- 69. Functionalized Nitroalkanes in Organic Synthesis. The First Concise Preparation of 4-Hydroxyheptadecan-7-one and 14-Hydroxyoctadecan-8-one, Two New Hydroxy Ketones Isolated from Chiococca alba
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The 4-hydroxyheptadecan-7-one (1) and 14-hydroxyoctadecan-8-one (2), two new hydroxyketones isolated from leaves of Chiococca alba, were synthesized, for the first time, by hydroxy-functionalized nitroalkanes 4 and 9, respectively, via two chemoselective key steps: i) nitroaldol condensation with basic alumina, and ii) direct Nef conversion of nitroalkanes to carbonyl derivatives with sodium hypophosphite, in order to preserve the OH group.
- Ballini, Roberto,Bosica, Giovanna,Rafaiani, Gianni
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- Porphyrin-templated synthetic G-quartet (PorphySQ): A second prototype of G-quartet-based G-quadruplex ligand
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Template-assembled synthetic G-quartet (TASQ) has been reported recently as a G-quadruplex ligand interacting with DNA according to an unprecedented, nature-inspired 'like likes like' approach, based on the association between two G-quartets, one being native (quadruplex) and the other one artificial (ligand). Herein, a novel TASQ-based ligand is designed, synthesized and its quadruplex-recognition properties are evaluated in vitro: PorphySQ (for porphyrin-templated synthetic G-quartet) displays enhanced quadruplex recognition properties as compared to the very first reported prototype (DOTASQ, for DOTA-templated synthetic G-quartet), since the porphyrin template insures a more stable intramolecular G-quartet fold due to self-stabilizing interactions that may take place intramolecularly between the porphyrin ring and the formed G-quartet. The Royal Society of Chemistry 2012.
- Xu, Hai-Jun,Stefan, Loic,Haudecoeur, Romain,Vuong, Sophie,Richard, Philippe,Denat, Franck,Barbe, Jean-Michel,Gros, Claude P.,Monchaud, David
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- Diastereoseletive Transannular Oxa-Conjugate Addition Generates the 2,6-cis-Disubstituted Tetrahydropyran of Neopeltolide
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Transannular 2,6-disubstituted pyrans, like the one found in the cytotoxic marine natural product neopeltolide, are a key functional group in many polyketides. While oxa-conjugate additions have been shown to provide direct and rapid access to tetrahydropyrans in acyclic neopeltolide intermediates, a transannular strategy for construction of this ring system in a macrocyclic core has not been investigated. In this study, we demonstrate that a transannular oxa-conjugate addition strategy is a viable approach to the construction of the bicyclic core of neopeltolide. We show that transannular addition occurs readily with an α,β-unsaturated ketone as the Michael acceptor and does not occur when an α,β-unsaturated ester is the Michael acceptor. Our data indicates that oxa-conjugate addition is reversible and that the stereochemical outcome can be under thermodynamic control. Using computational chemistry, we show that the lowest energy diastereomer is the desired cis-pyran found in neopeltolide, and we experimentally demonstrate that the trans and cis diastereomers are interconvertible under reaction conditions with the cis-pyran product predominating. This oxa-conjugate addition strategy should provide a viable route to accessing the fully elaborated macrocyclic core of neopeltolide.
- Hari, Taylor P. A.,Wilke, Burkardt I.,Davey, James A.,Boddy, Christopher N.
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- Discovery of a novel class of inhaled dual pharmacology muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)
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The targeting of both the muscarinic and β-adrenergic pathways is a well validated therapeutic approach for the treatment of chronic obstructive pulmonary disease (COPD). In this communication we report our effort to incorporate two pharmacologies into a single chemical entity, whose characteristic must be suitable for a once daily inhaled administration. Contextually, we aimed at a locally acting therapy with limited systemic absorption to minimize side effects. Our lung-tailored design of bifunctional compounds that combine the muscarinic and β-adrenergic pharmacologies by the elaboration of the muscarinic inhibitor 7, successfully led to the potent, pharmacologically balanced muscarinic antagonist and β2 agonist (MABA) 13.
- Rancati, Fabio,Linney, Ian D.,Rizzi, Andrea,Delcanale, Maurizio,Knight, Chris K.,Schmidt, Wolfgang,Pastore, Fiorella,Riccardi, Benedetta,Mileo, Valentina,Carnini, Chiara,Cesari, Nicola,Blackaby, Wesley P.,Patacchini, Riccardo,Carzaniga, Laura
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supporting information
(2021/04/12)
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- Synthesis of C37-Alkenones for Past Climate Reconstructions
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The total syntheses of three C37 methyl-alkenones with different degrees of unsaturation and of their 13C-labelled analogues from commercially available starting materials are presented herein for the first time. These molecules are important to improve the reliability of the measurements and reconstructions of the sea surface temperature and salinity.
