The total synthesis of strychnine

Woodward, R. B.; Cava, Michael P.; Ollis, W. D.; Hunger, A.; Daeniker, H. U.; Schenker, K.

doi:10.1016/s0040-4020(01)98529-1

Cited by 253 publications

(112 citation statements)

References 60 publications

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“…As an organic chemist with exceptional qualifications in the area of natural products, Buckingham is well placed to have done just that. Imagine comparing the 14-step total synthesis of quinine by Padwa, [9] published last year, with Woodwards 28-step synthesis nearly 50 years ago, [10][11][12] which was universally hailed with triumph and with awe. Indeed, it took 38 more years subsequent to Woodwards brilliant success until the next reported synthesis of strychnine (in 25 steps) by Magnus [13,14] in 1992.…”

Section: Bitter Nemesismentioning

confidence: 99%

Bitter Nemesis. The Intimate History of Strychnine. By John Buckingham.

Seeman

2008

Angew Chem Int Ed

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Section: Bitter Nemesismentioning

confidence: 99%

Bitter Nemesis. The Intimate History of Strychnine. By John Buckingham.

Seeman

2008

Angew Chem Int Ed

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“…beginnen. [20] Natürlich hätte Woodward während seiner glanzvollen Karriere genauso gut "CHOLESTERIN! ", "RESERPIN!…”

Section: Der Kontextunclassified

Die Woodward‐Doering‐/Rabe‐Kindler‐Totalsynthese von Chinin: ein Mythos?

Seeman¹

2007

Angewandte Chemie

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1918 beschrieben Paul Rabe und Karl Kindler die dreistufige Umwandlung von d‐Chinotoxin in Chinin. Robert B. Woodward und William von Eggers Doering veröffentlichten 1944 die Totalsynthese von Homomerochinen und d‐Chinotoxin aus 7‐Hydroxyisochinolin. Auf der Grundlage der Umsetzungen von Rabe und Kindler beanspruchten Woodward und Doering im Titel zweier Arbeiten von 1944 und 1945 die “Total Synthesis of Quinine”. In den Jahren 2000 und 2001 stempelte Gilbert Stork Woodwards und Doerings Anspruch aber als ungültig, weil sie in Cambridge nur Homomerochinen und d‐Chinotoxin, nicht aber synthetisches Chinin hergestellt hatten. Tatsächlich haben Rabe und Kindler die experimentellen Einzelheiten ihrer Umwandlung von d‐Chinotoxin in Chinin nie veröffentlicht. Dieser Aufsatz stellt die Ergebnisse einer detaillierten Untersuchung der Synthesechemie von Cinchona‐Alkaloiden vor und gibt anhand von bisher unveröffentlichtem Material sowie zahlreichen Interviews einen Einblick in das Leben der Hauptpersonen dieser fast 100 Jahre währenden Geschichte.

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“…The first total synthesis of strychnine, one of the most significant achievements in the history of organic synthesis, was reported by Woodward in 1954. 37,38) Nearly 40 years after Woodward's pioneering work, a number of groups reported the total synthesis, [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] four of which culminated in an enantioselective synthesis of the natural enantiomer. 41,42,44,45,47,48,52) As summarized in Bonjoch's excellent review, 34) the major stumbling blocks in the synthesis are the generation of the spirocenter at C7 and the assembly of the bridged framework (CDE core ring).…”

Section: )mentioning

confidence: 99%

“…Finally, removal of the acetyl group provided the crude Wieland-Gumlich aldehyde, which was converted to (Ϫ)-strychnine (4) by the established method. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] 2-2. Development of the Stable, Storable, and Reusable Asymmetric Catalyst La-O-linked-BINOL Complex for a Catalytic Asymmetric Michael Reaction [22][23][24] The ALB complex is a highly efficient catalyst for the Michael reaction of malonates to cyclic enones.…”

Section: )mentioning

confidence: 99%

Enantioselective Total Syntheses of Several Bioactive Natural Products Based on the Development of Practical Asymmetric Catalysis

Ohshima

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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I present herewith enantioselective total syntheses of several bioactive natural products, such as (؊)-strychnine, (؉)-decursin, (؊)-cryptocaryolone diacetate, (؊)-fluoxetine, and aeruginosin 298-A, based on practical asymmetric catalyses (Michael reaction, epoxidation, and phase-transfer reaction) that I developed with coworkers in Prof. Shibasaki's group over the past 5 years. In the first part of this review, I discuss the great improvement of catalyst efficiency in an ALB-catalyzed asymmetric Michael reaction of malonate and application to the pre-manufacturing scale (greater than kilogram scale) and enantioselective total synthesis of (؊)-strychnine with the development of novel domino cyclization. To broaden the substrate generality of the Michael reaction, we developed a highly stable, storable, and reusable La-O-linked-BINOL complex. Further extension of the reaction using b b-keto ester as a Michael donor was achieved with the development of a La-NR-linked-BINOL complex, thereby improving indole alkaloid syntheses. In the second section, I discuss enantioselective total synthesis of (؉)-decursin using catalytic asymmetric epoxidation. To achieve the synthesis, we developed a new La-BINOL-Ph 3 As‫؍‬O (1 : 1 : 1) complex catalyst system, which has much higher reactivity and broader substrate generality than the previously developed catalyst systems. This allowed us to achieve catalytic asymmetric epoxidation of a a,b b-unsaturated carboxylic acid derivatives with high enantioselectivity and broad substrate generality for the first time by changing the lanthanide metal and reaction conditions. Among them, catalytic asymmetric epoxidation of a a,b b-unsaturated morpholinyl amides is quite useful in terms of synthetic utility of the corresponding a a,b b-epoxy morpholinyl amides. Highly catalyst-controlled enantio-or diastereoselective epoxidation of the a a,b b-unsaturated morpholinyl amides, coupled with diastereoselective reduction of b b-hydroxy ketones, enabled the synthesis of all possible stereoisomers of 1,3-polyol arrays with successful enantioselective total synthesis of several 1,3-polyol natural products, such as (؊)-cryptocaryolone diacetate. In addition, the development of a new regioselective epoxide-opening reaction of a a,b b-epoxy amides to the corresponding a a-and b b-hydroxy amides enhanced the usefulness of the present epoxidation and was applied to the enantioselective total synthesis of (؊)-fluoxetine. In the final section, I report the development of a new asymmetric two-center organocatalyst (TaDiAS) and its application to the enantioselective synthesis of aeruginosin 298-A and its analogues. Because of the remarkable structural diversity of TaDiAS, a practical asymmetric phase-transfer reaction with broad substrate generality was achieved. As a result, we succeeded in developing a highly versatile synthetic method for aeruginosin 298-A and its analogues. Inhibitory activity studies of the compounds against the serine protease trypsin provided preliminary information about their str...

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The total synthesis of strychnine

Cited by 253 publications

References 60 publications

Bitter Nemesis. The Intimate History of Strychnine. By John Buckingham.

Bitter Nemesis. The Intimate History of Strychnine. By John Buckingham.

Die Woodward‐Doering‐/Rabe‐Kindler‐Totalsynthese von Chinin: ein Mythos?

Enantioselective Total Syntheses of Several Bioactive Natural Products Based on the Development of Practical Asymmetric Catalysis

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