ChemInform Abstract: PSEUROTIN, A NEW METABOLITE OF PSEUDEUROTIUM OVALIS STOLK HAVING AN UNUSUAL HETERO‐SPIROCYCLIC SYSTEM. (PRELIMINARY COMMUNICATION)

Bloch, Peter; Tamm, Christoph; Bollinger, Pietro; Petcher, Trevor J.; Weber, Hans Peter

doi:10.1002/chin.197615393

Cited by 9 publications

(12 citation statements)

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“…S econdary fungal metabolites with 1-oxa-7-azaspiro [4.4]non-2-ene-4,6-dione framework constitute a family of natural products with over 25 members. Since the first isolation of pseurotin A (1, Figure 1), 1 diverse secondary metabolites with structural variations around the spirocyclic core have been discovered (Figure 1). 2 It is important to note that potent cytotoxicities have been noticed among this family of natural products.…”

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confidence: 99%

Total Synthesis of (−)-FD-838 and (−)-Cephalimysin A

Han

2019

Org. Lett.

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We completed a nine-step total synthesis of (−)-FD-838 and (−)-cephalimysin A. Our synthesis features a biogenetically guided assembly of the highly oxidized spirocyclic core by Snider-type tandem epoxidations of the chiral substrate derived from an amino acid derivative. Our synthetic approach provides a general and versatile solution to access spirocyclic PKS-NRPS-based secondary fungal metabolites.

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confidence: 99%

Total Synthesis of (−)-FD-838 and (−)-Cephalimysin A

Han

2019

Org. Lett.

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“…The isolated compounds included a series of benzodiazepine alkaloids analogues; cyclopeptin ( 1 ) which were isolated as two conformers, A and B, in a 4:6 ratio at room temperature which coalesced into a single conformer at 85 °C [ 21 ]: dehydrocyclopeptin ( 2 ) [ 22 , 23 ]; cyclopenin ( 3 ) [ 23 , 24 , 25 ]; cyclopeniol ( 4 ) [ 23 , 24 , 25 ]; two hydroxyquinolone alkaloids viridicatins analogues, viridicatol ( 5 ) [ 26 , 27 ] and 3-O-methylviridicatin ( 6 ) [ 28 , 29 ]; the alkaloid peniamidone A ( 7 ) [ 30 ]; a scytalone analogue, E -4-hydroxy-6-deoxyscytalone ( 8 ) [ 31 ]; pseurotin A ( 9 ) [ 32 , 33 , 34 ]; fructigenine A ( 10 ) [ 35 ], and finally penipratynolene ( 11 )[ 36 ]. All compounds were fully characterized by comparing their HRMS, 1 H, 13 C and HSQC spectral data and optical rotation data with the reported literature ( supplementary data, Figures S1–S54 ).…”

Section: Resultsmentioning

confidence: 99%

Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34

et al. 2021

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SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36–0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.

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“…(BRF 030) was fractionated using a cytotoxicity-guided approach, and yielded compounds pseurotin A (1) (Bloch et al 1976), pseurotin D (2) (Breitenstein et al 1981), bis(dethio)bis(methylthio)gliotoxin (3) (Yi et al 2012), methylsulochrin (Turner 1965) (4), fumitremorgin C (5) (Cole et al 1977), 12,13-dihydroxyfumitremorgin C (6) (Abraham & Arfmann 1990) and pseurotin FD-838 (7) (Mizoue et al 1987) (Figure 1). The elucidation of the structures of all the isolated compounds was established mainly on the basis of their 1D and 2D NMR spectroscopic data, and comparison with the literature data.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic compounds from the marine-derived fungusAspergillussp. recovered from the sediments of the Brazilian coast

Saraiva

Rodrigues

Jimenez

et al. 2014

Natural Product Research

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A fungal strain of Aspergillus sp. (BRF 030) was isolated from the sediments collected in the northeast coast of Brazil, and the cytotoxic activity of its secondary metabolites was investigated against HCT-116 tumour cell line. The cytotoxicity-guided fractionation of the extracts from this fungus cultured in potato-dextrose-sea water for 14 days at room temperature yielded the hetero-spirocyclic γ-lactams pseurotin A (1), pseurotin D (2) and pseurotin FD-838 (7), the alkaloids fumitremorgin C (5), 12,13-dihydroxy fumitremorgin C (6), methylsulochrin (4) and bis(dethio)bis(methylthio)gliotoxin (3). Among them, fumitremorgin C (5) and 12,13-dihydroxy fumitremorgin C (6) were the most active. The cytotoxic activities of the extracts from Aspergillus sp. grown from 7 to 28 days were investigated, and they were associated with the kinetic production of the compounds. The most active extracts (14 and 21 days) were those with the highest relative concentrations of the compounds fumitremorgin C (5) and 12,13-dihydroxy fumitremorgin C (6).

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ChemInform Abstract: PSEUROTIN, A NEW METABOLITE OF PSEUDEUROTIUM OVALIS STOLK HAVING AN UNUSUAL HETERO‐SPIROCYCLIC SYSTEM. (PRELIMINARY COMMUNICATION)

Cited by 9 publications

References 1 publication

Total Synthesis of (−)-FD-838 and (−)-Cephalimysin A

Total Synthesis of (−)-FD-838 and (−)-Cephalimysin A

Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34

Cytotoxic compounds from the marine-derived fungusAspergillussp. recovered from the sediments of the Brazilian coast

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