Organic & Biomolecular Chemistry最新文献

SFM4-3, KOD DGLNK, and Therminator polymerase are investigated for their compatibility with SELection with Modified Aptamers (SELMA), an aptamer discovery method that enables incorporation of large nucleobase modifications such as glycans. We demonstrated that with suitable modifications to the primer design and protocol, these enzymes are compatible with SELMA, enabling 2'-fluoro or 2'-methoxy ribose modifications at all positions. In the case of 2'-fluoro modifications, Therminator exhibits cleaner incorporation of an alkyne-modified nucleobase for click chemistry.

3,3'-Bipyrrole units often occur in biologically significant and materials-relevant compounds. However, the current efficient routes to afford these compounds are underdeveloped. Herein, a two-step approach for assembling substituted bipyrroles starting from 1,3-diyne and N-benzyl azomethine ylide has been demonstrated. In the first step, tungsten catalyzed twofold 1,3-dipolar cycloaddition gave rise to tetrahydrobipyrrole products in 42-85% yields. In the second step, a range of tetrahydrobipyrroles smoothly underwent copper-catalyzed dehydrogenative aromatization and provided 3,3'-bipyrroles in 54-80% yields. In addition, synthetic utilization and preliminary mechanistic studies were also performed. These bipyrroles might have potential utility in drug discovery and materials science.

A general approach for the α-C-H alkylation of alcohols has been established, offering access to highly functionalized alcohols via visible light irradiation with TBAP as a co-catalyst. The methodology exhibits excellent functional group tolerance and a wide substrate scope. Its practicality is underscored by successful gram-scale synthesis and a sunlight-driven reaction demonstration.

Imidazole-based chemicals exhibit significant potential in various scientific fields, mainly in the chemical and pharmaceutical sciences. The imidazole ring is a five-membered aromatic heterocycle found in several natural and synthetic substances. Its distinctive structural property, which includes a desirable electron-rich characteristic, allows imidazole derivatives to readily bond with a wide range of anions, cations, and neutral organic molecules. This review aims to assemble the sensing qualities of the most recently reported imidazole derivatives and analyse their potential as sensors. Among all other ions, fluoride sensing is primarily targeted for this context, because fluoride ions have garnered a lot of attention in recent decades due to their distinctive physiochemical properties and essential roles in many biological, chemical, pharmaceutical, and environmental processes. Fluoride ion detection is a broad field, and several fluorescent probes are continuously introduced to bind fluoride ions in aqueous and organic media. A few reviews have been published, emphasizing macrocycle cages, nanomaterial probes, bio-material sensors, and large organic molecule chemosensors for F^- detection. A special review focusing solely on fluoride sensing by the imidazole-based moiety has not yet been addressed. Imidazole compounds have surged in prominence over the last few years, making them particularly desirable for developing efficient, sensitive, and selective fluoride detection methods. The present review concisely represents the contribution of a wide variety of imidazole fluorophores for fluoride ion detection.

A novel catalytic system has been developed, comprising 3,6-dichloro-1,2,4,5-tetrazine as the catalyst, zinc acetate as an additive, dichloromethane as the solvent, and air as the oxidizing agent. Under ambient conditions, this system effectively activates C-S bonds. Specifically, it facilitates the reaction between α-benzylthioglycine ester and electron-rich aromatics, achieving functionalization of the C-S bond. This method exhibits mild reaction conditions, broad substrate compatibility, and yields up to 91%. A plausible free radical mechanism is proposed to explain the observed reactivity.

This study investigates the effects of buffer type, pH, and temperature on the kinetics of strain-promoted alkyne-azide cycloaddition (SPAAC) reactions. Using 3-azido-L-alanine and 1-azido-1-deoxy-β-D-glucopyranoside as model azides and sulfo DBCO-amine as the alkyne, we examined reaction rates in a series of buffers, including PBS, HEPES, MES, borate buffer, and cell culture media (DMEM and RPMI), with pH values ranging from 5 to 10 and temperatures of 25 and 37 °C. Absorbance spectrophotometric data revealed that PBS (pH 7) exhibited among the lowest rate constants (0.32-0.85 M^-1 s^-1), whereas HEPES (pH 7) had the highest (0.55-1.22 M^-1 s^-1). Additionally, reactions in DMEM were faster than in RPMI (0.59-0.97 vs. 0.27-0.77 M^-1 s^-1). We observed that higher pH values generally increased reaction rates, except in HEPES buffer. Notably, 1-azido-1-deoxy-β-D-glucopyranoside reacted faster than 3-azido-L-alanine, highlighting the importance of considering the electron-donating capacity of azides in the optimisation of SPAAC reactions. Additional experiments with DBCO-modified antibodies (DBCO-trastuzumab and DBCO-PEG5-trastuzumab) corroborated the trends related to buffer and azide selection. The presence of a PEG linker notably enhanced reaction rates (0.18-0.37 M^-1 s^-1) by 31 ± 16%. This study offers useful insights into the factors affecting SPAAC kinetics, facilitating the development of optimised bioconjugation strategies.

An efficient NBS-promoted three-component thiocyanatothiolation of alkenes with free thiols and NH₄SCN has been developed. This protocol avoids tedious preactivation of thiols and employs a diverse range of accessible thiols directly as sulfur sources. Moreover, the reaction exhibits regioselectivity and shows high compatibility with styrenes and unactivated alkenes. Preliminary mechanism studies revealed that both a radical pathway and thiol-oxidation-coupling were involved in this protocol.

Driven by our recent medicinal chemistry research, we have investigated the coupling reaction between aliphatic N-hydroxyphthalimide esters and terminal 2-trifluoromethylalkenes. This reaction was driven by the photochemical activity of the electron donor-acceptor (EDA) complex. The reaction's efficiency hinges on the olefin's electronic effect, with electron-withdrawing groups yielding much better results. Furthermore, this reaction is also applicable to trifluoromethyl alkyl alkenes, enabling the synthesis of target products in moderate yields. By employing this method, we successfully synthesized a series of bioactive molecules, among which compounds 3k, 3l and 3m demonstrated robust antitumor activity against both A549 and SK-hep-1 cancer cell lines.

Acetylpyranuloses and β-oxodithioesters, recognized as notable electrophiles and trinucleophiles, are frequently employed in intricate cyclization reactions. Nevertheless, there is a lack of literature documenting the cyclization products derived from these two reagents. This paper unveils a base-mediated sequential Michael addition and S_N2-type cyclization reactions involving acetylpyranuloses and β-oxodithioesters. A total of 23 functionalized bicyclic molecules featuring a thieno[2,3-b] pyran scaffold have been obtained diastereoselectively in moderate to good yields. This novel method could aid in the development of new drugs and enrich the toolbox for synthesizing pharmaceuticals and natural products.

The transesterification of unactivated carboxylic esters with alcohols was achieved in one pot through acid/halide cooperative catalysis. By this strategy, various weakly nucleophilic phenols could react with unactivated methyl esters to produce the corresponding phenolic esters in good to high yields. Aliphatic alcohols could also be used as the nucleophiles and showed higher reactivity. Moreover, high functional group tolerance has been demonstrated. This reaction is also applicable to the late-stage modification of clinical drug derivatives. These results clearly show the potential synthetic value of this new reaction in organic synthesis.