1,Tb,in.,2 and maskless lithography with resolution below 20,nm are demonstrated at writing times of 10,,s per bit/pixel. [source] Synthesis of Novel Polycyclic Indole-Annulated Thiopyranocoumarin Derivatives via Domino Knoevenagel,Hetero- Diels,Alder Reaction in Aqueous MediaHELVETICA CHIMICA ACTA, Issue 5 2010Firouz, Matloubi Moghaddam Abstract An efficient synthesis of polycyclic indole derivatives is achieved via domino Knoevenagel,hetero- Diels,Alder reaction of O -acrylated salicylaldehyde derivatives with dihydroindole-2-thiones in H2O as solvent. The products are formed in good-to-excellent yields with high regio- and stereoselectivity. [source] Reactivity and Selectivity of Captodative Olefins as Dienes in Hetero -Diels,Alder ReactionsHELVETICA CHIMICA ACTA, Issue 10 2008Rubén Sanabria Abstract The reactivity and selectivity of the the captodative olefins 1-acylvinyl benzoates 1a,1f and 3a as heterodienes in hetero -Diels,Alder reactions in the presence of electron-rich dienophiles is described. Heterodienes 1 undergo regioselective cycloaddition with the alkyl vinyl etherdienophiles 6a,b and 9 to give the corresponding dihydro-2H -pyrans 7, 8, and 10 under thermal conditions. The reactivity of these cycloadditions depends, to a large extent, on the electronic demand of the substituent in the aroyloxy group of the heterodiene. Frontier-molecular-orbital (FMO; ab initio) and density-functional-theory (DFT) calculations of the ground and transition states account for the reactivity and regioselectivity observed in these processes. [source] The Orthogonal (e,e,e)-Tris-Adduct of 9,10-Dimethylanthracene with C60 -Fullerene: A Hidden Cornerstone of Fullerene Chemistry.HELVETICA CHIMICA ACTA, Issue 8 2008Preliminary Communication Abstract Tris(9,,10,-dimethyl[9,10]ethanoanthracene[11,,12,:,1,9;11,,12,:,16,17;11,,,,12,,,:,30,31])[5,6]fullerene C60, the orthogonal (e,e,e)-tris-adduct of C60 and 9,10-dimethylanthracene, was obtained from [4+2]-cycloaddition (Diels,Alder reaction) at room temperature. The thermally unstable orange red (e,e,e)-tris-adduct was purified by chromatography and was isolated in the form of red monoclinic crystals. Its C3 -symmetric addition pattern was established spectroscopically. Its structure could be further investigated by single crystal X-ray diffraction. The (e,e,e)-tris-adduct of C60 and 9,10-dimethylanthracene has earlier been suggested as intermediate and reversibly formed critical component in ,template directed' addition reactions of C60. This previously elusive compound has now been isolated and structurally characterized. [source] Total Synthesis of Murrayanine Involving 4,5-Dimethyleneoxazolidin-2-ones and a Palladium(0)-Catalyzed Diaryl InsertionHELVETICA CHIMICA ACTA, Issue 8 2007Pablo Bernal Abstract A new total synthesis of the natural carbazole murrayanine (1) was developed by using the 4,5-dimethyleneoxazolidin-2-one 12 as starting material. The latter underwent a highly regioselective Diels,Alder cycloaddition with acrylaldehyde (=prop-2-enal; 13) to give adduct 14 (Scheme,3). Conversion of this adduct into diarylamine derivative 9 was carried out via hydrolysis and methylation (Scheme,4). Differing from our previous synthesis, in which such a diarylamine derivative was transformed into 1 by a PdII -stoichiometric cyclization, this new approach comprised an improved cyclization through a more efficient Pd0 -catalyzed intramolecular diaryl coupling which was applied to 9, thus obtaining the natural carbazole 1 in a higher overall yield. [source] Benzo[a]heptalenes from Heptaleno[1,2- c]furans.HELVETICA CHIMICA ACTA, Issue 4 2007Abstract It is shown in this ,Part 2' that heptaleno[1,2- c]furans 1 react thermally in a Diels,Alder -type [4+2] cycloaddition at the furan ring with vinylene carbonate (VC), phenylsulfonylallene (PSA), , -(acetyloxy)acrylonitrile (AAN), and (1Z)-1,2-bis(phenylsulfonyl)ethene (ZSE) to yield the corresponding 1,4-epoxybenzo[d]heptalenes (cf. Schemes,1, 5, 6, and 8). The thermal reaction of 1a and 1b with VC at 130° and 