Total Syntheses of the Amaryllidaceae Alkaloids Zephycandidine III and Lycosinine A and Their Evaluation as Inhibitors of Acetylcholinesterase

Xu, Xingjun; Kim, Hye‐Sun; Chen, Weimin; Ma, Xiang; Correy, G.J.; Banwell, Martin G.; Jackson, Colin J.; Willis, Anthony C.; Carr, P.D.

doi:10.1002/ejoc.201700705

Cited by 9 publications

(6 citation statements)

References 23 publications

(32 reference statements)

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“…While we have yet to explore such processes in any comprehensive fashion, early indications have been very positive. Thus, as shown in Scheme for example, the cross-coupling of aryl iodide 51 with bromide 52 under our by now standard conditions provided the desired biaryl 53 (60%) . This last compound was readily elaborated to the alkaloid zephycandidine III, a natural product reported to possess acetylcholinesterase (AChE) inhibitory properties, which were not evident in the synthetically derived material despite the spectroscopic equivalence of the natural and synthetic materials.…”

Section: Application To the Synthesis Of Heterocyclesmentioning

confidence: 89%

“…Thus, as shown in Scheme for example, the cross-coupling of aryl iodide 51 with bromide 52 under our by now standard conditions provided the desired biaryl 53 (60%) . This last compound was readily elaborated to the alkaloid zephycandidine III, a natural product reported to possess acetylcholinesterase (AChE) inhibitory properties, which were not evident in the synthetically derived material despite the spectroscopic equivalence of the natural and synthetic materials. More pertinent to the present discussion is that all our attempts to prepare compound 53 and related systems using Suzuki–Miyaura cross-coupling reactions were unsuccessful …”

Section: Application To the Synthesis Of Heterocyclesmentioning

confidence: 99%

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The Palladium-Catalyzed Ullmann Cross-Coupling Reaction: A Modern Variant on a Time-Honored Process

et al. 2018

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Cross-coupling reactions, especially those that are catalyzed by palladium, have revolutionized the way in which carbon-carbon bonds can be formed. The most commonly deployed variants of such processes are the Suzuki-Miyaura, Mizoroki-Heck, Stille, and Negishi cross-coupling reactions, and these normally involve the linking of an organohalide or pseudohalide (such as a triflate or nonaflate) with an organo-metallic or -metalloid such as an organo-boron, -magnesium, -tin, or -zinc species. Since the latter type of coupling partner is often prepared from the corresponding halide, methods that allow for the direct cross-coupling of two distinct halogen-containing compounds would provide valuable and more atom-economical capacities for the formation of carbon-carbon bonds. While the venerable Ullmann reaction can in principle achieve this, it has a number of drawbacks, the most significant of which is that homocoupling of the reaction partners is a competitive, if not the dominant, process. Furthermore, such reactions normally occur only under forcing conditions (viz., often at temperatures in excess of 250 °C). As such, the Ullmann reaction has seen only limited application in this regard, especially as a mid- to late-stage feature of complex natural product synthesis. This Account details the development of the palladium-catalyzed Ullmann cross-coupling reaction as a useful method for the assembly of a range of heterocyclic systems relevant to medicinal and/or natural products chemistry. These couplings normally proceed under relatively mild conditions (<100 °C) over short periods of time and, usually, to the exclusion of (unwanted) homocoupling events. The keys to success are the appropriate choice of coupling partners, the form of the copper metal employed, and the choice of reaction solvent. At the present time, the cross-coupling partners capable of engaging in the title reaction are confined to halogenated and otherwise electron-deficient arenes and, as complementary reactants, α- or β-halogenated, α,β-unsaturated aldehydes, ketones, esters, lactones, lactams, and cycloimides. Nitro-substituted (and halogenated) arenes, in particular, serve as effective participants in these reactions, and the products of their coupling with the above-mentioned carbonyl-containing systems can be manipulated in a number of different ways. Depending on the positional relationship between the nitro and carbonyl groups in the cross-coupling product, the reduction of the former group, which can be achieved under a range of different conditions, provides, through intramolecular nucleophilic addition reactions, including Schiff base condensations, access to a diverse range of heterocyclic systems. These include indoles, quinolines, quinolones, isoquinolines, carbazoles, and carbolines. Tandem variants of such cyclization processes, in which Raney cobalt is used as a catalyst for the chemoselective reduction (by dihydrogen) of nitro and nitrile groups (but not olefins), allow for the assembly of a range of structurally challenging nat...

