Physical Sciences and Mathematics Commons^™

Interactions Of Vanadium Compounds With Reducing Equivalents: Evidence Of Free Radical Involvement And Possible Mechanisms Of Toxicity, Randal J. Keller

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Vanadium compounds have been reported to cause numerous toxicological effects including NAD(P)H oxidation and lipid peroxidation. The purpose of this thesis is to determine the active form of vanadium in causing these effects, and to determine any possible free radical involvement in these processes. Vanadium-stimulated oxidation of NADH was studied spectrophotometrically and by electron spin resonance spectroscopy. In 25 mM sodium phosphate buffer at pH 7. 4, vanadyl, (V(IV)), is slightly more effective in stimulating NADH oxidation than was vanadate (V(V)). Addition of a superoxide generating system, xanthine/xanthine oxidase, results in a marked increase in NADH oxidation by vanadyl, and …

Structure-Activity Relationships Of Retinoids In Developmental Toxicology, W. Brian Howard

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The teratogenic potency of retinoid analogs was determined in Syrian hamsters and compared to the teratogenic potency of all-trans-retinoic acid (all-trans-RA, ED₅₀ = 10.5 mg/kg). A total of 15 analogs having variations in the cyclohexene ring were evaluated following various amounts of single oral doses on day 8 of gestation. Retinoids containing a five- or six-membered ring were as teratogenic as all-trans-RA, provided they had sufficient lipophilic substituents on the ring. The same pattern emerged for retinoids that had six-membered aromatic ring substitution for the natural cyclohexene ring of vitamin A. Incorporation of a supplementary …

1-Acyldihydropyridones As Synthetic Intermediates, Michael Andrew Foley

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The most efficient and stereoselective total synthesis of (+/-)- lausbine II to date has been achieved. The key steps in this are the copper-mediated conjugate addition reaction of the Grignard reagent of 1-bromo-4-chlorobutane to a dihydropyridone and a stereoselective reduction of a quinolizidinone.

Methodology has been developed for the convenient synthesis of 1-acyl-2-substituted-1,2,5,6-tetrahydropyridines. This was accomplished by adding novel alkylzinc iodides to the 1-acyliminium ion derived from N-phenoxycarbonyl-4-methoxy-1,2,3,4-tetrahydropyridine.

Synthetic Studies Toward Key Portions Of The Didemnins, Ok-Soon Kim

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Three different synthetic approaches toward N-[(2SR, 4S) - 4-hydroxy-2,5-dimethyl-3-oxohexanoyl]-Lleucine methyl esters were carried out by use of i) aldol condensation and amination ii) Claisen condensation and soft acid coupling reaction iii) methylation of Hia-Leu derivative in relatively high yields. (4S)-3-[(2SR, 4S)-2,5-Dimethyl-1,3-dioxo-4-(methoxyethoxy-methyloxy)hexyl]-4-(1-methyletheyl-2-oxazolidinone was prepared by the reaction of aldol condensation of lithium enolate of Evans' chiral auxilary in 80:20 diastereomeric ratio. A new method for the synthesis of (4S)-4-(t-butoxycarbonyl)amino-5-methyl-3-oxoheptanoic acid ethyl ester (Statone) was developed by the reaction of Boc-leucine with Meldrum's acid, followed by transesterification and decarboxylation in modest yield. Other a-amino acids also were applied to this methodology in …