Metal‐Free C–S Bond Cleavage to Access N ‐Substituted Acrylamide and β‐Aminopropanamide

Yang

et al. 2023

J. Agric. Food Chem.

Based on the structural features of both succinate dehydrogenase inhibitors (SDHIs) and targeted covalent inhibitors, a series of N-phenylpropiolamides containing a Michael acceptor moiety were designed to find new antifungal compounds. Nineteen compounds showed potent inhibition activity in vitro on nine species of plant pathogenic fungi. Compounds 9 and 13 showed higher activity on most of the fungi than the standard drug azoxystrobin. Compound 13 could completely inhibit Physalospora piricola infection on apples at 200 μg/mL concentration over 7 days and showed high safety to seed germination and seedling growth of plants at ≤100 μg/mL concentration. The action mechanism showed that 13 is an SDH inhibitor with a median inhibitory concentration, IC 50 , value of 0.55 μg/mL, comparable with that of the positive drug boscalid. Molecular docking studies revealed that 13 can bind well to the ubiquinone-binding region of SDH by hydrogen bonds and undergoes π−alkyl interaction and π−cation interaction. At the cellular level, 1 as the parent compound could destruct the mycelial structure of P. piricola and partly dissolve the cell wall and/or membrane. Structure−activity relationship analysis showed that the acetenyl group should be a structure determinant for the activity, and the substitution pattern of the phenyl ring can significantly impact the activity. Thus, Nphenylpropiolamide emerged as a novel and promising lead scaffold for the development of new SDHIs for plant protection.

Section: Methodssupporting

confidence: 89%

Discovery of N-Phenylpropiolamide as a Novel Succinate Dehydrogenase Inhibitor Scaffold with Broad-Spectrum Antifungal Activity on Phytopathogenic Fungi

Yang

et al. 2023

J. Agric. Food Chem.

“…α-Acyloxy sulfides with other S-substituents (R 2 ) instead of the S-methyl group were subjected to the above reaction conditions (Table 2). In the cases of α- On the basis of these experimental results and previous work, [17] tentative mechanisms for the formation of the N-functionalized products 3 and 3' are proposed (Scheme 3). The α-acyloxy sulfide (2) may first undergo elimination of a thiolate group to form an oxonium species (A) (path a).…”

mentioning

confidence: 55%

Transition‐Metal‐Free N‐Functionalization of Benzimidazoles and Related Azaheterocycles with α‐Acyloxy Sulfides

et al. 2022

Direct N‐functionalization of benzimidazoles and related azaheterocycles has been achieved using readily accessible α‐acyloxy sulfides under transition metal‐free conditions. In the presence of the base, potassium carbonate, a variety of N‐functionalized azaheterocyclic compounds bearing an N‐alkyl ester moiety were synthesized from corresponding heterocyclic precursors. The present reaction does not use transition metals, is operationally simple, and has broad substrate scope.

“…2-Methylthiobenzamides 1 were prepared from corresponding 2-thiobenzoic acid (2.0 mmol) and amines (3.0 mmol) in DCM at room temperature according to the reported procedure. , …”

Section: Methodsmentioning

confidence: 99%

Silver-Promoted Site-Selective Intramolecular Cyclization of 2-Methylthiobenzamide Through α-C(sp³)–H Functionalization

Yang

Niu

et al. 2019

J. Org. Chem.

Self Cite

Silver-mediated intramolecular α-C(sp3)–H bond functionalization of the methylthio group has been established in the presence of Selectfluor as an additive. This novel strategy provides efficient access to various diverse sulfur-based heterocycles with good yields and functional group compatibility. It is noteworthy that the completely novel benzooxathiin-4-imine skeletons were reported for the first time in this study.