The aminophosphinoylation of alcohols with amines and H-phosphine oxides provides an efficient and mild approach to access various α-aminoalkylphosphine oxides in good yields with good tolerance of functional groups using H₂O as a clean solvent.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is pivotal in the immune defense against infections and cancer. However, aberrant activation of this pathway can trigger autoimmune and inflammatory diseases by inducing excessive production of type I interferon (IFN) and pro-inflammatory cytokines. Inhibition of the aberrant activation of the cGAS-STING signaling pathway by targeting STING represents a novel therapeutic strategy for these autoimmune and inflammatory disorders. In this study, we discovered three novel STING antagonists based on surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and ISRE (interferon stimulated response element)-luciferase assays. The efficacy and pharmacological mechanisms of the three STING antagonists for treating imiquimod (IMQ)-induced psoriasis-like dermatitis by western blotting (WB), flow fluorescence, and immunostaining. The three STING antagonists exhibited pan-inhibitory activities on the activation of both the human and mouse cGAS-STING signaling pathway. Intravenous and topical administration of the three antagonists alleviated the inflammation and skin lesions associated with IMQ-induced psoriasis-like dermatitis via suppression of the inflammatory cascade mediated by the IMQ-TLR-7-NF-κB/cGAS-STING-NF-κB/IL-1β-IL-1R-NF-κB/TNFα-TNF-R-NF-κB signaling axis. In conclusion, we identified three novel STING antagonists with pan-inhibitory activities against human and mouse STING, providing lead compounds for the future development of both STING antagonists and immune agents for therapeutically manipulating STING-driven diseases, such as psoriasis. Our findings offer another new therapeutic strategy for managing STING-driven autoimmune and inflammatory diseases, while also reemphasizing the critical role of the cGAS-STING signaling pathway in such conditions.

A variety of phosphoryl compounds were smoothly constructed up to 89% yield via NaIO ₄ /air-initiated phosphorylation of alcohols with H-phosphine oxides in water, providing an alternative method for constructing P(O)–O bonds.