Part I: In the first study of pyrethroids, twenty-one novel pyrethroid esters bearing strong electron-withdrawing groups (e.g., halomethylketo and nitro groups) in the double bond side chain of the cyclopropane acid moiety have been synthesized and evaluated for insect toxicity. Rather than the usually employed Wittig reaction for these syntheses, the novel pyrethroid acid moieties were prepared by amino acidcatalyzed Knoevenagel condensations under mild conditions. In the second study of pyrethroids, fourteen pyrethroid-like carbonates were synthesized by condensation of a variety of alcohols and the chloroformates of the corresponding known pyrethroid alcohols.

No description available.

Three diterpenes of the abietane class, 7b-acetoxy-6b-hydroxyroyleanone (I), 6b,7b- dihydroxyroyleanone (II) and ent-pimara-8(14),15-diene-3b,11a-diol (III) and three triterpenes, 2a,3a,19 -trihydroxyurs-12-en-28-oic acid (IV), stigmasterol (V) and lupeol (VI) were isolated from the stem and leaf material of Plectranthus hadiensis. The structures of the compounds were elucidated using 2D NMR spectroscopy and Mass spectrometry. All six compounds have been isolated previously, but this is the first occurrence of compounds III-VI in Plectranthus hadiensis. This is also the first report of the isolation of a pimarene from Plectranthus, which provides a biochemical link to other genera in the family Lamiaceae where this class of compounds exist. Compounds I to IV were tested for their antibacterial activity against Enterococcus faecalis and Pseudomonas aeruginosa as well as their anticancer activity against breast (MCF-7), renal (TK- 10) and melanoma (UACC-62) cell lines. Compounds I and II exhibited good antibacterial activity against Enterococcus faecalis and Pseudomonas aeruginosa and although the entpimara- 8(14),15-diene-3 ,11 -diol (III), was inactive against E. faecalis, it was very active against P. aeruginosa. Compound IV, the triterpenoid, was structurally different to I-III and did not show any anti-bacterial activity. Compounds I-III were weakly active toward the cancerous renal (TK-10), melanoma (UACC-62) and breast (MCF-7) cell lines, while IV was inactive in all of the cell lines. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1991. / Vita. Abstract. Includes bibliographical references (leaves 196-207). Also available via the Internet.

No description available.

Heterocycles are privileged structural motifs found in many natural products and biologically active compounds. Given the prevalence of this structural unit, there has been considerable interest and challenge in developing methods for construction optically pure heterocycles in organic synthesis and pharmaceutical chemistry. The skeleton of hydronaphthalene and indole are pervasive structural motifs in the pharmaceutical drugs that exhibit various bioactivities. This dissertation is mainly focused on the development of transition-metal-catalyzed asymmetric functionalization of alkenes, including the hydroselenation and hydroamination of various oxa/azabicyclic olefins for the synthesis of bioactive compounds and structural modification of oleanolic acid. An efficient rhodium catalytic system consisting of Rh(COD)2OTf/(S)-xyl-Binap, and n-Bu4NI was developed for the asymmetric hydroselenation of various oxa/azabicyclic olefins with diaryl diselenides instead of the unstable, malodorous selenol compounds. Under these reaction conditions, a wide range of heterobicyclic alkenes produced selenol containing hydronaphthalene derivatives in high yields (up to 96%) along with excellent enantioselectivities (up to 97%), overcoming the self- promoted racemic hydroselenation. The exo-configuration of the exclusive addition product was confirmed by X-ray crystal structure analysis. The strategy has also been applied to the kinetic resolution of unsymmetric oxabenzonorbornadiene. Further, these selenium compounds can catalyze the oxidative coupling reaction of 2-naphthols. Then, for the synthesis of trans 1-indolyl dihydronaphthalenols, a highly enantioselective Rh/Pd dual-metal sequentially catalytic system was revealed through intermolecular and intramolecular cascade hydroamination in the reaction of oxabenzonorbornadienes with 2-alkynylanilines. The exclusive trans-configuration of 1-(2-phenyl)indolyl dihydronaphthalenol was identified by X-ray crystal analysis. Various substituents, such as aryl, heteroaryl, alkyl, and silyl groups on alkynyl starting material can be used as compatible nucleophiles in the reaction to give excellent iii enantiomeric excesses (up to 99%) with good yields (up to 88%) under mild conditions. The reaction can be performed on a gram scale, while the indole derivatives could be transformed at the hydroxyl and indolyl funtionalities. The in silico and in vitro screening showed that the novel 1-indolyl dihydronaphthalenol products can serve as potential lead compounds for treating inflammation disease. At last, a series of functional groups, including carboxyl, phosphate, sulfone, triazole, tertiary amine, and glycosyl have been incorporated into oleanolic acid to improve its water solubility. A wide range of their derivatives have been obtained, and it was found that carboxyl salt, phosphate salt, and sulfonate salt contribute to the increase of the solubilities in water; up to 8 g/L was gained for carboxylate salt, which also provides the possibility to improve the bioavailability of these compounds

