- Metathesis Cascade-Triggered Depolymerization of Enyne Self-Immolative Polymers**
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A novel class of enyne self-immolative polymers (SIPs) capable of metathesis cascade-triggered depolymerization is reported. Studies on model compounds established 1,6-enyne structures for efficient metathesis cascade reactions. SIPs incorporating the optimized 1,6-enyne motif were prepared via both polycondensation and iterative exponential growth approaches. These SIPs demonstrated excellent stability in strong acid, base, nucleophiles, or at elevated temperatures, and can undergo efficient and complete depolymerization once triggered by a metathesis catalyst. Further studies revealed that introducing a terminal alkene to the chain end of the enyne SIPs improved the depolymerization efficiency, and established their potential as stimuli-responsive materials.
- Giardino, Gavin J.,Niu, Jia,Yuan, Jingsong
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supporting information
p. 24800 - 24805
(2021/10/07)
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- D3 RECEPTOR AGONIST COMPOUNDS; METHODS OF PREPARATION; INTERMEDIATES THEREOF; AND METHODS OF USE THEREOF
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Disclosed herein are novel compounds including dopamine D3 receptor agonists, compositions thereof, methods of use thereof, and processes of synthesizing the same. Further disclosed are D3R selective agonist compounds, specifically bitopic ligands comprising chirality.
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Paragraph 0083; 0118
(2020/10/21)
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- The Significance of Chirality in Drug Design and Synthesis of Bitopic Ligands as D3 Receptor (D3R) Selective Agonists
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Because of the large degree of homology among dopamine D2-like receptors, discovering ligands capable of discriminating between the D2, D3, and D4 receptor subtypes remains a significant challenge. Previous work has exemplified the use of bitopic ligands as a powerful strategy in achieving subtype selectivity for agonists and antagonists alike. Inspired by the potential for chemical modification of the D3 preferential agonists (+)-PD128,907 (1) and PF592,379 (2), we synthesized bitopic structures to further improve their D3R selectivity. We found that the (2S,5S) conformation of scaffold 2 resulted in a privileged architecture with increased affinity and selectivity for the D3R. In addition, a cyclopropyl moiety incorporated into the linker and full resolution of the chiral centers resulted in lead compound 53 and eutomer 53a that demonstrate significantly higher D3R binding selectivities than the reference compounds. Moreover, the favorable metabolic stability in rat liver microsomes supports future studies in in vivo models of dopamine system dysregulation.
- Battiti, Francisco O.,Cemaj, Sophie L.,Guerrero, Adrian M.,Shaik, Anver Basha,Lam, Jenny,Rais, Rana,Slusher, Barbara S.,Deschamps, Jeffery R.,Imler, Greg H.,Newman, Amy Hauck,Bonifazi, Alessandro
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p. 6287 - 6314
(2019/08/02)
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- Axinellamines as broad-spectrum antibacterial agents: Scalable synthesis and biology
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Antibiotic-resistant bacteria present an ongoing challenge to both chemists and biologists as they seek novel compounds and modes of action to out-maneuver continually evolving resistance pathways, especially against Gram-negative strains. The dimeric pyrrole-imidazole alkaloids represent a unique marine natural product class with diverse primary biological activity and chemical architecture. This full account traces the strategy used to develop a second-generation route to key spirocycle 9, culminating in a practical synthesis of the axinellamines and enabling their discovery as broad-spectrum antibacterial agents, with promising activity against both Gram-positive and Gram-negative bacteria. While their detailed mode of antibacterial action remains unclear, the axinellamines appear to cause secondary membrane destabilization and impart an aberrant cellular morphology consistent with the inhibition of normal septum formation. This study serves as a rare example of a natural product initially reported to be devoid of biological activity surfacing as an active antibacterial agent with an intriguing mode of action.
- Rodriguez, Rodrigo A.,Barrios Steed, Danielle,Kawamata, Yu,Su, Shun,Smith, Peter A.,Steed, Tyler C.,Romesberg, Floyd E.,Baran, Phil S.
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supporting information
p. 15403 - 15413
(2015/01/09)
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- Continuous flow olefin metathesis using a multijet oscillating disk reactor as the reaction platform
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The multijet oscillating disk (MJOD) flow reactor is a relatively new technology for continuous flow synthesis. This technology is still under investigation as an all-round platform for flow synthesis. In this article, findings are disclosed from a project where a MJOD flow reactor rig (reactor volume of ≈50 mL) was investigated as the reaction platform for ring closing metathesis and cross (self) metathesis reaction, using reaction mixture volumes down to only ≈5 mL. The Hoveyda-Grubbs second-generation catalyst was used without an inert atmosphere. The results of the flow synthesis provided excellent selectivity and high yield. For comparison purposes, the syntheses conducted in the MJOD reactor were compared with similar literature experiments performed with other flow technologies and batch conditions.
- Bjorsvik, Hans-Ren,Liguori, Lucia
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p. 1509 - 1515
(2015/02/19)
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- C10 Dialdehyde, Synthetic Method Thereof, and Synthetic Method of Beta-Carotene Using the Same
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The novel intermediate compound which can be efficiently utilized in the synthesis of carotenoid compounds based on the sulfone chemistry, the preparation method of the same, and the practical synthetic process for preparing β-carotene by the use of the above novel compound are disclosed. The synthesis of β-carotene is characterized by the double elimination reactions of the C40 compound containing both the benzenesulfonyl group and the group X (either halogen or ether), which can be prepared by the coupling reaction of the novel C10 dialdehyde with two equivalents of the C15 allylic sulfone, followed by the functional group transformation of the resulting C40 diol either to the corresponding halide or to the ether, to produce the fully conjugated polyene chain.
