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 π-conjugated system at C-2 contributed to an increased scavenging effect, since analogue 5 was more active than 6, α-tocopherol, and 4c in the ABTS^•+ assay.

中文翻译：

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含多酚片段的桦木酸的功能化，以开发新型两亲性抗氧化剂

目前的工作旨在通过将生物质衍生的化合物转化为具有增强的抗氧化性能的新的增值化合物来实现其价值。在这种情况下，用多酚片段修饰了桦木酸（BA），并获得了多羟基化的（E）-2-亚苄基-19,28-环氧-环氧乙烷-3,28-二酮4a - d。为此，合成策略依赖于苯丙酮酸甲酯的碱促进的羟醛缩合反应，该反应以前是由天然BA与适当的苯甲醛制备的，然后用BBr ₃裂解甲基保护基。。值得注意的是，在裂解反应的过程中，HBr的释放导致预期的牛磺酸的衍生物的卢潘型骨架重新排列为齐墩果型化合物4a – d。合成的化合物4a – d被设计为在三萜骨架的C-2处具有特定的取代模式，从而建立了结构-活性关系。使用2,2-二苯基-1-吡啶并肼基（DPPH ^•）和2,2'-叠氮基双（3-乙基苯并噻唑啉-6-磺酸基）阳离子（ABTS ^•+）评价4a - d的自由基清除能力。）清除分析，尤其是衍生工具带有邻苯二酚单元的4c被证明是对自由基DPPH ^•和ABTS ^•+的最有效清除剂。随后，我们设计了命中衍生物4c的两个类似物，以获得更有效的抗氧化剂：（i）第一个类似物在C-2的侧链上带有一个额外的不饱和键（类似物5），以及（ii）第二个类似物，E形环保持开放状态（类似物6）。观察到在C-2处存在扩展的π共轭体系有助于提高清除效果，因为在ABTS ^•+中，类似物5的活性高于6，α-生育酚和4c。 分析。