First Iridium-Catalyzed Highly Enantioselective Hydrogenation of β‑Nitroacrylates

The first highly chemo- and enantioselective hydrogenation of β-nitroacrylates was accomplished with an iridium catalyst (<b>Ir-4</b>) with yields and enantioselectivities of up to 96% and 98% ee, respectively. The resulting α-chiral β-nitro propionates are attractive building blocks for the synthesis of chiral β²-amino acids, which are the core scaffolds of bioactive natural products, pharmaceuticals, and β-peptides

Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines

Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides <b>4ag</b> as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC₅₀ values of 0.58, 0.42, and 2.10 mg/L, respectively. <i>In vivo</i> bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality

“Carbon Assimilation” Inspired Design and Divergent Synthesis of Drimane Meroterpenoid Mimics as Novel Fungicidal Leads

With structural diversity and versatile biological properties, drimane meroterpenoids have drawn remarkable attention in drug development. The stagnant progress made in the structure optimization and SAR study of this kind of natural product for agrochemicals was mainly a result of inefficient construction. Compared with the reported challenging coupling reaction (“1 + 1” tactic), “carbon assimilation” was conceived and used for the rapid construction of drimanyl meroterpenoid mimics, in which the newly formed covalent bond was directly from the old one of the drimanyl subunit (“2 + 0” tactic), which features atom economy, step economy, and facile preparation. The accompanying introduction of versatile heterocycles and application of easily available feedstocks are beneficial for novel green agrochemical discovery, in view of economic efficiency and improvement of physicochemical properities. Heterocyclic mimics <b>3a</b> and <b>3c</b> are presented as potent fungicidal leads with novel skeletons against <i>Botrytis cinerea</i>, >25-fold and >40-fold more promising than the commercial fungicide carbendazim, respectively. Our design was also rationalized by the 6-step synthesis and antifungal assay of the original model of natural meroterpenoids. This tactic can also be fostered or transferred directly to the design of novel natural product mimics for medicinal chemistry or other related biological exploration