Site-selective oxidation of unactivated C-H sp3 bonds of oleanane triterpenes by Streptomyces griseus ATCC 13273

The oxidization of unactivated C-H bonds is of great interests in the structural modification of pentacyclic triterpenes. Herein we discovered the unique capability of Streptomyces griseus ATCC 13273 to catalyze the site-selective oxidation of C-29 methyl group to carboxyl group over a range of oleanane triterpenes, oleanolic acid (1), hederagenin (2), echinocystic acid (3), quillaic acid (4) and senegenin (5). Along with this reaction the hydroxylation on C-24 and C-21 were also discovered on some substrates. As a result, eight new compounds (1c, 2a∼5a and 2b∼4b) among the ten metabolites were isolated. The anti-inflammatory activities of these compounds were evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages, and the products with hydroxyl group on C-21 (1c, 2b and 5a) showed significantly enhanced activities with the IC50 values of 1.230, 0.078 and 0.015 μM, respectively. Thus S. griseus ATCC 13273 was further proved as a useful biocatalyst to expand the structural diversity of oleanane triterpenes for medicinal chemistry research.

Graphical abstractS. griseus ATCC 13273 showed high efficient site-selective oxiaization of unactivated C-H bonds at C-29 methyl group over the oleanane triterpenes, whereas the products with hydroxyl group at C-21 (1c, 2b and 5a) exhibited significantly increased inhibitory activities on NO production in RAW 264.7 cells.Download high-res image (188KB)Download full-size image