Three new benzene derivatives,named daldins A-C(1-3),together with a known analogue,2-hydroxymethyl-3-(1-hydroxypropyl)phenol(4)have been isolated from cultures of ascomycete Daldinia concentrica.The structures of 1-4...Three new benzene derivatives,named daldins A-C(1-3),together with a known analogue,2-hydroxymethyl-3-(1-hydroxypropyl)phenol(4)have been isolated from cultures of ascomycete Daldinia concentrica.The structures of 1-4 with absolute configuration were established by means of spectroscopic methods and X-ray diffraction.All compounds showed no significant inhibition on five human cancer cell lines with IC50 values>40μmol.展开更多
Two skeletally undescribed polyketide-indole hybrids(PIHs), named indolchromins A and B,were generated from indole-3-carbinol(I3 C) in the fungal culture(Daldinia eschscholzii). The indolchromin structures were elucid...Two skeletally undescribed polyketide-indole hybrids(PIHs), named indolchromins A and B,were generated from indole-3-carbinol(I3 C) in the fungal culture(Daldinia eschscholzii). The indolchromin structures were elucidated mainly by their 1 D and 2 D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism(CD) spectra with the electronic CD(ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions,including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase(AONS),C(sp3)-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3–8.6 μmol/L,(2 S,4 R)-and(2 R,4 S)-indolchromin A and(2 R,4 S)-indolchromin B are inhibitory against Clostridium perfringens, Clostridium difficile, Veillonella sp.,Bacteroides fragilis, and Streptococcus pyogenes.(2 R,4 S)-Indolchromin A and(2 S,4 S)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC50 values of 27.9 and131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7(IC_(50)94.4 nmol/L).展开更多
Two new and rare bioactive indoles named dalesindoloids A （1） and B （3）, along with 3-（1H-indole-3ylmethyl）-2-oxindole （2）, were characterized from the indole-3-carbinot （13C）-exposed culture of Daldinia esc...Two new and rare bioactive indoles named dalesindoloids A （1） and B （3）, along with 3-（1H-indole-3ylmethyl）-2-oxindole （2）, were characterized from the indole-3-carbinot （13C）-exposed culture of Daldinia eschscholzii. The absolute configuration of 2 was determined by quantum chemical calculations of the electronic circular dichroism （ECD） spectrum. Dalesindoloids A and B were cytotoxic against the leukemia HL-60 cell line with the IC50 values of 1.0 and 7.4 μmol/L, respectively, with the former being inhibitory on Staphylococcus aureus （MIC： 9.1 μmol/L）. The simultaneous characterization of the alkaloids from the 13C-exposed fungal culture highlighted that the 2,3-epoxyindoline motif can be transformed into both lactam and indolin-3-one moieties. This is the first-time description of the 2,3-epoxyindoline chemical versatility and Wagner-Meerwein rearrangement （WMR） reaction in the microbial culture.展开更多
Replacement of the native promoter of the global regulator Lae A-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, wh...Replacement of the native promoter of the global regulator Lae A-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism(ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.展开更多
A plenty of cytochrome P450s have been annotated in the Daldinia eschosholzii genome.Inspired by the fact that some P450s have been reported to catalyze the carbon-nitrogen(C-N)bond formation,we were curious about whe...A plenty of cytochrome P450s have been annotated in the Daldinia eschosholzii genome.Inspired by the fact that some P450s have been reported to catalyze the carbon-nitrogen(C-N)bond formation,we were curious about whether hybrids through C-N bond formation could be generated in the indole-3-carbinol(I3C)exposed culture of D.eschscholzii.As expected,two skeletally undescribed polyketide-indole hybrids,designated as indolpolyketone A and B(1 and 2),were isolated and assigned to be constructed through C-N bond formation.Their structures were elucidated by 1D and 2D NMR spectra.The absolute configurations of 1 and 2 were determined by comparing the recorded and calculated electronic circular dichroism(ECD)spectra.Furthermore,the plausible biosynthetic pathways for 1 and 2 were proposed.Compounds 1 and 2 exhibited significant antiviral activity against H1N1 with IC_(50) values of 45.2 and 31.4μM,respectively.In brief,compounds 1 and 2 were reported here for the first time and were the first example of polyketide-indole hybrids pieced together through C-N bond formation in the I3C-exposed culture of D.eschscholzii.Therefore,this study expands the knowledge about the chemical production of D.eschscholzii through precursor-directed biosynthesis(PDB).展开更多
基金This project was supported by the National Basic Research Program of China(973 Program,2009CB522300)the National Natural Sciences Foundation of China(30830113,81102346)Youth Innovation Promotion Association CAS.
文摘Three new benzene derivatives,named daldins A-C(1-3),together with a known analogue,2-hydroxymethyl-3-(1-hydroxypropyl)phenol(4)have been isolated from cultures of ascomycete Daldinia concentrica.The structures of 1-4 with absolute configuration were established by means of spectroscopic methods and X-ray diffraction.All compounds showed no significant inhibition on five human cancer cell lines with IC50 values>40μmol.
基金supported by the National Natural Science Foundation of China(Grant Nos.81530089,21661140001,21672101,and 81503232)National Key R&D Program of China(2018YFC1706200)the Drug Innovation Major Project(2018ZX09711-001-007-004,China)for generous support
文摘Two skeletally undescribed polyketide-indole hybrids(PIHs), named indolchromins A and B,were generated from indole-3-carbinol(I3 C) in the fungal culture(Daldinia eschscholzii). The indolchromin structures were elucidated mainly by their 1 D and 2 D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism(CD) spectra with the electronic CD(ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions,including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase(AONS),C(sp3)-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3–8.6 μmol/L,(2 S,4 R)-and(2 R,4 S)-indolchromin A and(2 R,4 S)-indolchromin B are inhibitory against Clostridium perfringens, Clostridium difficile, Veillonella sp.,Bacteroides fragilis, and Streptococcus pyogenes.(2 R,4 S)-Indolchromin A and(2 S,4 S)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC50 values of 27.9 and131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7(IC_(50)94.4 nmol/L).
基金We thank the National Natural Science Foundation of China （Nos. 81530089, 81503232, 21672101, and 21661140001） and State Project for Essential Drug Research and Development （No. 2018ZX09711001-007-004） for generous support.
文摘Two new and rare bioactive indoles named dalesindoloids A （1） and B （3）, along with 3-（1H-indole-3ylmethyl）-2-oxindole （2）, were characterized from the indole-3-carbinot （13C）-exposed culture of Daldinia eschscholzii. The absolute configuration of 2 was determined by quantum chemical calculations of the electronic circular dichroism （ECD） spectrum. Dalesindoloids A and B were cytotoxic against the leukemia HL-60 cell line with the IC50 values of 1.0 and 7.4 μmol/L, respectively, with the former being inhibitory on Staphylococcus aureus （MIC： 9.1 μmol/L）. The simultaneous characterization of the alkaloids from the 13C-exposed fungal culture highlighted that the 2,3-epoxyindoline motif can be transformed into both lactam and indolin-3-one moieties. This is the first-time description of the 2,3-epoxyindoline chemical versatility and Wagner-Meerwein rearrangement （WMR） reaction in the microbial culture.
基金supported by the National Natural Science Foundation of China(Nos.21672101,21702099 and 81673333)
文摘Replacement of the native promoter of the global regulator Lae A-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism(ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.
基金This work was co-financed by grants from the National Natural Science Foundation of China(NSFC)(82073721 and 81991524)National Key R&D Program of China(2018YFC1706205).
文摘A plenty of cytochrome P450s have been annotated in the Daldinia eschosholzii genome.Inspired by the fact that some P450s have been reported to catalyze the carbon-nitrogen(C-N)bond formation,we were curious about whether hybrids through C-N bond formation could be generated in the indole-3-carbinol(I3C)exposed culture of D.eschscholzii.As expected,two skeletally undescribed polyketide-indole hybrids,designated as indolpolyketone A and B(1 and 2),were isolated and assigned to be constructed through C-N bond formation.Their structures were elucidated by 1D and 2D NMR spectra.The absolute configurations of 1 and 2 were determined by comparing the recorded and calculated electronic circular dichroism(ECD)spectra.Furthermore,the plausible biosynthetic pathways for 1 and 2 were proposed.Compounds 1 and 2 exhibited significant antiviral activity against H1N1 with IC_(50) values of 45.2 and 31.4μM,respectively.In brief,compounds 1 and 2 were reported here for the first time and were the first example of polyketide-indole hybrids pieced together through C-N bond formation in the I3C-exposed culture of D.eschscholzii.Therefore,this study expands the knowledge about the chemical production of D.eschscholzii through precursor-directed biosynthesis(PDB).
