Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Heterocyclic Communications

Editor-in-Chief: Henary, Maged


IMPACT FACTOR 2018: 0.810

CiteScore 2018: 0.77

SCImago Journal Rank (SJR) 2018: 0.208
Source Normalized Impact per Paper (SNIP) 2018: 0.264

Open Access
Online
ISSN
2191-0197
See all formats and pricing
More options …
Volume 20, Issue 3

Issues

5-(2,2-Dimethyl-4H-1,3-benzodioxin)methanol: the synthetic precursor to o-formyl-m-hydroxycinnamic acid, the most oxidized salicylaldehyde-type phytotoxin isolated from rice blast fungus, Magnaporthe grisea

Akihito Saito / Konosuke Hiramatsu / Hai-Qun Cao
  • Graduate School of Agricultural Science, Tohoku University, Tohoku, Japan
  • Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Kita, Okayama 700-8530, Japan
  • School of Plant Protection, Anhui Agricultural University, Hefei, Anhui Province, 230036, P.R. China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yuta Nagashima / Koji Tanaka / Ayaka Sasaki / Teiko Yamada / Shigefumi Kuwahara / Manabu Nukina / Hiromasa Kiyota
  • Corresponding author
  • Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Kita, Okayama 700-8530, Japan
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-05-12 | DOI: https://doi.org/10.1515/hc-2014-0053

Abstract

o-Formyl-m-hydroxycinnamic acid, the most oxidized salicylaldehyde-type phytotoxin isolated from rice blast fungus, Magnaporthe grisea, was synthesized for the first time using 5-(2,2-dimethyl-4H-1,3-benzodioxin)methanol as the starting material, and the proposed structure was confirmed.

Keywords: Magnaporthe grisea; phytotoxins; pyriculone; rice blast fungus; synthesis

Introduction

Rice blast disease, caused by infection of rice blast fungus, Magnaporthe grisea (Hebert) Barr, is one of the most harmful diseases for rice [1]. Several salicylaldehyde derivatives, such as pyriculol (2) [2], pyriculariol (3) [3], pyriculone (4) [4], and pyricuol (5) [5], have been isolated from the fungus as suspicious compounds responsible for the disease; they induce dark necrotic spot, when being applied to wounded rice leaves. In addition, o-formyl-m-hydroxycinnamic acid (6), probably further oxidized compound derived from 4, has also been found in the culture extract of the fungus [6] (Scheme 1). We have reported the synthesis of the derivatives 13, 5 using a common intermediate, 5-(2,2-dimethyl-4H-1,3-benzodioxin)methanol (7) (Scheme 2) [7–10]. In continuation of our synthetic studies of these compounds [7–13], the most oxidized derivative 6 was prepared for the first time from 7. Isolation and synthesis of o-carboxy-m-hydroxycinnamic acid, the related phytotoxin from other sources, has been reported [14–16]. Details of the synthesis are described in this report.

Biogenetic pathways of salicylaldehyde-type phytotoxin isolated from rice blast fungus.
Scheme 1

Biogenetic pathways of salicylaldehyde-type phytotoxin isolated from rice blast fungus.

5-(2,2-Dimethyl-4H-1,3-benzodioxin)methanol (7) as the key synthetic intermediate for the synthesis of the phytotoxins.
Scheme 2

5-(2,2-Dimethyl-4H-1,3-benzodioxin)methanol (7) as the key synthetic intermediate for the synthesis of the phytotoxins.

Results and discussion

We have already reported the preparation of compounds with the same carbon skeleton as 6, as intermediates towards the synthesis of pyricuol (5) [9, 10]. Thus, we chose the intermediate 7 as the starting material. Partial oxidation of 7 and the Horner-Wadsworth-Emmons reaction afforded ester 8, which was then reduced to give aldehyde 9 according to our procedure [10] (Scheme 3). At first, the aldehyde 9 was oxidized with Jones reagent to give acid 10, and then the acetonide protecting group was removed under acidic conditions. However, the resulting dihydroxy acid 11 could barely be purified because of its high hydrophilicity. Thus, we restarted the synthesis from the ester 8, and the acetonide group was removed under acidic conditions. The desired diol 12 was obtained as a colorless oil after silica gel purification in 45% yield. Then, the alcoholic hydroxy group was oxidized using MnO2 in DMSO/CHCl3 [10] to give aldehyde 13 in 97% yield. The alkaline hydrolysis of the ester group was examined. The use of K2 CO3 or KOH in EtOH/H2 O resulted in a complex mixture. Finally, we found that LiOH in EtOH/H2 O was the best choice that afforded the target compound 6 as colorless needles (mp 132–133°C) in 59% yield. The overall yield was 26% from 8. The 1H NMR spectra of the natural product 6 and synthetic compound 6 were virtually identical.

