- Hemiacetal anions: A model for tetrahedral reaction intermediates
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A deprotonated hemiacetal ion is used as a model intermediate for nucleophilic addition reactions at a carbonyl group. The acidity of the cyclic hemiacetal 2-hydroxytetrahydropyran has been estimated to be ΔGoacid ≥ 351 ± 2 kcal/mol. The basicity of the deprotonated ion was found to be 347 ± 2 kcal/mol, different from the acidity by 4 kcal/mol. This difference is ascribed to an isomerization reaction in the ion. The electron affinity of the neutral radical corresponding to removal of an electron from the ion was measured with use of electron photodetachment spectroscopy and was found to be 49.6 ± 2.5 kcal/mol. The structure of the isomerized ion is assigned as a hydrogen bond stabilized enolate ion. The implications of the strong acidity of the hemiacetal for the stability of tetrahedral reaction intermediates are discussed. Thermochemical arguments suggest that tetrahedral adducts of this type are often global minima on the reaction potential surface. The addition reactions of different alkoxide-alcohol complexes with benzaldehyde are discussed in terms of the stability of the corresponding tetrahedral addition product.
- Baer, Susan,Brinkman, Elizabeth A.,Brauman, John I.
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- Three-Step Synthesis of 3-Aminoseptanoside Derivatives by Using Lithiated Methoxyallene and δ-Siloxynitrones
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A three-step approach to enantiomerically pure 3-aminoseptanoside derivatives by addition of lithiated methoxyallene to δ-silylated aldopentose-derived nitrones, followed by Bronsted acid mediated cyclization and chemoselective N-O bond scission is presented. For the addition of the methoxyallene anion leading to 3,6-dihydro-1,2-oxazines, excellent syn-diastereoselectivities were observed in the case of d-xylose- and l-arabinose-derived nitrones, whereas the d-ribose analogue provided syn- and anti-configured products in an approximately 2:1 ratio. Subsequent proton-induced reactions provided the corresponding dimethyl ketals as kinetic products, which slowly converted into bicyclic oxepanoides formed in a highly cis-selective manner. The final reductive ring opening was performed in good yields by using an excess of samarium(II) iodide. With a selected compound it was demonstrated that this type of product is a suitable precursor for the preparation of polyfunctionalized oxepanopyrrolidine derivatives.
- Jasiński, Marcin,Utecht, Greta,Fruziński, Andrzej,Reissig, Hans-Ulrich
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- A novel and general α-regioselective and highly enantioselective prenylation of aldehydes
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This communication describes a novel and general method for the α-regioselective prenylation of carbonyl compounds. This method which employs chiral γ-prenyl-1,5 diol as the prenyl source using a catalytic amount of Lewis or Bronsted acid affords the products in excellent enantioselectivies (up to 98% ee) and good yields (up to 95% yield). Furthermore, the reaction is highly chemoselective, reacting selectively with the aldehyde without affecting the enone and the α,β-unsaturated ester functionalities. Detailed mechanistic studies disclose the facile epimerization of aromatic alcohol in dichloromethane in the presence of In(OTf)3. The use of non-polar solvents such as hexane in the presence of In(OTf)3 or TfOH effectively suppresses this epimerization. Copyright
- Cheng, Hin-Soon,Loh, Teck-Peng
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- Total synthesis of (±)-quinolizidine 217A
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Several 1,4-disubstituted quinolizidines have been isolated in minute quantities from the skin of certain poisonous frogs and toads. The structures of these alkaloids have been proposed mainly on the basis of MS and IR spectroscopic data. We report the first total synthesis of a naturally occurring alkaloid of this type, quinolizidine 217A. After examination of several azide-based routes, the cyclization of an azide onto an ester- bearing alkene provided a 3,4,5,6-tetrahydropyridine that was reduced in a stereoselective fashion to produce a cis-2,6-disubstituted piperidine (25 → 31 → 32). Transformation of 32 into quinolizidine 217A (2) and its C(1) epimer (41) were accomplished in a straightforward fashion. Synthetic quinolizidine 217A was found to be identical to the natural alkaloid, confirming its stereostructure. Compound 41 has the same stereostructure as that proposed for the alkaloid quinolizidine 207I, a compound whose configuration was recently revised as a result of synthetic studies by Momose et al., who synthesized a 1,4-disubstituted quinolizidine with the configuration previously proposed for quinolizidine 207I and found the synthetic material to be epimeric with the natural material. Compound 41 should provide a useful point of comparison for future studies on the stereostructure of natural or synthetic quinolizidine 207I.
- Pearson,Suga
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- Oxasqualenoids from Laurencia viridis: Combined spectroscopic-computational analysis and antifouling potential
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The chemical study of the red alga Laurencia viridis has led to the isolation of four new polyether triterpenoids: 28-hydroxysaiyacenol B (2), saiyacenol C (3), 15,16-epoxythyrsiferol A (4), and 15,16-epoxythyrsiferol B (5). The structures of 2 and 3 were established mainly by NMR data analysis and comparison with the well-known metabolite dehydrothyrsiferol (1). However, due to the existence of a nonprotonated carbon within the epoxide functionality, stereochemical assignments in 4 and 5 required an in-depth structural study that included NOESY data, J-based configuration analysis, comparison with synthetic models, and DFT calculations. The biological activities of the new metabolites and other related oxasqualenoids were evaluated for the first time against a panel of relevant biofouling marine organisms, and structure-activity conclusions were obtained.
- Cen-Pacheco, Francisco,Santiago-Benítez, Adrián J.,García, Celina,álvarez-Méndez, Sergio J.,Martín-Rodríguez, Alberto J.,Norte, Manuel,Martín, Victor S.,Gavín, José A.,Fernández, José J.,Daranas, Antonio Hernández
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- Mechanistically Guided Design of an Efficient and Enantioselective Aminocatalytic α-Chlorination of Aldehydes
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The enantioselective aminocatalytic α-chlorination of aldehydes is a challenging reaction because of its tendency to proceed through neutral intermediates in unselective pathways. Herein we report the rational shift to a highly selective reaction pathway involving charged intermediates using hexafluoroisopropanol as solvent. This change in mechanism has enabled us to match and improve upon the yields and enantioselectivities displayed by previous methods while using cheaper aminocatalysts and chlorinating agents, 80-95% less amount of catalyst, convenient temperatures, and shorter reaction times.
