Facile Access to Tricyclic Molecular Architectures through Photo-Reversible Dearomative 6π-Desymmetrizations: Scope, Applications, Bioactivity Study, and Mechanistic Nuances.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Facile Access to Tricyclic Molecular Architectures through Photo-Reversible Dearomative 6π-Desymmetrizations: Scope, Applications, Bioactivity Study, and Mechanistic Nuances.
Συγγραφείς:	Zhang X; School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China., Sun Y; School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China., Wu W; School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China., Zhang M; School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China., Lin HW; Department of Pharmacy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Xu J; Department of Pharmacy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Zhou Q; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States., Houk KN; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States., Zou Y; School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China., Yang F; Department of Pharmacy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Sun Y; School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China.
Πηγή:	Journal of the American Chemical Society [J Am Chem Soc] 2025 Dec 10; Vol. 147 (49), pp. 45691-45700. Date of Electronic Publication: 2025 Nov 28.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE
Imprint Name(s):	Publication: Washington, DC : American Chemical Society Original Publication: Easton, Pa. [etc.]
Ιατρικοί όροι (MeSH):	Molecular Structure* , Photochemical Processes*, Stereoisomerism ; Ultraviolet Rays
Περίληψη:	The synthesis of complex natural products bearing fused polycyclic architectures presents formidable synthetic challenges, yet offers significant opportunities for drug discovery. Herein, we report a photoreversible dearomative desymmetrization strategy that enables efficient access to structurally diverse tricyclic frameworks. Employing alkenyl phenol precursors, UV (ultraviolet) light (λ = 310 nm) triggers a stereoselective 6π-desymmetrization, affording four types of skeletons─including scaffolds with vicinal quaternary stereocenters. Additionally, visible light (λ = 450 nm) reverses this process, selectively deconstructing the tricyclic systems back to alkenyl phenol precursors. This methodology's utility is demonstrated through the scalable synthesis of the norzoanthamine alkaloid core, enabling the first total syntheses of 15-hydroxynorzoanthamine, norzoanthamide B, and norzoanthaminone. Subsequent anti-inflammatory profiling of these compounds revealed key structure-activity relationships (SAR) for IL-6 inhibition. Further, 6π-product 2r emerged as a potent TNF-α inhibitor in lipopolysaccharide (LPS)-stimulated THP-1 cells, and norzoanthamine derivative 9 exhibited an antipulmonary fibrosis effect. Mechanistic studies via density functional theory (DFT) calculations elucidated the wavelength-dependent reversibility, correlating excited-state pathways with experimental photochemical control.
Entry Date(s):	Date Created: 20251128 Date Completed: 20251211 Latest Revision: 20251211
Update Code:	20260130
DOI:	10.1021/jacs.5c17371
PMID:	41312684
Βάση Δεδομένων:	MEDLINE

Περιγραφή
ISSN:	1520-5126
DOI:	10.1021/jacs.5c17371