Hydroxylation of the diterpenes ent-kaur-16-en-19-oic and ent-beyer-15-en-19-oic acids by the fungus Aspergillus niger.
The diterpenes ent-kaur-16-en-19-oic acid (1) and ent-beyer-15-en-19-oic acid (2) are the major constituents of a spasmolytic diterpenic mixture obtained from the roots of Viguiera hypargyrea, a Mexican medicinal plant. Microbial transformation of 1 and 2 was performed with Aspergillus niger. Two metabolites, ent-7alpha,11beta-dihydroxy-kaur-16-en-19-oic acid (4) and ent-1beta,7alpha-dihydroxy-kaur-16-en-19-oic acid (5), were isolated from the incubation of 1, and one metabolite, ent-1beta,7alpha-dihydroxy-beyer-15-en-19-oic acid (6), was isolated in high yield (40%) from 2. The structures were elucidated on the basis of spectroscopic analyses and confirmed by X-ray crystallographic studies. Compounds 1-4 and 6 and methyl ester derivatives 4a and 6a were evaluated for their ability to inhibit the electrically induced contraction of guinea-pig ileum. Compounds 1, 3, 4, 4a and 5 were significantly active. These results showed that dihydroxylation of 1 at 7beta, 11alpha-, and 1alpha, 7beta-positions resulted in a loss of potency.
Marquina
Silvia
S
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
Parra
José Luis
JL
González
Manasés
M
Zamilpa
Alejandro
A
Escalante
Jaime
J
Trejo-Hernández
María R
MR
Alvarez
Laura
L
D000818:Animals; D001234:Aspergillus niger / Q000378:metabolism*; D019659:Asteraceae / Q000737:chemistry*; D001711:Biotransformation; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000378:metabolism*; D006168:Guinea Pigs; D006900:Hydroxylation; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018517:Plant Roots
D004224:Diterpenes; D010276:Parasympatholytics; D010936:Plant Extracts; C458719:beyerenoic acid; C051436:kaurenoic acid