Synthesis and Anti‐Oomycete Preliminary Mechanism of Sulfonate Derivatives of Ethyl Maltol

Abstract

To discover novel molecules with unique mechanism against plant pathogenic oomycetes, sixteen new sulfonate derivatives of ethyl maltol (3a–p) were synthesized by structural modification of 2‐ethyl‐3‐hydroxy‐4H‐pyran‐4‐one, and their anti‐oomycete activity against a serious agricultural disease, Phytophthora capsici Leonian was determined in this study. Among all tested compounds, derivatives 3e, 3m and 3p exhibited the most potent anti‐oomycete activity against P. capsici with EC50 values of 19.40, 21.04 and 31.10 mg/L, respectively; especially 3e and 3m showed the best promising and pronounced anti‐oomycete activity than zoxamide (EC50=26.87 mg/L). The results further proved that 4‐tert‐butylphenylsulfonyl group, 3‐nitro‐4‐chlorophenylsulfonyl group and 8‐quinolinesulfonyl group introduced at the hydroxy position of ethyl maltol or maltol were necessary for obtaining the most potent compounds. Further mechanism studies of P. capsici treated with 3e demonstrated that this compound can affect the growth of mycelia by disrupting the integrity of the membrane, and the higher the concentration of the compound is, the greater the degree of membrane integrity damage. These important results will pave the way for further modification of ethyl maltol to develop potential new fungicides.

Synthesis of Hinokitiol Sulfonate Derivatives and Their Anti‐Oomycete and Nematicidal Activities

“…Hinokitiol (1) reacted with RSO 2 Cl (2a -p) to prepare a series of hinokitiol ester derivatives (3a -p) in suitable yields. [23][24][25][26][27][28][29][30][31] The structures of all title compounds were well confirmed by 1 H-NMR, 13 C-NMR, HRMS, and m.p., and the data of compounds 3a-p can be found in the Supporting Information. Interestingly, the two methyl groups on the isopropyl group at position C-4 in the structure of hinokitiol are not coupled with the hydrogen atom on the tertiary carbon atom, and both methyl groups are singlets.…”

“…The synthetic route of the target compounds is depicted in Scheme 1. Hinokitiol ( 1 ) reacted with RSO 2 Cl ( 2a – p ) to prepare a series of hinokitiol ester derivatives ( 3a – p ) in suitable yields [23–31] . The structures of all title compounds were well confirmed by 1 H‐NMR, 13 C‐NMR, HRMS, and m.p., and the data of compounds 3a – p can be found in the Supporting Information .…”

“…brine (20 mL), dried over anhydrous Na 2 SO 4 , concentrated under reduced pressure, and purified by CC to obtain hinokitiol ester derivatives (3a -p) in 17 -54 % yields. [23][24][25][26][27][28][29][30][31][32][33] The data of title compounds 3a-p can be found in the Supporting Information.…”

“…Our previous studies showed that sulfonate derivatives of 3-methoxyphenol (I-1, Figure 1), 2-hydroxyacetophenone (I-2, Figure 1), paeonol (I-3, Figure 1), Fenjuntong (I-4, Figure 1), α/βnaphthol (II-1/II-2, Figure 1), maltol/ethyl maltol (III-1/ III-2, Figure 1), eugenol/dihydroeugenol (IV-1/IV-2, Figure 1), and carvacrol/thymol (V-1/V-2, Figure 1) have clear anti-oomycete activity against P. capsici. [23][24][25][26][27][28][29][30][31] In addition, componds I-3 and III-1 have nematicidal activity against Heterodera glycines Ichinohe and Bursaphelenchus xylophilus (Steiner et Buhrer), respectively. [25,29] Overall, to the best of our knowledge, study on the synthesis of novel 2-sulfonyloxyhinokitiol derivatives (3a -p, Figure 1) as anti-oomycete and nematicidal agents against P. capsici has not yet been reported.…”

“…Previous studies have shown that hinokitiol has a wide range of pharmacological effects and biological activities, [16–22] such as antibacterial activity, [18] antifungal activity, [19] neuroprotective activity, [16] anti‐inflammatory activity, [20] anti‐plasmodial activity, [21] antitumor activity, [22] etc. Our previous studies showed that sulfonate derivatives of 3‐methoxyphenol ( I‐1 , Figure 1), 2‐hydroxyacetophenone ( I‐2 , Figure 1), paeonol ( I‐3 , Figure 1), Fenjuntong ( I‐4 , Figure 1), α/β‐naphthol ( II‐1/II‐2 , Figure 1), maltol/ethyl maltol ( III‐1/III‐2 , Figure 1), eugenol/dihydroeugenol ( IV‐1/IV‐2 , Figure 1), and carvacrol/thymol ( V‐1/V‐2 , Figure 1) have clear anti‐oomycete activity against P. capsici [23–31] . In addition, componds I‐3 and III‐1 have nematicidal activity against Heterodera glycines Ichinohe and Bursaphelenchus xylophilus (Steiner et Buhrer), respectively [25,29] .…”