Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

Rational design, synthesis and binding mechanisms of novel benzyl geranate derivatives as potential eco-friendly aphid repellents.

BACKGROUND: The push-pull strategy is considered as a promising eco-friendly method for pest management. Plant volatile organic compounds (PVOCs) act as semiochemicals constitute the key factor in implementing this strategy. Benzyl alcohol and geraniol, as functional PVOCs, were reported to regulate insect behavior, showing the potential application in pest control. Using geraniol as lead, a geraniol derivative 5i with fine repellent activity was discovered in our previous work. In order to explore novel, eco-friendly aphid control agents, a series of benzyl geranate derivatives was designed and synthesized using 5i as the lead and benzyl alcohol as the active fragment. RESULTS: Benzyl alcohol was firstly evaluated to have repellent activity to Acyrthosiphon pisum. Based on this repellent fragment, a series of novel benzyl geranate derivatives was rationally designed and synthesized using a scaffold-hopping strategy. Among them, compound T9, with a binding affinity (Kd = 0.43 µm) and a substantial repellency of 64.7% against A. pisum, is the most promising compound. Molecule docking showed that hydrophobic and hydrogen-bonding interactions substantially influenced the binding affinity of compounds with ApisOBP9. Additionally, T9 exhibited low-toxicity to honeybees and ladybugs. CONCLUSION: Using a simple scaffold-hopping strategy combined with active fragment benzyl alcohol, a new derivative T9, with high aphid-repellency and low-toxicity to nontarget organisms, can be considered as a novel potential eco-friendly aphid control agent for sustainable agriculture. © 2023 Society of Chemical Industry.

Sustainable Natural Resources for Aphid Management: ß-Ionone and Its Derivatives as Promising Ecofriendly Botanical-Based Products.

ß-Ionone, sustainably derived from Petunia hybrida as a natural bioresource, was identified as a lead compound for integrated aphid management. A series of ß-ionone derivatives containing ester groups were designed and synthesized for the purpose of discovering renewable botanical-based products. The odorant-binding protein (OBP) binding test indicated that ß-ionone and its derivatives displayed binding affinities with Acyrthosiphon pisum OBP9 (ApisOBP9) and Harmonia axyridis OBP15 (HaxyOBP15). Bioactivity assays revealed that most ß-ionone derivatives exhibited a higher repellent activity than that of ß-ionone. ß-Ionone and derivatives 4g and 4l displayed attractiveness to H. axyridis. Specifically, 4g was a highly promising derivative, possessing good repellent activity against A. pisum and attractiveness to H. axyridis. Molecular dynamics simulations revealed that integrating the hydrophobic ester group into the ß-ionone framework strengthened the van der Waals interactions of 4g with ApisOBP9/HaxyOBP15, improving the binding affinity with OBPs and producing higher push-pull activity than ß-ionone; 4g also had low toxicity toward nontarget organisms. Thus, 4g is a potential ecofriendly, botanical-based option for aphid management.

Association of hormone replacement therapy and the risk of knee osteoarthritis: A meta-analysis.

BACKGROUND: The relationship between hormone replacement therapy (HRT) and osteoarthritis is controversial in epidemiological studies. With the aim of better understanding the effect of HRT use, this first meta-analysis was implemented to explore the association of HRT and knee OA. METHODS: A series of data is retrieved from Web of Science, PubMed, and Embase databases to observe the association of HRT and knee osteoarthritis up to December 2021. Two separated reviewers chose the research, extracted the data, and evaluated the study quality. Pooled estimates of 95% CI and HRs were acquired through a random-effects model. RESULTS: Finally, there existed 13 pieces of research, containing one case-control research, four cross-sectional pieces of research, as well as eight cohort pieces of research, involving 2573,164 participants. The overall results showed that the use of HRT was related to a raised risk of knee OA (HR = 1.24, 95% CI 1.07-1.45). And the pooled analysis showed a statistically significant raised risk of knee joint replacement (HR = 1.30, 95% CI 1.09-1.54) when using HRT. In addition, the outcome exhibits the raised knee OA risk for the present users of HRT (HR = 1.40, 95% CI 1.16-1.68) according to HRT status. In the past users of HRT, the augment of knee OA risk was not statistically evident (HR = 1.16, 95% CI 0.94-1.42). CONCLUSION: We observed that HRT use was related to a raised knee OA risk. Furthermore, future studies might focus on relevant mechanistic to verify our observed associations.

Cooperative Ligand-Promoted P(III)-Directed Ruthenium-Catalyzed Remote Meta-C-H Alkylation of Tertiary Phosphines.

Herein, we disclose a ruthenium-catalyzed meta-selective C-H activation of phosphines by using intrinsic P(III) as a directing group. 2,2,6,6-Tetramethylheptane-3,5-dione acts as the ligand and exhibits an excellent performance in boosting the meta-alkylation. The protocol allows an efficient and straightforward synthesis of meta-alkylated tertiary phosphines. Several meta-alkylated phosphines were evaluated for Pd-catalyzed Suzuki coupling and found to be superior to commercially available ortho-substituted phosphines. The practicability of this methodology is further demonstrated by the synthesis of difunctionalized phosphines.

Remote and Selective C(sp2)-H Olefination for Sequential Regioselective Linkage of Phenanthrenes.

Biphenylcarboxylic acid with two competing C(sp2)-H sites was designed for site selective C(sp2)-H functionalization by developing carboxylic acids assisted remote and selective olefination via 7-membered palladacycle. Mechanism investigation and DFT calculations reveal a kinetics-determined process, which could be utilized to explore a variety of remote site selectivity. The practicability of this method was highlighted by the precise construction of phenathrene under sequential site selectivity.

Carboxylate-Assisted Pd(II)-Catalyzed ortho-C-H and Remote C-H Activation: Economical Synthesis of Pyrano[4,3- b]Indol-1(5 H)-ones.

An original Pd(II)-catalyzed domino two C-H activations strategy has been designed to synthesize pyrano[4,3- b]indol-1(5 H)-one motifs from inexpensive and commercially available olefins and heteroaromatic acids by carboxylate-directed sequential ortho-C-H alkenylation and remote C-H lactonization. Importantly, this protocol overcomes the selectivity for carboxylic acids with acrylates of the conventional Michael addition-type process. Preliminary studies of mechanism indicate that both aryl and olefinlic C-H activations may participate in this catalytic system.

Facile synthesis of unnatural ß-germyl-α-amino amides via Pd(ii)-catalyzed primary and secondary C(sp3)-H bond germylation.

Pd(ii)-Catalyzed direct C(sp3)-H germylation of α-AA derivatives with the assistance of a bidentate auxiliary for the efficient synthesis of ß-germyl-α-amino amides is reported. This protocol features good generality for primary and secondary C-H bonds of aliphatic amides. Mechanistic studies show that a crucial five-membered palladacycle intermediate may play a key role in this process.

Monoprotected Amino Acid (MPAA) Ligand Enabled C-H Alkynylation of Phenyl Acetic Acid.

A weakly carboxylate-directed palladium(II)-catalyzed ortho-C-H alkynylation of diverse phenylacetic acids promoted by monoprotected amino acid ligand enabled is reported. The reaction has a broad substrate scope including α-secondary, tertiary, and quaternary phenylacetic acids. Notably, the direct ortho-C-H alkynylation of α-quaternary phenylacetic acids and chiral α-tertiary phenylacetic acids was achieved for the first time. Moreover, this method could be used for simple and efficient gram-scale synthesis and diversification of an anti-inflammatory drug.