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Page/Page column 6
(2008/12/04)
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- ClO DIALDEHYDE, SYNTHETIC METHOD THEREOF, AND SYNTHETIC METHOD OF BETA-CAROTENE USING THE SAME
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The novel intermediate compound which can be efficiently utilized in the synthesis of carotenoid compounds based on the sulfone chemistry, the preparation method of the same, and the practical synthetic process for preparing β-carotene by the use of the above novel compound are disclosed. The synthesis of β-carotene is characterized by the double elimination reactions of the C40 compound containing both the benzenesulfonyl group and the group X (either halogen or ether), which can be prepared by the coupling reaction of the novel C10 dialdehyde with two equivalents of the C15 allylic sulfone, followed by the functional group transformation of the resulting C40 diol either to the corresponding halide or to the ether, to produce the fully conjugated polyene chain.
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Page/Page column 9-10
(2010/10/20)
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- Palladium(0)-catalyzed allylation of highly acidic and non-nucleophilic arenesulfonamides, sulfamide, and cyanamide. II. Formation of medium and large heterocycles
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Arenesulfonamides 10, cyanamide 29, and sulfamide 32 react with allylic bis-carbonates 8 (Z and E) and 9 under Pd(0)-catalysis to afford medium and large unsaturated heterocycles instead of three and/or five-membered ring compounds. Stable 15-membered palladium-containing rings were also isolated from arenesulfonamides and 8, with three trans olefinic systems coordinated to the metal. NMR and MALDI-TOF MS experiments were used for structure elucidations. Suitable hydrogenation conditions to give the saturated macrocycles have been found.
- Cerezo, Silvia,Cortes, Jordi,Lopez-Romero, Juan-Manuel,Moreno-Manas, Marcial,Parella, Teodor,Pleixats, Roser,Roglans, Anna
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p. 14885 - 14904
(2007/10/03)
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- Azole compounds and fungicides containing these compounds
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Azole compounds of the formula STR1 where V is oxygen or sulfur, X is hydrogen, halogen, alkyl, alkoxy, trifluoromethyl, phenyl or phenoxy, m is an integer from 1 to 5, W is an olefin group which is unsubstituted or substituted, or is alkynyl, Z is CH or N, and Y is C=O or CR3 OR4, where R3 is hydrogen, alkyl, alkenyl or alkynyl, and R4 is hydrogen, alkyl, alkenyl, alkynyl or alkanoyl, and their plant-tolerated addition salts with acids and metal complexes, and fungicides which contain these compounds.
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- A reinvestigation of the vapor phase bromination of 2-bromobutane
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The soltuion phase photobromination of 2-bromobutane yields 2,2-dibromobutane, meso-2,3-dibromobutane, dl-2,3-dibromo-dibromobutane, small amounts of 1,2-dibromobutane, and 2,2,3-tribromobutane.However, in the corresponding vapor phase bromination these products appear along with other polybrominated products.The yield of these polybromides increases with temperature.The increase in yield of the polyhalogenated materials is rationalized by considering the thermal instabilty of the β-bromoalkyl radical, which eliminates a bromine atom to form the corresponding alkene.It is demonstrated that in the vapor phase allylic bromination competes succesfully with bromine addition.Reaction schemes are suggested to explain the formation of polybromides.An explanation is also offered for the dicrepancy between these results and those of previously reported vapor phase work.
- Tanner, Dennis D.,Ruo, Tomoki C. S.,Kosugi, Yoshio,Potter, Alan
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p. 2310 - 2316
(2007/10/02)
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- Competing Mechanistic Pathways in the Bromination of 1,3-Butadiene with Molecular Bromine, Pyridine-Bromine Complex, and Tribromide Ion
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The kinetics and product distribution of the reactions of 1,3-butadiene with molecular bromine, with the pyridine-bromine charge-transfer complex (PyBr2), and with tetra-n-butylammonium tribromide in 1,2-dichloroethane and dichloromethane have been investigated.Whereas the reaction with Br2 is second order in halogen, those with the other two reagents are first order in the halogenating species, and evidence is presented that both act as independent electrophiles, rather than as sources of molecular bromine.In the reaction with PyBr2 (and to a lesser extent in that with Br3(1-) in the presence of pyridine) substantial amounts of N-(4-bromo-1-buten-3-yl)pyridinium bromide are formed besides the expected 1,2- and 1,4-dibromo adducts.This is converted into the corresponding tribromide as long as free Br2 or PyBr2 is present in the medium.The resulting tribromide ion remains as the only brominating species during the later stages of the reaction.The change from 1,2-dichloroethane to the slightly less polar dichloromethane as solvent produces a threefold decrease in rate of reaction with Br2 and a fourfold increase in that with Br3(1-).Possible mechanisms for the reactions of butadiene with Br2, PyBr2, and Br3(1-) are discussed in terms of the present and previous results on these reactions.These have revealed very significant differences in the ratios of 1,2- to 1,4-adducts on changing from molecular Br2 to complexed bromine as the reagents, which are interpreted in the light of these mechanisms.
- Bellucci, Giuseppe,Berti, Giancarlo,Bianchini, Roberto,Ingrosso, Giovanni,Yates, Keith
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p. 2315 - 2323
(2007/10/02)
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- Novel fluorohydrocarbons
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Novel fluorohydrocarbons include a fluoroalkyl unit terminating in a tertiary carbon atom which is directly linked to an aliphatic moiety of the compound. The compounds contain at least 9 carbon atoms and usually no more than 13 carbon atoms. The compounds are synthesized by addition of a fluoride atom to the tertiary carbon atom of a fluorocarbon material to form a carbanion followed by alkylation of the carbanion. The fluorohydrocarbons will find use as blood substitutes or as electronic fluids.
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