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Section: Application To the Synthesis Of Heterocyclesmentioning

confidence: 89%

Section: Application To the Synthesis Of Heterocyclesmentioning

confidence: 99%

The Palladium-Catalyzed Ullmann Cross-Coupling Reaction: A Modern Variant on a Time-Honored Process

et al. 2018

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“…Banwell and co-workers: Banwell and co-workers, after failing to form the important aryl-aryl bond between two relevant precursors for their synthesis of the two Amaryllidacea alkaloids zephycandidine III, 298 and lycosinine A 272 via the anticipated Suzuki-Miyaura cross coupling protocol, resorted to the palladiumcatalysed Ullmann cross coupling which proved more successful [54]. Thus reduction of aldehyde 293 with sodium borohydride and methylation of the resulting primary alcohol with methyl iodide in DMSO containing KOH, afforded methyl ether 294 (63% for the two steps).…”

Section: Viii) Total Syntheses Of Zephycandidine III and Lycosinine Amentioning

confidence: 99%

“…vi) Synthesis of phenanthridinone alkaloids via Suzuki-Miyaura cross-coupling, by Tanimori and co-workers: Tanimori and coworkers extended their developed protocol for the synthesis of some new phenanthridone alkaloids via Suzuki-Miyaura cross-coupling in the following way [52]. Reaction between ester 199 and 2aminobenzeneboronic acid catalysed by Pd(OAc) 2 , (S)-phos and viii) Total syntheses of zephycandidine III and lycosinine A, by Banwell and co-workers: Banwell and co-workers, after failing to form the important aryl-aryl bond between two relevant precursors for their synthesis of the two Amaryllidacea alkaloids zephycandidine III, 298 and lycosinine A 272 via the anticipated Suzuki-Miyaura cross coupling protocol, resorted to the palladiumcatalysed Ullmann cross coupling which proved more successful [54]. Thus reduction of aldehyde 293 with sodium borohydride and methylation of the resulting primary alcohol with methyl iodide in DMSO containing KOH, afforded methyl ether 294 (63% for the two steps).…”

Section: Recent Syntheses Of Amaryllidaceae Alkaloids and Isocarbostyrilsmentioning

confidence: 99%

A Review on Recent Syntheses of Amaryllidaceae Alkaloids and Isocarbostyrils (Time period mid-2016 to 2017)

Otterlo

Green

2018

Natural Product Communications

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Alkaloids from the Amaryllidaceae have become valuable targets for synthetic organic chemists, mainly due to their wide variety of bioactivities and potential for utilization in medicinal chemistry ventures. In addition, the structural complexity of a number of these alkaloids has also been a reason for the interest in these compounds. In this review, the last 18 months of literature was perused and synthetic highlights have been presented here, with the hope to further focus attention on this interesting class of compounds and to encourage others to synthesize these compounds and their derivatives and/or analogues. The review contains examples of syntheses from most of the important alkaloid scaffold classes previously isolated from the Amaryllidaceae, namely: lycorine, crinine, galanthamine, tazettine, montanine, phenanthridone, phenanthridine, plicamine, mesembrine and some minor scaffolds (like gracilamine).

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“…Banwell wird für seine Arbeiten zur Naturstoffsynthese und für seinen internationalen Ansatz zur wissenschaftlichen Forschung ausgezeichnet. In Chemistry—An Asian Journal berichtete er über die Struktur des Sorbicillinoids Rezishanon C und im European Journal of Organic Chemistry über die Totalsynthese von Zephycandidin III und Lycosinin A . Banwell gehört dem internationalen Beirat des Asian Journal of Organic Chemistry an.…”

Section: Ausgezeichnet …unclassified

Ryoji Noyori ACES Award: M. G. Banwell / Liebig‐Denkmünze: W. Schnick / Izatt–Christensen Award: P. A. Gale / Cram Lehn Pedersen Prize: R. Klajn

2018

Angewandte Chemie

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Total Syntheses of the Amaryllidaceae Alkaloids Zephycandidine III and Lycosinine A and Their Evaluation as Inhibitors of Acetylcholinesterase

Cited by 9 publications

References 23 publications

The Palladium-Catalyzed Ullmann Cross-Coupling Reaction: A Modern Variant on a Time-Honored Process

The Palladium-Catalyzed Ullmann Cross-Coupling Reaction: A Modern Variant on a Time-Honored Process

A Review on Recent Syntheses of Amaryllidaceae Alkaloids and Isocarbostyrils (Time period mid-2016 to 2017)

Ryoji Noyori ACES Award: M. G. Banwell / Liebig‐Denkmünze: W. Schnick / Izatt–Christensen Award: P. A. Gale / Cram Lehn Pedersen Prize: R. Klajn

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