Synthesis of the C22–C37 segment of prorocentin

Takemura, Atsushi; Katagiri, Yasushi; Fujiwara, Kenshu; Kawai, Hidetoshi; Suzuki, Takanori

doi:10.1016/j.tetlet.2011.01.042

Cited by 6 publications

(7 citation statements)

References 12 publications

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“…Subsequent Sharpless asymmetric epoxidation furnished an inseparable diastereomeric mixture 7a and 7b (dr 1:1). Oxidation of the primary hydroxyl group of this diastereomeric mixture followed by 2C-Wittig reaction provided epoxy esters 6a and 6b (dr 1:1), which were subjected to silyl deprotection using − TBAF for 36 h, resulting in the chromatographically separable five-membered 14 and six-membered 15 along with the epoxy alcohol 16a in the ratio of (4.1:1:5.2) and in 93% combined yield. Interestingly, the treatment of 6a and 6b (dr 1:1) with HF–pyridine in THF at 0 °C to rt gave the same results, except that the 14 to 15 ratios (1:5.1) were reversed.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, we expected that the stable epoxy alcohol 16a should be with the required stereochemistry to deliver the curvularide E ( 5 ). Accordingly, 16a was treated , with 0.2 equiv of CSA in CH 2 Cl 2 at 0 °C to rt for 8 h to furnish chromatographically separable five-membered 19 and six-membered 20 in favor of the required one (4.1:0.9) in 97% combined yield. Finally, ester hydrolysis of 19 and subsequent coupling with l -isoleucinol gave the desired curvularide E ( 5 ) in 85% yield.…”

Section: Resultsmentioning

confidence: 99%

“…11,12 with 0.2 equiv of CSA in CH 2 Cl 2 at 0 °C to rt for 8 h to furnish chromatographically separable five-membered 19 and sixmembered 20 in favor of the required one (4.…”

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confidence: 99%

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Total Synthesis and Absolute Configuration of Curvularides A-E

2012

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The first total synthesis of curvularides A-E, isolated from a culture broth of the endophytic fungus Curvularia geniculata, is described. The divergent total synthesis reported herein confirmed the absolute configurations of curvularides A-E and supported that these natural products might be obtained from a common biosynthetic pathway. The key steps involved in the synthesis were the diastereoselective hydrogenation of exo-methylene-γ-butyrolactone to α-methyl-γ-butyrolactone, Sharpless kinetic resolution, Sharpless asymmetric epoxidations, and intramolecular and intermolecular epoxide openings.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Total Synthesis and Absolute Configuration of Curvularides A-E

2012

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“…For a compound of such prominent biosynthetic pedigree, structural intricacy, and exceedingly short supply, prorocentin received surprisingly little attention from the synthetic community in the past. Only a model study directed toward the C22–C37 segment was published, from which no firm conclusion as to the unknown stereochemical interrelation between the core and the side chain could be drawn . This very preliminary report, which appeared in the press in 2011, stands in striking contrast to a short symposium proceeding published by the same group already a year earlier, which insinuates that a total synthesis had been completed at that time .…”

Section: Introductionmentioning

confidence: 99%

Total Syntheses of Nominal and Actual Prorocentin

et al. 2023

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The dinoflagellate-derived polyether prorocentin is a co-metabolite of the archetypical serine/threonine phosphatase inhibitor okadaic acid. Whereas a structural relationship cannot be missed and a biosynthetic link was proposed, it is currently unknown whether there is any parallel in the bioactivity profile of these natural products. However, it was insinuated in the past that the structure assigned to prorocentin might need to be revised. Indeed, re-examination of the published spectra cast doubts as to the constitution of the fused/spirotricyclic BCD-ring system in the core. To clarify this issue, a flexible synthesis blueprint was devised that allowed us to obtain the originally proposed structure as well as the most plausible amended structure. The key to success was late-stage gold-catalyzed spirocyclization reactions that furnished the isomeric central segments with excellent selectivity. The lexicon of catalytic transformations used to make the required cyclization precursors comprised a titanium-mediated ester methylenation/metathesis cascade, a rare example of a gold-catalyzed allylic substitution, and chain extensions via organocatalytic asymmetric aldehyde propargylation. A wing sector to be attached to the isomeric cores was obtained by Krische allylation, followed by a superbly selective cobalt-catalyzed oxidative cyclization of the resulting di-unsaturated alcohol with the formation of a 2,5-trans-disubstituted tetrahydrofuran; the remaining terminal alkene was elaborated into an appropriate handle for fragment coupling by platinum-catalyzed asymmetric diboration/oxidation. The assembly of the different building blocks to the envisaged isomeric target compounds proved that the structure of prorocentin needs to be revised as disclosed herein.

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“…What is more, serious doubts were raised in an early conference proceeding as to the actual structure assignment to the core; 6 for unknown reasons, however, this claim has not been substantiated in a peerreviewed publication in the more than 10 years that followed the preliminary disclosure. 7 While a detailed reassessment of the published spectra certainly reinforced the doubts, an unambiguous decision as to the actual constitution of prorocentin could not be made; 8 moreover, the data did not provide any indication whatsoever concerning the absolute configuration. Therefore, our group embarked on an extensive synthesis campaign, which targeted the originally proposed as well as a revised structure that was deemed to most likely represent the actual natural product.…”

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confidence: 97%

Second-Generation Total Synthesis of Prorocentin

2023

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After a recent total synthesis had resolved all issues surrounding the constitution and stereostructure of prorocentin, it was possible to devise a new approach aiming at an improved supply of this scarce marine natural product; this compound is a cometabolite of the prototypical phosphatase inhibitor okadaic acid but still awaits detailed biological profiling. The revised entry starts from 2-deoxy-D-glucose; keys to success were a telescoped hemiacetal reduction/acetal cleavage and an exquisitely selective gold/Brønsted acid-cocatalyzed spiroacetalization.

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Synthesis of the C22–C37 segment of prorocentin

Cited by 6 publications

References 12 publications

Total Synthesis and Absolute Configuration of Curvularides A-E

Total Synthesis and Absolute Configuration of Curvularides A-E

Total Syntheses of Nominal and Actual Prorocentin

Second-Generation Total Synthesis of Prorocentin

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