- Some preparation methods of a tricyclo[4.1.0.02,7]hept-4-en-3-one skeleton
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β-Elimination of acetic acid was elaborated in our synthetic method of a tricyclo[4.1.0.02,7]hept-4-en-3-one (tropovalene) skeleton. Presented was a new synthetic method of this skeleton, which consists of a reaction sequence of 1,4-addition of propanethiol to bicyclo[3.2.0]hepta-3,6-dien-2-one, photochemical construction of bicyclobutane skeleton, oxidation, and thermal elimination of sulfenic acid.
- Wakabayashi,Saito,Sugihara,Sugimura,Murata
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- Synthesis and helical structures of poly(ω-alkynamide)s having chiral side chains: Effect of solvent on their screw-sense inversion
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New ω-alkynamides, (S)-HC≡CCH2CONHCH2CH-(CH3)CH2CH3 (1) and (S)-HC≡CCH2CH2CONHCH-(CH3)CH2CH2CH2CH2CH3 (2) were synthesized and polymerized with a rhodium catalyst in CHCl3 to obtain cis-stereoregular poly(ω-alkynamide)s (poly(1) and poly(2)). Polarimetric, CD, and IR spectroscopic studies revealed that in solution the polymers adopted predominantly one-handed helical structures stabilized by intramolecular hydrogen bonds between the pendent amide groups. This behavior was similar to that of the corresponding poly(N-alkynylamide) counterparts (poly(3) and poly(4)) reported previously, whereas the helical senses were opposite to each other. The helical structures of the poly(ω-alkynamide)s were stable upon heating similar to those of the poly(N-alkynylamide)s, but the solvent response was completely different. An increase in MeOH content in CHCl3/MeOH resulted in inversion of the predominant screw-sense for poly(1) and poly(2). Conversely, poly(3) was transformed into a random coil, and poly(4) maintained the predominant screw-sense irrespective of MeOH content. The solvent dependence of predominant screw-sense for poly(1) and poly(2) was reasonably explained by molecular orbital studies using the conductor-like screening model (COSMO).
- Suzuki, Yuji,Miyagi, Yu,Shiotsuki, Masashi,Inai, Yoshihito,Masuda, Toshio,Sanda, Fumio
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- Total Syntheses of Atrovenetin and Atrovenetinone: A Naphthalene-Annulation Approach to a Discoid Tricycle Using Allenic Acid
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A total synthesis of atrovenetin has been achieved. The discoid tricyclic motif was constructed by a novel three-carbon annulation of naphthalene derivative and allenic acid under acidic conditions. An effective protocol for the conversion of atrovenetin
- Matsushita, Kyohei,Suzuki, Keisuke,Ohmori, Ken
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- Allenamides as orthogonal handles for selective modification of cysteine in peptides and proteins
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In this study, a remarkably simple and direct strategy has been successfully developed to selectively label target cysteine residues in fully unprotected peptides and proteins. The strategy is based on the reaction between allenamides and the cysteine thiol, and proceeds swiftly in aqueous medium with excellent selectivity and quantitative conversion, thus forming a stable and irreversible conjugate. The combined simplicity and mildness of the process project allenamide as robust and versatile handles to target cysteines and has potential use in biological systems. Additionally, fluorescent-labeling studies demonstrated that the installation of a C-terminal allenamide moiety onto various molecules of interest may supply a new methodology towards the site-specific labeling of cysteine-containing proteins. Such a new labeling strategy may thus open a window for its application in the field of life sciences.
- Abbas, Ata,Xing, Bengang,Loh, Teck-Peng
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- 3D-QSAR assisted identification of FABP4 inhibitors: An effective scaffold hopping analysis/QSAR evaluation
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Following on the recent publication of pharmacologically relevant effects, small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have attracted high interest. FABP4 is mainly expressed in macrophages and adipose tissue, where it regulates fatty acid storage and lipolysis, being also an important mediator of inflammation. In this regard, FABP4 recently demonstrated an interesting molecular target for the treatment of type 2 diabetes, other metabolic diseases and some type of cancers. In the past years, hundreds of effective FABP4 inhibitors have been synthesized. In this paper, a quantitative structure-activity relationship (QSAR) model has been produced, in order to predict the bioactivity of FABP4 inhibitors. The methodology has been combined with a scaffold-hopping approach, allowing to identify three new molecules that act as effective inhibitors of this protein. These molecules, synthesized and tested for their FABP4 inhibitor activity, showed IC50 values between 3.70 and 5.59 μM, with a high level of agreement with the predicted values.
