In total synthesis, the Quinine total synthesis describes the efforts in synthesis of quinine over a 150 year period. The development of synthetic quinine is considered a milestone in organic chemistry although it has never been produced industrially as a substitute for natural occurring quinine. The subject has also been attended with some controversy.
The aromatic part of the quinine molecule is a quinoline with a methoxy substituent. The amine component has a quinuclidine skeleton and the methylene bridge in between has an hydroxide group. The substituent at the carbon-3 position is a vinyl group. The molecule is optically active with four stereogenic groups making synthesis potentially difficult because it is one of 16 stereoisomers.
Quinine total synthesis timeline
1817: First isolation of quinine from cinchona tree by Pierre Joseph Pelletier and Joseph Caventou
1856: William Henry Perkin attempts quinine synthesis by oxidation of N-allyl toluidine based on the simple but erroneous idea that 2 equivalents of this compound with chemical formula C10H13N plus three equivalents of oxygen yield one equivalent of C20H24N202 (quinine's chemical formula) and one equivalent of water  His oxidations with other toluidines sets him on the path of mauveine which eventually leads to the birth of chemical industry.
1907: the correct atom connectivity established by Paul Rabe 
1918: Paul Rabe and Karl Kindler synthesize quinine from quinotoxine, reversing the Pasteur chemistry. The lack of experimental details in this publication would become a major issue in the Stork/Woodward controversy almost a century later.
The first step in this sequence is sodium hypobromite addition to quinotoxine to an N-bromo intermediate possibly with structure 2. The second step is organic oxidation with sodium ethoxide in ethanol. Because of the basic conditions the initial product quininone interconverts with quinidinone via a common enol intermediate and mutarotation is observed. In the third step the ketone group is reduced with aluminum powder and sodium ethoxide in ethanol and quinine can be identified. Quinotoxine is the first relay molecule in the Woodward/Doering claim.
1939: Rabe and Kindler re investigate a sample left over from their 1918 experiments and identify and isolate quinine (again) together with diastereomersquinidine, epi-quinine and epi-quinidine
1940: Robert Burns Woodward signs on as a consultant for the Polaroid Corporation at the request of Edwin H. Land. Quinine is of interest to Polaroid for its light polarizing properties.
1943: Prelog and Proštenik interconvert an allyl piperidine called homomeroquinene and quinotoxine . Homomeroquinene (the second relay molecule in the Woodward/Doering claim) is obtained in several steps from the biomolecule cinchonine (related to quinidine but without the methoxy group):
1944: Bob Woodward and W.E. Doering report the synthesis of quinine  starting from 7-hydroxyisoquinoline. Although the title of their 1 page publication is The total synthesis of quinine it is oddly not the synthesis of quinine but that of the precursor homomeroquinene (racemic) and then with groundwork already provided by Prelog a year earlier to quinotoxine (enantiopure after chiral resolution) that is described.
Woodward and Doering argue that Rabe in 1918 already proved that this compound will eventually give quinine but do not repeat Rabe's work. In this project 27 year old assistant-professor Woodward is the theorist and post doc Doering (age 26) the bench worker. According to William, Bob was able to boil water but an egg would be a challenge. As many natural quinine resources are tied up in the enemy-held Dutch East Indies synthetic quinine is a promising alternative for fighting malaria on the battlefield and both men become instant war heroes making headlines in the New York Times, Newsweek and Life magazine.
1944: The then 22 year old Gilbert Stork writes to Woodward asking him if he did repeat Rabe's work.
1945: Woodward and Doering publish their second lengthy Quinine paper . One of the two referees rejects the manuscript (too much historic material, too much experimental details and poor literary style with inclusion of words like adumbrated and apposite) but it is published without changes nonetheless.
1974: Kondo & Mori synthesize racemic vinylic gamma-lactones, a key starting meterial in Storks 2001 quinine synthesis. :
The starting materials are trans-2-butene-1,4-diol and ethyl orthoacetate and the key step is a
2001: Gilbert Stork publishes his stereoselective quinine synthesis . He questions the validity of the Woodward/Doering claim: "the basis of their characterization of Rabe’s claim as “established” is unclear". The Chemical & Engineering News is equally critical .
2007: Researcher Jeffrey I Seeman in a 30 page review  concludes that the Woodward–Doering/ Rabe–Kindler total synthesis of quinine is a valid achievement. He notes that Paul Rabe was an extremely experienced alkaloid chemist, that he had ample opportunity to compare his quinine reaction product with authentic samples and that the described 1918 chemistry was repeated by Rabe although not with quinotoxine itself but still with closely related derivatives.
Stork quinine total synthesis
The Stork quinine synthesis starts from chiral (S)-4-vinylbutyrolactone 1. The compound is obtained by chiral resolution and in fact, in the subsequent steps all stereogenic centers are put in place by chiral induction: the sequence does not contain asymmetric steps.
The 1944 Woodward / Doering synthesis starts from 7-hydroxyisoquinoline 3 for the quinuclidine skeleton which is somewhat counter intuitive because one goes from a stable heterocyclic aromat to a completely saturated bicyclic ring. This compound (already known since 1895) is prepared in two steps.
Quinine's vinyl group is then constructed by Hofmann elimination with sodium hydroxide in water at 140°C. This process is accompanied by hydrolysis of both the ester and the amide group but it is not the free amine that is isolated but the urea14 by reaction with potassium cyanate. In the next step the carboxylic acid group is esterified with ethanol and the urea group replaced with a benzoyl group. The final step is a claisen condensation of 15 with ethyl quininate 16, which after acidic workup yields racemic quinotoxine 17. The desired enantiomer is obtained by chiral resolution with the chiral dibenzoyl ester of Tartaric acid. The conversion of this compound to quinine is based on the Rabe/Kindler chemistry discussed in the timelime.
^ P. Rabe, K. Kindler, Ber. Dtsch. Chem. Ges. B 1939, 72, 263–264.
^ Proštenik, M.; Prelog, V. HelV. Chim. Acta 1943, 26, 1965.
^The Total Synthesis of Quinine R. B. Woodward and W. E. Doering J. Am. Chem. Soc.; 1944; 66(5) pp 849 - 849; doi:10.1021/ja01233a516
^The Total Synthesis of Quinine R. B. Woodward and W. E. Doering J. Am. Chem. Soc.; 1945; 67(5) pp 860 - 874; doi:10.1021/ja01221a051
^SYNTHESIS OF γ-LACTONES BY THE CONDENSATION OF 2-ALKENE-1,4-DIOLS WITH ORTHOCARBOXYLIC ESTERS Kiyosi Kondo and Fumio Mori Chemistry Letters Vol.3 (1974) , No.7 pp.741-742 doi:10.1246/cl.1974.741
^ Synthesis and Absolute Configuration of the Acetalic Lignan (+)-Phrymarolin Fumito Ishibashi and Eiji Taniguchi Bulletin of the Chemical Society of Japan Vol.61 (1988) , No.12 pp.4361-4366 doi:10.1246/bcsj.61.4361
^The First Stereoselective Total Synthesis of Quinine Gilbert Stork, Deqiang Niu, A. Fujimoto, Emil R. Koft, James M. Balkovec, James R. Tata, and Gregory R. Dake J. Am. Chem. Soc.; 2001; 123(14) pp 3239 - 3242; (Article) doi:10.1021/ja004325r.