Rodriguez-Garcia David, Uceda Carlos, Barahona Laura, Ruiz-Nuñez Marta, Ballesteros Antonio O, Desmet Tom, Sanz-Aparicio Julia, Fernandez-Lobato Maria, Gonzalez-Alfonso Jose L, Plou Francisco J
Instituto de Catálisis y Petroleoquímica, CSIC, 28049 Madrid, Spain.
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
Org Biomol Chem. 2025 Jan 29;23(5):1136-1145. doi: 10.1039/d4ob01682c.
Although dihydromyricetin exhibits strong potential for pharmaceutical applications, its limited aqueous solubility, permeability and stability restrict its use. In this work, we have synthesized a series of glucosides and acyl-glucosides of dihydromyricetin that could increase the bioavailability of this molecule. First, the R134A variant of sucrose phosphorylase from catalyzed the formation of three monoglucosides, and the major one was identified as dihydromyricetin 4'--α-D-glucopyranoside (>75% conversion yield). The molecular features that define this specificity for the 4'-OH phenolic group were investigated through induced-fit docking analysis of each potential derivative. Furthermore, the acylation of the 4'-monoglucoside with fatty acid vinyl esters (C8, C12, and C16) was performed with high efficiency using the lipase from . Three novel acyl derivatives of dihydromyricetin were characterized. Furthermore, the water solubility and antioxidant activity (ABTS, DPPH) of the synthesized compounds were measured, concluding that the location of the glucosyl moiety may affect their physicochemical properties and, as a result, their bioactivity.
尽管二氢杨梅素在药物应用方面展现出强大潜力，但其有限的水溶性、渗透性和稳定性限制了它的使用。在这项工作中，我们合成了一系列二氢杨梅素的糖苷和酰基糖苷，这些化合物能够提高该分子的生物利用度。首先，来自[具体来源]的蔗糖磷酸化酶的R134A变体催化形成了三种单糖苷，其中主要的一种被鉴定为二氢杨梅素4'-α-D-吡喃葡萄糖苷（转化率>75%）。通过对每种潜在衍生物的诱导契合对接分析，研究了决定对4'-OH酚羟基具有这种特异性的分子特征。此外，使用来自[具体来源]的脂肪酶，高效地将4'-单糖苷与脂肪酸乙烯酯（C8、C12和C16）进行了酰化反应。对三种新型二氢杨梅素酰基衍生物进行了表征。此外，还测定了合成化合物的水溶性和抗氧化活性（ABTS、DPPH），得出结论：葡萄糖基部分的位置可能会影响它们的物理化学性质，进而影响它们的生物活性。
