A Diels–Alder reaction of possible biosynthetic importance

Porter, A. E. A.; Sammes, Peter G.

doi:10.1039/c2970001103a

Cited by 117 publications

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“…(1)]. [6,7] Although [42] cycloadditions are used extensively in synthetic organic chemistry, such pericyclic reactions are quite rare in Nature, and in only a few cases has experimental evidence been obtained to support the intermediacy of a Diels ± Alder type of cycloaddition. [7,8] Our research efforts have thus focused on the biogenesis of these compounds, with particular emphasis on the key cycloaddition step.…”

mentioning

confidence: 99%

“…To our knowledge this is the first successful 8-endo-dig cyclization of a samarium ketyl. [6] Since they were more readily accessible, [7] the disubstituted alkynes 5 ± 7 were first subjected to samarium diiodide cyclization conditions. However, we obtained products derived from neither an 8-endo-dig cyclization nor from the more likely 7-exo-dig-reaction, but surprisingly cyclohexadienes 11 ± 13 which were formed by attack on aryl substituents.…”

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confidence: 99%

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Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Stocking¹,

Sanz‐Cervera²,

Williams³

1999

Angew. Chem. Int. Ed.

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Both a face-selective and a non-face-selective mode of formation of quaternary centers of isoprene-derived structural moieties of the natural alkaloid paraherquamide A (1) have been discovered by feeding experiments on Penicillium fellutanum with [U- C ]-glucose and [ C ]-acetate. The labeling patterns suggest that the methyl groups (C22, C23) are introduced in a non-face-selective manner by a reverse prenyl transferase. The C unit comprising the dioxepin moiety retains stereochemical integrity indicative of a single, face-selective addition of the phenolic group to the dimethylallyl group.

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confidence: 99%

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confidence: 99%

Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Stocking¹,

Sanz‐Cervera²,

Williams³

1999

Angew. Chem. Int. Ed.

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“…A provocative biosynthetic hypothesis involving an oxidative hetero-Diels-Alder cycloaddition, that generates the central diazabicyclo[2.2.2]octane core, was proposed by Porter and Sammes [7]. Based on that, biomimetic synthetic strategies were pursued independently by Williams [8], Liebscher [9], and more recently by Scheerer [10][11][12][13] and others [14,15].…”

Section: Introductionmentioning

confidence: 99%

Oxidative radical cyclizations of diketopiperazines bearing an amidomalonate unit. Heterointermediate reaction sequences toward the asperparalines and stephacidins

Amatov

Gebauer

Pohl

et al. 2016

Free Radical Research

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A novel approach to the diazabicyclo[2.2.2]octane core of prenylated bridged diketopiperazine alkaloids is described by direct oxidative cyclizations of functionalized diketopiperazines mediated by ferrocenium hexafluorophosphate or the Mn(OAc) 3 2H 2 O/Cu(OTf) 2 system. Divergent reaction pathways take place depending on the substitution pattern of the substrates and the oxidation conditions such as temperature or the presence or absence of persistent radical TEMPO. For ester-substituted diketopiperazines, the ester group exerts a significant influence on the reaction outcome and stereochemistry of the radical cyclizations.ARTICLE HISTORY

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“…3). 27) Experimental support for this notion was further presented by the Diels-Alder cycloadditions of dimethyl acetylenedicarboxylate and norbornadiene with the pyrazine derivatives shown below in Chart 6.…”

Section: The Brevianamides and Austamidesmentioning

confidence: 95%

“…Stereochemical Relationships of the Brevianamides as Determined by Williams et al 29,30) Chart 6. Biomimetic Diels-Alder Cycloadditions 27) Fig. 4.…”

Section: Synthesis Of (؊)-Brevianamide B Reveals Unusual Biogenesismentioning

confidence: 99%

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Williams

2002

Chem. Pharm. Bull.

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The paraherquamides constitute an unusual family of prenylated indole alkaloids that are secondary metabolites produced by Penicillium sp. and Aspergillus sp. fungi. This review will cover both the biosynthesis as well as the chemical synthesis of this family of natural products. Particular emphasis will be placed on the provocative hypothesis that the core bicyclo[2.2.2]diazaoctan ring system, which is common to this entire family, is formed by a biological DielsAlder reaction.Despite its widespread use in synthetic organic chemistry, the Diels-Alder cycloaddition reaction does not occur frequently in nature. 1,2) There are just a few reports in the literature claiming the identification of an enzyme that catalyzes this most ubiquitous synthetic ring-forming reaction. [3][4][5][6] A possible explanation for this is that, enzymes generally catalyze reactions by stabilizing the structure and charge of the developing transition state. For most reactions subject to this stratagem of catalysis, both the starting substrate and the product differ significantly with respect to structure from the transition state; it is this fundamental difference that allows for turnover; i.e., both the product and the starting substrate must bind to the enzyme less tightly than the transition state structure. In the Diels-Alder reaction, the transition state is highly ordered and closely resembles the structure of the product (see Fig. 1, below). In other words, an enzyme that was designed to stabilize the transition state structure for this reaction would be expected to be inhibited by the product (via tight binding) and turnover (thus catalysis) would be precluded. It is from within the excitement of this fundamental question, that this review will hold as a guiding light.The only examples of protein-catalyzed Diels-Alder reactions are those of catalytic antibodies that have recently been shown to catalyze the intermolecular [4ϩ2] cycloaddition reaction.7-9) In these cases, the initial Diels-Alder adducts were high-energy substances that significantly change their structure or conformation after the initial cyclocondensation and were subsequently released from the antibody CDR (allowing for turnover). In addition, ribozymes have been reported to catalyze the Diels-Alder reaction and findings in this area have been reviewed. 10) The Penicillium sp. that produces the brevianamides/paraherquamides may be a rare, but vitally important example of the existence of DielsAlderases. It is further significant to note in the context of the catalytic antibody stratagem that, the brevianamide DielsAlder adducts (which are proposed to be the brevianamides themselves) are very rigid substances; therefore, a significant change in conformation or structure is either impossible or highly unlikely. Elucidation of the mechanism for turnover in the purported paraherquamide and brevianamide [4ϩ2] cycloaddition reaction should be an extremely interesting and significant finding.In order to do proper justice to the history of the biosynthetic Diels-Alder p...

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A Diels–Alder reaction of possible biosynthetic importance

Cited by 117 publications

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Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Oxidative radical cyclizations of diketopiperazines bearing an amidomalonate unit. Heterointermediate reaction sequences toward the asperparalines and stephacidins

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

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A Diels–Alder reaction of possible biosynthetic importance

Cited by 117 publications

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Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Oxidative radical cyclizations of diketopiperazines bearing an amidomalonate unit. Heterointermediate reaction sequences toward the asperparalines and stephacidins

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels&ndash;Alder Construction

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Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction