Journal article
Using a Bioactive Eremophila-Derived Serrulatane Scaffold to Generate a Unique Carbamate Library for Anti-infective Evaluations
C Zhang, KY Lum, AC Taki, RB Gasser, JJ Byrne, LJ Montaner, I Tietjen, VM Avery, RA Davis
Journal of Natural Products | AMER CHEMICAL SOC | Published : 2023
Open access
Abstract
The known Eremophila microtheca-derived diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was targeted for large-scale purification, as this bioactive plant compound has proven to be an attractive scaffold for semisynthetic studies and subsequent library generation. Compound 1 was converted to a selectively protected trimethyl derivative, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester (2), using simple and rapid methylation conditions. The resulting scaffold 2 was reacted with a diverse series of commercially available isocyanates to generate an 11-membered carbamate-based library. The chemical structures of the 11 new semisynthetic analogues were fully characterized..
View full abstractGrants
Awarded by National Institute on Drug Abuse
Funding Acknowledgements
The authors acknowledge the Australian Research Council (ARC) for support toward NMR and MS equipment (grants LE0668477, LE140100119, and LE0237908) . We gratefully acknowledge Nature Bank for supply of the plant sample investigated during these studies. C.Z. would like to thank Griffith University for Ph.D. scholarships (GUPRS and GUIPRS) . The authors thank Dr. Sandra Duffy , Discovery Biology, for technical assistance. The authors also thank and acknowledge the Australian Red Cross Blood Bank for the provision of fresh red blood cells, critical for antiplasmodial research. Research at the University of Melbourne (Gasser Lab) was supported by the ARC , Yourgene Health and Melbourne Water Corporation. The HIV screening was supported by the Canadian Institutes for Health Research (CIHR PJT-153057) (I.T.) . This work was also supported by the following grants to L.J.M.: The BEAT-HIV Delaney Collaboratory cofunded by NHLBI, NINDS, NIDDK, NIDA, and the National Institute of Allergy and Infectious Diseases (UM1 AI164570) . It was also supported by the Robert I . Jacobs Fund of The Philadelphia Foundation and the Herbert Kean, M.D., Family Professorship.