Synthesis of peptides, peptidomimetics, aminopolyols, and aza-sugars from organoboronic acids, amines and carbonyl compounds

This dissertation describes the development of new variations of boron-based three-component reactions---the reactions between carbonyl compounds, amines and boronic acids. These new methodologies have been successfully applied to the synthesis of linear peptides, peptidomimetics, benzodiazepines aminopolyols and aza-sugars. Solid phase studies of the three-component reactions are also briefly studied.; Chapter 1 gives a brief introduction to the multicomponent reactions, the properties of organoboron compounds and recent development using alkenyl or aryl boronic acids or esters in organic synthesis. This chapter also reviews previous work in our and other laboratories involving three-component reactions.; Chapter 2 describes a new synthesis of amino amides by employing glyoxamides as the carbonyl compounds. The ultimately goal of this methodology is the synthesis of linear peptides and peptidomimetics on the solid support by using a cleavable amine in the reaction. This strategy is first demonstrated in the solution phase, then on the solid support. We have also discovered that molecules accommodating both glyoxamide and amine moieties react readily with boronic acids in an intramolecular way to give diverse, biological important benzodiazepine-2-ones, which are presented in Chapter 3.; Chapter 4 offers an extension of the three-component reaction between carbonhydrates, amines and boronic acids to the use of disaccharides, the synthesis is highly stereocontrolled and can be achieved without tedious protection and deprotection steps. Further determination of the stereochemistry and studies of the influences of chiral amines in the reaction are presented.; Chapter 5 describes the design of the synthesis of a cyclic hydroxy aminol-chiral hydroxy aldehyde and amine accommodated in the same molecule, which reacts readily with a boronic acid to give directly unprotected polyhydroxy piperidines. The uses of the polyhydroxy piperidines as important intermediates to the synthesis of indolizidines, quinolizidine and pipecolic acid are demonstrated.; Chapter 6 shows the investigation of our three-component reactions in the solid phase synthesis by proper attachment of amines, boronic acid and aldehydes on the solid support.