New 30-norlupane derivatives through chemical-microbial semi-synthesis of betulinic acid and their neuroprotective effect
- Bioorg Med Chem Lett. 2020 Sep 1;30(17):127407. doi: 10.1016/j.bmcl.2020.127407.
- 1. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
- 2. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Panum, Maersk Tower, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
- 3. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
- 4. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: [email protected].
- 5. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: [email protected].
In this study, seven 30-norlupane derivatives (2-8) wasobtained from the chemical oxidation ofbetulinic acidfollowed bybiotransformationviaBacillus megateriumCGMCC 1.1741. And metabolites 2-4 and 6-8 were newly identified products. In the first step, betulinic acid was chemically oxidizedto platanic acid (1). Following the chemical oxidation, B. megaterium catalyzed the hydroxylation at C-7, C-11, C-15 and C-23 of platanic acid (1) as well as the oxidation of C-3 hydroxyl group. Compared to the labor-intensive isolation from natural Plants, this chemical-microbial semi-synthesis is more capable to provide increased structural diversity of oxygenated 30-norlupane. Finally, the potential neuroprotective effect of the derivatives was assessed on neuron-like PC12 cells induced by cobalt chloride (CoCl2). Metabolite 6 showed a potent neuroprotective activity.