- Floresta, Giuseppe,Cilibrizzi, Agostino,Abbate, Vincenzo,Spampinato, Ambra,Zagni, Chiara,Rescifina, Antonio
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p. 276 - 284
(2018/12/11)
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- Tandem Regioselective Hydroformylation-Hydrogenation of Internal Alkynes Using a Supramolecular Catalyst
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New supramolecular ligands containing an acyl guanidine function were designed based on the strategy of increasing the π-acceptor ability of phosphine ligands by introducing electron-withdrawing groups. By applying this novel catalytic system, a general protocol for the Rh-catalysed hydroformylation-hydrogenation of unsymmetrical internal alkynes, functionalized with a carboxylic acid, was found to furnish aliphatic aldehydes in high regio- and chemoselectivities. Control experiments confirm the enzyme-like supramolecular catalyst mode of action.
- Fang, Weiwei,Breit, Bernhard
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supporting information
p. 14817 - 14821
(2018/10/24)
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- 3-butynoic acid preparation method
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The present invention discloses a 3-butynoic acid preparation method comprising the following steps: (1) magnesium chips and an organic solvent are added into a reaction vessel, propargyl bromide is added dropwise under nitrogen protection, and after the addition is complete, reaction is performed for 40 to 80 minutes at room temperature; excess amount of carbon dioxide is introduced, and heated to 50 DEG C-70 DEG C for reaction for 1 to 3 hours to obtain a reaction solution; (2) the reaction solution is poured into a cooled saturated ammonium chloride aqueous solution, an organic layer is separated by extraction and layering, the organic layer is dried, filtered and concentrated to obtain crude 3-butynoic acid; (3) the crude 3-butynoic acid is recrystallized with methyl tert-butyl ether, and filtered to obtain a crystal, and then the crystal is dried to obtain pure 3-butynoic acid. No water is produced in the preparation of the 3-butynoic acid final product, the 3-butynoic acid purification process is simplified, and the 3-butynoic acid final product is less in impurities and high in purity.
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Paragraph 0021; 0022
(2016/11/24)
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- Enantioselective halogenative semi-pinacol rearrangement: Extension of substrate scope and mechanistic investigations
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The present Full Paper article discloses a survey of our recent results obtained in the context of the enantioselective halogenation-initiated semi-pinacol rearrangement. Commencing with the fluorination/semi-pinacol reaction first and moving to the heavier halogens (bromine and iodine) second, the scope and limitations of the halogenative phase-transfer methodology will be discussed and compared. An extension of the fluorination/semi-pinacol reaction to the ring-expansion of five-membered allylic cyclopentanols will be also described, as well as some preliminary results on substrates prone to desymmetrization will be given. Finally, the present manuscript will culminate with a detailed mechanistic investigation of the canonical fluorination/semi-pinacol reaction. Our mechanistic discussion will be based on in situ reaction progress monitoring, complemented with substituent effect, kinetic isotopic effect and non-linear behaviour studies.
- Romanov-Michailidis, Fedor,Romanova-Michaelides, Maria,Pupier, Marion,Alexakis, Alexandre
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supporting information
p. 5561 - 5583
(2015/03/30)
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- Catalytic Enantioselective Allenoate-Alkene [2 + 2] Cycloadditions
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Catalytic enantioselective [2 + 2] cycloadditions between allenoates and alkenes is disclosed. The method functions well for a variety of alkenes, and the products are generated with excellent levels of enantioselectivity. One of the most significant aspe
- Conner, Michael L.,Xu, Yao,Brown, M. Kevin
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supporting information
p. 3482 - 3485
(2015/03/30)
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- ALLENAMIDE AS AN ORTHOGONAL HANDLE FOR SELECTIVE MODIFICATION OF CYSTEINE IN PEPTIDES AND PROTEINS
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There is provided a compound of formula I, having the structure: wherein R1 to R5 have the meanings given in the description.
