In the Mists of a Fungal Metabolite: An Unexpected Reaction of 2,4,5-Trimethoxyphenylglyoxylic Acid
"> Figure 1
<p>Structure emodine, chrysophanol and daunorubicin isolated from fungi or lichens and <span class="html-italic">p</span>-quinone methide (<span class="html-italic">p</span>-QM) derived natural products rugaurones A–C and cherylline.</p> "> Figure 2
<p><sup>1</sup>H-NMR Spectra of the intermediate <b>15</b>; temperatures: <b>violet</b>, 40 °C; <b>cyan</b>, 27 °C; <b>green</b>, −30 °C; red, −50 °C.</p> "> Figure 3
<p>NMR Spectra of the intermediate <b>15</b> in different solvents; CDCl<sub>3</sub> (<b>red</b>), toluene-d<sub>8</sub> (<b>green</b>), DMSO-d<sub>6</sub> (<b>blue</b>) at room temperature.</p> "> Figure 4
<p>The molecular structure of compound <b>6</b> in the crystal. Displacement ellipsoids of C and O atoms drawn at the 50% probability level, H atoms as spheres of arbitrary size.</p> "> Figure 5
<p>Intermolecular π interactions in compound <b>6</b>, resulting in a one-dimensional supramolecular structure extending along the crystallographic <span class="html-italic">a</span> axis.</p> "> Scheme 1
<p>Reactions and conditions: (<b>a</b>) SeO<sub>2</sub>, pyridine, 80 °C, 4 h, 57%; (<b>b</b>) TiCl<sub>4</sub>, ClC(=O)CO<sub>2</sub>Et, DCM, −20 °C, 2 h, 94%; (<b>c</b>) KOH, MeOH, H<sub>2</sub>O, r.t. 99%; (<b>d</b>) AlCl<sub>3</sub>, DCM, microwave, 50 °C, 3 h, 13%; (<b>e</b>) aq. HCl, 40 °C, 3 h, 56%; (<b>f</b>) <b>3</b>, HCl, 40 °C, 4 h, 96%; (<b>g</b>) aq. HCl, 40 °C, 4 h, 49%; (<b>h</b>) Ac<sub>2</sub>O, BF<sub>3</sub><sup>.</sup>Et<sub>2</sub>O, 85 °C, 1 h, 66%; (<b>i</b>) SeO<sub>2</sub>, pyridine, 80 °C, 20 h, 44%; (<b>j</b>) DCM, oxalyl chloride, DMF, r.t. 14 h, 36%; (<b>k</b>) DCM, oxalyl chloride, DMF, 0 °C, 2h, traces.</p> "> Scheme 2
<p>Reactions and conditions: (<b>a</b>) AcCl, TiCl<sub>4</sub>, DCM, −20 °C, 2 h, 95%; b) SeO<sub>2</sub>, pyridine, 80 °C, 4 h, 53%; (<b>c</b>) aq. HCl, 0 °C, 2 h, 3%; (<b>d</b>) aq. HCl, Δ,2 h, 48%.</p> "> Scheme 3
<p>Proposed mechanism for the formation of <b>6</b> (TMP = 2,4,5-trimethoxyphenyl; TMB = 1,2,4-trimethoxybenzene).</p> "> Scheme 4
<p>Reactions and conditions: (<b>a</b>) anisole, HCl, 40 °C, 4 h, 74%; (<b>b</b>) Boc-aniline, HCl, 40 °C, 4 h, 43%; (<b>c</b>) BzCl, NEt<sub>3</sub>, DCM, r.t. 6 h, 69%; (<b>d</b>) Zn/HCl, 0 °C, 4 h, 43%; (<b>e</b>) benzene, HCl, 2 h, 18%.</p> ">
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
4. Experimental
4.1. 2,4,5-Trimethoxyphenylglyoxylic Acid (2)
4.2. 2,4,5-Trimethoxyphenyl-glyoxylic Acid Ethyl-ester (4)
4.3. 2-Hydroxy-4,5-dimethoxyphenyl-glyoxylic Acid (5)
4.4. 5-Methoxy-3-(2,4,5-trimethoxyphenyl)benzofuran-2,6-dione (6)
4.5. 1-(6-Hydroxybenzo[d][1,3]dioxol-5-yl)ethan-1-one (9)
4.6. 2-(6-Hydroxybenzo[d][1,3]dioxol-5-yl)-2-oxoacetic Acid (10)
4.7. [1,3]Dioxolo[4,5-f]benzofuran-6,7-dione (11)
4.8. 1-(2,4,5-Trimethoxyphenyl)ethan-1-one-1-13C (12)
4.9. 2-Oxo-2-(2,4,5-trimethoxyphenyl)acetic-2-13C Acid (13)
4.10. 6-Hydroxy-5-methoxy-3,3-bis(2,4,5-trimethoxyphenyl)benzofuran-2(3H)-one-3-13C (15)
4.11. 6-Hydroxy-5-methoxy-3-(2,4,5-trimethoxyphenyl)benzofuran-2(3H)-one (17)
4.12. 5-Methoxy-3-(2-methoxyphenyl)benzofuran-2,6-dione (18)
4.13. 3-(4-Aminophenyl)-5-methoxybenzofuran-2,6-dione (19)
4.14. N-(4-(5-Methoxy-2,6-dioxo-2,6-dihydrobenzofuran-3-yl)phenyl)benzamide (20)
4.15. 6-Hydroxy-5-methoxy-3-phenyl-3-(2,4,5-trimethoxyphenyl)benzofuran-2(3H)-one (21)
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of all compounds are available from the authors. |
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Serbian, I.; Loesche, A.; Sommerwerk, S.; Liebing, P.; Ströhl, D.; Csuk, R. In the Mists of a Fungal Metabolite: An Unexpected Reaction of 2,4,5-Trimethoxyphenylglyoxylic Acid. Molecules 2020, 25, 1978. https://doi.org/10.3390/molecules25081978
Serbian I, Loesche A, Sommerwerk S, Liebing P, Ströhl D, Csuk R. In the Mists of a Fungal Metabolite: An Unexpected Reaction of 2,4,5-Trimethoxyphenylglyoxylic Acid. Molecules. 2020; 25(8):1978. https://doi.org/10.3390/molecules25081978
Chicago/Turabian StyleSerbian, Immo, Anne Loesche, Sven Sommerwerk, Phil Liebing, Dieter Ströhl, and René Csuk. 2020. "In the Mists of a Fungal Metabolite: An Unexpected Reaction of 2,4,5-Trimethoxyphenylglyoxylic Acid" Molecules 25, no. 8: 1978. https://doi.org/10.3390/molecules25081978