Total Synthesis of the Marine Macrolide Amphidinolide F

Ferrié, Laurent; Fenneteau, Johan; Figadère, Bruno

doi:10.1021/acs.orglett.8b01020

Cited by 19 publications

(28 citation statements)

References 78 publications

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“…As a result, we lost a large quantity of material at this step, the product having been adsorbed presumably by TPAP re-agent. Its quality seems crucial since the same batch of reagent was used successfully two years ago in the total synthesis of amphidinolide F. 35 The final step was to cleave the remaining three TBS ethers, which was performed for two weeks with HF•pyridine in THF and pyridine. As a result, the synthetic sample of amphidinolide C2 was isolated with 0.4 mg and would appear to match the natural sample with respect to NMR data.…”

Section: Scheme 18 Total Synthesis Of Amphidinolide C2 (2)mentioning

confidence: 99%

Amphidinolides F and C2: An Odyssey in Total Synthesis

et al. 2022

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Section: Scheme 18 Total Synthesis Of Amphidinolide C2 (2)mentioning

confidence: 99%

Amphidinolides F and C2: An Odyssey in Total Synthesis

et al. 2022

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“…Compound 5 is therefore surprisingly inactive, although it contains a hydroxyl group in the side chain [14]. The interesting biological properties of these compounds have attracted the attention of different authors who have described either total syntheses [15,16] or synthetic approaches to various molecular fragments [17][18][19]. For instance, Fürstner and coworkers took advantage of the structural similarity of 1 and 4 to perform an elegant total synthesis of both compounds [15].…”

Section: Amphidinolidesmentioning

confidence: 99%

The Tetrahydrofuran Motif in Polyketide Marine Drugs

et al. 2022

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Oxygen heterocycles are units that are abundant in a great number of marine natural products. Among them, marine polyketides containing tetrahydrofuran rings have attracted great attention within the scientific community due to their challenging structures and promising biological activities. An overview of the most important marine tetrahydrofuran polyketides, with a focused discussion on their isolation, structure determination, approaches to their total synthesis, and biological studies is provided.

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“…There is no evidence in the original chagosensine publication that this caveat had been taken into account . In this context, however, it is important to note that the southern hemisphere of chagosensine bears great similarity to a substructure of amphidinolide C and F (except for the missing methylene group between the carboxylate and the tetrahydrofuran ring), − even though the J -values are again at variance (see the Supporting Information). Anyway, this overall situation leaves serious doubt: if the configuration of the 1,2-diol stereochemistry is downgraded to “unsecure”, four possible isomers of the southern segment must be taken into consideration.…”

Section: Introductionmentioning

confidence: 99%

Chagosensine: A Riddle Wrapped in a Mystery Inside an Enigma

et al. 2020

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The marine macrolide chagosensine is supposedly distinguished by a (Z,Z)-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two trans-2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The “northern” THF ring and the anti-configured diol in the “southern” sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved. To meet the challenge, the preparation of the required building blocks was optimized, and a convergent strategy for their assembly was developed. A key role was played by the cobalt-catalyzed oxidative cyclization of alken-5-ol derivatives (“Mukaiyama cyclization”), which is shown to be exquisitely chemoselective for terminal alkenes, leaving even terminal alkynes (and other sites of unsaturation) untouched. Likewise, a palladium-catalyzed alkyne alkoxycarbonylation reaction with formation of an α-methylene-γ-lactone proved instrumental, which had not found application in natural product synthesis before. Further enabling steps were a nickel-catalyzed “Tamaru-type” homocrotylation, stereodivergent aldehyde homologations, radical hydroindation, and palladium-catalyzed alkyne-1,2-bis-stannation. The different building blocks were assembled in a serial fashion to give the idiosyncratic chlorodienes by an unprecedented site-selective Stille coupling followed by copper-mediated tin/chlorine exchange. The macrolactones were closed under forcing Yamaguchi conditions, and the resulting products were elaborated into the targeted compound library. Yet, only one of the eight diastereomers turned out to be stable in the solvent mixture that had been used to analyze the natural product; all other isomers were prone to ring opening and/or ring expansion. In addition to this stability issue, our self-consistent data set suggests that chagosensine has almost certainly little to do with the structure originally proposed by the isolation team.

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Total Synthesis of the Marine Macrolide Amphidinolide F

Cited by 19 publications

References 78 publications

Amphidinolides F and C2: An Odyssey in Total Synthesis

Amphidinolides F and C2: An Odyssey in Total Synthesis

The Tetrahydrofuran Motif in Polyketide Marine Drugs

Chagosensine: A Riddle Wrapped in a Mystery Inside an Enigma

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