- Berton, Giacomo,Pizzini, Sarah,Fabris, Fabrizio,Bertolin, Tommaso,Pafumi, Eugenia,Ceccon, Leonardo,Daelemans, Jonas,Borsato, Giuseppe,Scarso, Alessandro,Piazza, Rossano,Ferretti, Patrizia
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p. 3542 - 3551
(2020/03/26)
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- IONIZABLE AMINE LIPIDS
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The disclosure provides ionizable amine lipids and salts thereof (e.g., pharmaceutically acceptable salts thereof) useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The ionizable amine lipids disclosed herein are useful as ionizable lipids in the formulation of lipid nanoparticle-based compositions.
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Page/Page column 69-70; 76
(2020/05/15)
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- Catalytic asymmetric [4+2]-cycloaddition of dienes with aldehydes
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Despite its significant potential, a general catalytic asymmetric [4+2]-cycloaddition of simple and electronically unbiased dienes with any type of aldehyde has long been unknown. Previously developed methodologies invariably require activated, electronically engineered substrates. We now provide a general solution to this problem. We show that highly acidic and confined imidodiphosphorimidates (IDPis) are extremely effective Br?nsted acid catalysts of the hetero-Diels-Alder reaction of a wide variety of aldehydes and dienes to give enantiomerically enriched dihydropyrans. Excellent stereoselectivity is generally observed and a variety of scents and natural products can be easily accessed.
- Liu, Luping,Kim, Hyejin,Xie, Youwei,Fares, Christophe,Kaib, Philip S.J.,Goddard, Richard,List, Benjamin
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p. 13656 - 13659
(2017/11/06)
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- Porphyrin-based design of bioinspired multitarget quadruplex ligands
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Secondary nucleic acid structures, such as DNA and RNA quadruplexes, are potential targets for cancer therapies. Ligands that interact with these targets could thus find application as anticancer agents. Synthetic G-quartets have recently found numerous applications, including use as bioinspired G-quadruplex ligands. Herein, the design, synthesis and preliminary biophysical evaluation of a new prototype multitarget G-quadruplex ligand, PNAPorphySQ, are reported, where peptidic nucleic acid guanine (PNAG) was incorporated in the porphyrin-templated synthetic G-quartet (PorphySQ). Using fluorescence resonance energy transfer (FRET)-melting experiments, PorphySQ was shown to possess enhanced quadruplex-interacting properties thanks to the presence of four positively charged PNAG residues that improve its electrostatic interactions with the binding site of both DNA and RNA quadruplexes (i.e., their negatively charged and accessible G-quartets), thereby making PNAPorphySQ an interesting prototype of a multitarget ligand. Both the chemical stability and water solubility of PNAPorphySQ are improved over the non-PNA derivative (PorphySQ), which are desirable properties for drug development, and while improvements remain to be made, this ligand is a promising lead for the further development of multitarget G-quadruplex ligands.
- Laguerre, Aurélien,Desbois, Nicolas,Stefan, Loic,Richard, Philippe,Gros, Claude P.,Monchaud, David
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supporting information
p. 2035 - 2039
(2014/11/07)
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- Oxidation of unsaturated primary alcohols and ω-haloalkanols with 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate
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Unsaturated primary alcohols and ω-haloalkanols, all applied in pheromone synthesis, are oxidized to the corresponding aldehydes using 4-acetylamino-2,2,6,6-tetramethylpiperidine- 1-oxoammonium tetrafluoroborate (1a). Three methods are compared with one another; oxidations with la and silica gel, oxidations with la in the presence of pyridine, and pyridinium chlorochromate (PCC). Georg Thieme Verlag Stuttgart.
- Zakrzewski, Jerzy,Grodner, Jacek,Bobbitt, James M.,Karpinska, Monika
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p. 2491 - 2494
(2008/02/13)
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- PHEROMONES
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The apple leaf midge and raspberry cane midge pheromones have been found to be acetoxyheptadecenone and acetoxyundecanone, respectively, and uses for the related C9-19 oxoalkyl or oxoalkenyl molecules substituted with a lower alkanoyloxy group are provided, including monitoring population levels of the midge and control of midge populations by disrupting mating patterns.
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Page/Page column 17-18
(2008/06/13)
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- Ethynylation of the ether derivatives of ω-haloalkanols with lithium acetylide-ethylenediamide complex
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A new operationally simple and highly efficient procedure for the ethynylation of ether derivatives of ω-haloalkanols with lithium acetylide-ethylenediamine complex in N,N-dimethylacetamide is described.
