Determining the absolute configuration of vanitaracin A, an anti-hepatitis B virus agent

• Published in: Journal of antibiotics Vol. 75; no. 2; pp. 92 - 97
• Main Authors: Kamisuki, Shinji, Shibasaki, Hisanobu, Ashikawa, Koudai, Kanno, Kazuki, Watashi, Koichi, Sugawara, Fumio, Kuramochi, Kouji
• Format: Journal Article
• Language: English
• Published: LONDON Springer Nature 01.02.2022; Nature Publishing Group
• Subjects: Absolute configuration; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biotechnology & Applied Microbiology; Carboxylic acids; Cell culture; Configurations; Hepatitis; Hepatitis B; Hepatitis B virus - drug effects; Hydrolysis; Immunology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Microbiology; Molecular Conformation; Molecular Structure; NMR; Nuclear magnetic resonance; Pharmacology & Pharmacy; Polyketides - chemistry; Polyketides - pharmacology; Science & Technology; Structure-Activity Relationship; Talaromyces - chemistry; Viruses; FUNGUS; ENTRY
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-021-00496-1

Vanitaracin A is an anti-hepatitis B virus (anti-HBV) compound isolated from the culture broth of the fungus Talaromyces sp. Vanitaracin A inhibits the entry of HBV into target cells with sub-micromolar IC50 values. While a structure-activity relationship study is highly desirable, a synthetic approach still needs to be developed, which is difficult because the absolute configurations of the six stereogenic centers in the structure of vanitaracin A have not yet been determined. In the present study, we used the crystalline sponge method to clarify the configuration of the compound after determining the absolute configuration of the secondary alcohol using a modified Mosher ester method. Combining these analyses with the NOESY spectrum of vanitaracin A and NMR analyses of the crude side-chain carboxylic acid obtained by the alkaline hydrolysis of vanitaracin A revealed the absolute configurations of all stereogenic centers in this important compound.