Precise Synthesis of Complex Si–Si Molecular Frameworks

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(4), С. 2938 - 2959

Опубликована: Янв. 16, 2025

In this Perspective, we highlight the emergence of target-oriented syntheses complex molecules composed Si-Si (oligosilanes) rather than C-C bonds. Saturated oligosilanes structurally resemble alkanes with respect to a tetrahedral geometry, preference for staggered conformation in linear chains, ability form stable small rings, and stereochemistry at asymmetrically functionalized Si centers. There are also critical differences, example, differences multiple bonding penta- hexacoordinated structures, that mean chemical reactivity and, particular, rules stereoselective synthesis do not cleanly translate from carbon silicon. This Perspective will discuss recent achievements precise, controlled comprised mainly bonds mechanistic insights enabling increased molecular complexity. New tools, such as electrochemical catalytic reactions, be discussed well problem controlling relative configuration containing stereogenic-at-silicon These synthetic facilitate discovery new properties, including insight into light absorption, conformation, mechanical properties.

Язык: Английский

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New Compounds with Enhanced Biological Activity Through the Strategic Introduction of Silylated Groups into Hydroxystearic Acids

Molecules, Год журнала: 2025, Номер 30(3), С. 440 - 440

Опубликована: Янв. 21, 2025

In the field of medicinal chemistry, introduction silylated groups is an important strategy to alter activity, selectivity, and pharmacokinetics compounds based on diverse traits silicon, including atomic size, electronegativity, hydrophobicity. The hydroxy group C-9 or C-10 hydroxystearic acids have been functionalized as t-butyl dimethyl silyl ether. target fully characterized tested for in vitro cytotoxicity tumor cells HT29, HCT116, CaCo2, HeLa, MCF7, U2OS, Jurkat J6 normal I407 cells. particular, derivative (R)-9-hydroxystearic acid was more active colon cancer Analyses cell proliferation, oxidative status, histones post-translational modifications, protein phosphorylation, gene expression, DNA damage were performed obtain information antitumor properties new molecules comparison with unmodified acid’s previously studied effects. Our results suggest that incorporation a functionality may be useful tool structural development pharmaceutically against cancer.

Язык: Английский

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Self-immolative menthol-based thermosets: Sustainable design and chemical recycling via on-command depolymerization

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160197 - 160197

Опубликована: Фев. 1, 2025

Язык: Английский

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Synthesis, antiproliferative activity, and biological profiling of C-19 trityl and silyl ether andrographolide analogs in colon cancer and breast cancer cells

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2025, Номер 121, С. 130163 - 130163

Опубликована: Март 3, 2025

Язык: Английский

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Silaproline-bearing nirmatrelvir derivatives are potent inhibitors of the SARS-CoV-2 main protease highlighting the value of silicon-derivatives in structure-activity-relationship studies

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 117603 - 117603

Опубликована: Апрель 1, 2025

Nirmatrelvir is a substrate-related inhibitor of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) main protease (Mpro) that clinically used in combination with ritonavir to treat COVID-19. Derivatives nirmatrelvir, modified at substrate P2-equivalent position, have been developed fine-tune properties and are now clinical use. We report synthesis nirmatrelvir derivatives (R)-4,4-dimethyl-4-silaproline (silaproline) group position. Mass spectrometry (MS)-based assays demonstrate silaproline-bearing efficiently inhibit isolated recombinant Mpro, albeit reduced potency compared nirmatrelvir. Investigations SARS-CoV-2 infected VeroE6 cells reveal inhibitors CF3 P4-equivalent position viral progression, implying incorporating silicon atoms into Mpro can yield vivo active appropriate optimization. MS crystallographic studies show nucleophilic site cysteine residue (Cys145) reacts nitrile inhibitors. Substituting electrophilic for non-activated terminal alkyne shifts inhibition mode from reversible covalent irreversible inhibition. One two prochiral silaproline methyl groups occupies space S2 pocket unoccupied Mpro:nirmatrelvir complex structures, highlighting value sila-derivatives structure-activity-relationship (SAR) studies. The combined results highlight potential silicon-containing molecules and, by implication, other enzymes.

Язык: Английский

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Cobalt-Catalyzed Regioselective Intramolecular Hydrosilylation of Olefins to Access Sila-heterocycles

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

An efficient and straightforward cobalt-catalyzed regioselective intramolecular hydrosilylation of olefins has been developed. Regioselectivity is controlled by the choice ligands substrates, which operate through two distinct mechanisms. This method successfully applied to both terminal internal alkenes phenyl alkyl tethers between silane alkene, demonstrating its versatility across a broad range substrates.

Язык: Английский

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Development and characterization of sodium alginate and β-cyclodextrin nanoemulsions encapsulating betel leaf (Piper betle L.) extract for enhanced antimicrobial efficacy against foodborne pathogen

Food Chemistry, Год журнала: 2024, Номер unknown, С. 141227 - 141227

Опубликована: Сен. 1, 2024

Язык: Английский

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Organophotocatalytic Regioselective Silylation/Germylation and Cascade Cyclization of N-Alkenyl α-CF₃ Acrylamides: Access to Densely Functionalized 4-Pyrrolin-2-ones

Organic Letters, Год журнала: 2024, Номер 26(43), С. 9269 - 9275

Опубликована: Окт. 21, 2024

We report an organophotoredox-catalyzed silylation/germylation cascade cyclization of

Язык: Английский

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Carbon-silicon-switch effect in enantioselective construction of silicon-stereogenic center from silacyclohexadienones

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 15, 2024

Carbon-silicon-switch strategy, replacing one specific carbon atom in organic molecules with a silicon, has garnered significant interest for developing new functional molecules. However, the influence of reaction regarding its selectivity and reactivity by carbon-silicon-switch strategy far less been investigated. Here we discover an unusual effect enantioselective construction silicon-stereogenic center. It is found that there change desymmetrization silacyclohexadienones using asymmetric conjugate addition or oxidative Heck aryl/alkyl nucleophiles when compared their analogues cyclohexadienones. Specifically, leads to reversal enantioselectivity arylzinc as nucleophile same chiral catalyst, results totally different arylboronic acid nucleophile. Control experiments density theory (DFT) calculations have shown comes from unique stereoelectronic feature silicon. Silicon incorporated into place under principle that, given they belong periodic group, could be similar. Here, authors perform desymmetrizations on silacyclohexenone analogue, two substrates yielding opposite enantiomers, showing our understanding similarities atoms incomplete.

Язык: Английский

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First Sila-Vitamin D Analogues: Design, Synthesis, Structural Analysis and Biological Activity

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(23), С. 21505 - 21519

Опубликована: Ноя. 29, 2024

The incorporation of silicon bioisosteres into pharmacological structures has been used as a strategy to improve the therapeutic potential drugs. However, no secosteroidal silicon-containing VDR ligands have developed. Here we report design, synthesis, and biological activity six analogues natural hormone 1,25-dihydroxyvitamin D3 (1,25D3), which incorporate atom side chain-C25 isostere. were synthesized by Wittig-Horner approach starting from Inhoffen-Lythgoe diol. crystal complexes formed sila-analogues with ligand binding domain revealed additional interactions sila-containing chains that stabilize active conformation. These show similar transcriptional in comparison 1,25D3, but significantly less hypercalcemic activity. new analogues, when combined chemotherapy, decrease cell proliferation.

Язык: Английский

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