- The synthesis of epiboxidine and related analogues as potential pharmacological agents
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Methyl epiboxidine-N-carboxylate (8) was synthesized from 7 under reductive Heck conditions (Scheme 2). The C-C coupling of the new epiboxidine analog 9 with aryl and heteroaryl halides gave by hydroarylation C-aryl, N-(3-methylisoxazol-5-yl)-substituted
- Kulu, Irem,Ocal, Nuket
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scheme or table
p. 2054 - 2060
(2012/01/04)
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- First intermolecular Pauson-Khand reaction of 7-azanorbornenes. Control of the regioselectivity by the effect of the substituents attached to the olefinic partner
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High regioselectivity in the intermolecular Pauson-Khand reaction of 7-azanorborn-5-enes has been found by using 5-bromo-2-endo-tosyl derivatives as the olefinic partner.
- Arjona, Odón,Csák?, Aurelio G.,Medel, Rocío,Plumet, Joaquín
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p. 3085 - 3087
(2007/10/03)
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- Synthesis of conduramines from N-tert-butoxycarbonylpyrrole
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Two related synthetic strategies were devised to convert the Diels- Alder adduct 3c of Boc-pyrrole and p-toluenesulfonylacetylene into various racemic and optically pure conduramines. One process consists of the regio- and stereoselective hydroxylation of 3c to the tri- and dihydroxylated azabicyclo-[2.2.1]heptane derivatives 10b (Scheme 2) and the exo-endo mixture 13-14 (Scheme 3). Anionic fragmentation of 10b (methylmagnesium bromide) and of the 13-14 sulfone mixture (lithium bis-(trimethylsilyl)amide) generated the corresponding tri- and dihyroxylated aminocyclohexenes 17 and 16 (Scheme 3). Compound 17 is an aminocyclitol with a stereochemistry and partial aminotriol sequence identical to that found in neoinosamine. Compound 16 served as a source of the protected and free aminodiols 35b and 35a (Scheme 6), which were stereospecifically epoxidized to 36 (Scheme 6) and 40 (Scheme 7). Phenylselenide cleavage of these epoxides provided 37 (Scheme 6) and 41a (Scheme 7), which after selenoxide cycloelimination and protecting group manipulation were converted into (±)-conduramine C-1 (39a, Scheme 6) and the previously unreported, all-cis-conduramine D-1 (43a, Scheme 7). In a second process, anionic fragmentation of the bicyclic system is effected prior to introduction of the hydroxyl groups, as exemplified by the high-yielding conversion of the exo-endo mixture of azabicycloheptenes 11 and 12 into the aminocyclohexadiene 15 (Scheme 3). Osmate catalyzed cis-dihydroxylation of the derived bis-Boc derivative 20 (Scheme 4) led stereospecifically to the α-cis-diol 21 which was transformed into (±)-conduramine A-1 (27a) and its tetraacetyl derivative 27b via the epoxy compound 24. On the other hand, peracid oxidation of the diene 15 gave the β-epoxide 28 (Scheme 5) which was cleaved to the trans-diol 29 with aqueous sulfuric acid. This diol was converted into (±)-conduramine F-1 (34a) and its tetraacetyl derivative (34b) by a reaction sequence similar to that used for the other conduramine syntheses. Fractional crystallization of the diastereomeric mixture of Michael adducts obtained from (±)-3c and (-)-methyl lactate gave (-)-44a and (-)-45a both in ≤47% yield (Scheme 8). Both the carboxylic acid (+)-44b and the primary alcohol (+)-46 derived from (-)-44a were converted into (-)-3c with excess methylmagnesium bromide (ca. 40% overall yield). In the same way (-)-45a was transformed into optically pure (+)-3c. (-)-3c and (+)-3c were then converted into (-)-conduramine C-1 [(-)-39a] and (+)-conduramine D-1 [(+)-43a] by procedures identical to those used for the racemic compounds.
- Leung-Toung, Regis,Liu, Yanzhou,Muchowski, Joseph M.,Wu, Yu-Lin
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p. 3235 - 3250
(2007/10/03)
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- 2-(Het)aryl-substituted 7-azabicyclo[2.2.1]heptane systems
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Epibatidine (1) is a recently discovered trace alkaloid found in the skin of a Latin-Amencan poisonous frog. Its remarkably high analgetic activity is accompanied by high toxicity. Therefore, in order to tune its biological activity, a convergent and effi
- Otten, Albert,Namyslo, Jan Christoph,Stoermer, Martin,Kaufmann, Dieter E.
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p. 1997 - 2001
(2007/10/03)
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- The total synthesis of the analgesic alkaloid epibatidine
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Several synthetic routes to the analgesic alkaloid epibatidine have been explored. Approaches starting from tropinone, involving either ring-cleavage followed by intramolecular aldol reaction, or Favorskii ring-contraction, were not successful. A successf
- Giblin, Gerard M. P.,Jones, Clifford D.,Simpkins, Nigel S.
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p. 3689 - 3697
(2007/10/03)
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- Mechanistic studies on the iron-promoted deamination reactions of 7-azanorbornadiene derivatives
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The reaction mechanism for the fragmentation of 7-azanorbornadiene derivatives (ANB; 7-azabicyclo[2.2.1]hepta-2,5-diene) mediated by iron carbonyl compounds was analyzed by substituent effects. The reactions proceed through two stages: a tetracarbonyliron
- Hwang, Jiunn-Jye,Ding, Mei-Fang,Wen, Yuh-Sheng,Chow, Tahsin J.
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p. 119 - 123
(2007/10/03)
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- A concise stereoselective synthesis of epibatidine employing conjugate addition to an alkenyl sulfone intermediate as the key step
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A new synthesis of racemic epibatidine has been achieved, which involves conjugate addition of a metallated 2-methoxypyridine derivative to a suitably protected azabicyclic alkenyl sulfone as the key step.
- Giblin, Gerrard M. P.,Jones, Clifford D.,Simpkins, Nigel S.
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p. 589 - 590
(2007/10/03)
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- Synthesis of Highly Functionalized 7-Azabicycloheptadienes
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Highly functionalized 7-azabicycloheptadiene derivatives have been synthesized via a cycloaddition reaction between N-acyl-3,4-disubstituted pyrroles and ethynyl p-tolyl sulfone 5.
- Chen, Zhengming,Trudell, Mark L.
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p. 9649 - 9652
(2007/10/02)
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- A Total Synthesis of (+/-)-Epibatidine
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A total synthesis of the potent non-opiate analgesic alcaloid epibatidine is described, in which the key step is reductive palladium-catalysed Heck-type coupling.The synthesis is concise (two steps from known compounds), highly convergent, and completely sttereoselective for the desired exo-isomer. - Key Words: Epibatidine, Analgesic, Alkaloid, Palladium-catalysed Coupling
- Clayton, Simon C.,Regan, Andrew C.
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p. 7493 - 7496
(2007/10/02)
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