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Page/Page column 23; 24
(2015/11/09)
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- METHODS AND COMPOSITIONS FOR RIBOSOMAL SYNTHESIS OF MACROCYCLIC PEPTIDES
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Methods and compositions are provided for generating macrocyclic peptides from genetically encoded, ribosomally produced polypeptide precursors. Also provided are nucleic acid molecules, polypeptides, and methods for generating combinatorial libraries of
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Paragraph 00209
(2015/12/08)
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- A clean and selective radical homocoupling employing carboxylic acids with titania photoredox catalysis
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A titania photoredox catalysis protocol was developed for the homocoupling of C-centered radicals derived from carboxylic acids. Intermolecular reactions were generally efficient and selective, furnishing the desired dimers in good yields under mild neutral conditions. Selective cross-coupling with two acids proved unsuccessful. An intra-molecular adaptation enabled macrocycles to be prepared, albeit in modest yields. (Chemical Equation Presented).
- Manley, David W.,Walton, John C.
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supporting information
p. 5394 - 5397
(2015/02/19)
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- Enantioselective organocatalytic fluorination-induced Wagner-Meerwein rearrangement
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Cracked under strain: Strained allylic cyclobutanols and cyclopropanols readily undergo a ring expansion described by the title rearrangement. This reaction is promoted by catalytic amounts of 1 and displays high tolerance with respect to the substrate scope. The corresponding β-fluoro spiroketone products are isolated in high yields and with excellent stereoselectivities. EDG=electron-donating group, EWG=electron-withdrawing group. Copyright
- Romanov-Michailidis, Fedor,Guénée, Laure,Alexakis, Alexandre
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supporting information
p. 9266 - 9270
(2013/09/12)
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- 2H-pyran-2-ones from trichoderma viride and trichoderma asperellum
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Volatiles emitted by the soil fungi Trichoderma viride 272 and Trichoderma asperellum 328 were collected by using the closed loop stripping analysis (CLSA) headspace technique, and the obtained extracts were analysed by GC/MS. Several alkyl- and alkenyl-2H-pyran-2-ones, including known compounds 6-pentyl-2H-pyran-2-one and (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and the new derivatives (E)-6-(pent-2-en-1-yl)-2H-pyran-2-one, 6-propyl-2H-pyran-2-one, and 6-heptyl-2H-pyran-2-one were found. The alkenyl derivative (E)-6-(hept-1-en-1- yl)-2H-pyran-2-one, previously tentatively identified from a marine Botrytis by MS analysis, was also detected. All alkenyl pyrones were synthesised by using a reported Stille coupling followed by lactonisation, whereas the alkylated pyrones were obtained through a reported synthetic approach by radical bromination of 5-alkylpent-2-en-5-olides and dehydrobromination. Because the yields in both cases were not satisfactory and fell a long way short of the yields reported for similar compounds, all compounds were synthesised again using a gold-catalysed coupling of terminal alkynes with propiolic acid recently developed by Schreiber and co-workers, giving high yields in all cases. A comparison of the synthetic methods is given. Copyright
- Wickel, Susanne M.,Citron, Christian A.,Dickschat, Jeroen S.
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supporting information
p. 2906 - 2913
(2013/06/27)
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- Bioorthogonal chemical reporters for monitoring protein acetylation
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"Chemical equation presented" Protein acetylation is a key post-translational modification that regulates diverse biological activities in eukaryotes. Here we report bioorthogonal chemical reporters that enable direct in-gel fluorescent visualization and
- Yang, Yu-Ying,Ascano, Janice M.,Hang, Howard C.
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supporting information; experimental part
p. 3640 - 3641
(2010/05/15)
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- Small-molecule inhibitors of protein geranylgeranyltransferase type I
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Small molecules that inhibit the geranylgeranylation of K-Ras4B and RhoA by protein geranylgeranyltransferase type I (GGTase-I) were identified from chemical genetic screens of heterocycles synthesized through phosphine catalysis of allenes. To further improve the efficacy of the GGTase-I inhibitors (GGTIs), 4288 related compounds bearing core dihydropyrrole/pyrrolidine and tetrahydropyridine/piperidine scaffolds were synthesized on SynPhase lanterns in a split-pool manner through phosphine-catalyzed [3 + 2] and [4 + 2] annulations of resin-bound allenoates. Testing of the 4288 analogues resulted in several GGTIs exhibiting submicromolar IC50 values. Because proteins such as Ras and Rho GTPases are implicated in oncogenesis and metastasis, these GGTIs might ultimately lead to the development of novel antitumor therapeutics. Copyright
- Castellano, Sabrina,Fiji, Hannah D. G.,Kinderman, Sape S.,Watanabe, Masaru,De Leon, Pablo,Tamanoi, Fuyuhiko,Kwon, Ohyun
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p. 5843 - 5845
(2008/03/14)
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- Chromium catalyzed oxidation of (homo-)allylic and (homo-)propargylic alcohols with sodium periodate to ketones or carboxylic acids
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Primary and secondary (homo-)allylic and (homo-)propargylic alcohols can be oxidized under slightly acidic conditions at or below room- temperature with sodium periodate in the presence of sodium dichromate as the catalyst to the corresponding carboxylic acids and ketones, respectively.
