Cinchona Alkaloids in Pneumonia. I. Miscellaneous Alkaloids and Some Hydrocupreine Ethers

Butler, C. L.; Nelson, Wendel L.; Renfrew, Alice G.; Cretcher, Leonard H.

doi:10.1021/ja01306a057

Cited by 8 publications

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“…Addition of water (10), hydrogen chloride (35), or hydrogen iodide (101, 102) gives rise to Cio isomers, as noted in section I. Very low action in vitro has been reported for hydroxydihydroquinine (10). Halogen in the side chain slightly lessens the antipneumococcic action, as observed by the Japanese workers (81, 82).…”

Section: Variations In the Quinuclidine Nucleusmentioning

confidence: 80%

Section: Variations In the Quinuclidine Nucleusmentioning

confidence: 86%

“…Of these four, epiquinidine is the most effective against the pneumococcus, although all are low in power (73). Another asymmetric center is Cio when unsymmetrical additions have been made to the double bond of the vinyl side chain; there is little difference in the antimalarial power of the a-isomer as compared with the /3-isomer of chlorodihydroquinine (35) or in the antipneumococcic power of the a-and /3-hydroxydihydroquinines (10).…”

Section: )mentioning

confidence: 99%

“…With chromic acid oxidation the alcohol group is converted to a ketone and, surprisingly, Cretcher and Renfrew (100) found that the cinchonas were converted to the corresponding ketones in fair yield during reaction with sodium amide. Dihydroquininone has little action against the pneumococcus (10) and no antimalarial action (43, page 443), but Morgenroth and Bumke (83) claim small antipneumococcic action in vitro for 9-ketooptochin.…”

Section: Variations Of the Secondary Alcohol Bridgementioning

confidence: 99%

“…The best-known naturally occurring alkaloids are the stereoisomeric 6'-methoxy compounds, quinine and quinidine, and the corresponding methoxyl-free compounds, cinchonidine and cinchonine. These have little antipneumococcic action (73,10).…”

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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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Section: Variations In the Quinuclidine Nucleusmentioning

confidence: 80%

Section: Variations In the Quinuclidine Nucleusmentioning

confidence: 86%