Theoretical organic chemistry and organic biology: Using theoretical tools to understand the mechanisms and predict the origins of stereoselectivity of asymmetric organic reactions and protein catalysis

This dissertation describes theoretical studies aimed at elucidating the mechanism, reactivity, and stereo selectivity of asymmetric organic reactions and protein---catalytic antibody and enzyme---catalysis.; Chapter 1 describes a general understanding of molecular recognition and catalysis. Section 1 reviews the binding affinities of host-guest, protein-ligand, and protein-transition state complexes. Section 2 investigates the origins of enzyme proficiencies.; Chapter 2 describes computational studies to predict the origins of stereoselective antibody and enzyme catalysis. Section 1 involves theoretical analysis of Diels-Alder catalysis by 39A11 and its germ-line antibody. Section 2 inspects the mechanism of the glutathione transferase-catalyzed conversion of the antitumor 2-crotonyloxymethyl-2-cycloalkenones to the GSH adducts. Section 3 presents the quantum mechanics calculations of deoxyribose phosphate aldolase (DERA) catalyzed aldol reaction as well as uncatalyzed and amine catalyzed aldol reactions as comparisons.; Chapter 3 describes torquoselectivity, i.e. mechanistic studies of cyclobutene ring-openings. Section 1 examines the origins of inward torquoselectivity by silyl groups and other sigma-Acceptors. Section 2 covers the theoretical exploration of the torquoselectivity through protonation of basic substituents.; Chapter 4 describes mechanistic studies of novel reactions, intermediates and stereoselective organocatalysts. Section 1 studies the mechanism of cis-enamide formation from N-(alpha-silyl)allyl amides and explore the synthetic potential of stepwise dyotropic rearrangements. Section 2 reports the transition state models for the stereo selectivity of strain-release allylations.