Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants.

ABSTRACT: The present work aimed at the valorization of biomass derived compounds by their transformation into new added-value compounds with enhanced antioxidant properties. In this context, betulinic acid (BA) was decorated with polyphenolic fragments, and polyhydroxylated (E)-2-benzylidene-19,28-epoxyoleanane-3,28-diones 4a-d were obtained. For that, the synthetic strategy relied on base-promoted aldol condensation reactions of methyl betulonate, which was previously prepared from natural BA, with appropriate benzaldehydes, followed by cleavage of the methyl protecting groups with BBr₃. It is noteworthy that the HBr release during the work-up of the cleavage reactions led to the rearrangement of the lupane-type skeleton of the expected betulonic acid derivatives into oleanane-type compounds 4a-d. The synthesized compounds 4a-d were designed to have specific substitution patterns at C-2 of the triterpene scaffold, allowing the establishment of a structure-activity relationship. The radical scavenging ability of 4a-d was evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH^•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS^•+) scavenging assays. In particular, derivative 4c, bearing a catechol unit, revealed to be the most efficient scavenger against both free radicals DPPH^• and ABTS^•+. Subsequently, we designed two analogues of the hit derivative 4c in order to achieve more potent antioxidant agents: (i) the first analogue carries an additional unsaturation in its lateral chain at C-2 (analogue 5) and (ii) in the second analogue, E-ring was kept in its open form (analogue 6). It was observed that the presence of an extended ?-conjugated system at C-2 contributed to an increased scavenging effect, since analogue 5 was more active than 6, ?-tocopherol, and 4c in the ABTS^•+ assay.

SUBMITTER: Sousa JLC 

PROVIDER: S-EPMC7909560 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature