Persistent Link:
http://hdl.handle.net/10150/187040
Title:
Bioactive agents from Grindelia tarapacana Phil. (Asteraceae).
Author:
Zhou, Lin.
Issue Date:
1994
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
This dissertation deals with the phytochemical and biological investigations of Grindelia tarapacana Phil. (Asteraceae), a plant species native to the Desert of Atacama in Chile. Ten compounds were isolated by using various chromatographic techniques. Of these, seven are new and two are known diterpenoids of the manoyloxide type. One known steroid was also characterized during the course of this study. New diterpenoids included 14S,15-dihydroxy-13-epi-manoyloxide (tarapacol), 15-acetoxy-14S-hydroxy-13-epi-manoyloxide (tarapacol 15-acetate), 14S,15-diacetoxy-13-epi-manoyloxide (tarapacol diacetate), 11α,14S,15-trihydroxy-13-epi-manoyloxide (tarapacanol A), 14S,15-diacetoxy-11α-hydroxy-13-epi-manoyloxide (tarapacanol A 14, 15-diacetate), 12α,14S,15-trihydroxy-13-epi-manoyloxide (tarapacanol B) and 14S,15-dihydroxy-11-keto-13-epi-manoyloxide (tarapacanone). The chemical structures and stereochemistry were established on the basis of extensive spectral analyses including 2D NMR and NOE techniques. X-ray diffraction analysis of tarapacol 15-acetate supported its absolute configuration. The configurations of the other new remaining diterpenoids were assigned based on biogenetic considerations. The two known diterpenoids were 13-epi-manoyloxide and 12α-hydroxy-13-epi-manoyloxide. The steroid was identified as α-spinasterol. The characterization of the known compounds was based on the comparisons of their spectral and physical constants with those reported in the literature for standard samples. Ten known flavonoids were also identified. As part of screening studies for biological activity, anti-HIV and anti-Mycobacterium tuberculosis tests were carried out for the isolated compounds. Five diterpenoids were found to exhibit biological activities. In an anti-HIV test, 12α-hydroxy-13-epi-manoyloxide (at 31 μg/mL) strongly decreased the HIV antigen release to a 10% level and still kept the 84% cell survival, suggesting anti-HIV activity with high selectivity in vitro. The activity of several diterpenoids against Mycobacterium tuberculosis reference strain H₃₇ Ra in vitro was very positive. Three diterpenoids, tarapacol (MIC = 32 μg/mL), tarapacol 15-acetate (MIC = 32 μg/mL) and tarapacanol A 14,15-diacetate (MIC = 32 μg/mL) showed a potency similar to that obtained for the anti-tuberculosis agent pyrazinamide (MIC = 40 μg/mL). Tarapacol diacetate (MIC = 16 μg/mL) was found to be much more potent than pyrazinamide.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Grindelia tarapacana.; Compositae.; Bioactive compounds.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Timmermann, Barbara N.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleBioactive agents from Grindelia tarapacana Phil. (Asteraceae).en_US
dc.creatorZhou, Lin.en_US
dc.contributor.authorZhou, Lin.en_US
dc.date.issued1994en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThis dissertation deals with the phytochemical and biological investigations of Grindelia tarapacana Phil. (Asteraceae), a plant species native to the Desert of Atacama in Chile. Ten compounds were isolated by using various chromatographic techniques. Of these, seven are new and two are known diterpenoids of the manoyloxide type. One known steroid was also characterized during the course of this study. New diterpenoids included 14S,15-dihydroxy-13-epi-manoyloxide (tarapacol), 15-acetoxy-14S-hydroxy-13-epi-manoyloxide (tarapacol 15-acetate), 14S,15-diacetoxy-13-epi-manoyloxide (tarapacol diacetate), 11α,14S,15-trihydroxy-13-epi-manoyloxide (tarapacanol A), 14S,15-diacetoxy-11α-hydroxy-13-epi-manoyloxide (tarapacanol A 14, 15-diacetate), 12α,14S,15-trihydroxy-13-epi-manoyloxide (tarapacanol B) and 14S,15-dihydroxy-11-keto-13-epi-manoyloxide (tarapacanone). The chemical structures and stereochemistry were established on the basis of extensive spectral analyses including 2D NMR and NOE techniques. X-ray diffraction analysis of tarapacol 15-acetate supported its absolute configuration. The configurations of the other new remaining diterpenoids were assigned based on biogenetic considerations. The two known diterpenoids were 13-epi-manoyloxide and 12α-hydroxy-13-epi-manoyloxide. The steroid was identified as α-spinasterol. The characterization of the known compounds was based on the comparisons of their spectral and physical constants with those reported in the literature for standard samples. Ten known flavonoids were also identified. As part of screening studies for biological activity, anti-HIV and anti-Mycobacterium tuberculosis tests were carried out for the isolated compounds. Five diterpenoids were found to exhibit biological activities. In an anti-HIV test, 12α-hydroxy-13-epi-manoyloxide (at 31 μg/mL) strongly decreased the HIV antigen release to a 10% level and still kept the 84% cell survival, suggesting anti-HIV activity with high selectivity in vitro. The activity of several diterpenoids against Mycobacterium tuberculosis reference strain H₃₇ Ra in vitro was very positive. Three diterpenoids, tarapacol (MIC = 32 μg/mL), tarapacol 15-acetate (MIC = 32 μg/mL) and tarapacanol A 14,15-diacetate (MIC = 32 μg/mL) showed a potency similar to that obtained for the anti-tuberculosis agent pyrazinamide (MIC = 40 μg/mL). Tarapacol diacetate (MIC = 16 μg/mL) was found to be much more potent than pyrazinamide.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectGrindelia tarapacana.en_US
dc.subjectCompositae.en_US
dc.subjectBioactive compounds.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairTimmermann, Barbara N.en_US
dc.contributor.committeememberHoffmann, Joseph J.en_US
dc.contributor.committeememberMartin, Arnold R.en_US
dc.contributor.committeememberMash, Eugene A. Jr.en_US
dc.contributor.committeememberGervay, Jacquelynen_US
dc.identifier.proquest9528000en_US
dc.identifier.oclc703881013en_US
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