Transformation of steviol-16alpha,17-epoxide by Streptomyces griseus and Cunninghamella bainieri.
Eight new ent-beyerane metabolites, 5-8, 12, and 14-16, and four new ent-kaurane metabolites, 3, 10, 11, and 13, together with two known metabolites, 4 and 9, were isolated from the microbial transformations of steviol-16alpha,17-epoxide using Streptomyces griseus ATCC 10137 and Cunninghamella bainieri ATCC 9244. The structures of the metabolites were characterized by IR, HRFABMS, and 1D and 2D NMR data. In addition, a GRE (glucocorticoid response element)-mediated luciferase reporter assay was used to initially screen for the biological activity of the 11 metabolites and stevioside. Steviol (1), steviol-16alpha,17-epoxide (2), ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic acid (3), ent-17-hydroxy-16-ketobeyeran-19-oic acid (4), ent-9alpha,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (10), ent-9alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (12), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (14), and stevioside showed significant effects; in particular, stevioside showed almost equal potency as dexamethasone.
Chang
Shwu-Fen
SF
Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, Republic of China.
Yang
Li-Ming
LM
Hsu
Feng-Lin
FL
Hsu
Ju-Yin
JY
Liaw
Jia-Horng
JH
Lin
Shwu-Jiuan
SJ
D000818:Animals; D020093:Cunninghamella / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D048888:Fireflies / Q000201:enzymology; D008156:Luciferases / Q000378:metabolism; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013305:Streptomyces griseus / Q000378:metabolism*
D004224:Diterpenes; D011965:Receptors, Glucocorticoid; C515259:steviol-16alpha,17-epoxide; D003907:Dexamethasone; D008156:Luciferases