- Hutchinson, George,Alamillo-Ferrer, Carla,Burés, Jordi
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supporting information
p. 6805 - 6809
(2021/05/29)
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- 6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS
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The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.
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Paragraph 1066; 1067
(2021/11/13)
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- Size- And Shape-Selective Catalysis with a Functionalized Self-Assembled Cage Host
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A self-assembled Fe4L6 cage with internally oriented carboxylic acid functions was shown to catalyze a variety of dissociative nucleophilic substitution reactions that proceed via oxocarbenium ion or carbocation intermediates. The catalytic behavior of the cage was compared to that of other small acid catalysts, which illustrated large differences in reactivity of the cage-catalyzed reactions, dependent on the structure of the substrate. For example, only a 5% cage confers a 1000-fold rate acceleration of the thioetherification of vinyldiphenylmethanol when compared to the rate with free carboxylic acid surrogates but only a 52-fold acceleration in the formation of small thioacetals. Multiple factors control the variable reactivity in the host, including substrate inhibition, binding affinity, and accessibility of reactive groups once bound. Simple effective concentration increases or the overall charge of the cage does not explain the variations in reactivity shown by highly similar reactants in the host: small differences in structure can have large effects on reactivity. Reaction of large spherical guests is highly dependent on substitution, whereas flat guests are almost unaffected by size and shape differences. The cage is a promiscuous catalyst but has strong selectivity for particular substrate shapes, reminiscent of enzymatic activity.
- Da Camara, Bryce,Hooley, Richard J.,Ngai, Courtney,Woods, Connor Z.
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p. 12862 - 12871
(2021/09/28)
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- Dual C(sp3)-H Functionalization of Cyclic Ethers via Singlet Oxygen-Mediated Ring Opening and Ring Closing
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A metal-free dual C(sp3)-H bond functionalization of saturated cyclic ethers via photooxidative singlet oxygen-mediated ring opening and ring closing has been developed, providing a method for generating hydrobenzofurans/pyrans/dioxins. Mechanistic studies have confirmed that ring-opening intermediates were effectively generated by singlet oxygen-mediated C(sp3)-H activation and efficiently reacted with aldehydes and activated methylene compounds to form a wide array of products with high diastereoselectivities (up to >95:5 dr). This study is a rare example of α,β-dual C(sp3)-H bond functionalization of ethers.
- Yuan, Xu,Yu, Xianglin,He, Kun,Zhang, Ruihan,Xiao, Weilie,Lin, Jun,Zhan, Zhajun,Cheng, Xiaohong,Shao, Zhihui,Jin, Yi
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supporting information
p. 8267 - 8272
(2021/10/25)
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- A new catalytic approach for aerobic oxidation of primary alcohols based on a Copper(I)-thiophene carbaldimines
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We report here novel Cu(I) thiophene carbaldimine catalysts for the selective aerobic oxidation of primary alcohols to their corresponding aldehydes and various diols to lactones or lactols. In the presence of the in situ generated Cu(I) species, a persistent radical (2,2,6,6-tetramethylpiperdine-N-oxyl (TEMPO)) and N-methylimidazole (NMI) as an auxiliary ligand, the reaction proceeds under aerobic conditions and at ambient temperature. Especially the catalytic system of 1-(thiophen-2-yl)-N-(4-(trifluoromethoxy)phenyl)methanimine (ligand L2) with copper(I)-iodide showed high reactivity for all kind of alcohols (benzylic, allylic and aliphatic). In the case of benzyl alcohol even 2.5 mol% of copper loading gave quantitative yield. Beside high activity under aerobic conditions, the catalysts ability to oxidize 1,5-pentadiol to the corresponding lactol (86% in 4 h) and N-phenyldiethanolamine to the corresponding morpholine derivate lactol (86% in 24 h) is particularly noteworthy.
- Lagerspets, Emi,Valbonetti, Evelyn,Eronen, Aleksi,Repo, Timo
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- Tweaking the acid-sensitivity of transiently thermoresponsive Polyacrylamides with cyclic acetal repeating units
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Merging the characteristics of thermoresponsive and stimuli-degradable polymers yields so-called transiently thermoresponsive polymers, which can find application for the design of injectable gels, nanoparticles, etc. within a biomedical context. Among these polymers, only a limited number is reported which shows selective degradation under mild acidic conditions. However, extension of the library of transiently thermoresponsive polymers is desired to broadening the biomaterials toolbox to suit specific needs. Three monomers were developed by modification of 2-hydroxyethylacrylamide (HEAm) via tetrahydropyranylation or -furanylation with 3,4-dihydro-2H-pyran (DHP), 2,3-dihydrofuran (DHF) or 2,3-dihydro-5-methylfuran (MeDHF). The presence of an acetal or ketal bond provided the monomers a pH-dependent hydrolysis behavior ranging from minutes to days. RAFT polymerisation allowed for the construction of homopolymers with temperature responsive behavior and pH-dependent hydrolysis which was strongly influenced by nature of the monomeric repeating units.
- De Geest, Bruno G.,Van Herck, Simon
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- Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization
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Flavin-dependent "ene"-reductases can generate stabilized alkyl radicals when irradiated with visible light; however, they are not known to form unstabilized radicals. Here, we report an enantioselective radical cyclization using alkyl iodides as precursors to unstabilized nucleophilic radicals. Evidence suggests this species is accessed by photoexcitation of a charge-transfer complex that forms between flavin and substrate within the protein active site. Stereoselective delivery of a hydrogen atom from the flavin semiquinone to the prochiral radical formed after cyclization provides high levels of enantioselectivity across a variety of substrates. Overall, this transformation demonstrates that photoenzymatic catalysis can address long-standing selectivity challenges in the radical literature.
- Clayman, Phillip D.,Hyster, Todd K.
