The Total Synthesis of Quinine

Abstract

The Total Synthesis of Quinine 861 reconversion, first of cinchotoxine,11 and later, of quinotoxine,12 into cinchonine and quinine. Quinotoxine was converted by the action of sodium hypobromite into N-bromoquinotoxine (V), which was cyclized by alkali, with loss of hydrogen bromide, to give quininone (VI). Reduction of the ketone (VI) with aluminum powder and ethanol in the presence of sodium ethoxide gave a mixture of stereoisomeric alcohols, from which both quinine (I) and quinidine were isolated.13 At this point it seemed likely that by conden-

Separation of the Mixtures of Chiral Compounds by Crystallization

“…As an example can be mentioned the first ever resolution by salt formation accomplished by Pasteur wher the "d-quinotoxined-tartrate" obtained was a hexahydrate. 54 Of course it can be found numerous similar examples in the literature. 55 It is not rare the phenomenon that the selective solvate formation of diastereomers gives a much better separation or the solvate formation is essential for successful resolution.…”

Bonding Beyond Borders: The Nozoe Autograph Books and Other Collections

“…Koji was particularly playful as he often is when relaxing at restaurants that serve sake. But Gilbert asked a very serious question, a question whose meaning and substance I would only discover nearly ten years later when I was studying [35] the validity of Stork's claim [36][37][38][39] that the Woodward-Doering total synthesis of quinine [40,41] was a "myth." (Woodward received the Nobel Prize in 1965.)…”

“…The Woodward-Doering/Rabe-Kindler total synthesis of quinine. [40,41,43] Perhaps this should have been named the Woodward-Doering/Proštenik-Prelog/Rabe-Kindler total synthesis of quinine, given that Proštenik and Prelog [42] reported the conversion of homomeroquinene into quinotoxine in 1943, a year before Woodward and Doering's first communication. Stork's message to Prelog written in the author's travelling autograph book ( Figure 9) inquired if Prelog, or anyone known to Prelog, had repeated the Rabe and Kindler conversion of quinotoxine to quinine.…”

Quinina: 470 anos de história, controvérsias e desenvolvimento

“…16 Este trabalho, apenas uma comunicação inicial, foi seguido por uma publicação completa em 1945 e deu origem a uma das grandes controvérsias do século XX. 17 Nas duas publicações, Woodward e Doering recorreram ao trabalho de Rabe e Kindler para afirmar que haviam sintetizado a quinina (2). Na verdade, o que Woodward e Doering obtiveram foi a síntese do homomeroquineno (6) racêmico e também a quinotoxina (3) (Figura 6).…”