Positron emission tomography (PET) has become an essential tool in nuclear medicine, driving the continuous development of new radiotracers. Owing to the short half-life of fluorine-18 (110 min), radiotracer production requires fast, robust, and fully automated synthetic protocols. Reactive functional groups present on precursor molecules must be protected to prevent competition during radiofluorination, with deprotection typically achieved under harsh chemical conditions that may compromise automation and lead to partial molecular degradation. Herein, we report a general biocatalytic deprotection strategy based on porcine liver esterase (PLE) as a mild and efficient alternative to conventional chemical methods. Three protecting groups (valerate, pivaloyloxymethyl and pivaloyl ethylidene carbamate) were selected to enable the PLE-deprotection of a broad range of functional groups found in radiotracers and drugs (alcohols, phenols, carboxylic acids, amines, anilines, sulfonamides). The PivEC protective group of amines, anilines and sulfonamides was specifically developed for allowing an esterase deprotection. This approach was validated across a broad substrate scope and was successfully automated on ORA-Neptis modules for clinically relevant PET tracers, including [18F]FMISO, [18F]CABS13, and [18F]Nifene. This work establishes enzymatic deprotection as a versatile and practical strategy for PET scan application.

Reported in this paper is an I2/Cu-mediated method for the synthesis of 3-difluoroacetate-functionalized chromones via cascade reactions between o-hydroxyaryl enaminones and alkyl difluoroacetates. The product construction involves a key in situ iodination generating 3-iodochromones, which enables the subsequent Cu(0)-mediated reductive coupling to provide the titled products under relatively mild conditions with a short reaction time without using any noble metal reagent.

Acid-catalyzed condensation of N-alkyltripyrranes with a cyclopentadiene trialdehyde, followed by oxidation with aqueous ferric chloride solutions, gave unusual tripyrrolic byproducts in addition to previously reported carbaporphyrins and oxycarbaporphyrins. These stable nonaromatic structures incorporate aldehyde substituents, macrocyclic ketones, two conjugated pyrrole units, and a pyrrolo[1,2-a]pyrrole moiety. The NMR and UV-vis data were consistent with a nonaromatic system, and single-crystal X-ray diffraction confirmed that these structures are highly distorted. Structural characterization of a related aromatic carbaporphyrin triketone was also accomplished.

The first successful example of the stereoselective conjugate addition of azlactones to ynones is reported. Diaminomethylenemalononitrile organocatalysts efficiently promoted the asymmetric conjugate addition of azlactones to ynones, affording the corresponding α-vinyl quaternary α-amino acid derivatives in high yields with good to high enantioselectivities (up to 91% ee).

The synthesis of methylene-bridged cyclic compounds, including 3-arylalkyl chromones and methylene-bridged bis-chromones, and methylene-bridged bis-cyclic compounds such as indole, coumarin, and pyranone has been realized with rongalite under catalyst-free or simple iodine-mediated conditions. The simple method provides facile accesses to new methylene-bridged scaffolds and discloses expanded application of rongalite in the synthesis of methylene-bridged organic molecules.

A novel ruthenium-catalyzed C-H activation/cyclization reaction of benzoic acid with trifluoromethyl-imidoyl sulfoxonium ylides has been developed for the first time, enabling the rapid synthesis of various trifluoromethyl-functionalized 3,3-disubstituted isocoumarin derivatives in ten minutes with moderate to good yields. This practical methodology with mild reaction conditions exhibits broad scope of substrates, good regioselectivity and high efficiency.

C-heteroatom bonds represent core structural motifs within the scaffolds of pharmaceuticals, agrochemicals, and functional materials. Consequently, developing mild and efficient methodologies for their construction is of paramount importance in modern organic synthesis. Herein, we present a visible-light-driven metallaphotoredox platform that leverages either nickel or copper co-catalysis for the efficient cross-coupling of ArTT salts with diverse heteroatom nucleophiles. This synergistic strategy facilitates the rapid construction of C-S, C-N, and C-O bonds under exceptionally mild conditions. The protocol exhibits a remarkably broad substrate scope and excellent functional group tolerance, proving to be highly compatible with a wide array of thiol and amine nucleophiles. Furthermore, for phenolic substrates exhibiting poor reactivity under our nickel-catalyzed system, the desired C-O bond formation was successfully achieved by pivoting to a photoredox/copper dual-catalytic regime. Furthermore, this method is readily amenable to continuous-flow scale-up without compromising catalytic efficiency, thereby underscoring its robust practical utility.

A Pd/Tl bimetallic catalytic method for the regioselective C8-H alkenylation of dimethoxycoumarin scaffolds was developed. The synergistic effects of Tl(OCOCF3)3 and a Pd-thioether ligand catalytic system enabled electrophilic C-H bond activation, followed by Heck-type alkenylation at the C8 position of the coumarin ring, affording a series of C8-alkenylated dimethoxycoumarin derivatives in yields of up to 90%. Notably, the bimetallic catalytic system promoted electrophilic C-H activation of electron-rich coumarin scaffolds using only a catalytic amount of Tl(OCOCF3)3, enabling efficient C-H functionalization of the benzene moiety with excellent regioselectivity. This method provides a versatile and step-economical approach to highly functionalized coumarins and serves as a complementary strategy for the late-stage functionalization of coumarin-based natural products and fluorescent compounds.