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supporting information
p. 15673 - 15677
(2020/10/18)
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- A phosphine-free iron complex-catalyzed synthesis of cycloalkanes: Via the borrowing hydrogen strategy
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Herein we report a diaminocyclopentadienone iron tricarbonyl complex catalyzed synthesis of substituted cyclopentane, cyclohexane and cycloheptane compounds using the borrowing hydrogen strategy in the presence of various substituted primary and secondary 1,n diols as alkylating reagents. Deuterium labeling experiments confirm that the diols were the hydride source in this cascade process. This journal is
- Bettoni, Léo,Gaillard, Sylvain,Renaud, Jean-Luc
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supporting information
p. 12909 - 12912
(2020/11/07)
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- Influence of Some Factors on the Progress of a New Reaction in the Chemistry of Organoaluminum Compounds
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Abstract: We earlier discovered a new reaction in the chemistry of organoaluminum compounds (OACs), specifically, the formation of O-isobutyl acetals on low-temperature (–70°C) treatment of seven-membered lactones with a double (or more) molar amount of diisobutylaluminum hydride (DIBAH) in methylene chloride. To assess the boundaries for the formation of isobutyl acetals depending on the ring size, we involved in the low-temperature hydride reduction six-, eight-, and thirteen-membered lactones. To determine how the scope of the new reaction depends on the nature of the organoaluminum reagent, we tested triisobutylaluminum (TIBA). To determine how the formation of isobutyl acetals on low-temperature (–70°C) reduction with excess DIBAH in CH2Cl2 depends on whether the starting ester is cyclic or acyclic and, if the former is the case, on the ring size in the ester, we used the acyclic methyl octadecanoate as the starting compound. It was found that the new reaction in the chemistry of AOC with DIBAH as the reducer is characteristic only of seven-membered lactones and atypical of acyclic methyl octadecanoate and ricinoleate (i.e. acids with the carbon chain length more than 6).
- Ishmuratov, G. Yu.,Vydrina, V. A.,Yakovleva, M. P.
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p. 1353 - 1358
(2020/10/02)
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- Citronellyl ester compound, preparation method thereof and spice
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The invention relates to a citronellyl ester compound, a preparation method thereof and spice. The preparation method of the compound comprises the following steps of performing Mitsunobu reaction on2-hydroxytetrahydropyran and 1, 4-butanediol, preparing 4-(2-oxy-tetrahydropyrane) butanol, oxidizing the 4-(2-oxy-tetrahydropyrane) butanol into 4-(2-oxy-tetrahydropyrane) butyric acid, and performing esterification reaction on the 4-(2-oxy-tetrahydropyrane) butyric acid and rhodinol to prepare a citronellol ester compound 4-(2-oxy-tetrahydropyrane) butyrate-3, 7-dimethyl-6-octenyl ester. The compound still has animal musk while having jasmine fragrance, is long in fragrance lasting time, and is widely applied to the field of flavor blending.
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Paragraph 0079-0125
(2020/07/13)
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- Production of Hydroxy Acids: Selective Double Oxidation of Diols by Flavoprotein Alcohol Oxidase
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Flavoprotein oxidases can catalyze oxidations of alcohols and amines by merely using molecular oxygen as the oxidant, making this class of enzymes appealing for biocatalysis. The FAD-containing (FAD=flavin adenine dinucleotide) alcohol oxidase from P. chrysosporium facilitated double and triple oxidations for a range of aliphatic diols. Interestingly, depending on the diol substrate, these reactions result in formation of either lactones or hydroxy acids. For example, diethylene glycol could be selectively and fully converted into 2-(2-hydroxyethoxy)acetic acid. Such a facile cofactor-independent biocatalytic route towards hydroxy acids opens up new avenues for the preparation of polyester building blocks.
- Fraaije, Marco W.,Martin, Caterina,Trajkovic, Milos
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p. 4869 - 4872
(2020/02/11)
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- Secondary amine salt catalyzed controlled activation of 2-deoxy sugar lactols towards alpha-selective dehydrative glycosylation
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A new organocatalytic glycosylation method exploiting the lactol functionality has been disclosed. The catalytic generation of glycosyl oxacarbenium ions from lactols under forcible conditions via weakly Br?nsted-acidic, readily available secondary amine salts affects the diastereoselective glycosylation of 2-deoxypyranoses and furanoses. This operationally simple iminium catalyzed activation of 2-deoxy hemi-acetals is a potential alternative to the existing cumbersome methods that need specialized handling. The mechanisms for this unique transformation and kinetic/thermodynamic effects have been discussed based on both experimental evidence and theoretical studies.
- Ghosh, Titli,Mukherji, Ananya,Srivastava, Hemant Kumar,Kancharla, Pavan K.
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supporting information
p. 2870 - 2875
(2018/05/03)
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- Asymmetric Cycloetherification by Bifunctional Organocatalyst
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Attempts to obtain enantiomerically enriched tetrahydrofuran derivatives via an intramolecular oxy -Michael addition reaction of ?-hydroxyenone is discussed. Despite previous difficulties associated with the asymmetric induction of this reaction, which can proceed even without a catalyst, a highly efficient asymmetric induction was realized using a bifunctional organocatalyst derived from a cinchona alkaloid. The reaction could be extended to ζ-hydroxyenone to yield an optically active tetrahydropyran derivative with a high ee. In these reactions, it is important for the gentle acidic and basic sites in the bifunctional organocatalyst to be arranged properly within the molecular skeleton of the catalyst. The high performance asymmetric induction relied on the affinity of the catalyst for the substrate, which played an important role. A disubstituted tetrahydropyran synthesis could be effectively performed via kinetic resolution using ζ-hydroxyenone containing a secondary alcohol moiety using a chiral phosphoric acid catalyst.
- Asano, Keisuke,Matsubara, Seijiro
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supporting information
p. 4243 - 4253
(2018/07/03)
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- BRYOSTATIN COMPOUNDS AND METHODS OF PREPARING THE SAME
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Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.
