Cinchona Alkaloids in Pneumonia. IV. Derivatives of Ethylapocupreine<sup>1</sup>

Butler, C. L.; Renfrew, Alice G.; Cretcher, Leonard H.; Souther, B. L.

doi:10.1021/ja01281a002

Cited by 7 publications

(8 citation statements)

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“…Bis(pyrrolo [3,4-d])tetrathiafulvalene [43] (4; Scheme 1), 2-(2-iododethoxy)-ethyl-p-toluenesulfonate [44] (5; Scheme 1), 4-[bis(4-tert-butylphenyl)(4-ethylphenyl)methyl]phenol [21] (9; Scheme 1), compound [28d] 12 (Scheme 1), the chloride [21] 17 (Scheme 2 and 4), 1,1''-[1,4-phenylenebis(methylene)]bis(4,4'-bipyridin-1-ium) bis-(hexafluorophosphate) [45] (16·2 PF 6 ) (Schemes 3 and 5), the iodide [28h] 18 (Scheme 4), 4,5-bis(2-cyanoethylthio)-1,3-dithiole-2-thione [46] (19; Scheme 4), 5-tosyl-(1,3)-dithiolo-[4,5-c]pyrrole-2-one [43] (21; Scheme 4), and 2-(2-chloroethoxy)-ethyl-p-toluenesulfonate [47] (25; Scheme 4) were all prepared according to literature procedures. Solvents were dried according to literature procedures.…”

Section: Methodsmentioning

confidence: 99%

“…The tosyl protecting group on the MPTTF unit was removed in good yield (87 %) using NaOMe in a THF/MeOH mixture. The resultant pyrrole nitrogen atom in 24 was alkylated with compound 25, [47] affording the chloride 26 in 75 % yield. The chloride in compound 26 was initially converted to (26!27) an iodide in 99 % yield and then to (27!28) a thiocyanate group in 99 % yield.…”

Section: Rbpttfmentioning

confidence: 99%

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Ground‐State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Choi

Flood

Steuerman

et al. 2005

Chemistry A European J

225

228

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We report on the kinetics and ground-state thermodynamics associated with electrochemically driven molecular mechanical switching of three bistable [2]rotaxanes in acetonitrile solution, polymer electrolyte gels, and molecular-switch tunnel junctions (MSTJs). For all rotaxanes a pi-electron-deficient cyclobis(paraquat-p-phenylene) (CBPQT4+) ring component encircles one of two recognition sites within a dumbbell component. Two rotaxanes (RATTF4+ and RTTF4+) contain tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) recognition units, but different hydrophilic stoppers. For these rotaxanes, the CBPQT4+ ring encircles predominantly (>90 %) the TTF unit at equilibrium, and this equilibrium is relatively temperature independent. In the third rotaxane (RBPTTF4+), the TTF unit is replaced by a pi-extended analogue (a bispyrrolotetrathiafulvalene (BPTTF) unit), and the CBPQT4+ ring encircles almost equally both recognition sites at equilibrium. This equilibrium exhibits strong temperature dependence. These thermodynamic differences were rationalized by reference to binding constants obtained by isothermal titration calorimetry for the complexation of model guests by the CBPQT4+ host in acetonitrile. For all bistable rotaxanes, oxidation of the TTF (BPTTF) unit is accompanied by movement of the CBPQT4+ ring to the DNP site. Reduction back to TTF0 (BPTTF0) is followed by relaxation to the equilibrium distribution of translational isomers. The relaxation kinetics are strongly environmentally dependent, yet consistent with a single electromechanical-switching mechanism in acetonitrile, polymer electrolyte gels, and MSTJs. The ground-state equilibrium properties of all three bistable [2]rotaxanes were reflective of molecular structure in all environments. These results provide direct evidence for the control by molecular structure of the electronic properties exhibited by the MSTJs.

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Section: Methodsmentioning

confidence: 99%

Section: Rbpttfmentioning

confidence: 99%

Ground‐State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Choi

Flood

Steuerman

et al. 2005

Chemistry A European J

225

228

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“…Methylapocupreine (isoquinine) is more effective than quinine or dihydroquinine (39,89; also unpublished work); ethylapocupreine has about the same antipneumococcic action as optochin (13, 80, 89). The apocupreine (apoquinine) ethers have lower toxicity than the corresponding ethers of the hydrocupreine or cupreine series, as is apparent in the data cited by Maclachlan (56, 72, 73), Butler (10,13), and Gundel and Seitz (39). Conversion of the vinyl group to an ethylidene group introduces the possibility of geometric isomerism.…”

