Skyrins

Bräse, Stefan; Gläser, Franziska; Kramer, Carsten S.; Lindner, Stephanie; Linsenmeier, Anna M.; Masters, Kye-Simeon; Meister, Anne C.; Ruff, Bettina M.; Zhong, Sabilla

doi:10.1007/978-3-7091-1312-7_12

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…Resorcylic acid lactones (RALs), such as hypothemycin ( 265 ), are a family of benzannulated macrolides produced by fungi with a 12- or 14-member macrolactone and many contain a cis -enone. RALs exhibit a variety of biological properties including antifungal, antibiotic, antitumor, and antiviral activities by inhibiting heat shock protein 90 (HSP90), mitogen activated protein kinases (MAPKs), herpes simplex virus 1 (HSV1), and the NF-κB pathway . The cis -enone functionality of many RALs leads to irreversible, covalent inhibition of kinases in the MAPK signaling pathway by hetero-Michael addition of a conserved cysteine located in the ATP binding pocket .…”

Section: αβ-Unsaturated Ketones (Enones)mentioning

confidence: 99%

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

et al. 2016

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Although Michael acceptors display a potent and broad spectrum of bioactivity, they have largely been ignored in drug discovery because of their presumed indiscriminate reactivity. As such, a dearth of information exists relevant to the thiol reactivity of natural products and their analogs possessing this moiety. In the midst of recently approved acrylamide-containing drugs, it is clear that a good understanding of the hetero-Michael addition reaction and the relative reactivities of biological thiols with Michael acceptors under physiological conditions is needed for the design and use of these compounds as biological tools and potential therapeutics. This perspective provides information that will contribute to this understanding, such as kinetics of thiol addition reactions, bioactivities, as well as steric and electronic factors that influence the electrophilicity and reversibility of Michael acceptors. This perspective is focused on α,β-unsaturated carbonyls given their preponderance in bioactive natural products.

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Section: αβ-Unsaturated Ketones (Enones)mentioning

confidence: 99%

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

et al. 2016

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“…For more than a half century, aflatoxins, a family of mycotoxins, have attracted extensive synthetic attention as a result of their widespread prevalence in nature and their potent biological effects, which include toxicity, carcinogenicity, antimitoticity, antimicrobiality, and platelet-aggregating inhibition activity, etc. (Figure ).…”

mentioning

confidence: 99%

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D₂ and (−)- and (+)-Microminutinin

et al. 2017

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An efficient method has been developed for the enantioselective synthesis of the aflatoxin system with multiple stereocenters via a sequence of organocatalytic Michael-acetalization-reduction-Nef reactions that proceed with high enantioselectivities (90-99% ee). The one-pot reaction sequence provides a facile entry to the aflatoxin system, including dihydroaflatoxin D, which includes a formal total synthesis of aflatoxin B. The first total synthesis of (-)- and (+)-microminutinin was also achieved via this protocol.

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Phenotyping the genus Hypericum by secondary metabolite profiling: emodin vs. skyrin, two possible key intermediates in hypericin biosynthesis

Kimáková

Idkowiak

et al. 2018

Anal Bioanal Chem

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A wide range of compounds that occur in the genus Hypericum are listed as effective drugs of natural origin. The main biological activities of several Hypericum representatives are due to the presence of naphthodianthrones, phloroglucinols, and other diverse groups of secondary metabolites that synergistically contribute to their therapeutic effects. The regulation of biosynthesis of hypericin as the key bioactive naphthodianthrone remains uncertain. Here, we present liquid chromatography mass spectrometry-based phenotyping of 17 Hypericum species, the results of which suggest an important role for skyrin and its derivatives in the polyketide pathway that leads to hypericin formation. Moreover, we report for the first time the presence of new metabolites in the genus Hypericum that are related to classes of anthraquinones, their derivatives, and phloroglucinols. As skyrin and other species of anthraquinones are rarely found in higher plants but frequently occur in fungal microorganisms, the obtained results suggest that further research on the synthesis pathways of hypericin and the role of anthraquinone derivatives in plant metabolism should be carried out. The fact that these compounds are commonly synthesized in endophytic fungi and perhaps there is some similarity in the metabolic pathways between these organisms should also be investigated.Electronic supplementary materialThe online version of this article (10.1007/s00216-018-1384-0) contains supplementary material, which is available to authorized users.

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Skyrins

Cited by 3 publications

References 33 publications

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D₂ and (−)- and (+)-Microminutinin

Phenotyping the genus Hypericum by secondary metabolite profiling: emodin vs. skyrin, two possible key intermediates in hypericin biosynthesis

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Skyrins

Cited by 3 publications

References 33 publications

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D2 and (−)- and (+)-Microminutinin

Phenotyping the genus Hypericum by secondary metabolite profiling: emodin vs. skyrin, two possible key intermediates in hypericin biosynthesis

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Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D₂ and (−)- and (+)-Microminutinin