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Page/Page column 73
(2018/04/21)
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- Facile Conversion of α-Acyloxy Amides into 3-Hydroxy-lactams
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The new synthetic route to α-acyloxy amides based on Passerini multicomponent reaction followed by transformation into the corresponding five-, six-, and seven-membered 3-hydroxy-lactams has been proposed. The influence of the reaction conditions, which includes substrate structure on the reaction course that led to desired lactams, was studied. The use of various oxo components in the Passerini multicomponent reaction (P-MCR) has been evaluated. The first example of a semicyclic O,O-acetal employed as an aldehyde equivalent in the P-MCR has been reported. Finally, the established protocol was successfully applied for the enantioselective synthesis of 3-hydroxy-lactams, which play a crucial role in the synthesis of the number of bioactive compounds.
- Koszelewski, Dominik,Trzepizur, Damian,Zaorska, Ewelina,Madej, Arleta,Brodzka, Anna,Paprocki, Daniel,Borys, Filip,Wilk, Monika,Ostaszewski, Ryszard
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p. 3280 - 3290
(2018/07/13)
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- Production of 1,5-pentanediol via upgrading of tetrahydrofurfuryl alcohol
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A method of making 1,5-pentanediol from tetrahydrofurfural alcohol. The method includes the steps of dehydrating tetrahydrofurfural alcohol (THFA) to dihydropyran (DHP); hydrating at least a portion of the DHP to 2-hydroxy-tetrahydropyran (2-HY-THP) in the presence of a solid acid catalyst; and hydrogenating at least a portion of the 2-HY-THP to 1,5-pentanediol. The method can be conducted entirely in the absence of noble metal catalysts.
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Page/Page column 13; 19; 20; 21; 23
(2018/10/11)
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- Synthetic method of 5-amion-1-pentanol
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The invention discloses a synthetic method of 5-amion-1-pentanol. The synthetic method comprises the following step: carrying out a hydration reaction and a reductive amination reaction on 3,4-dihydro-2H-furan under the condition that the temperature is smaller than or equal to 120 DEG C and the pressure is smaller than or equal to 3PMa to prepare the 5-amion-1-pentanol. By taking 3,4-dihydro-2H-furan as a raw material, the 5-amion-1-pentanol is prepared through the hydration reaction and the reductive amination reaction under mild conditions, the reaction process is green and efficient, the yield of 5-amion-1-pentanol can reach 93%, the method is simple and safe to operate, the investment and production cost of a production device are lowered obviously, and scaled industrial production isachieved conveniently.
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Paragraph 0045; 0049; 0054; 0058;
(2019/01/08)
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- Transiently Thermoresponsive Acetal Polymers for Safe and Effective Administration of Amphotericin B as a Vaccine Adjuvant
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The quest for new potent and safe adjuvants with which to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll-like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration approved antifungal drug, has recently been discovered to possess TLR-triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant. We present a new class of transiently thermoresponsive polymers that, in their native state, have a phase-transition temperature below room temperature but gradually transform into fully soluble polymers through acetal hydrolysis at endosomal pH values. RAFT polymerization afforded well-defined block copolymers that self-assemble into micellar nanoparticles and efficiently encapsulate AmpB. Importantly, nanoencapsulation strongly reduced the cytotoxic effect of AmpB but maintained its TLR-triggering capacity. Studies in mice showed that AmpB-loaded nanoparticles can adjuvant an RSV vaccine candidate with almost equal potency as a highly immunogenic oil-in-water benchmark adjuvant.
- Van Herck, Simon,Van Hoecke, Lien,Louage, Benoit,Lybaert, Lien,De Coen, Ruben,Kasmi, Sabah,Esser-Kahn, Aaron P.,David, Sunil A.,Nuhn, Lutz,Schepens, Bert,Saelens, Xavier,De Geest, Bruno G.
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p. 748 - 760
(2017/12/18)
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- Branched-Selective Hydroformylation of Nonactivated Olefins Using an N-Triphos/Rh Catalyst
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We report a catalytic system comprised of nitrogen-centered di- or triphosphine ligands in conjunction with rhodium that is capable of delivering branched aldehydes from terminal olefin substrates which commonly give more linear aldehydes than branched. The incorporation of an apical nitrogen atom into the ligand backbone dramatically improves the reaction rate. Mechanistic and labeling studies suggest the unusual selectivity is due to the irreversible trapping of the Rh-alkyl species along the branched pathway, in comparison to the more reversible linear pathway. A precatalytic equilibrium mixture of rhodium species was observed by high-pressure in situ NMR spectroscopy, suggesting this equilibrium is the catalytic resting state.
- Phanopoulos, Andreas,Nozaki, Kyoko
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p. 5799 - 5809
(2018/05/29)
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- PRODUCTION OF 1,5-PENTANEDIOL VIA UPGRADING OF TETRAHYDROFUFURYL ALCOHOL
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A method of making 1,5-pentanediol from tetrahydrofurfural alcohol. The method includes the steps of dehydrating tetrahydrofurfural alcohol (THFA) to dihydropyran (DHP); hydrating at least a portion of the DHP to 2-hydroxy-tetrahydropyran (2-HY-THP) in the absence of homogeneous acid; and hydrogenating at least a portion of the 2-HY-THP to 1,5-pentanediol. The method can be conducted entirely in the absence of noble metal catalysts.
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Paragraph 0074; 0075
(2017/09/05)
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- Regioselective Ni-Catalyzed Carboxylation of Allylic and Propargylic Alcohols with Carbon Dioxide
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An efficient Ni-catalyzed reductive carboxylation of allylic alcohols with CO2 has been successfully developed, providing linear β,γ-unsaturated carboxylic acids as the sole regioisomer with generally high E/Z stereoselectivity. In addition, the carboxylic acids can be generated from propargylic alcohols via hydrogenation to give allylic alcohol intermediates, followed by carboxylation. A preliminary mechanistic investigation suggests that the hydrogenation step is made possible by a Ni hydride intermediate produced by a hydrogen atom transfer from water.