Synthesis of o-formyl-m-hydroxycinnamic acid (6).
Scheme 3

Synthesis of o-formyl-m-hydroxycinnamic acid (6).

Conclusion

o-Formyl-m-hydroxycinnamic acid, the most oxidized salicylaldehyde-type phytotoxin isolated from rice blast fungus, Magnaporthe grisea, was successfully synthesized for the first time using 5-(2,2-dimethyl-4H-1,3-benzodioxin)methanol as the starting material.

Experimental

General

Melting point was measured on a Yanako MP-J3 instrument and is uncorrected. FT-IR spectra were recorded as films by a Jasco 4100 spectrometer (ATR, Zn-Se). 1H NMR spectra were recorded with a Varian 400 MR (400 MHz) spectrometer in CDCl3 with CHCl3H 7.26 ppm) or CD3 OD with CD3 OH (δH 3.30 ppm) as internal standard. Mass spectra were recorded with a Jeol JMS-700 spectrometer. Merck silica gel 60 (70–230 mesh) was used for column chromatography. Merck silica gel 60 F254 (0.25 mm thickness) was used for TLC analysis.

Ethyl (E)-3-(3′-hydroxy-2′-hydroxymethylphenyl)ethenoate (12)

A solution of 8 [9, 10] (82.0 mg, 0.31 mmol) and p-TsOH×H2 O (21.0 mg, mmol) in THF/H2 O (ca. 1 mL) was stirred at room temperature for 3 days and then treated with a saturated aqueous solution of NaHCO3. The resulting mixture was extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was chromatographed on silica gel (hexane/EtOAc, 3:1) to give 12 (31.1 mg, 0.14 mmol, 45%) as a colorless oil; Rf = 0.16 (hexane/EtOAc, 1:1); IR: ν 3450 (br. s, O–H), 2924 (m), 2854 (w), 1701 (w, C=O), 1640 (w), 1019 (s, C–O), 953 (m) cm-1; 1H NMR (CDCl3, 400 MHz): δ 7.90 (1H, d, J = 15.6 Hz, H-3), 7.70 (1H, s, ArOH), 7.22 (1H, pseudo t, J = 8.0 Hz, H-5′), 7.08 (1H, d, J = 8 Hz), 6.93 (1H, d, J = 8 Hz), 6.30 (1H, d, J = 15.6 Hz, H-2), 5.08 (2H, d, J = 5 Hz, CH2 OH), 4.26 (2H, q, J = 7 Hz, CH2 CH3), 2.24 (1H, br., CH2 OH), 1.34 (3H, t, J = 7 Hz, CH2 CH3). HR-FABMS. Calcd for C12 H12 O4 Na ([M+Na]+): m/z 245.0789. Found: m/z 245.0792.

Ethyl (E)-3-(2′-formyl-3′-hydroxyphenyl)ethenoate (13)

A suspension of 12 (31.1 mg, 0.14 mmol) and MnO2 (500 mg) in DMSO/CHCl3 (7:3, 10 mL) was stirred at room temperature for 5 h. The mixture was filtered through a Celite pad and the filtrate was concentrated in vacuo. The residue was chromatographed on silica gel (hexane/EtOAc, 2:1) to give 13 (30.0 mg, 0.14 mmol, 97%) as a pale yellow oil; Rf = 0.69 (hexane/EtOAc, 1:1); IR: ν 2982 (w), 2957 (w), 2925 (w), 1717 (s, C=O), 1651 (s), 1456 (m), 1335 (m), 1265 (m), 1184 (m), 1161 (m) cm-1; 1H NMR (CDCl3, 400 MHz): δ 11.92 (1H, s, HC=O), 10.38 (1H, s, OH), 8.22 (1H, d, J = 15.8 Hz, H-3′), 7.52 (1H, t, J = 8.0 Hz, H-5′), 7.06 (1H, d, J = 7.5 Hz), 7.02 (1H, d, J = 8.8 Hz), 6.37 (1H, d, J = 15.8 Hz), 4.26 (2H, q, J = 7.2 Hz, CH2 CH3), 1.34 (3H, t, J = 7.2 Hz, CH2 CH3). HR-EIMS. Calcd for C12 H12 O4 (M+.): m/z 220.0736. Found: m/z 220.0736.

