UV-activated alkyne-alkene [2 + 2] cycloaddition has served as an important tool to access cyclobutenes. Although broadly adopted, the limitations with UV light as an energy source prompted us to explore an alternative method. Here we report alkyne-alkene [2 + 2] cycloaddition based on visible light photocatalysis allowing the synthesis of diverse cyclobutenes and 1,3-dienes via inter-and intramolecular reactions. Extensive mechanistic studies suggest that the localized spin densities at sp 2 carbons of alkenes account for the productive sensitization of alkenes despite their similar triplet levels of alkenes and alkynes. Moreover, the efficient formation of 1,3-dienes via tandem triplet activation of the resulting cyclobutenes is observed when intramolecular enyne cycloaddition is performed, which may serve as a complementary means to the Ru(II)-catalyzed enyne metathesis. In addition, the utility of the [2 + 2] cycloaddition has been demonstrated by several synthetic transformations including synthesis of various extended π-systems.

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD.

Oxidative [3+3] cycloadditions offer an efficient route for six-membered-ring formation. This approach has been realized based on an electrochemical oxidative coupling of indoles/enamines with active methylene compounds followed by tandem 6p-electrocyclization leading to the synthesis of dihydropyrano[4,3-b]indoles and 2,3-dihydrofurans. The radical-radical cross-coupling of the radical species generated by anodic oxidation combined with the cathodic generation of the base from O 2 allows for mild reaction conditions for the synthesis of structurally complex heterocycles.

Site-selective modification of oligonucleotides serves as an indispensable tool in many fields of research including research of fundamental biological processes, biotechnology, and nanotechnology. Here we report chemo- and regioselective modification of oligonucleotides based on rhodium(I)-carbene catalysis in a programmable fashion. Extensive screening identifies a rhodium(I)-catalyst that displays robust chemoselectivity toward base-unpaired guanosines in single and double-strand oligonucleotides with structurally complex secondary structures. Moreover, high regioselectivity among multiple guanosines in a substrate is achieved by introducing guanosine-bulge loops in a duplex. This approach allows the introduction of multiple unique functional handles in an iterative fashion, the utility of which is exemplified in DNA-protein cross-linking in cell lysates.

Synthesis of heterocycles from 1,2‐diarylalkene derivatives through electrosynthesis under metal‐ and oxidant‐free conditions has been discovered. Cathodic reduction of 2‐alkenylbenzoic acid or anodic oxidation of 2‐alkenylbenzamide, 2‐alkenylphenol and 2‐alkenylaniline leads to the formation of reactive radical intermediates which afford corresponding phthalide, isochroman‐1‐one, isoindolin‐1‐one, benzofuran, and indole in satisfying yields with good functional group tolerance. Interestingly, different chemoselectivities were found in different reaction solvents. Several mechanistic investigations including cyclic voltammetry studies and control experiments were carried out to elucidate the reaction mechanisms.