Combinatorial Synthesis of Novel 1-Sulfonyloxy/acyloxyeugenol Derivatives as Fungicidal Agents

Background: Developing the high-efficiency and low-risk small-molecule green-fungicide is the key to effective control of the plant pathogenic oomycetes. Essential oils play a very important role in novel fungicide discovery for their unique sources and potential target sites. Eugenol, a kind of plant essential oil, was mainly isolated from the unopened and dried flower buds of Syzygium aromaticum of the Myrtaceae family. Due to its unique structural skeleton, eugenol and its derivatives have exhibited a wide range of biological activities. However, study on the synthesis of novel 1-sulfonyloxy/acyloxyeugenol derivatives as fungicidal agents against Phytophthora capsici has not yet been reported. Methods: Twenty-six novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) were prepared and their structures were well characterized by 1H NMR, HRMS, and m.p.. Their fungicidal activity was evaluated against P. capsici by using the mycelial growth rate method. Results: To find novel natural-product-based fungicidal agents to control the plant pathogenic oomycetes, we herein designed and synthesized two series of novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) as fungicidal agents against P. capsici Leonian, in vitro. Results of fungicidal activity revealed that, among all compounds, especially compounds 3a, 3f, and 3n displayed the most potent anti-oomycete activity against P. capsici with EC50 values of 79.05, 75.05, and 70.80, respectively. Conclusion: The results revealed that the anti-oomycete activity of eugenol with the sulfonyloxy group was higher than that with the acyloxy group. It is suggested that the fungicidal activity of eugenol can be improved by introducing the sulfonyloxy group. This will pave the way for further design, structural modification, and to develop eugenol derivatives as fungicidal agents.

The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study

An efficient asymmetric synthesis of GlaxoSmithKline’s potent PDE4 inhibitor was accomplished in eight steps from a catechol-derived nitroalkene. The key intermediate (3-acyloxymethyl-substituted 1,2-oxazine) was prepared in a straightforward manner by tandem acylation/(3,3)-sigmatropic rearrangement of the corresponding 1,2-oxazine-N-oxide. The latter was assembled by a (4 + 2)-cycloaddition between the suitably substituted nitroalkene and vinyl ether. Facile acetal epimerization at the C-6 position in 1,2-oxazine ring was observed in the course of reduction with NaBH3CN in AcOH. Density functional theory (DFT) calculations suggest that the epimerization may proceed through an unusual tricyclic oxazolo(1,2)oxazinium cation formed via double anchimeric assistance from a distant acyloxy group and the nitrogen atom of the 1,2-oxazine ring.

SYNTHESIS OF 2- (2I – ACYLOXY-ETHOXY) ETHYL CHLORIDE AND THEIR INTERACTION WITH AMIDES AND ALKALI METAL RHODANIDES

This work is aimed at studying the reaction of nucleophilic substitution of the chlorine atom in 2-(2'-acyloxy-ethoxy) ethylchlorides with amines and a rhodanide ion and developing methods of synthesizing a 2-(2'-acyloxy-ethoxy) ethylchlorides, rhodanides, and their derivatives previously unknown in specialized literature. In the chlorohydrin molecule of diethylene glycol, there are two reaction centers that allow carrying out nucleophilic substitution reactions, as well as reactions that promote them with electrophilic reagents. The authors carried out several experiments for acylating diethylene glycol chlorohydrine with carbonic acids, reactions of nucleophilic substitution of the chlorine atom in 2-(2'-acyloxy-ethoxy) ethylchlorides with various amines as well as synthesized the chloracetoxyethyl ether of rhodane acetic acid. While studying the nucleophilic substitution of 2-(2'-acyloxy-ethoxy) ethylchlorides with the rhodanide ion, it was discovered that only the chlorine atom was replaced. The possibility of the nucleophilic substitution of the ethylene chlorohydrine was shown by the example of N-methyl and N-ethylanilines. It was discovered that the hydroxyl group of diethylene glycol could react with carbonic acids in the presences of catalysts and, therefore, encourage esterification. It has been found out that the nucleophilic substitution of the chlorine atom in 2-(2'-acyloxy-ethoxy) ethylchlorides with the rhodanide ion goes smoothly in the presence of potassium iodide acting as an activator and that the acyloxy group is unaffected. It has been discovered that the primary role in the nucleophilic substitution of alcoxyalkylhalides is played by the basicity of amines and the essence and position of substituents relative to the alcoxyl group of the haloid atom.