- De Vondervoort, Lizette Schmieder-Van,Bouttemy, Sabine,Padrón, José M.,Le Bras, Jean,Muzart, Jacques,Alsters, Paul L.
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p. 243 - 246
(2007/10/03)
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- Total synthesis of (±)-nisamycin
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We have developed a highly convergent synthesis of the manumycin-type m- C7N-antibiotic nisamycin that is applicable to other members of this family of antibiotics. The synthesis features a three-step sequence to the epoxyquinol core that serves as a scaffold for the attachment of the polyene side chains. The eastern polyene side chain was constructed via a novel organozirconocene-mediated synthesis. Zirconocene methodology was also applied to the synthesis of the polyene side chains of asukamycin. The southern side chain of nisamycin was introduced via a Stille reaction that employed a vinyl bromo ketone, derived from an acid-sensitive bromo ketal. Pd-mediated coupling of the vinyl bromide with a stannyl TIPS ester gave TIPS-protected nisamycin that was readily converted to the natural product.
- Wipf, Peter,Coish, Philip D. G.
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p. 5053 - 5061
(2007/10/03)
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- Organozirconocene-mediated polyene synthesis: Preparation of asukamycin and manumycin a side chains
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Hydrozirconation of a functionalized alkyne followed by transmetalation and 1,2-addition to α,β-unsaturated aldehydes was used for the syntheses of the eastern side chain of asukamycin and a precursor to the southern side chain common to asukamycin and manumycin A. These routes facilitate analog preparation, and the convergent zirconocene strategy represents an alternative to stepwise Wittig condensations or Stille couplings in polyene synthesis.
- Wipf, Peter,Coish, Philip D. G.
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p. 5073 - 5076
(2007/10/03)
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- Synthesis and Nuclear Magnetic Resonance Studies on a Series of Synthesis Long-chain Tellurophene Fatty Esters
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The synthesis and the results of the 1H and 13C NMR spectroscopic analyses of thirteen 2,5-disubstituted tellurophene fatty esters, containing substituents of different chain lengths, and of a monosubstituted tellurophene ester are repported.The tellurophene esters are obtained by cyclization of the corresponding conjugated intermediates with Na2Te in the presence of AgOAc in methanol.The tellurophene moiety in the alkyl chain induces a deshielding effect on the protons of the adjacent methylene prtons.The shift parameters of the tellurophene moiety on the shifts of the adjacent methylene carbon atoms are also determined.
- Jie, Marcel S. F. Lie Ken,Chau, Sherman H.
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p. 2642 - 2657
(2007/10/03)
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- Synthesis and Gastrointestinal Pharmacology of a 3E,5Z Diene Analogue of Misoprostol
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A stereospecific synthesis and the gastric antisecretory and diarrheal activity of a 3E,5Z diene analogue of misoprostol are described.The key intermediate in the synthesis was an α chain truncated acetylene that was obtained by a cuprate/enolate capture procedure on the corresponding cyclopentenone.Palladium-catalyzed coupling of the acetylene with methyl 4-iodo-3(E)-butenoate provided the conjugated enyne.Although selected hydrogenation of the enyne with Lindlar catalyst failed, the desired 3E,5Z diene was obtained with P-2 nickel as a catalyst.The diene was about 3 times more potent than misoprostol in inhibiting gastric acid secretion in dogs and also in producing diarrhea in rats.
- Collins, Paul W.,Kramer, Steven W.,Gasiecki, Alan F.,Weier, Richard M.,Jones, Peter H.,et al.
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p. 193 - 197
(2007/10/02)
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- Lewis Acid Catalyzed Cycloaddition of Methyl 2,3-Butadienoate to Alkenes
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Methyl 2,3-butadienoate (1) undergoes EtAlCl2-catalyzed stereospecific cycloadditions with alkenes to give methyl cyclobutylideneacetates in good yield.The stereospecificity and ratios of E and Z isomers suggest a ?2s + sub
- Snider, Barry B.,Spindell, David K.
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p. 5017 - 5020
(2007/10/02)
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