Synthesis of methyl dihydrooleanolate and study of its pharmacokinetics and bioavailability
LI Wei
LI Shu-min
LI Yong
DU Ke-si
FAN Ju-di
ZHANG Ji-quan
TANG Lei
Abstract：Objective:To synthesize methyl dihydrooleanolate and evaluate its pharmacokinetic profiles and absolute bioavailability in rats.Methods:The target compound was synthesized through esterification,acetylation,oxidation,Huang-Minlon reduction,and final esterification.The concentration of target compound in rats plasma was determined by using UPLC-QTOF mass spectrometer.Results:Methyl dihydrooleanolate (1) obtained via 5 steps reaction with an overall yield of 36.6％,which was verified by 1H-NMR,13C-NMR and ESI-MS.The drug concentration-time curve of 1 from pharmacokinetic experiment indicated that it fitted a two-compartment model with first order absorption of 1 in rats.The absolute bioavailability of 1 was 40.96％ from intragastric administration and intravenous injection.Conclusion:Compound 1,which was prepared via double bond reduction and carboxyl esterification of oleanlic acid (OA),showed about 58-fold higher than that of OA (0.7％).Meanwhile,an LC/MS/MS analytic method was also established for the detection of biological samples,which may provide a reference for the in vivo analysis of OA and its derivatives.
Keywords：methy dihydrooleanolatesynthesispharmacokineticsbioavalability
Publication Date：2018-02-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：5( 351-355 )