Chemistry-Switzerland最新文献

Thiochromen-4-ones are known to possess useful optical properties and rich bioactivities, including antioxidant, antimicrobial, and anticancer properties. They are known to inhibit tumor cell growth, induce apoptosis, and have antiplatelet aggregation effects. Thiochromen-4-ones are also used as synthons and precursors in organic synthesis for bioactive agents. Although many synthetic approaches to oxygen-containing counterparts, chromones, have been reported, research on the synthesis of thiochromen-4-ones is scarce. The synthesis of thiochromen-4-ones can be challenging due to the inherent nature of sulfur, including its multiple oxidation states and tendency to form diverse bonding patterns. Here, we report the one-pot synthesis of thiochromen-4-ones, where two transformations of the starting material, 3-(arylthio)propanoic acid, are performed within a single reaction vessel, eliminating the need for an intermediate purification step. This one-pot reaction worked well with a variety of substrates with both electron-withdrawing and donating groups on the aromatic ring of 3-(arylthio)propanoic acids to give thiochromen-4-ones with good yields (up to 81%). This approach offers advantages like time and cost savings, increased efficiency, and reduced waste. This synthetic approach will allow access to a broader scope of thiochromen-4-ones due to the readily available thiophenols.

This review focuses on photocyclization reactions involving alkenes and arenes. Photochemistry opens up synthetic opportunities difficult for thermal methods, using light as a versatile tool to convert stable ground-state molecules into their reactive excited counterparts. This difference can be particularly striking for aromatic molecules, which, according to Baird's rule, transform from highly stable entities into their antiaromatic "evil twins". We highlight classical reactions, such as the photocyclization of stilbenes, to show how alkenes and aromatic rings can undergo intramolecular cyclizations to form complex structures. When possible, we explain how antiaromaticity develops in excited states and how this can expand synthetic possibilities. The review also examines how factors such as oxidants, substituents, and reaction conditions influence product selectivity, providing useful insights for improving reaction outcomes and demonstrating how photochemical methods can drive the development of new synthetic strategies.

We present a protocol for the facile conversion of linear alkenyl N-alkoxy carbamates into cyclic bromo carbonates. The reaction is operationally simple, uses widely available, inexpensive reagents, and requires no rigorous exclusion of air or moisture. A broad range of functional groups is compatible, and the reaction diastereoselectivities range from good to excellent. The reactions are scalable, and the product carbonates can be further transformed.

Influenza has been a global health concern for the past century. Current seasonal influenza vaccines primarily elicit an antibody response that targets the immunodominant head domain of the viral glycoprotein hemagglutinin (HA), which consistently mutates due to selective pressure. To circumvent this problem, we introduce a "tethered antigenic suppression" strategy to shield the HA head domain and refocus the immune response towards the conserved but immunosubdominant stalk domain of HA. Specifically, we tethered an antibody fragment (Fab) that recognizes the Sb antigenic site in the HA head domain to the HA protein with a linker. We immunized separate groups of female mice with the Fab-tethered HA or regular HA and characterized the elicited antibody response. We demonstrate that shielding the HA head domain with a tethered Fab suppresses the antibody titers towards all five key antigenic sites in the HA head domain while eliciting a robust anti-stalk antibody response. Our work highlights the potential of tethered antigenic suppression as a strategy to refocus the antibody response towards conserved epitopes on protein antigens.

The dopamine D₂ agonist MCL-524 is selective for the D₂ receptor in the high-affinity state (D₂^high), and, therefore, the PET analogue, [¹⁸F]MCL-524, may facilitate the elucidation of the role of D₂^high in disorders such as schizophrenia. However, the previously reported synthesis of [¹⁸F]MCL-524 proved difficult to replicate and was lacking experimental details. We therefore developed a new synthesis of [¹⁸F]MCL-524 using a "non-anhydrous, minimally basic" (NAMB) approach. In this method, [¹⁸F]F^- is eluted from a small (10-12 mg) trap-and-release column with tetraethylammonium tosylate (2.37 mg) in 7:3 MeCN:H₂O (0.1 mL), rather than the basic carbonate or bicarbonate solution that is most often used for [¹⁸F]F^- recovery. The tosylated precursor (1 mg) in 0.9 mL anhydrous acetonitrile was added directly to the eluate, without azeotropic drying, and the solution was heated (150 °C/15 min). The catechol was then deprotected with the Lewis acid In(OTf)₃ (10 equiv.; 150 °C/20 min). In contrast to deprotection with protic acids, Lewis-acid-based deprotection facilitated the efficient removal of byproducts by HPLC and eliminated the need for SPE extraction prior to HPLC purification. Using the NAMB approach, [¹⁸F]MCL-524 was obtained in 5-9% RCY (decay-corrected, n = 3), confirming the utility of this improved method for the multistep synthesis of [¹⁸F]MCL-524 and suggesting that it may applicable to the synthesis of other ¹⁸F-labeled radiotracers.