1'-(2-Phenyl-ethylene)-ditryptophenaline, a New Dimeric Diketopiperazine from Aspergillus flavus

Barrow, Colin J.; Sedlock, David M.

doi:10.1021/np50111a008

Cited by 35 publications

(44 citation statements)

References 3 publications

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“…[2] (À)-Ditryptophenaline 4 was extracted from several strains of Aspergillus flavus, and although structurally related to (+)-WIN 64821 (1), it shows only moderate activity in the same assays. [3] (+)-Verticillin A 3 was obtained from Verticillium sp. and exhibits antimicrobial activity against Gram positive bacteria and potent antitumor activity in HeLa cell lines.…”

Section: Introductionmentioning

confidence: 99%

Stereocontrolled and Versatile Total Synthesis of Bispyrrolidinoindoline Diketopiperazine Alkaloids: Structural Revision of the Fungal Isolate (+)‐Asperdimin

Pérez‐Balado

Rodríguez-Graña

Lera

2009

Chemistry A European J

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Homo- and heterodimeric bispyrrolidinoindoline diketopiperazine alkaloids have been synthesized following a concise, versatile, and stereoselective route. Highlights of the sequence are a diastereoselective construction of the C3a-bromo-hexahydropyrrolo[2,3-b]indole nucleus, its Co(I)-induced C3a-C3a' dimerization, and the twofold or sequential amide-bond formation before cyclization to the diketopiperazine of the homo- or heterodimeric alkaloids, respectively. Stereochemical diversity is achieved through the choice of the appropriate amino acids combined with the base-induced epimerization of the C2-acyl-hexahydropyrrolo[2,3-b]indole at C2. According to this strategy, the natural products (+)-WIN 64821 1, (+)-WIN 64745 2 and (+)-asperdimin 6 as well as analogues (5, 22, 32, 44) with different relative and absolute configuration have been efficiently synthesized. The flexibility of this synthetic methodology has facilitated the structural revision of the natural product (+)-asperdimin, whose structure has been corrected to diastereomer 6.

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Section: Introductionmentioning

confidence: 99%

Stereocontrolled and Versatile Total Synthesis of Bispyrrolidinoindoline Diketopiperazine Alkaloids: Structural Revision of the Fungal Isolate (+)‐Asperdimin

Pérez‐Balado

Rodríguez-Graña

Lera

2009

Chemistry A European J

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“…9). Though DTP has been shown to have weak activity as an inhibitor of the neurotransmitter, substance P, in animal models, its function in the biology of A. flavus is not known 110) .…”

Section: -7 Ditryptophenaline Clustermentioning

confidence: 99%

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

et al. 2018

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Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of these secondary metabolites have been identified from A. flavus cultures, analysis of the genome has predicted the existence of at least 56 secondary metabolite gene clusters. Many of these gene clusters are not expressed during growth of the fungus on standard laboratory media. This presents researchers with a major challenge of devising novel strategies to manipulate the fungus and its genome so as to activate secondary metabolite gene expression and allow identification of associated cluster metabolites. In this review, we discuss the genetic, biochemical and bioinformatic methods that are being used to identify previously uncharacterized secondary metabolite gene clusters and their associated metabolites. It is important to identify as many of these compounds as possible to determine their bioactivity with respect to fungal development, survival, virulence and especially with respect to any potential synergistic toxic effects with aflatoxin.

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“…It can also increase the valency of a compound, affording the molecule a higher affinity for its target or higher stability upon forming a complex with its target [6]. Compound 1 [7] and its related compound WIN 64821 ( Figure 2) [8] originally isolated from Aspergillus versicolor exhibit useful biological activities, such as an inhibition of substance P receptor for potential analgesic and anti-inflammatory activities. Despite their complex chemical structures, their formation seemed relatively simple, involving dimerization of diketopiperazine monomers formed through condensation of two amino acids at the initial stage.…”

Section: Ditryptophenalinementioning

confidence: 99%

“…Figure 2. Chemical structures of dimeric diketopiperazine alkaloids, (-)-ditryptophenaline 1 [7] and (+)-WIN 64821 [8].…”

Section: Ditryptophenalinementioning

confidence: 99%

“…Once the phenylalanine-derived amide nitrogen of the diketopiperazine core is N-methylated, a ring closure within the monomer and a subsequent monomer-monomer crosslinking through oxidation reactions involving the tryptophan indole ring can lead to the formation of a homodimer of 1. [7] and (+)-WIN 64821 [8]. More recently, 1 was found to be produced by another fungus, Aspergillus flavus [9].…”

Section: Ditryptophenalinementioning

confidence: 99%

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Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids

et al. 2016

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Abstract:Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid), saframycin (tetrahydroisoquinoline alkaloid), strictosidine (monoterpene indole alkaloid), ergotamine (ergot alkaloid) and opiates (benzylisoquinoline and morphinan alkaloid). This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details.

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1'-(2-Phenyl-ethylene)-ditryptophenaline, a New Dimeric Diketopiperazine from Aspergillus flavus

Cited by 35 publications

References 3 publications

Stereocontrolled and Versatile Total Synthesis of Bispyrrolidinoindoline Diketopiperazine Alkaloids: Structural Revision of the Fungal Isolate (+)‐Asperdimin

Stereocontrolled and Versatile Total Synthesis of Bispyrrolidinoindoline Diketopiperazine Alkaloids: Structural Revision of the Fungal Isolate (+)‐Asperdimin

<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids

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