Journal article
Design, synthesis and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold
C Zhang, KY Lum, AC Taki, RB Gasser, JJ Byrne, T Wang, MAT Blaskovich, ET Register, LJ Montaner, I Tietjen, RA Davis
Phytochemistry | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2021
Abstract
Chemical studies of the aerial parts of the Australian desert plant Eremophila microtheca afforded the targeted and known diterpenoid scaffolds, 3,7,8-trihydroxyserrulat-14-en-19-oic acid and 3-acetoxy-7,8-dihydroxyserrulat-14-en-19-oic acid. The most abundant serrulatane scaffold was converted to the poly-methyl derivatives, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester and 3,7,8-trimethoxyserrulat-14-en-19-oic acid methyl ester using simple and rapid methylation conditions consisting of DMSO, NaOH and MeI at room temperature. Subsequently a 12-membered amide library was synthesised by reacting the methylated scaffolds with a diverse series of commercial primary amines. The..
View full abstractGrants
Awarded by Wellcome Trust
Funding Acknowledgements
The authors acknowledge the Australian Research Council (ARC) for support towards NMR and MS equipment (grants LE0668477, LE140100119, and LE0237908) . Research at The University of Mel-bourne (Gasser Lab) was supported by ARC and Yourgene Health (Singapore) . The Community for Open Antimicrobial Drug Discovery (CO-ADD) would like to acknowledge funding from the Wellcome Trust (UK) (Strategic Award 104797/Z/14/Z) and The University of Queens-land (Australia) . The HIV screening was supported by the Canadian Institutes for Health Research (CIHR PJT-153057) (I.T.) , the New Frontiers in Research Fund - Explorations (NRFRE-2018-01386) (I.T.) and a Griffith University-Simon Fraser University Collaborative Travel Grant (I.T., R.A.D.) . This work was also supported by the following grants to L.J.M.: Beyond Antiretroviral Treatment (BEAT) -HIV Delaney Collaboratory Grant UM1AI126620. It was also supported by the Robert I. Jacobs Fund of The Philadelphia Foundation; Penn Center for AIDS Research Grant P30 AI 045008; and the Herbert Kean, M.D., Family Professorship.