Daphneodorins A–C, Anti-HIV Gnidimacrin Related Macrocyclic Daphnane Orthoesters from Daphne odora

• Published in: Organic letters Vol. 22; no. 1; pp. 11 - 15
• Main Authors: Otsuki, Kouharu, Li, Wei, Asada, Yoshihisa, Chen, Chin-Ho, Lee, Kuo-Hsiung, Koike, Kazuo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.01.2020; Amer Chemical Soc
• Subjects: Anti-HIV Agents - chemistry; Anti-HIV Agents - isolation & purification; Anti-HIV Agents - pharmacology; antiretroviral agents; chemical reactions; chemical structure; Chemistry; Chemistry, Organic; Daphne - chemistry; Daphne odora; Dose-Response Relationship, Drug; drug development; HIV-1 - drug effects; Human immunodeficiency virus 1; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - isolation & purification; Macrocyclic Compounds - pharmacology; median effective concentration; Microbial Sensitivity Tests; Molecular Conformation; ortho esters; Physical Sciences; Science & Technology; spectral analysis; Structure-Activity Relationship; virus replication; Virus Replication - drug effects; DITERPENOID ESTERS
• ISSN: 1523-7060; 1523-7052; 1523-7052
• DOI: 10.1021/acs.orglett.9b03539

Three novel gnidimacrin related macrocyclic daphnanes (GMDs), daphneodorins A–C (2–4), were isolated from Daphne odora Thunb., together with gnidimacrin (1). Their structures were established by extensive physicochemical and spectroscopic analyses. Compounds 2 and 3 potently inhibited HIV-1 replication at subnanomolar concentrations (EC50 0.16 and 0.25 nM, respectively). Compounds 2–4 represent a novel type of GMDs that are highly oxygenated on the macrocyclic ring, suggesting good potential for anti-HIV drug development by further chemical modification.