Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea.
School of Pharmacy, Jeonbuk National University, Jeonju 54896, Korea.
Molecules. 2020 May 8;25(9):2215. doi: 10.3390/molecules25092215.
Despite numerous reports on the beneficial effects of catechin or epicatechin contained in tea and cacao extract on human health, a conclusive and precise molecular mechanism has not been elucidated. Metabolism of chemical compounds in gut microbiota recently gained significant attention, and extensive studies have been devoted in this field. In conjunction with these results, our group focused on the anti-inflammatory effects of both enantiomers of DHPV (5-(3',4'-dihydroxyphenyl)-γ-valerolactone), produced in the intestine by microbiota metabolism, on IEC-6 cells. Divergent and efficient enantioselective synthesis of ()- and ()-DHPV was efficiently achieved by cross-metathesis and Sharpless asymmetric dihydroxylation as a key reaction for four steps in 16% and 14% overall yields, respectively. The anti-inflammatory effects of two enantiomers were tested on IEC-6 cells, and we found that ()-DHPV was more active than ()-DHPV. This result implicates that the metabolite produced in the gut has beneficial effects on IEC-6 cells of rat intestines, and the chirality of the metabolite is important for its anti-inflammatory activity. This also provided information for the future discovery of novel small molecular therapeutics for the treatment of inflammatory bowel disease.
尽管有大量关于茶和可可提取物中儿茶素或表儿茶素对人体健康有益影响的报道，但尚未阐明明确而精确的分子机制。肠道微生物群中化合物的代谢最近受到了广泛关注，并且在该领域进行了广泛的研究。结合这些结果，我们的小组专注于由微生物群代谢在肠道中产生的 DHPV（5-(3'，4'-二羟基苯基）-γ-缬草酸内酯）的两种对映异构体（）-和（）-DHPV 的抗炎作用对 IEC-6 细胞。通过交叉复分解和 Sharpless 不对称双羟化反应作为关键反应，以 16%和 14%的总收率分别高效地实现了（）-和（）-DHPV 的高效对映选择性合成。我们在 IEC-6 细胞上测试了两种对映异构体的抗炎作用，发现（）-DHPV 比（）-DHPV 更有效。这一结果表明，肠道中产生的代谢物对大鼠肠道的 IEC-6 细胞具有有益的影响，并且代谢物的手性对其抗炎活性很重要。这也为未来发现治疗炎症性肠病的新型小分子治疗药物提供了信息。
