Biomimetic Synthesis Enables the Structure Revision of Furoerioaustralasine

Coleman, Matthew A.; Burchill, Laura; Sumby, Christopher J.; George, Jonathan H.

doi:10.1021/acs.orglett.9b03392

Cited by 18 publications

(16 citation statements)

References 12 publications

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“…This hypothesis was proven with a short biomimetic synthesis of 10 (Scheme 10). 60 Initial chromeny-lation of 2,4-dihydroxyquinoline (99) with citral (70) under standard conditions gave 100. 61 Based on a similar procedure reported by Riveira and co-workers, 62 thermal rearrangement of 100 adsorbed on silica gel gave a mixture of trans-decalin 102 and cis-decalin 103 via a cascade of retro-6π-electrocyclization, alkene isomerization, and intramolecular hetero-Diels−Alder of the intermediate enone 101.…”

Section: ■ Biomimetic Cascade Reactions Of 2h-chromenesmentioning

confidence: 91%

Biomimetic Dearomatization Strategies in the Total Synthesis of Meroterpenoid Natural Products

George

2021

Acc. Chem. Res.

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Conspectus Natural products are biosynthesized from a limited pool of starting materials via pathways that obey the same chemical logic as textbook organic reactions. Given the structure of a natural product, it is therefore often possible to predict its likely biosynthesis. Although biosynthesis mainly occurs in the highly specific chemical environments of enzymes, the field of biomimetic total synthesis attempts to replicate predisposed pathways using chemical reagents. We have followed several guidelines in our biomimetic approach to total synthesis. The overarching aim is to construct the same skeletal C–C and C–heteroatom bonds and in the same order as our biosynthetic hypothesis. In order to explore the innate reactivity of (bio)synthetic intermediates, the use of protecting groups is avoided or at least minimized. The key step, which is usually a cascade reaction, should be predisposed to selectively generate molecular complexity under substrate control (e.g., cycloadditions, radical cyclizations, carbocation rearrangements). In general, simple reagents and mild conditions are used; many of the total syntheses presented in this Account could be achieved using pre-1980s methodology. We have focused almost exclusively on the synthesis of meroterpenoids, that is, natural products of mixed terpene and aromatic polyketide origin, using commercially available terpenes and electron-rich aromatic compounds as starting materials. Finally, all of the syntheses in this Account involve a dearomatization step as a means to trigger a cascade reaction or to construct stereochemical complexity from a planar, aromatic intermediate. A biomimetic strategy can offer several advantages to a total synthesis project. Most obviously, successful biomimetic syntheses are usually concise and efficient, naturally adhering to the atom, step, and redox economies of synthesis. For example, in this Account, we describe a four-step synthesis of garcibracteatone and a three-step synthesis of nyingchinoid A. It is difficult to imagine shorter, non-biomimetic syntheses of these intricate molecules. Furthermore, biomimetic synthesis gives insight into biosynthesis by revealing the chemical relationships between biosynthetic intermediates. Access to these natural substrates allows collaboration with biochemists to help uncover the function of newly discovered enzymes and elucidate biosynthetic pathways, as demonstrated in our work on the napyradiomycin family. Third, by making biosynthetic connections between natural products, we can sometimes highlight incorrect structural assignments, and herein we discuss structure revisions of siphonodictyal B, rasumatranin D, and furoerioaustralasine. Last, biomimetic synthesis motivates the prediction of “undiscovered natural products” (i.e., missing links in biosynthesis), which inspired the isolation of prenylbruceol A and isobruceol.

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Section: ■ Biomimetic Cascade Reactions Of 2h-chromenesmentioning

confidence: 91%

Biomimetic Dearomatization Strategies in the Total Synthesis of Meroterpenoid Natural Products

George

2021

Acc. Chem. Res.