(E)-3-(2′-Formyl-3′-hydroxyphenyl)ethenoic acid [(E)-o-formyl-m-hydroxycinnnamic acid] 5

A solution of 13 (20.0 mg, 0.091 mmol) and LiOH×H2 O (40.8 mg, 0.972 mmol) in THF/H2 O (3:1, 2 mL) was stirred at 0°C for 5 h. The solution was neutralized with citric acid and the mixture extracted with CH2 Cl2. The combined organic layer was concentrated in vacuo. The residue was chromatographed on silica gel (CHCl3/MeOH, 15:1) and crystallized from hexane/EtOAc to give 6 (10.2 mg, 0.053 mmol, 59%) as colorless needles; mp 132–133°C; Rf = 0.18 (CHCl3/MeOH, 15:1); IR: ν 3400 (br. s, O–H), 2948 (m), 2833 (w), 1653 (w), 1449 (w), 1021 (s) cm-1; 1H NMR (CD3 OD, 400 MHz): δ 10.46 (1H, s, HC=O), 8.31 (1H, d, J = 15.7 Hz, H-2), 7.54 (1H, t, J = 8 Hz, H-5′), 7.17 (1H, d, J = 8 Hz), 6.99 (1H, d, J = 8 Hz), 6.39 (1H, d, J = 15.7 Hz, H-3); 1H NMR (CDCl3, 400 MHz): δ 11.92 (1H, s, HC=O), 10.39 (1H, s, OH), 8.31 (1H, d, J = 15.8 Hz, H-3′), 7.54 (1H, t, J = 8 Hz, H-5′), 7.09 (1H, d, J = 8 Hz), 7.05 (1H, d, J = 8 Hz), 6.40 (1H, d, J = 15.7 Hz). HR-FABMS. Calcd for C10 H7 O4 ([M–H]): m/z 191.0344. Found: m/z 191.0341.

Acknowledgments

Financial support by grant-in-aid from JSPS KAKENHI (numbers 17580092, 19580120, 22560112, and 25450144), the Agricultural Chemical Research Foundation, Intelligent Cosmos Foundation, and the Naito Foundation are gratefully acknowledged.

References

  • [1]

    Umetsu, N.; Kaji, J.; Tamari, K. Investigation on the toxin production by several blast fungus strains and isolation of tenuazonic acid as a novel toxin. Agric. Biol. Chem. 1972, 36, 859–866 (and references cited therein).CrossrefGoogle Scholar

  • [2]

    Iwasaki, S.; Nozoe, S.; Okuda, S.; Sato, Z.; Kozaka, T. Isolation and structural elucidation of a pyhtotoxic substance produced by Pyricularia oryzae Cavara. Tetrahedron Lett. 1969, 45, 3977–3980.Google Scholar

  • [3]

    Nukina, M.; Ikeda, M.; Umezawa, T.; Tasaki, H. Pyriculariol, a new phytotoxic metabolite of Pyricularia oryzae Cavara. Agric. Biol. Chem. 1981, 45, 2161–2162.Google Scholar

  • [4]

    Nukina, M.; Otuki, T.; Kurebayashi, T.; Hosokawa, K.; Sekine, M.; Ito, S.; Suenaga, M.; Sato, A.; Sassa, T. New phytotoxic metabolites produced by the blast disease fungi and microbial conversion of aromatic and aliphatic hydrocarbons as well as carbonyls by them. Abstract paper of 38th Symposium on the Chemistry of Natural Products, 1996, 391–396 (CAS No. 126: 16550).Google Scholar

  • [5]

    Kim, J.-C.; Min, J.-Y.; Kim, H.-T.; Cho, K.-Y.; Yu, S.-H. Pyricuol, a new phytotoxin from Magnaporthe grisea. Biosci. Biotechnol. Biochem. 1998, 62, 173–174.CrossrefGoogle Scholar

  • [6]

    Nukina, M. Secondary metabolites produced by the blast disease fungi–chemotaxonomical classification based on them. Kagaku Seibutsu 1998, 36, 582–588 (in Japanese). The spectral data for 5 were not published.Google Scholar

  • [7]

    Suzuki, M.; Sugiyama, T.; Watanabe, M.; Murayama, T.; Yamashita, K. Synthesis and absolute configuration of pyriculol. Agr. Biol. Chem. 1987, 51, 1121–1127.Google Scholar

  • [8]

    Kiyota, H.; Sasaki, A.; Tanaka, K.; Nakamura, Y.; Ueda, R.; Suzuki, Y.; Kuwahara, S.; Nukina, M. Synthetic studies of salicylaldehyde-type phytotoxins isolated from rice blast fungus. Tennen Yuki Kagobutsu Toronkai Koen Yoshishu 2011, 53, 661–666.Google Scholar

  • [9]

    Kiyota, H.; Ueda, R.; Oritani, T.; Kuwahara, S. First synthesis of (±)-pyricuol, a plant pathogen isolated from rice blast disease fungus Magnaporthe grisea. Synlett 2003, 2, 219–220.CrossrefGoogle Scholar

  • [10]

    Tanaka, K.; Nakamura, Y.; Sasaki, A.; Ueda, R.; Suzuki, Y.; Kuwahara, S.; Kiyota, H. Synthesis and plant growth inhibitory activity of both enantiomers of pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea. Tetrahedron 2009, 65, 6115–6122.Web of ScienceCrossrefGoogle Scholar

  • [11]

    Tanaka, K.; Sasaki, A.; Cao, H.-Q.; Yamada, T.; Igarashi, M.; Komine, I.; Nakahigashi, H.; Minami, N.; Kuwahara, S.; Nukina, M.; et al. Biotransformation of plausible biosynthetic intermediates of salicylaldehyde-type phytotoxins of rice blast fungus, Magnaporthe grisea. Eur. J. Org. Chem. 2011, 6276–6280.Web of ScienceCrossrefGoogle Scholar

  • [12]

    Nakamura, Y.; Kiyota, H.; Ueda, R.; Kuwahara, S. Synthesis to determine the absolute configuration of (–)-pyricuol, a phytotoxin isolated from rice blast disease fungus, Magnaporthe grisea. Tetrahedron Lett. 2005, 46, 7107–7109.CrossrefGoogle Scholar

  • [13]

    Sasaki, A.; Tanaka, K.; Sato, Y.; Kuwahara, S.; Kiyota, H. First synthesis and absolute configuration of (–)-pyriculariol, a phytotoxin isolated from rice blast fungus, Magnaporthe grisea. Use of microwave irradiation to control Stille coupling reaction products. Tetrahedron Lett. 2009, 50, 4637–4638.Web of ScienceCrossrefGoogle Scholar

  • [14]

    Stierle, A. A.; Upadhyay, R.; Hershenhorn, J.; Strobel, G. A.; Molina, G. The phytotoxins of Mycosphaerella fijiensis, the causative agent of Black Sigatoka disease of bananas and plantains. Experientia 1991, 47, 853–859.CrossrefGoogle Scholar

  • [15]

    Trost, B. M.; Rivers, G. T.; Gold, J. M. Regiocontrolled synthesis of hydroxyphthalides. Synthesis of (±)-isoochracinic acid and a zealeranone intermediate. J. Org. Chem. 1980, 45, 1835–1838.CrossrefGoogle Scholar

  • [16]

    Yeola, S. N.; Mali, R. S. A convenient total synthesis of (±)-isoochracinic acid, a phthalide from Alternaria kikuchiana. Indian J. Chem. 1986, 25B, 804–806.Google Scholar

About the article

Corresponding author: Hiromasa Kiyota, Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Kita, Okayama 700-8530, Japan, e-mail:


Received: 2014-03-24

Accepted: 2014-03-31

Published Online: 2014-05-12

Published in Print: 2014-06-01


Citation Information: Heterocyclic Communications, Volume 20, Issue 3, Pages 185–188, ISSN (Online) 2191-0197, ISSN (Print) 0793-0283, DOI: https://doi.org/10.1515/hc-2014-0053.

Export Citation

©2014 by Walter de Gruyter Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Hiromasa Kiyota
Journal of Synthetic Organic Chemistry, Japan, 2019, Volume 77, Number 2, Page 173

Comments (0)

Please log in or register to comment.
Log in