Biomimetic diels–alder cyclizations for the construction of the brevianamide, paraherquamide, sclerotamide, asperparaline and VM55599 ring systems

Williams, Robert M.; Sanz‐Cervera, Juan F.; Sancenón, Félix; Marco, and J. Alberto; Halligan, Kathleen M.

doi:10.1016/s0968-0896(98)00102-3

Cited by 59 publications

(23 citation statements)

References 32 publications

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“…Significant experimental evidence suggests that the bicyclo[2.2.2]diazaoctane core common to all of these natural products arises biosynthetically via an intramolecular hetero-Diels-Alder (IMDA) reaction of a 5-hydroxypyrazin-2(1 H )-one 4,9. Indeed, we have applied such IMDA cycloaddition strategies to the total synthesis of several of these prenylated indole alkaloids, including D,L- stephacidin A,11,12 D,L- brevianamide B,13,14,15 D,L- marcfortine C,16 D,L- notoamide B,12 D,L- and (−)-VM55599,17,18 and most recently D,L- malbrancheamide and D,L- malbrancheamide B 19…”

mentioning

confidence: 99%

Asymmetric total syntheses of (+)- and (−)-versicolamide B and biosynthetic implications

2009

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The Diels-Alder reaction is one of the most well-studied, synthetically useful organic transformations. While a significant number of naturally occurring substances are postulated to arise by biosynthetic Diels-Alder reactions, rigorous confirmation of a mechanistically distinct natural Diels-Alderase enzyme remains elusive. Within this context, several related fungi within the Aspergillus genus produce a number of metabolites of opposite absolute configuration including (+)- or (−)-versicolamide B. These alkaloids are hypothesized to arise via biosynthetic Diels-Alder reactions implying that each Aspergillus species possesses enantiomerically distinct Diels-Alderases. Herein, experimental validation of these biosynthetic proposals via deployment of the IMDA reaction as a key step in the asymmetric total syntheses of (+)- and (−)-versicolamide B is described. Laboratory validation of the proposed biosynthetic Diels-Alder construction, coupled with the secondary metabolite profile of the producing fungi, reveals that each Aspergillus species has evolved enantiomerically distinct indole oxidases, as well as enantiomerically distinct Diels-Alderases.

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confidence: 99%

Asymmetric total syntheses of (+)- and (−)-versicolamide B and biosynthetic implications

2009

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“…These investigations provided additional insights as to the intrinsic facial bias of this cycloaddition with respect to the syn -/ anti -diastereoselectivity. 56–60 Theoretical calculations on these azadiene IMDA reactions published by our collaborator Domingo et al ., 54,55 provide an important backdrop to the laboratory and putative biosynthetic constructions. The strategies for generating the key azadiene species evolved to ever more efficient protocols over the years and are shown here chronologically.…”

Section: Biomimetic Total Synthesesmentioning

confidence: 99%

“…60,85 Reverse-prenylated tryptophan species 47 was coupled with β-hydroxyproline ethyl ester to give dipeptide 48 that was deprotected and cyclized to 49 . Mitsunobu dehydration of 49 in dichloromethane at 40 °C led directly to the production of meta-stable azadiene species 50 that spontaneously underwent IMDA cycloaddition to give a 2.1 : 1, syn : anti diastereomeric mixture that were readily separated by chromatography.…”

Section: Biomimetic Total Synthesesmentioning

confidence: 99%

Structural and stereochemical diversity in prenylated indole alkaloids containing the bicyclo[2.2.2]diazaoctane ring system from marine and terrestrial fungi

et al. 2018

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Various fungi of the genera Aspergillus, Penicillium, and Malbranchea produce prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane ring system. After the discovery of distinct enantiomers of the natural alkaloids stephacidin A and notoamide B, from A. protuberus MF297-2 and A. amoenus NRRL 35660, another fungi, A. taichungensis, was found to produce their diastereomers, 6-epi-stephacidin A and versicolamide B, as major metabolites. Distinct enantiomers of stephacidin A and 6-epi-stephacidin A may be derived from a common precursor, notoamide S, by enzymes that form a bicyclo[2.2.2] diazaoctane core via a putative intramolecular hetero-Diels–Alder cycloaddition. This review provides our current understanding of the structural and stereochemical homologies and disparities of these alkaloids. Through the deployment of biomimetic syntheses, whole-genome sequencing, and biochemical studies, a unified biogenesis of both the dioxopiperazine and the monooxopiperazine families of prenylated indole alkaloids constituted of bicyclo[2.2.2]diazaoctane ring systems is presented.

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“…Compounds 5 – 10 were identified as 6-(3-carboxybutyl)-7-hydroxy-5-methoxy -4-methylphthalan-1-one [18], 7-hydroxy-6-[2-hydroxy-2-(2-methyl-5-oxotetrahydro-2-furyl) ethyl]-5-methoxy-4-methyl-1-phthalanone [10], 5-hydroxy-7-methoxy-4 –methylphtalide [19], mycochromenic acid [10,20], (−)-brevianamide C [21], and (+)-brevianamide A [22], respectively.…”

Section: Resultsmentioning

confidence: 99%

Brevianamides and Mycophenolic Acid Derivatives from the Deep-Sea-Derived Fungus Penicillium brevicompactum DFFSCS025

Zhang

Nong

et al. 2017

Marine Drugs

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Four new compounds (1–4), including two brevianamides and two mycochromenic acid derivatives along with six known compounds were isolated from the deep-sea-derived fungus Penicillium brevicompactum DFFSCS025. Their structures were elucidated by spectroscopic analysis. Moreover, the absolute configurations of 1 and 2 were determined by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compound 9 showed moderate cytotoxicity against human colon cancer HCT116 cell line with IC50 value of 15.6 μM. In addition, 3 and 5 had significant antifouling activity against Bugula neritina larval settlement with EC50 values of 13.7 and 22.6 μM, respectively. The NMR data of 6, 8, and 9 were assigned for the first time.

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Biomimetic diels–alder cyclizations for the construction of the brevianamide, paraherquamide, sclerotamide, asperparaline and VM55599 ring systems

Cited by 59 publications

References 32 publications

Asymmetric total syntheses of (+)- and (−)-versicolamide B and biosynthetic implications

Asymmetric total syntheses of (+)- and (−)-versicolamide B and biosynthetic implications

Structural and stereochemical diversity in prenylated indole alkaloids containing the bicyclo[2.2.2]diazaoctane ring system from marine and terrestrial fungi

Brevianamides and Mycophenolic Acid Derivatives from the Deep-Sea-Derived Fungus Penicillium brevicompactum DFFSCS025

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