A Short, Stereocontrolled Synthesis of Strychnine

Rawal, Viresh H.; Iwasa, Seiji

doi:10.1021/jo00089a008

Cited by 161 publications

(85 citation statements)

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“…Der Gruppe von Woodward gelang die erste Totalsynthese, die bis heute als Meilenstein der organischen Chemie gilt. [4] Es dauerte mehr als 30 Jahre, bis weitere Arbeitsgruppen die Synthese von racemischem [5,6] oder enantiomerenreinem [7] Strychnin publizierten. Jede der beschriebenen Synthesen basierte auf neu entwickelten Methoden, die einen zunehmend effizienteren Zugang zu Strychnos-Alkaloiden ermöglichten.…”

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Eine kurze formale Strychnin‐Totalsynthese mit einer Samariumdiiodid‐induzierten Kaskadenreaktion als Schlüsselschritt

Beemelmanns

Reißig

2010

Angewandte Chemie

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Eine kurze formale Strychnin‐Totalsynthese mit einer Samariumdiiodid‐induzierten Kaskadenreaktion als Schlüsselschritt

Beemelmanns

Reißig

2010

Angewandte Chemie

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“…50) Rawal and Iwasa's synthetic process was particularly remarkable, although strychnine obtained in their process is a racemic form. 51) Eichberg and Vollhardt succeeded in the total synthesis of (Ϯ)-strychnine using an ingenious cobalt-catalyzed [2ϩ2ϩ2] cycloaddition as a key step. 52) In the past decade, many synthetic approaches to strychnine have been successful.…”

Section: Total Synthesis Of (؊)-Strychninementioning

confidence: 99%

Development of a Novel Synthetic Method for Ring Construction Using Organometallic Complexes and Its Application to the Total Syntheses of Natural Products

Mori

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Organometallic complexes are useful tools in synthetic organic chemistry. In particular, they play an important role in carbon-carbon bond formation. A metalacycle, i.e., a ring compound containing a transition metal, is a useful intermediate in synthetic organic chemistry. Oxidative cyclization of unsaturated hydrocarbons, such as alkene, alkyne, carbonyl compounds, or nitrile, using a low-valent transition metal is a useful reaction for synthesis of metalacycles. It is known that a metalacycle formed from a late transition metal and unsaturated hydrocarbons is not stable and is easily converted into the reductive elimination product or b-hydrogen elimination product (Eq. 1). Since the low-valent metal complex is regenerated in this reaction, the reaction proceeds with a catalytic amount of the transition metal. On the other hand, the metalacycle formed from an early transition metal and unsaturated hydrocarbons is fairly stable and can be converted into various compounds with functional groups by treatment with various agents (Eq. 2). Therefore a stoichiometric amount of the metal complex is required in this reaction.(1) (2) Negishi et al.2) and Nugent and Calabrese 3) reported the syntheses of zirconacycles 2 from diene, enyne, and diyne 1 using zirconocene (Cp 2 Zr). Hydrolysis of zirconacycle afforded the cyclized compound 3 (Chart 1).Negishi et al. also found a synthetic method of dibutylzirconocene (Cp 2 ZrBu 2 ) from zirconocenedichloride (Cp 2 ZrCl 2 ) and butyl lithium, and dibutylzirconocene is easily converted into zirconocene coordinated by a butene ligand in situ at room temperature 4) (Eq. 3).This was a great discovery in zirconium chemistry because it is difficult to isolate zirconocene with no ligand. We were interested in those results and attempted to form carbon-carbon bonds between the unsaturated hydrocarbons, such as enyne and diene, using zirconocene. Synthesis of Heterocycles Using Zirconium-Mediated Cyclization and Total Synthesis of (؊)-DendrobineThe zirconacycles 2 were easily synthesized in situ from Cp 2 ZrCl 2 and diene, enyne, or diyne 1. To a THF solution of Cp 2 ZrCl 2 and unsaturated hydrocarbon 1 was added BuLi at Ϫ78°C under argon gas, and the solution was stirred at room Organometallic complexes are useful tools in synthetic organic chemistry. We investigated a novel synthetic method for ring construction using organometallic complexes and synthesized natural products and biologically active substances using these methods. Metalacycles formed from an early transition metal and diene, enyne, and diyne are stable under the reaction conditions and they are easily converted into compounds with functional groups by the addition of various agents. We have developed a novel synthetic method of heterocycles from enyne and diene using Cp 2 ZrBu 2 . The total syntheses of (؊)-dendrobine, (؎)-mecembrane, and (؎)-mecembrine were achieved using this procedure. To synthesize these natural products as a chiral form, a novel palladium-catalyzed asymmetric allylic amination was developed, an...

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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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A Short, Stereocontrolled Synthesis of Strychnine

Cited by 161 publications

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Eine kurze formale Strychnin‐Totalsynthese mit einer Samariumdiiodid‐induzierten Kaskadenreaktion als Schlüsselschritt

Eine kurze formale Strychnin‐Totalsynthese mit einer Samariumdiiodid‐induzierten Kaskadenreaktion als Schlüsselschritt

Development of a Novel Synthetic Method for Ring Construction Using Organometallic Complexes and Its Application to the Total Syntheses of Natural Products

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

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