Date of Award
Doctor of Philosophy (PhD)
Donaldson, William A.
Sem, Daniel S.
Yi, Chae S.
GENERATION OF DIVERSE MOLECULAR COMPLEXITY
Mohamed F. El Mansy, B.Sc, M.Sc.
Marquette University, 2014
The use of simple hydrocarbons as starting materials for the synthesis of complex molecules relies on efficient methods for oxidation, functionalization or rearrangement. For example, various researchers have explored cyclopentadiene or cycloheptatriene as precursors for the preparation of a wide variety of drug candidates, natural products and synthetic products. The purpose of this research is to explore methods to transform the simple hydrocarbon, cyclooctatetraene (COT) into complex target molecules.
Tricarbonyl (cyclooctatetraene)iron, readily prepared from COT, reacts with a variety of electrophiles to form (dienyl)iron cations. These steps may be regarded as branching pathways in diversity oriented synthesis. Reaction of these cations with a variety of nucleophiles, followed by oxidative decomplexation gave the corresponding racemic polyenes. Further manipulation of the generated polyenes can be effected by cycloaddition, oxidation, oxidative cleavage, rearrangement or reduction.
Utilizing these reactions, a variety of stereochemically diverse polyhydroxy aminocycloalkanes ("aminocyclitols") have been prepared. The inhibitory activity of these aminocyclitols against beta-glucosidase (from almonds) was reported. Conversely, ring-rearrangement metathesis of the polyenes containing a pendant olefin tether leads to a variety of carbocycles and heterocycles by what can be considered folding pathways in diversity oriented synthesis. This strategy has lead to a number of biologically active or natural product-line structures from the simple hydrocarbon cyclooctatetraene in a short number of steps.