- Chen, Yue-Gang,Shuai, Bin,Ma, Cong,Zhang, Xiu-Jie,Fang, Ping,Mei, Tian-Sheng
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supporting information
p. 2969 - 2972
(2017/06/07)
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- Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode
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A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding Ki and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both Gq-coupled intracellular Ca2+ flux and Gs-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.
- Jurica, Elizabeth A.,Wu, Ximao,Williams, Kristin N.,Hernandez, Andres S.,Nirschl, David S.,Rampulla, Richard A.,Mathur, Arvind,Zhou, Min,Cao, Gary,Xie, Chunshan,Jacob, Biji,Cai, Hong,Wang, Tao,Murphy, Brian J.,Liu, Heng,Xu, Carrie,Kunselman, Lori K.,Hicks, Michael B.,Sun, Qin,Schnur, Dora M.,Sitkoff, Doree F.,Dierks, Elizabeth A.,Apedo, Atsu,Moore, Douglas B.,Foster, Kimberly A.,Cvijic, Mary Ellen,Panemangalore, Reshma,Flynn, Neil A.,Maxwell, Brad D.,Hong, Yang,Tian, Yuan,Wilkes, Jason J.,Zinker, Bradley A.,Whaley, Jean M.,Barrish, Joel C.,Robl, Jeffrey A.,Ewing, William R.,Ellsworth, Bruce A.
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supporting information
p. 1417 - 1431
(2017/03/08)
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- Peptide-Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide
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The tripeptide H-dPro-Pro-Asn-NH2is presented as a catalyst for asymmetric conjugate addition reactions of aldehydes to maleimide. The peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields. The obtained products were readily derivatized to the corresponding pyrrolidines, lactams, lactones, and peptide-like compounds.1H NMR spectroscopic, crystallographic, and computational investigations provided insight into the conformational properties of H-dPro-Pro-Asn-NH2and revealed the importance of hydrogen bonding between the peptide and maleimide for catalyzing the stereoselective C?C bond formation.
- Grünenfelder, Claudio E.,Kisunzu, Jessica K.,Wennemers, Helma
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supporting information
p. 8571 - 8574
(2016/07/21)
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- Comparison of “on water” and solventless procedures in the rhodium-catalyzed hydroformylation of diolefins, alkynes, and unsaturated alcohols
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Catalytic systems containing Rh(acac)(CO)2 or Rh/PAA (PAA?=?polyacrylic acid) and hydrophobic phosphine (PPh3) were used in the hydroformylation of diolefins, alkynes, and unsaturated alcohols under solventless and “on water” conditions. The total yield of dialdehydes obtained from 1,5-hexadiene and 1,7-octadiene reached 99%, and regioselectivity towards linear dialdehydes was higher in the “on water” system. The tandem hydroformylation-hydrogenation of phenylacetylene led to the formation of saturated aldehydes (3-phenylpropanal and 2-phenylpropanal) at 98% conversion with a good regioselectivity towards the linear aldehyde in the “on water” reaction. In contrast, solventless conditions appeared better in the hydroformylation of 1-propen-3-ol. 4-Hydroxybutanal, formed in this reaction with an excellent selectivity, was next transformed to tetrahydrofuran-2-ol via a ring-closure process. Cyclic products were also obtained in hydroformylation of 1-buten-3-ol. In reaction of undec-1-ol and 2-allylphenol linear aldehydes were formed with the yield 69–87%. The hydroformylation of 3-buten-1-ol performed under “on water” conditions showed very good regioselectivity towards a linear aldehyde, 5-hydroxypentanal. Further cyclization of the aldehyde to tetrahydropyran-2-ol was observed.
- Alsalahi,Trzeciak
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- Sequential O-H/C-H bond insertion of phenols initiated by the gold(I)-catalyzed cyclization of 1-bromo-1,5-enynes
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The development of a sequential O-H/C-H bond functionalization of phenols initiated by the cationic gold(I)-catalyzed cyclization of 1-bromo-1,5-enynes to produce (2-bromocyclopent-2-en-1-yl)phenols is reported. This unprecedented domino transformation efficiently proceeds under mild conditions (5 mol % of (t-Bu)3PAuNTf2, CH2Cl2, 0-23 °C) via an intermediate aryl alkyl ether which collapses at ambient temperature to undergo a 1,2-hydride shift followed by C-H insertion of the phenol.
- Speck, Klaus,Karaghiosoff, Konstantin,Magauer, Thomas
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supporting information
p. 1982 - 1985
(2015/04/27)
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- Spirastrellolide E: Synthesis of an advanced C(1)-C(24) southern hemisphere
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The synthesis of a C(1)-C(24) advanced southern hemisphere fragment towards the total synthesis of spirastrellolide E has been achieved. Highlights of the route include a highly convergent Type I Anion Relay Chemistry (ARC) tactic for fragment assembly, in conjunction with a directed, regioselective gold-catalyzed alkyne functionalization to generate the central unsaturated [6,6]-spiroketal.
- Sokolsky, Alexander,Wang, Xiaozhao,Smith, Amos B.
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supporting information
p. 3160 - 3164
(2015/03/04)
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- Highly Regioselective Palladium-Catalyzed Carboxylation of Allylic Alcohols with CO2
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Various allylic alcohols were carboxylated in the presence of a catalytic amount of PdCl2 and PPh3 using ZnEt2 as a stoichiometric transmetalation agent under a CO2 atmosphere (1atm). This carboxylation proceeded in a highly regioselective manner to afford branched carboxylic acids predominantly. The β,γ-unsaturated carboxylic acid thus obtained was successfully converted into an optically active γ-butyrolactone, a known intermediate of (R)-baclofen.
- Mita, Tsuyoshi,Higuchi, Yuki,Sato, Yoshihiro
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supporting information
p. 16391 - 16394
(2015/11/09)
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- Broadening the chemical scope of laccases: Selective deprotection of N-benzyl groups
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Laccase from Trametes versicolor together with TEMPO has been found to be a very efficient system to deprotect N-benzylated primary amines, differing from previously described methods since it uses oxygen as a mild oxidant in aqueous medium. Chemoselective removal of the benzyl group was achieved with excellent yields when secondary amines and alcohol moieties were also present.
- Martínez-Montero, Lía,Díaz-Rodríguez, Alba,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
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supporting information
p. 2794 - 2798
(2015/05/27)
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- Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols
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Cu/nitroxyl catalysts have been identified that promote highly efficient and selective aerobic oxidative lactonization of diols under mild reaction conditions using ambient air as the oxidant. The chemo- and regioselectivity of the reaction may be tuned by changing the identity of the nitroxyl cocatalyst. A Cu/ABNO catalyst system (ABNO = 9-azabicyclo[3.3.1]nonan-N-oxyl) shows excellent reactivity with symmetrical diols and hindered unsymmetrical diols, whereas a Cu/TEMPO catalyst system (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl) displays excellent chemo- and regioselectivity for the oxidation of less hindered unsymmetrical diols. These catalyst systems are compatible with all classes of alcohols (benzylic, allylic, aliphatic), mediate efficient lactonization of 1,4-, 1,5-, and some 1,6-diols, and tolerate diverse functional groups, including alkenes, heterocycles, and other heteroatom-containing groups.
- Xie, Xiaomin,Stahl, Shannon S.
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supporting information
p. 3767 - 3770
(2015/04/14)
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- Cascade Michael addition/cycloketalization of cyclic 1,3-dicarbonyl compounds: Important role of the tethered alcohol of α,β-unsaturated carbonyl compounds on reaction rate and regioselectivity
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Reactions of α,β-unsaturated aldehydes and cyclic 1,3-dicarbonyl compounds proceed primarily by cascade Knoevenagel condensation/six-π-electron electrocyclization (K6EC, formal [3 + 3] cycloaddition), while α,β-unsaturated ketones usually react with cyclic 1,3-dicarbonyl compounds in a 1,4-addition manner. This paper discloses our findings that under acidic conditions, α,β-unsaturated carbonyl compounds (ketones and aldehydes) with a tethered alcohol react with cyclic 1,3-dicarbonyl compounds in a highly regioselective 1,4-addition fashion via in situ generation of a hypothetical α-methylene cyclic oxonium ion as the reactive Michael acceptor. Our studies uncovered the important effect of the tethered alcohol on the reaction rate and/or efficiency and some new mechanistic aspects of the cascade Michael addition/cycloketalization. Finally, the substrate scope was examined, and 43 analogues of penicipyrone and tenuipyrone were prepared in good to excellent yields.
- Yao, Hongliang,Song, Liyan,Liu, Yuan,Tong, Rongbiao
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p. 8774 - 8785
(2015/01/09)
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- Synthesis of functionalized bicyclic imines via intramolecular azide-alkene 1,3-dipolar cycloaddition/intramolecular stork alkylation cascade reaction
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A cascade intramolecular azide-alkene 1,3-dipolar cycloaddition/Stork alkylation reaction has been developed for the synthesis of functionalized cyclic imines with a pyrroline and piperideine structures, employing readily available ω-azidodienes. Copyright
- De Miguel, Irene,Velado, Marina,Herradon, Bernardo,Mann, Enrique
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supporting information
p. 1237 - 1242
(2013/06/27)
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- Asymmetric cycloetherifications by bifunctional aminothiourea catalysts: The importance of hydrogen bonding
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Chiral oxacyclic frameworks are prevalent in many natural products and bioactive compounds. In addition, a number of them are important synthetic intermediates. Thus, the synthesis of such structures is a significant goal in the field of organic chemistry. However, the development of catalytic asymmetric cycloetherification for the straightforward synthesis of these compounds remains a challenge. In this study, we propose the use of aminothiourea catalysis as an effective way to accomplish such a challenge. The asymmetric synthesis of chiral oxygen heterocycles, including tetrahydrofurans, tetrahydropyrans, and 1,3-dioxolanes, is demonstrated herein using intramolecular oxy-Michael addition mediated by bifunctional aminothiourea catalysts. Georg Thieme Verlag Stuttgart · New York.
- Fukata, Yukihiro,Miyaji, Ryota,Okamura, Takaaki,Asano, Keisuke,Matsubara, Seijiro
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supporting information
p. 1627 - 1634
(2013/07/27)
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- Regioselective silylation of 5-(2′-hydroxyethyl)cyclopent-2-en-1-ol and 6-(2′-hydroxyethyl)cyclohex-2-en-1-ol
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Herein we report regioselective and mild reactions for the tert-butyldimethylsilyl mono-protection of 5-(2′-hydroxyethyl)cyclopent-2- en-1-ol (2) and 6-(2′-hydroxyethyl)cycohex-2-en-1-ol (5) at the primary hydroxyl group or at the secondary allylic hydroxyl group. The different steric environment surrounding the secondary allylic and saturated primary alcohols is mainly invoked to rationalize the observed regioselectivity.
- Chen, Hao,Plettner, Erika
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supporting information; scheme or table
p. 2059 - 2062
(2012/07/14)
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- Asymmetric catalytic cycloetherification mediated by bifunctional organocatalysts
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Oxacyclic structures such as tetrahydrofuran (THF) rings are commonly found in many bioactive compounds, and this has led to several efforts toward their stereoselective syntheses. However, the process of catalytic asymmetric cycloetherification for their straightforward synthesis has remained a challenge. In this study, we demonstrate a novel asymmetric synthesis method for THF via the catalytic cycloetherification of ε-hydroxy-α,β- unsaturated ketones mediated by cinchona-alkaloid-thiourea-based bifunctional organocatalysts. This catalytic process represents a highly practical cycloetherification method that provides excellent enantioselectivities, even with low catalyst loadings at ambient temperature.
