贵州大学宋润江/宋宝安/金智超Sci. China Chem.:异硫脲催化α-芳基硒基取代羧酸的动态动力学拆分合成手性除草剂

摘要：

As a bioisostere of oxygen/sulfur, selenium (Se) has received increasing attention in drug modification and property optimization. Herein, we disclose an isothiourea-mediated dynamic kinetic resolution and ester exchange of α-arylselenocarboxylic acids, affording the target molecules with up to 95% yield and 96:4 e.r. value. The products can be efficiently transformed into the corresponding chiral α-arylselenocarboxylic acids in excellent yields without loss of optical purity. Notably, Se-based isosteres of the commercial herbicides Dichlorprop and Mecoprop exhibits excellent herbicidal activity against weeds and superior safety toward non-target crops such as soybeans and cotton. This study provides a practical asymmetric synthetic route and promising lead compounds for Se-based bioisosteric replacement.

研究背景

图1. 研究背景及本策略（图片来源于Sci. China Chem.）

研究内容：

图2. 条件优化（图片来源于Sci. China Chem.）

图3. 醇筛选（图片来源于Sci. China Chem.）

图4. 动态动力学拆分底物范围（图片来源于Sci. China Chem.）

图5. 克级反应、可能的机理及市售除草剂mecoprop和dichlorprop结构等（图片来源于Sci. China Chem.）

图6. 生物活性研究（图片来源于Sci. China Chem.）

总结：

In summary, we have developed a chiral isothiourea-mediated DKR strategy enabling the efficient enantioselective synthesis of α-arylselenocarboxylic acids. The reaction proceeds with broad substrate scope, excellent efficiency and enantioselectivity. The products can be readily transformed into the corresponding chiral carboxylic acids, providing access to Se-based analogs of the commercial herbicides DCPP and MCPP. Biological testing confirmed the excellent herbicidal activity of compounds (R)-1s and (R)-1r, with (R)-1s exhibiting superior inhibition of P. herba at low concentrations compared to the commercial herbicides. Molecular docking combined with MST experiments indicated that (R)-1s and (R)-1r possess stronger binding affinity for the target receptor TIR1. Notably, compounds 1s and 1r achieved satisfactory crop safety, exhibiting markedly lower phytotoxicity towards soybean and cotton compared to DCPP and MCPP.

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