Section: Variations In the Quinuclidine Nucleusmentioning

confidence: 93%

“…The product, called apoquinine by Hesse (49), consists of substances of different toxicities and antipneumococcic powers and these give derivatives of various biological properties. The name isoquinine (39)] and ethylapocupreine1 or [ethylapoquinine (13,14,22,45,52,56,72,73,76,79,80,81,89,90)] were reported by investigators in the United States, Germany, and Japan to have protective action in experimental pneumonias. Since 1934 Maclachlan et al have published results of the experimental testing of alkyl and hydroxylated alkyl ethers of apocupreine in lower animals and of the use of hydroxyethylapocupreine in the treatment of pneumonia in man.…”

mentioning

confidence: 99%

“…Formula I represents cupreine, and the corresponding methyl ether is quinine. The quinoline and quinuclidine nuclei linked through the secondary alcoholic apocupreine has been applied to the main component of the reaction product (13) and corresponds to the terms apoquinine (45,46), as used by Henry, and (3-isocupreine (55), as used by Suszko. N I Cupreine group are characteristic of the naturally occurring alkaloids (quinine, quinidine, cupreine, cinchonidine, and cinchonine, and their dihydro derivatives).…”

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confidence: 99%

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Structure and Antipneumococcic Activity in the Cinchona Series.

Renfrew¹,

Cretcher²

1942

Chem. Rev.

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The present survey gives particular emphasis to recent studies of the antipneumococcic action of some cinchona derivatives. A brief historical survey is presented and reference is made to speculations concerning the mode of action of cinchonas in the animal body. Antipneumococcic action is analyzed with regard to isomeric and structural modifications of the cinchona molecule. A summary of recent data on bacteriostasis, toxicity, animal protection, pharmacologic testing, and clinical studies is given. Synthetic analogs are discussed in relation to significant structural factors.Cinchona alkaloids have been used as antimalarials since 1630, but evidence of the specific antipneumococcic action of these compounds dates only from 1911. RIorgenroth's (84) study of cinchonas as antipneumococcic agents has been described as "the first striking instance of the successful application of a chemical to the treatment of a bacterial infection in a laboratory animal" (53). Because Morgenroth had been studying quinine in relation to trypanosome infections in animals and was acquainted with the capsule-formation characteristic of trypanosomes, spirilla, and the pneumococcus, he was led to investigate the action of the alkaloid in pneumococcic septicemia in mice. There followed an extensive study of hydrocupreine ethers with the synthesis of the well-known optochin, vuein, and eucupin. Between 1919 and 1924 Heidelberger and Jacobs (42, 54) a t the Rockefeller Institute and Giemsa (32, 33) in Germany published the results of further studies in the hydrocupreine series. These results have been reviewed by von Oettingen (111) and by Houben (50), and the clinical findings have been discussed by Moore and Chesney (87), by Kolmer (63), and by Solis-Cohen (107).The remarkable antipneumococcic action of optochin has been a spur to reinvestigation of this field. In again studying cinchona derivatives the search was not so much for a compound of greater power but rather for a compound free from deleterious side-effects. The last decade has brought extensive synthesis in the field of apocinchonas. In the early 1930's methylapocupreinel [or 1 At the time the term apocupreine (8) was suggested, its use was based firstly on the similarities of apocupreine (formula 11) and cupreine (formula I), which differ chemically only in the 3-substituent of ethylidene or vinyl, respectively, and secondly on the established usage of Leger (59, 66) in applying the terms apocinchonine and apocinchonidine (characterized by the ethylidene side chain) to the corresponding substances derived from cinchonine and cinchonidine. In the case of quinine, demethylation is accomplished by boiling with 60 per cent sulfuric acid; a shift of the double bond also occurs. The product, called apoquinine by Hesse (49), consists of substances of different toxicities and antipneumococcic powers and these give derivatives of various biological properties. The name 49

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Treatment of Pneumonia by Sulfapyridine and by Hydroxyethylapocupreine Dihydrochloride

Menten¹

1940

Arch Pediatr Adolesc Med

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Cinchona Alkaloids in Pneumonia. IV. Derivatives of Ethylapocupreine¹

Cited by 7 publications

References 0 publications

Ground‐State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Ground‐State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Structure and Antipneumococcic Activity in the Cinchona Series.

Treatment of Pneumonia by Sulfapyridine and by Hydroxyethylapocupreine Dihydrochloride

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Cinchona Alkaloids in Pneumonia. IV. Derivatives of Ethylapocupreine1

Cited by 7 publications

References 0 publications

Ground‐State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Ground‐State Equilibrium Thermodynamics and Switching Kinetics of Bistable [2]Rotaxanes Switched in Solution, Polymer Gels, and Molecular Electronic Devices

Structure and Antipneumococcic Activity in the Cinchona Series.

Treatment of Pneumonia by Sulfapyridine and by Hydroxyethylapocupreine Dihydrochloride

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Cinchona Alkaloids in Pneumonia. IV. Derivatives of Ethylapocupreine¹