150°, respectively, leads mainly to the 2,3- endo -cyclocarbonates 2,3- endo - 2a and - 2b and in minor amounts to the 2,3- exo -cyclocarbonates 2,3- exo - 2a and - 2b. In some cases, the (P*)- and (M*)-configured epimers were isolated and characterized (Scheme,1). Base-catalyzed cleavage of 2,3- endo - 2 gave the corresponding 2,3-diols 3, which were further transformed via reductive cleavage of their dimesylates 4 into the benzo[a]heptalenes 5a and 5b, respectively (Scheme,2). In another reaction sequence, the 2,3-diols 3 were converted into their cyclic carbonothioates 6, which on treatment with (EtO)3P gave the deoxygenated 1,4-dihydro-1,4-epoxybenzo[d]heptalenes 7. These were rearranged by acid catalysis into the benzo[a]heptalen-4-ols 8a and 8b, respectively (Scheme,2). Cyclocarbonate 2,3- endo - 2b reacted with lithium diisopropylamide (LDA) at ,70° under regioselective ring opening to the 3-hydroxy-substituted benzo[d]heptalen-2-yl carbamate 2,3- endo - 9b (Scheme,3). The latter was O -methylated to 2,3- endo -(P*)- 10b. The further way, to get finally the benzo[a]heptalene 13b with MeO groups in 1,2,3-position, could not be realized due to the fact that we found no way to cleave the carbamate group of 2,3- endo -(P*)- 10b without touching its 1,4-epoxy bridge (Scheme,3). The reaction of 1a with PSA in toluene at 120° was successful, in a way that we found regioisomeric as well as epimeric cycloadducts (Scheme,5). Unfortunately, the attempts to rearrange the products under strong-base catalysis as it had been shown successfully with other furan,PSA adducts were unsuccessful (Scheme,4). The thermal cycloaddition reaction of 1a and 1b with AAN yielded again regioisomeric and epimeric adducts, which could easily be transformed into the corresponding 2- and 3-oxo products (Scheme,6). Only the latter ones could be rearranged with Ac2O/H2SO4 into the corresponding benzo[a]heptalene-3,4-diol diacetates 20a and 20b, respectively, or with trimethylsilyl trifluoromethanesulfonate (TfOSiMe3/Et3N), followed by treatment with NH4Cl/H2O, into the corresponding benzo[a]heptalen-3,4-diols 21a and 21b (Scheme,7). The thermal cycloaddition reaction of 1 with ZSE in toluene gave the cycloadducts 2,3- exo - 22a and - 22b as well as 2- exo,3- endo - 22c in high yields (Scheme,8). All three adducts eliminated, by treatment with base, benzenesulfinic acid and yielded the corresponding 3-(phenylsulfonyl)-1,4-epoxybenzo[d]heptalenes 25. The latter turned out to be excellent Michael acceptors for H2O2 in basic media (Scheme,9). The Michael adducts lost H2O on treatment with Ac2O in pyridine and gave the 3-(phenylsulfonyl)benzo[d]heptalen-2-ones 28a and 3- exo - 28b, respectively. Rearrangement of these compounds in the presence of Ac2O/AcONa lead to the formation of the corresponding 3-(phenylsulfonyl)benzo[a]heptalene-1,2-diol diacetates 30a and 30b, which on treatment with MeONa/MeI gave the corresponding MeO-substituted compounds 31a and 31b. The reductive elimination of the PhSO2 group led finally to the 1,2-dimethoxybenzo[a]heptalenes 32a and 32b. Deprotonation experiments of 32a with t -BuLi/N,N,N,,N,-tetramethylethane-1,2-diamine (tmeda) and quenching with D2O showed that the most acid CH bond is HC(3) (Scheme,9). Some of the new structures were established by X-ray crystal-diffraction analyses (cf. Figs.,1, 3, 4, and 5). Moreover, nine of the new benzo[a]heptalenes were resolved on an anal. Chiralcel OD-H column, and their CD spectra were measured (cf. Figs.,8 and 9). As a result, the 1,2-dimethoxybenzo[a]heptalenes 32a and 32b showed unexpectedly new Cotton -effect bands just below 300,nm, which were assigned to chiral exciton coupling between the heptalene and benzo part of the structurally highly twisted compounds. The PhSO2 -substituted benzo[a]heptalenes 30b and 31b showed, in addition, a further pair of Cotton -effect bands in the range of 275,245,nm, due to chiral exciton coupling of the benzo[a]heptalene chromophore and the phenylsulfonyl chromophore (cf. Fig.,10). [source] | ||||||||||||||||||||||||||||