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“…In 2019, George and co‐workers revised the structure of furoerioaustralasine ( 186 ), a unique Australian alkaloid, based on a concise, biomimetic synthesis. The synthesis exploited a stereo‐ and regioselective epoxide–amide cyclization as a key step to form a central dihydrofuran fused to a quinoline ring system outline Scheme 43 [57] . The epoxidation of cis ‐fused tetracycle 183 with m ‐CPBA took place with low diastereoselectivity to generate exo ‐epoxide 184 and endo ‐epoxide 185 in a 2.2 : 1 diastereomeric ratio.…”

Section: Construction Of Benzo‐fused Heterocycles By Epoxide–o‐nucleo...mentioning

confidence: 99%

“…The synthesis exploited a stereo-and regioselective epoxide-amide cyclization as a key step to form a central dihydrofuran fused to a quinoline ring system outline Scheme 43. [57] The epoxidation of cis-fused tetracycle 183 with m-CPBA took place with low diastereoselectivity to generate exo-epoxide 184 and endo-epoxide 185 in a 2.2 : 1 diastereomeric ratio. Fortunately, these two epoxides could be separated by a flash chromatography which enabled the authors to isolate 184 and 185 in 47 % and 18 % yields, respectively.…”

Section: Construction Of Benzo-fused Heterocycles By Epoxide-o-nucleo...mentioning

confidence: 99%

Construction of Benzo‐Fused Heterocycles by Epoxide–Heteronucleophile Cyclization: Applications in the Synthesis of Natural Products and Designed Molecules

Das

2022

Eur J Org Chem

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Construction of benzo‐fused heterocycles, specifically which have one or more sp3 stereogenic carbon atoms on the heterocyclic ring, by intramolecular ring‐opening cyclization of epoxides with O‐ and N‐nucleophiles is a powerful synthetic tool in organic synthesis. In this Review, we analyze the efficiency of such a heterocyclization approach in natural product synthesis and synthetic methodologies published since the year 2000. In addition to briefly discussing the synthetic methods of accessing the requisite epoxide substrates, important aspects of the subsequent cyclization reaction, such as reaction conditions, endo‐ versus exo‐regioselectivity, protecting or functional group compatibility, and enantio‐ and distereoselectivity are surveyed. Although the literature of organic chemistry in the last four decades has witnessed a large number of reviews/book chapters on the epoxide ring‐opening chemistry, the title topic has never been reviewed. Herein, we have systematized it as a dedicated review for the first time.

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“…Furoerioaustralasine ( 373 ), a pentacyclic alkaloid was isolated in 1993 form a flowering plant belonging to Eriostemon banksii . [ 131 ] George and co‐workers [ 132 ] revised the structure of furoerioaustralasine by a biomimetic synthesis involving the formation of quinoline ring system from fused dihydrofuran via intramolecular epoxide ring opening (Scheme 44). The commercially available citral ( 368 ) on condensation with 2,4‐dihydroxyquinoline ( 367 ) in presence of EDDA delivered pyranoquinoline 369 .…”

Section: Miscellaneous Approaches In Pgf Total Synthesis Of Naturamentioning

confidence: 99%

Evolution of Strategies in Protecting‐Group‐Free Synthesis of Natural Products: A Recent Update

2020

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The synthesis of complex natural products must be realized with high economy and efficiency, contributing largely to sustainable development in synthetic organic chemistry. The new strategies should adopt protecting‐group‐free approaches enabling step‐economy and thereby enhancing efficiency. Various approaches based on chiral pool, auxiliary‐based methods, cascade, biomimetic, enzymatic and photocatalytic used in total synthesis of natural products and following the PGF‐criteria over the last two years (2018–2019) have been reviewed here. These should guide sustainable synthesis of natural products in the future.

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Biomimetic Synthesis Enables the Structure Revision of Furoerioaustralasine

Abstract: The structure of furoerioaustralasine, a unique Australian alkaloid, has been revised based on a concise, biomimetic synthesis. The key step is a stereospecific, intramolecular ring opening of an epoxide to form a central dihydrofuran fused to a quinoline ring system.

Cited by 18 publications

References 12 publications

Biomimetic Dearomatization Strategies in the Total Synthesis of Meroterpenoid Natural Products

Biomimetic Dearomatization Strategies in the Total Synthesis of Meroterpenoid Natural Products

Construction of Benzo‐Fused Heterocycles by Epoxide–Heteronucleophile Cyclization: Applications in the Synthesis of Natural Products and Designed Molecules

Evolution of Strategies in Protecting‐Group‐Free Synthesis of Natural Products: A Recent Update

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