| Non-proteinacous amino acids are important components of numerous biologically active compounds. As a consequence, there is much interest in the development of straightforward routes for their synthesis. A novel strategy for the synthesis of several classes of non-proteinacous α-amino acids from a variety of α-amino acids is presented in this thesis.; A general strategy of protecting the α-carboxyl group of serine, threonine, aspartic acid and glutamic acid as a cyclic ortho ester (OBO), sufficiently reduces the acidity of the α-proton to allow the use of a variety of basic reagents minimizing racemization at the α-proton.; The sidechain hydroxyl group in Boc/OBO protected serine and threonine is oxidized to the corresponding aldehyde and ketone without enolization. Grignard and Reformatsky additions produced predominantly threo-β-hydroxy-α-amino acids in good selectivity with no racemization. Adaptation of the methodology onto the solid phase also gave threo-β-hydroxy-α-amino acids albeit with some racemization.; The addition of various electrophiles to the enolate of N-Cbz-α-OBO-γ-methyl ester glutamic acid gave the 2S,4S stereoisomers with excellent selectivity and good yield. Alkylation, acylation, Aldol and Claisen reactions and the electrophilic addition of various heteroatoms is described.; Electrophilic additions to the enolate of N-Cbz-α-OBO-γ-methyl ester aspartic acid gave the more difficult to synthesize 2S,3 S stereoisomer with varying degrees of stereoselectivity and yields depending on the electrophile.; The stereochemistry of addition for the enolate chemistry is also explored. |
