Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.
Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Methodology applicable to the synthesis of peroxide-containing natural products
Abstract
An increasing number of biologically and pharmacologically active peroxide natural products have been isolated, characterized and studied. With this heightened awareness of the frequency and importance of peroxide containing compounds has emerged an augmented appreciation of the necessity for new and improved methodology applicable to the synthesis of compounds containing the labile peroxide functionality. The t-butyldimethylsilyl and t-butyldiphenylsilyl peroxy-ethers can be introduced under basic conditions. Unfortunately, the resulting peroxide is very susceptible to elimination to form carbonyls when an α-hydrogen is present. This increased lability limits the efficacy of these protecting groups for hydroperoxides. As part of our interest in dioxane-containing natural products, we wished to explore the stereoselective [4 + 2] cycloaddition of singlet oxygen and chiral dienol ethers as a potential route to the endoperoxide skeleton. Toward this end, we required a general method for the stereoselective preparation of chiral, geometrically pure 1-alkoxy-1,3dienol ethers as substrates for the stereoselective addition of singlet oxygen. Sonogashira couplings of 2-iodo enol ethers or ynol ethers provide enynes, which upon sernihydrogenation of the alkyne yields 4-alkyl-1,3-dienol ethers. (IZ, 3E), (1 E, 3Z) and (IZ, 3Z)-4-alkyl-1,3-dienol ethers are accessible using this strategy. Singlet oxygen reacts with dienol ethers via the three known reaction modes of singlet oxygen: ene reaction, [2 + 2] cycloaddition and [4 + 2] cycloaddition. The mode of reaction is dependent upon the substitution and geometry of the diene. 2-Methyl-1,3-dienol ethers undergo ene reaction to furnish hydroperoxides. (IE, 3Z) and (IZ, 3Z)-4-alkyl-1,3-dienol ethers yield carbonyl compounds via decomposition of 1,2-dioxetanes that originate from [2 + 2] cycloaddition. [4 + 2] Cycloaddition of singlet oxygen with chiral 3-methyl-1,3-dienol ethers, (IZ, 3E)-4-alkyl-1,3-dienol ethers and (I E, 3E)-4-alkyl-1,3-dienol ethers yields 1,2-dioxines with modest diastereoselectivity. The 1,2-dioxine skeleton can alternatively be synthesized via a sequence that includes acid catalyzed epoxide opening with hydrogen peroxide followed by selective ketalization of the hydroxy-hydroperoxide. Oxidation of the primary alcohol and chain extension furnishes a γ-peroxy-α,β-unsaturated aldehyde. Deprotection of the hydroperoxide and cyclization affords a 3-hydroxy-1,2-dioxine.
Subject Area
Organic chemistry
Recommended Citation
Sloss, Darby Gail, "Methodology applicable to the synthesis of peroxide-containing natural products" (1998). ETD collection for University of Nebraska-Lincoln. AAI9912696.
https://digitalcommons.unl.edu/dissertations/AAI9912696