Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells
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 extens...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/9/2215 |
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| author | Hyun Su Kim Sungkyun Chung Moon-Young Song Changjin Lim Hyeyoung Shin Joonseong Hur Hyuk Kwon Young-Ger Suh Eun-Hee Kim Dongyun Shin Seok-Ho Kim |
| author_facet | Hyun Su Kim Sungkyun Chung Moon-Young Song Changjin Lim Hyeyoung Shin Joonseong Hur Hyuk Kwon Young-Ger Suh Eun-Hee Kim Dongyun Shin Seok-Ho Kim |
| author_sort | Hyun Su Kim |
| collection | DOAJ |
| description | 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 (<i>S</i>)- and (<i>R</i>)-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 (<i>S</i>)-DHPV was more active than (<i>R</i>)-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. |
| first_indexed | 2024-03-10T19:57:25Z |
| format | Article |
| id | doaj.art-5f662863935849c3bbb064d3f07d54a4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:57:25Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5f662863935849c3bbb064d3f07d54a42023-11-19T23:51:38ZengMDPI AGMolecules1420-30492020-05-01259221510.3390/molecules25092215Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 CellsHyun Su Kim0Sungkyun Chung1Moon-Young Song2Changjin Lim3Hyeyoung Shin4Joonseong Hur5Hyuk Kwon6Young-Ger Suh7Eun-Hee Kim8Dongyun Shin9Seok-Ho Kim10Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaSchool of Pharmacy, Jeonbuk National University, Jeonju 54896, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaNatural Products Research Institute, Korea Institute of Science and Technology (KIST), 679 Saimdang-ro, Gangneung 25451, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaCollege of Pharmacy, Gachon University, 191 Hambangmoe-ro, Yeonsu-gu, Incheon 21936, KoreaDepartment of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, KoreaDespite 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 (<i>S</i>)- and (<i>R</i>)-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 (<i>S</i>)-DHPV was more active than (<i>R</i>)-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.https://www.mdpi.com/1420-3049/25/9/2215divergent synthesisasymmetric dihydroxylationDHPVanti-inflammatory effectNF-κBIκBα |
| spellingShingle | Hyun Su Kim Sungkyun Chung Moon-Young Song Changjin Lim Hyeyoung Shin Joonseong Hur Hyuk Kwon Young-Ger Suh Eun-Hee Kim Dongyun Shin Seok-Ho Kim Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells Molecules divergent synthesis asymmetric dihydroxylation DHPV anti-inflammatory effect NF-κB IκBα |
| title | Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells |
| title_full | Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells |
| title_fullStr | Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells |
| title_full_unstemmed | Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells |
| title_short | Efficient and Divergent Enantioselective Syntheses of DHPVs and Anti-Inflammatory Effect on IEC-6 Cells |
| title_sort | efficient and divergent enantioselective syntheses of dhpvs and anti inflammatory effect on iec 6 cells |
| topic | divergent synthesis asymmetric dihydroxylation DHPV anti-inflammatory effect NF-κB IκBα |
| url | https://www.mdpi.com/1420-3049/25/9/2215 |
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