- Asano, Keisuke,Matsubara, Seijiro
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supporting information; experimental part
p. 16711 - 16713
(2011/12/03)
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- Catalysis-based and protecting-group-free total syntheses of the marine oxylipins hybridalactone and the ecklonialactones A, B, and C
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Concise and protecting-group-free total syntheses of the marine oxylipins hybridalactone (1) and three members of the ecklonialactone family (2-4) were developed. They deliver these targets in optically pure form in 14 or 13 steps, respectively, in the longest linear sequence; five of these steps are metal-catalyzed and four others are metal-mediated. The route to either 1 or 2-4 diverges from the common building block 22, which is accessible in 7 steps from 2[5H]furanone by recourse to a rhodium-catalyzed asymmetric 1,4-addition reaction controlled by the carvone-derived diene ligand 35 and a ring-closing alkene metathesis (RCM) catalyzed by the ruthenium indenylidene complex 17 as the key operations. Alternatively, 22 can be made in 10 steps from furfural via a diastereoselective three-component coupling process. The further elaboration of 22 into hybridalactone as the structurally most complex target with seven contiguous chiral centers was based upon a sequence of cyclopropanation followed by a vanadium-catalyzed epoxidation, both of which were directed by the same free hydroxy group at C15. The macrocyclic scaffold was annulated to the headgroup by means of a ring-closing alkyne metathesis reaction (RCAM). In response to the unusually high propensity of the oxirane of the targeted oxylipins for ring opening, this transformation had to be performed with complexes of the type [(Ar3SiO)4Mo≡CPh] [K·OEt2] (43), which represent a new generation of exceedingly tolerant yet remarkably efficient catalysts. Their ancillary triarylsilanolate ligands temper the Lewis acidity of the molybdenum center but are not sufficiently nucleophilic to engage in the opening of the fragile epoxide ring. A final semireduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene completed the total synthesis of (-)-1. The fact that the route from the common fragment 22 to the ecklonialactones could follow a similar logic showcased the flexibility inherent to the chosen approach.
- Hickmann, Volker,Kondoh, Azusa,Gabor, Barbara,Alcarazo, Manuel,Fuerstner, Alois
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supporting information; experimental part
p. 13471 - 13480
(2011/10/10)
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- Expedient access to an N-phenylpyrrolidin-2-yl heterocycle via a base-induced intramolecular aza-michael reaction
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Ethyl 2-(1-phenylpiperidin-2-yl) acetate was formed in a spontaneous cyclization from (E)-ethyl 7-oxohept-2-enoate whereas ethyl [1-(2-bromophenyl)- 2-pyrrolidinyl] acetate could be synthesized in good overall yield when employing a stoichiometric amount of base to facilitate the intramolecular aza-Michael reaction.
- Ferreira Ramos, Josierika A.,Nagem, Tanus J.,Taylor, Jason G.
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experimental part
p. 225 - 230
(2012/03/11)
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- Evaluation of the key aroma compounds in beef and pork vegetable gravies a la chef by stable isotope dilution assays and aroma recombination experiments
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Although the aroma compounds of meat processed as such have been studied previously, data on complete homemade dishes containing beef and pork meat were scarcely studied. Recently, 38 odor-active compounds were characterized in beef and pork vegetable gravies using GC-olfactometry. In the present investigation, the most odor-active compounds were quantitated in a freshly prepared stewed beef vegetable gravy (BVG) as well as a stewed pork vegetable gravy (PVG) by means of stable isotope dilution assays. Calculation of odor activity values (OAVs; ratio of concentration to odor threshold) revealed 3-mercapto-2- methylpentan-1-ol, (E,E)-2,4-decadienal, (E,Z)-2,6-nonadienal, (E)-2-decenal, (E)-2-undecanal, and 3-hydroxy-4,5-dimethyl-2(5H)-furanone as the most potent odorants in both gravies. However, significantly different OAVs were found for 12-methyltridecanal, which was much higher in the BVG, whereas (E,Z)-2,4-decadienal showed a clearly higher OAV in the PVG. Aroma recombination experiments performed on the basis of the actual concentrations of the odorants in both gravies revealed a good similarity of the aromas of both model mixtures containing all odorants with OAVs > 1 with those of the original gravies.
- Christlbauer, Monika,Schieberle, Peter
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experimental part
p. 13122 - 13130
(2012/03/22)
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- Total syntheses of sterically locked phycocyanobilin derivatives bearing a 15Z-anti or a 15E-anti CD-ring component
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Total syntheses of sterically locked phycocyanobilin derivatives with a 15Z-anti or a 15E-anti CD-ring component were performed toward elucidation of the stereochemistry and function of the chromophore in phytochromes. In the course of the construction of a sterically locked 15E-anti CD-ring component employing 5-tosylpyrrolin-2-one derivatives as the D-ring, the Ts group was found to be rearranged under acidic conditions to give a mixture of regioisomers, both of which could be transformed into the same CD-ring precursor via detosylation with a base followed by Wittig-like coupling reaction. In addition, a sterically locked 15E-anti biliverdin derivative was also synthesized.
- Nishiyama, Kaori,Kamiya, Ayumi,Hammam, Mostafa A.S.,Kinoshita, Hideki,Fujinami, Shuhei,Ukaji, Yutaka,Inomata, Katsuhiko
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experimental part
p. 1309 - 1322
(2011/02/22)
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- Phase-selective catalysis in emulsions stabilized by Janus silica-nanoparticles
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Metal-containing Janus particles are used as interfacial catalyst/emulsifiers that catalyze reactions in biphasic systems with controlled "phase selectivity", that is, conversion of the desired reaction on one side of the emulsion. The reaction may affect
- Faria, Jimmy,Ruiz, M. Pilar,Resasco, Daniel E.
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supporting information; experimental part
p. 2359 - 2364
(2011/02/21)
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- Organocatalytic synthesis of an alkyltetrahydropyran
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The first synthesis of an alkyltetrahydropyran using a diarylprolinol organocatalyst is described. Georg Thieme Verlag Stuttgart.
- Díez,Nú?ez,Benéitez,Moro,Marcos,Basabe,Broughton,Urones
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scheme or table
p. 390 - 394
(2009/08/07)
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- Hydrolytic reactivity trends among potential prodrugs of the O 2-glycosylated diazeniumdiolate family. Targeting nitric oxide to macrophages for antileishmanial activity
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Glycosylated diazeniumdiolates of structure R2NN(O)=NO-R′ (R′ = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)=NO- ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)=NO-GlCNAc (where R2N = diethylamino or pyrrolidin-1-yl and GlcNAc = N-acetylglucosamin-1-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.
- Valdez, Carlos A.,Saavedra, Joseph E.,Showalter, Brett M.,Davies, Keith M.,Wilde, Thomas C.,Citro, Michael L.,Barchi Jr., Joseph J.,Deschamps, Jeffrey R.,Parrish, Damon,El-Gayar, Stefan,Schleicher, Ulrike,Bogdan, Christian,Keefer, Larry K.
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experimental part
p. 3961 - 3970
(2009/05/26)
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- Combinatorial synthesis of the 1,5-polyol system based on cross metathesis: Structure revision of amphidinol 3
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(Chemical Equation Presented) Combinatorial synthesis of a 1,5-polyol system corresponding to the C1-C14 unit of amphidinol 3 (AM3) and its diastereomers was achieved via chemoselective cross metathesis as the key step. Comparison of 13C NMR data of the synthetic specimens with that of AM3 led to a controversy regarding the originally proposed structure. From GC-MS analysis of the degradation product, the absolute configuration at C2 of AM3 has been revised to be R.
- Oishi, Tohru,Kanemoto, Mitsunori,Swasono, Respati,Matsumori, Nobuaki,Murata, Michio
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supporting information; experimental part
p. 5203 - 5206
(2009/06/18)
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- Traceless stereoinduction in the one-pot assembly of all three rings of hexahydrodibenzopyrans
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A one-pot method has been developed for the synthesis of all three rings of the hexahydrodibenzopyran ring system. This process involves a tandem sequence consisting of a benzannulation reaction of an alkenyl Fischer carbene complex and an alkyne followed by an elimination reaction that generates an o-quinone methide chromium tricarbonyl complex that is finally followed by an intramolecular heteroatom Diels-Alder cycloaddition. The stereoinduction for the overall process begins with the transfer of stereochemical information from the chiral center at the propargylic ether in the alkyne to the planar center of chirality in the in situ generated arene chromium tricarbonyl complexed intermediate and finally, after base-induced elimination to generate an o-quinone methide chromium tricarbonyl complexed intermediate, a transfer of chirality from the planar center of chirality in the o-quinone methide complex to the two new centers of chirality at positions 6a and 10a in the hexahydrodibenzopyran products upon intramolecular Diels-Alder reaction. The reactions of diastereomeric chiral propargyl ethers that contain an additional center of chirality can lead to high diastereoselectivity in the matched case and to low selectivity in the mismatched case. Copyright
- Korthals, Keith A.,Wulff, William D.
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p. 2898 - 2899
(2008/09/20)
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- Improved synthesis of (3E,7Z)-3,7-tetradecadienyl acetate, the major sex pheromone constituent of the potato pest Symmetrischema tangolias (Gyen)
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An efficient six-step synthesis of (3E,7Z)-3,7-tetradecadienyl acetate, the major component of the sex pheromone of the potato pest Symmetrischema tangolias (Gyen), is described, starting from the commercially available dihydropyran. The stereoselective formation of the 7Z double bond is accomplished by a Wittig reaction, while the 3E double bond is formed by a modified Knoevenagel condensation. The overall yield of the synthesis is 28%, giving the final product in high stereochemical purity (95%). The simplicity and the low cost of the herein reported synthesis suggest the potential practical use of the above pheromone in integrated management programs, for this serious insect pest.
- Ragoussis, Valentine,Perdikaris, Stamatis,Karamolegkos, Antonis,Magkiosi, Konstantina
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scheme or table
p. 11929 - 11932
(2010/03/25)
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- Branched-regioselective hydroformylation with catalytic amounts of a reversibly bound directing group
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(Chemical Equation Presented) Phosphinites do the trick and work as reversibly bound catalyst-directing groups in catalytic amounts to allow for the highly regioselective hydroformylation of homo-allylic alcohols with terminal and internal alkene functions in favor of the branched product.
- Gruenanger, Christian U.,Breit, Bernhard
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body text
p. 7346 - 7349
(2009/04/07)
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- A simple protocol for the generation of methyl(trifluoromethyl)dioxirane
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Methyl(trifluoromethyl)dioxirane, generated from an aqueous solution of 1,1,1-trifluoroacetone hydrate, sodium bicarbonate and peroxomonosulfate, is removed from the reaction mixture by the evolved gases and applied to the oxidation of substrates placed in a second reaction zone. The method is simple and robust, and allows for the application of methyl(trifluoromethyl)dioxirane in oxidation reactions on a preparative scale. Georg Thieme Verlag Stuttgart.
- Mello, Rossella,González-Nú?ez, Maria Elena,Asensio, Gregorio
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- Nickel-catalyzed multi-component connection reaction of isoprene, aldimines (lactamines), and diphenylzinc
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Ni(acac)2 catalyzes the four-component connection reaction of diphenylzinc, isoprene, aromatic aldehydes, and aromatic amines in this order and provides stereochemically homogeneous (E)-1-arylamino-1-aryl-3-methyl-5-phenyl-3-pentenes (1) in excellent yields. Aliphatic aldehydes react similarly and give (E)-1-arylamino-1-alkyl-3-methyl-5-phenyl-3-pentenes (1) in slightly reduced yields. When the alkyl groups are bulky, in addition to 1 are formed (E)-1-arylamino-1-alkyl-4-methyl-5-phenyl-3-pentenes (1′) as the minor products. Lactamines prepared in situ from five- and six-membered lactols and aromatic amines are more reactive than alkyl aldehyde aldimines and furnish (E)-4-arylamino-6-methyl-8-phenyl-6-octen-1-ols (4) and (E)-5-arylamino-7-methyl-9- phenyl-7-nonen-1-ols (5), respectively, in good yields with excellent E-stereoselectivity.
- Kojima, Keisuke,Kimura, Masanari,Ueda, Satoshi,Tamaru, Yoshinao
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p. 7512 - 7520
(2007/10/03)
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