- Karpinska,Lewandowska,Grodner
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p. 937 - 942
(2007/10/03)
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- Hydroformylation
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The present invention relates to a process for hydroformylating in the presence of a catalyst comprising at least one complex of a metal of transition group VIII with mono-phosphorus compounds which are capable of dimerizing via noncovalent bonds as ligands, to such catalysts and to their use.
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- Hydrogen bonding as a construction element for bidentate donor ligands in homogeneous catalysis: Regioselective hydroformylation of terminal alkenes
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A new concept for the construction of bidentate ligands for homogeneous metal complex catalysis is described. The concept relies on the self-assembly of monodentate ligands through hydrogen bonding. As a prototype of such systems, 6-diphenylphosphanyl-2-pyridone (6-DPPon) was shown to form a chelate in the coordination sphere of a transition metal center through unusual pyridone/hydroxypyridine hydrogen bonding (X-ray). This hydrogen bonding stays intact in a catalytic reaction as proven upon highly regioselective hydroformylation of terminal alkenes. Regioselectivities and reactivities observed rank the 6-DPPon/rhodium system among the most active and regioselective catalysts for n-selective hydroformylation of terminal alkenes. Copyright
- Breit, Bernhard,Seiche, Wolfgang
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p. 6608 - 6609
(2007/10/03)
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- Progress toward the development of a safe and effective agent for treating reentrant cardiac arrhythmias: Synthesis and evaluation of ibutilide analogues with enhanced metabolic stability and diminished proarrhythmic potential
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A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.
- Hester,Gibson,Buchanan,Cimini,Clark,Emmert,Glavanovich,Imbordino,LeMay,McMillan,Perricone,Squires,Walters
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p. 1099 - 1115
(2007/10/03)
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- Synthesis of (R)-(+)-patulolide A
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A new total synthesis of (R)-(+)-patulolide A [(11R,2E)-4-oxo-2-dodecen-11-olide] using the cyclization of hydroxy aldehydes with ketenylidenetriphenylphosphorane is described.
- Bestmann,Kellermann,Pecher
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p. 149 - 152
(2007/10/02)
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- Synthesis and Absolute Configuration of a Cytotoxic Fatty Acid Isolated from the Mushroom, Hericium erinaceum
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The naturally occurring (-)-enantiomer of a fatty acid isolated from the mushroom (Hericium erinaceum) was synthesized from (R)-(-)-benzyl glycidyl ether in 8 steps.A comparison of the specific rotation of the synthetic sample with that of the natural compound established the absolute configuration of the latter.
- Kuwahara, Shigefumi,Morihiro, Etsuko,Nemoto, Akira,Hiramatsu, Akira
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p. 1417 - 1419
(2007/10/02)
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- Enantioselective Total Synthesis of Harmonine, a Defence Alkaloid of Ladybugs (Coleoptera: Coccinellidae)
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An efficient and highly enantioselective (ee > 97percent) total synthesis of the ladybug defence alkaloid (17R,9Z)-1,17-diaminooctadec-9-ene in good overall yield is described.As the key step for the generation of the stereogenic center, asymmetric C-C bond formation by nucleophilic addition of methyllithium to an aldehyde SAMP hydrazone is used. Key Words: (17R,9Z)-1,17-Diaminooctadec-9-ene / Harmonine / Ladybug / SAMP hydrazone
- Enders, Dieter,Bartzen, Dominika
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p. 569 - 574
(2007/10/02)
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- Synthesis of Five-Membered Cyclic Ketones Using Potassium Tetracarbonylferrate(2-)
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Various five-membered cyclic ketones prepared from 1,4-dihaloalkanes and potassium tetracarbanylferrate(2-) in moderate to high yields.However, the yields of six- or seven-membered cyclic ketones from the corresponding dihalides were rather low.
- Yamashita, Masakazu,Uchida, Masaya,Tashika, Haruyoshi,Suemitsu, Rikisaku
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p. 2728 - 2729
(2007/10/02)
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- Carboxy-imidazole derivatives, compositions and use
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The imidazole derivatives of the general formula: STR1 [wherein m represents an integer of 4 to 9, R1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, and one of R2 and R3 represents a hydrogen atom, and the other represents a halogen atom or a phenyl group, or R2 and R3 together represent --(CH2)n --(in which n represents an integer of 4 to 6) or represent =CH2 ] and non-toxic salts thereof, which have a specifically inhibitory effect on the biosynthesis of thromboxane A2 (abbreviated as TXA2 hereafter) and are, therefore, useful as treating agents for diseases caused by TXA2 such as inflammation, cerebral apoplexy, myocardial infarction, acute cardiac death, cardiostenosis and thrombus etc.
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