title: Hydroxylation of the diterpenes ent-kaur-16-en-19-oic and ent-beyer-15-en-19-oic acids by the fungus Aspergillus niger.
abstract: 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.
authors.affiliation: Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marquina
authors.forename: José Luis
authors.initials: JL
authors.lastname: Parra
authors.forename: Manasés
authors.initials: M
authors.lastname: González
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zamilpa
authors.forename: Jaime
authors.initials: J
authors.lastname: Escalante
authors.forename: María R
authors.initials: MR
authors.lastname: Trejo-Hernández
authors.forename: Laura
authors.initials: L
authors.lastname: Alvarez
mesh_terms: 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
chemical_list: D004224:Diterpenes; D010276:Parasympatholytics; D010936:Plant Extracts; C458719:beyerenoic acid; C051436:kaurenoic acid