[Chemistry dissertation]

The enediyne moiety Is the core structure of a family of anti-cancer agents with DNA cleavage ability. This ability comes from a highly reactive species, the1,4-benzyne diradical, which is a cyclization product of enediyne. Described inPart One is our attempt to study the Bergman cyclization of enediyne radicalcations in Freon matrixes at liquid nitrogen temperature. Unfortunately, in the radical cation state, the enediyne was less likely to cyclize, and all we have observed was the open form enediyne radical cation. Semi-empirical calculations and orbital symmetry consideration are used to explain this result. A comparison was made between a flexible (for example, 1,5-hexadiene) radical cation and a rigid (for example, enediyne) radical cation, and it is concluded that the rigidity of enediyne radical cation necessitates the orbital symmetry rule to be strictly observed in such systems. Sultams are a family of cyclic sulfonamide compounds which have been recently discovered as potent HIV non-nucleoside reverse-transcriptase inhibitors.Described in Part Two is the successful design and implementation of a short,solid-phase synthesis route to sultams. In addition, solution-phase syntheses of sultams with N-side chain modification and trifluoromethylated derivative are described.Hyaluronic acid is a high molecular weight aminoglycan that is a major component of the extracellular matrix. It appears to play an essential role in cancer metastasis by interacting with the cancer cell's CD44 receptor. Our Continuing efforts are to synthesize hyaluronic acid oligosaccharide mimics, which are smaller molecules containing CH₂ linkages strategically placed at enzymatically labile positions. Described in Part Three is the synthesis of two building blocks, hyaluronic acid disaccharide and corresponding C-disaccharide,which would serve in the future for blockwise synthesis of hyaluronic acid oligosaccharide mimics. Three out of eight possible synthetic routes are described.