Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4:  Preparation of Fragment C7-24

Mickel, Stuart J.; Sedelmeier, Gottfried; Niederer, Daniel; Schuerch, Friedrich; Seger, Manuela; Schreiner, Klaus; Daeffler, Robert; Osmani, Adnan; Bixel, Dominique; Loiseleur, Olivier; Cercus, Jacques; Stettler, Hans; Schaer, and Karl; Gamboni, Remo; Bach, Andrew; Chen, Guang‐Pei; Chen, Wei‐Chun; Geng, Peng; Lee, George T.; Loeser, Eric; McKenna, Joseph; Kinder, Frederick R.; Königsberger, Kurt; Prasad, Kapa; Ramsey, Timothy M.; Reel, Noela; Repič, Oljan; Rogers, Larry; Shieh, Wen‐Chung; Wang, Run-Ming; Waykole, and Liladhar; Xue, Song; Florence, Gordon J.; Paterson, Ian

doi:10.1021/op034133r

Cited by 89 publications

(43 citation statements)

References 14 publications

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“…Moreover, obtaining a renewable supply of active compounds from biological sources may be problematic. Despite these barriers, total synthesis of the potent anticancer natural product discodermolide, recently performed in multigram scale (Mickel et al, 2004a;Mickel et al, 2004b;Mickel et al, 2004c;Mickel et al, 2004d;Mickel et al, 2004e), demonstrates that synthetic organic chemistry is a powerful tool for increasing efficiency of natural products of limited supply, those with very complex structures or those that present no biological desired properties (Nicolaou & Sorensen, 1996;Nicolaou & Snyder, 2003). In this chapter section, we describe two examples of chemical modifications done in natural products core to improve their activity and/or effectiveness.…”

Section: Drug Design Based On Natural Productsmentioning

confidence: 99%

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

Justo¹,

Souza²,

Fátima³

et al. 2011

Biological Diversity and Sustainable Resources Use

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Section: Drug Design Based On Natural Productsmentioning

confidence: 99%

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

Justo¹,

Souza²,

Fátima³

et al. 2011

Biological Diversity and Sustainable Resources Use

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“…La faible disponibilité naturelle de cette molécule complexe a néces-sité de la reproduire en laboratoire afin de disposer de quantités suffisantes pour effectuer des tests biologiques. Des chimistes organiciens du groupe pharmaceutique Novartis ont ainsi développé une synthèse totale du discodermolide (environ 60 g) dont une étape permettant de relier deux fragments de la molécule utilise une réaction de Suzuki ( Figure 1D) [8][9][10][11][12]. Comme l'a souligné le comité Nobel, les réactions de couplage au palladium développées par ces trois chimistes interviennent dans de très nombreux processus chimiques (environ 25 %) utilisés actuellement dans l'industrie pharmaceutique [13,14].…”

Section: Palladium Et Synthèse Organique Une Précieuse Rencontre Récounclassified

Palladium et synthèse organique

Bouyssi

Balme

2010

Med Sci (Paris)

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“…Without further purification, 16 was subjected to the cis-selective diene synthesis using allylsilane 17 that was developed by Paterson as part of a discodermolide synthesis. [29] Following in situ base-promoted Peterson elimination, [30] HCl was added to hydrolyze the ethylene ketal and this resulted in TES ether hydrolysis as well, giving 18 in 65% overall yield from 15. Resilylation with TESOTf was followed in situ by hydrazone formation to give 2 in 90% yield.…”

mentioning

confidence: 99%

“…[29] Following in situ base-promoted Peterson elimination, [30] HCl was added to hydrolyze the ethylene ketal and this resulted in TES ether hydrolysis as well, giving 18 in 65% overall yield from 15. Resilylation with TESOTf was followed in situ by hydrazone formation to give 2 in 90% yield.…”

mentioning

confidence: 99%

A Highly Step‐Economical Synthesis of Dictyostatin

Bucher

Leighton

2013

Angewandte Chemie

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In 1994 Petit reported the isolation and anti-cancer activity of the marine sponge-derived macrolide dictyostatin. [1] Wright subsequently isolated a sample that allowed initial biological characterization of dictyostatin as a potent inducer of tubulin polymerization, [2] and that was used by Wright and Paterson to make a full structural assignment in 2004. [3] This assignment was confirmed soon thereafter by total syntheses by Paterson [4] and Curran, [5] and the material thus obtained facilitated more detailed characterization of dictyostatin's mechanism of action. [6,7] Total syntheses by Phillips [8] and Ramachandran, [9] formal syntheses by Micalizio [10] and Cossy, [11] a synthesis of C(9)-epi-dictyostatin by Gennari, [12] second generation syntheses by Paterson [13] and Curran, [14] and several fragment syntheses [15] followed these initial reports. In addition, the Paterson/Wright [16] and Curran/Day [17] teams have reported extensive SAR studies, while the Paterson/Díaz/ Jiménez-Barbero [18] and Curran/Snyder [19] teams have advanced models for the interaction of dictyostatin with the taxane binding site on -tubulin. Because dictyostatin and some of the prepared analogs are among the most potent microtubule-stabilizing agents characterized to date, there has been and continues to be intense interest in the possibility of advancing dictyostatin or an analog thereof into the clinic, a goal which might be facilitated by the development of a significantly more efficient and step-economical synthesis. As part of a larger program devoted to the development of new strategies and methods for the synthesis of complex and precious marine macrolides with high levels of step-economy, efficiency, and scalability, [20] we have developed and report herein a synthesis of dictyostatin that comprises just 14 steps in the longest linear sequence.Similarly to the previous syntheses of dictyostatin, our retrosynthesis disconnected the target into three roughly equally complex fragments, 1, 2, and 3 (Fig. 1A). It was in the synthesis of the fragments, and especially the C(12)-C(14) and C(20)-C(22) stereotriad-containing fragments 1 and 2 that we saw an opportunity for a streamlining of the synthesis. Ever since its introduction by Roush more than 20 years ago, what might be called the "Roche ester strategy" has reigned supreme for the synthesis of such stereotriads, [21] and indeed was employed in the Paterson, Curran, and Ramachandran syntheses, in most of the approaches reported by others, and in most of the syntheses of the related natural product discodermolide. [22] In this approach, the requisite enantiomer of the Roche ester is protected, reduced, and oxidized to the corresponding aldehyde, which is then subjected to diastereoselective crotylation, followed by several additional functional group manipulations (Fig. 1B). Thus, these stereotriad syntheses typically comprise at least 6-7 steps of which all Correspondence to: James L. Leighton, leighton@chem.columbia.edu. Supporting information for this article is ava...

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Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C₇_-₂₄

Cited by 89 publications

References 14 publications

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

Palladium et synthèse organique

A Highly Step‐Economical Synthesis of Dictyostatin

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