A versatile synthetic strategy has been developed for the construction of a series of peripherally BN‑embedded fluoranthenes. The key step involves a tandem deprotonation/cyclization sequence from readily accessible imine precursors, affording the desired BN‑fluoranthene cores in good yields. Site‑selective bromination at the C‑5 position, which is remote from the BN‑embedded ring, was achieved and exploited for subsequent Suzuki and Sonogashira cross‑coupling reactions to install various aryl and alkynyl substituents. Structural analyses, including X‑ray crystallography and theoretical calculations, confirm a highly planar architecture with delocalized frontier molecular orbitals and show that replacing a C═C unit with a B-N bond markedly alters the local aromaticity of the five‑membered ring. When examined for their optical behavior, most of the synthesized derivatives exhibited intense fluorescence in dichloromethane, with quantum yields as high as 84%. Notably, while alkyl and aryl substituents caused little change in the spectral profiles, the incorporation of conjugated alkynyl groups led to consistent bathochromic shifts in both absorption and emission.

3-Hydroxy-2,4-diaminobutanoic acid (HODab) is a nonproteinogenic amino acid found in several cyclic peptide antibiotics. An efficient synthesis of the threo-HODab isomer suitably protected for Fmoc solid-phase peptide synthesis (SPPS) has never been developed. Here, we report an efficient synthesis of protected (2R,3S)-3-hydroxy-2,4-diaminobutanoic acid (Fmoc-D-threo-HODab(TBS,Boc)-OH) that employs a diastereoselective Henry reaction between the Fmoc-protected Garner's aldehyde and nitromethane as the key step.

A practical photoredox-driven protocol is described for the multicomponent synthesis of sulfonylated indole-fused medium-sized N-heterocycles using readily accessible, modular thianthrenium salts together with N-indolyl phenylacrylamides and DABCO·(SO2)2. Thianthrenium salts serve as general precursors of alkyl and aryl radicals, enabling the efficient and diverse generation of alkyl or aryl sulfonyl radicals via in situ capture of sulfur dioxide while avoiding the use of highly toxic sulfonyl chlorides or sulfonyl hydrazines as sulfonyl sources. Meanwhile, a gram-scale experiment afforded the sulfonylated indole-fused 1,4-diazepinone in good yield and recovered thianthrene in high yield, demonstrating high atom and step economy via the formation of multiple C-S and C-C bonds in a single orchestrated operation.

A site-selective reaction for the aminomethylation of imidazoheterocycles is developed using photoredox catalysis under mild conditions. A complementary metal free HFIP promoted reaction is also developed which gives corresponding anilines in good yields. Metal free conditions, scalability, less use of triazinanes, use of recyclable solvents, and ease of operation are the advantages of the developed protocol. Mechanistic studies were conducted to elucidate the mechanism underlying the alkylation reactions. Moreover, solvent recycling experiment has also been carried out to highlight the sustainability of the developed protocol.

Herein, we report a visible-light-mediated photoredox reaction for the synthesis of sulfonyl 4-(thio)chromones and 4-quinolone derivatives. This transformation employs easily accessible 2-alkynyl benzaldehydes and sodium sulfinates as starting materials, enabling a one-pot cascade process involving radical sulfonylation, cyclization, and isomerization under mild conditions. Notably, this strategy allows the straightforward assembly of protecting-group-free sulfonyl 4-quinolones. Benefiting from its operational simplicity, broad substrate scope, and excellent functional group compatibility, this protocol provides a practical approach for the construction of valuable 4-(thio)chromones and 4-quinolone derivatives with potential biological and synthetic applications.

Sulfur-functionalized isocoumarins have been successfully converted into 1,2,3,4-tetrasubstituted naphthalenes through the addition of ketene silyl acetals and the subsequent skeletal rearrangement triggered by fluoride. The densely and consecutively substituted structures of the resulting naphthalene products have enabled further ring closure between adjacent substituents on the aromatic scaffolds to give several π-extended dibenzothiophenes.

The divergent total synthesis of nocarterphenyls A-B and 2-dehydroxymethylnocarterphenyl A, as well as the formal synthesis of nocarterphenyl D, have been accomplished in five to six steps. The convergent route featured a novel one-step C-H functionalization of aniline to form the benzothiazole ring, a double Suzuki-Miyaura coupling to construct the thiazole-fused p-terphenyl core, and late-stage dehydrogenative couplings to afford nocarterphenyls divergently. Biological evaluation indicated that these natural products and their derivatives represent a new class of potent α-glucosidase inhibitors. Among all tested compounds, nocarterphenyl derivative 5 exhibited the strongest inhibitory effect, with an IC50 value of 9.82 ± 0.31 μM, which was markedly greater than that of the positive control acarbose (570 ± 4.40 μM). Enzyme kinetic assays demonstrated compound 5 to be a reversible, mixed-type α-glucosidase inhibitor. Circular dichroism (CD) spectroscopy further revealed that the binding of compound 5 induced pronounced conformational alterations and obvious changes in the microenvironment surrounding the secondary structure of α-glucosidase.