Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(11), P. 1484 - 1485
Published: Oct. 31, 2023
Language: Английский
Published: March 11, 2024
Aryl amines are one of the most common moieties in biologically active molecules, and approximately 37% drug candidates contain aromatic amines. Recent advancements medicinal chemistry, coined as “escaping from flatland”, have led to a greater focus on accessing highly functionalized C(sp3)-rich improve physiochemical pharmacokinetic properties compounds. This communication presents modular operationally straightforward three-component alkyl Petasis boron-Mannich (APBM) reaction that utilizes ubiquitous starting materials, including amines, aldehydes boronates. Overcoming long-standing synthetic hurdle accomplishing with boronate coupling partners was achieved via formation an electron donor-acceptor (EDA) complex sequential radical-radical coupling. By adapting this transformation high-throughput experimentation (HTE), it offers rapid access array diverse amenable for facile candidate development.
Language: Английский
Citations
0
Angewandte Chemie, Journal Year: 2024, Volume and Issue: 137(1)
Published: Aug. 14, 2024
Abstract Asymmetric diboration of terminal alkenes is well established, and subsequent selective functionalization the less hindered primary boronic ester commonly achieved. Conversely, sterically accessible secondary remains challenging. An alternative way to control chemoselective bis(boron) compounds by engendering different Lewis acidity two boryl moieties, since reactivity would then be dictated instead sterics. We report herein regio‐ enantioselective Pt‐catalyzed unactivated with (pin)B−B(dan). A broad range cyclic undergo furnish differentiable 1,2‐bis(boron) high levels enantiocontrol, giving access a wide variety novel building blocks from common intermediate. The reaction places acidic B(dan) group at position resulting 1,2‐bisboryl alkanes transformations B(pin) located more position. regioselectivity has been studied DFT calculations believed originate trans influence, which lowers activation barrier for formation regioisomer that weaker electron donor [B(pin) vs B(dan)] opposite strong (alkyl group) in platinum complex.
Language: Английский
Citations
0
Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 10, 2024
Lipid nanoparticles (LNPs) are an essential component of messenger RNA (mRNA) vaccines and genome editing therapeutics. Ionizable amino lipids, which play the most crucial role in enabling mRNA to overcome delivery barriers, have, date, been restricted two-dimensional (2D) architectures. Inspired by improved physicochemical properties resulting from incorporation three-dimensionality (3D) into small-molecule drugs, we report creation 3D ionizable lipid designs through introduction bicyclo[1.1.1]pentane (BCP) core motifs. BCP-based lipids enabled efficient vivo liver spleen with significantly greater performance over 2D benzene- cyclohexane-based analogues. Notably, lead BCP-NC2-C12 LNPs mediated ∼90% reduction PCSK9 serum protein level via CRISPR/Cas9 gene knockout, outperforming controls clinically used DLin-MC3-DMA at same dose. Here, introduce superior activity, thereby expanding chemical scope offering a promising avenue improve efficiency for continued development genetic medicines.
Language: Английский
Citations
0
Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(11), P. 1484 - 1485
Published: Oct. 31, 2023
Language: Английский
Citations
1