Heterocycles are privileged structural motifs found in many natural products and biologically active compounds. Given the prevalence of this structural unit, there has been considerable interest and challenge in developing methods for construction optically pure heterocycles in organic synthesis and pharmaceutical chemistry. The skeleton of hydronaphthalene and indole are pervasive structural motifs in the pharmaceutical drugs that exhibit various bioactivities. This dissertation is mainly focused on the development of transition-metal-catalyzed asymmetric functionalization of alkenes, including the hydroselenation and hydroamination of various oxa/azabicyclic olefins for the synthesis of bioactive compounds and structural modification of oleanolic acid. An efficient rhodium catalytic system consisting of Rh(COD)2OTf/(S)-xyl-Binap, and n-Bu4NI was developed for the asymmetric hydroselenation of various oxa/azabicyclic olefins with diaryl diselenides instead of the unstable, malodorous selenol compounds. Under these reaction conditions, a wide range of heterobicyclic alkenes produced selenol containing hydronaphthalene derivatives in high yields (up to 96%) along with excellent enantioselectivities (up to 97%), overcoming the self- promoted racemic hydroselenation. The exo-configuration of the exclusive addition product was confirmed by X-ray crystal structure analysis. The strategy has also been applied to the kinetic resolution of unsymmetric oxabenzonorbornadiene. Further, these selenium compounds can catalyze the oxidative coupling reaction of 2-naphthols. Then, for the synthesis of trans 1-indolyl dihydronaphthalenols, a highly enantioselective Rh/Pd dual-metal sequentially catalytic system was revealed through intermolecular and intramolecular cascade hydroamination in the reaction of oxabenzonorbornadienes with 2-alkynylanilines. The exclusive trans-configuration of 1-(2-phenyl)indolyl dihydronaphthalenol was identified by X-ray crystal analysis. Various substituents, such as aryl, heteroaryl, alkyl, and silyl groups on alkynyl starting material can be used as compatible nucleophiles in the reaction to give excellent iii enantiomeric excesses (up to 99%) with good yields (up to 88%) under mild conditions. The reaction can be performed on a gram scale, while the indole derivatives could be transformed at the hydroxyl and indolyl funtionalities. The in silico and in vitro screening showed that the novel 1-indolyl dihydronaphthalenol products can serve as potential lead compounds for treating inflammation disease. At last, a series of functional groups, including carboxyl, phosphate, sulfone, triazole, tertiary amine, and glycosyl have been incorporated into oleanolic acid to improve its water solubility. A wide range of their derivatives have been obtained, and it was found that carboxyl salt, phosphate salt, and sulfonate salt contribute to the increase of the solubilities in water; up to 8 g/L was gained for carboxylate salt, which also provides the possibility to improve the bioavailability of these compounds

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.

In order to test the dietary effects of bioactive compounds present in whole grains, we decided to observe the effect of varying types of sorghum bran on colon cancer promotion. We used 40 rats consuming diets containing 6% fiber from either cellulose or bran from white (contains phenolic acids), brown (contains tannins), or black (contains anthocyanins) sorghum (n=10). Diets were fed for 10 wk, during which two azoxymethane (AOM) injections (15 mg/kg BW) were administered in wk 3 and 4. We observed that the total number of aberrant crypts (AC) and high multiplicity aberrant crypt foci (HMACF) were lower in rats consuming black (p < 0.04) and brown (p < 0.006) sorghum diets when compared to the cellulose diet, and that these decreases were an inverse function of diet antioxidant activity (ABTS). These observations led us to evaluate the effect of these diets on endogenous enzymatic activities (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), redox status as measured by reduced and oxidized glutathione, and cell cycle processes, proliferation and apoptosis, in the rat colon. Total SOD activity was higher (p < 0.04) in rats consuming black sorghum when compared to all other diets. A similar, but not significant, trend occurred in mitochondrial SOD. The white sorghum diet had enhanced (p < 0.02) CAT activity compared to the cellulose diet, but the black and brown sorghum diets were intermediate. Finally, all sorghum diets suppressed GPx activity relative to cellulose (p < 0.04). However, no changes were seen in levels of reduced and oxidized glutathione or the ratio of the two. The black sorghum fed rats had a lower proliferative index (p < 0.01) and zone (p < 0.04) compared to cellulose; brown and white sorghum rats were intermediate. Apoptotic index was highest in brown sorghum rats compared to cellulose (p < 0.03), while other sorghum diets were intermediate. These data suggest that the suppression of AC and HMACF formation in rats consuming sorghum bran may have resulted through the differential actions of the sorghum brans on endogenous antioxidant enzymes, which may affect colonocyte proliferation and apoptosis.

Thesis (Ph. D.)--City University of New York, 2007. / Includes bibliographical references (leaves 100-120) and index. Also available for educational and research purposes in PDF format on the Internet.