| Part A. Although several strategies for the synthesis of cyclobutene and cyclobutene derivatives have been developed in the past, highly substituted cyclobutenes are not easily accessible.; In the current investigation, first we performed detailed study of the hydroalumination of 1-phenyl-4-trimethylsilylbut-3-yn-l-ol 172 and 2-phenyl-4-trimethylsilylbut-3-yn-l-ol 173 using one equivalent of diisobutylaluminum hydride using different solvent systems, Lewis additives, and temperatures, to furnish geometrically pure (E)-and ( Z)-1-phenyl-4-trimethylsilylbut-3-en-1-ol 170 and 2-phenyl-4-trimethylsilylbut-3-en-1-ol 171, respectively. Upon addition of one equivalent of diisobutylaluminum hydride to the substrates 1-phenyl-4-trimethylsilylbut-3-yn-1-ol 172 and 2-phenyl-4-trimethylsilylbut-3-yn-1-ol 173 at room temperature, an intermediate alkoxide was formed that readily underwent an in situ beta-elimination at room temperature to re-generate another mole of hydride and perform an intramolecular hydroalumination. We observed that donor solvents and a mixture of hydrocarbon solvent/Lewis base additives favor the formation of Z-isomer. However, a mixture of hydrocarbon solvent/Lewis acid favor the formation of E-isomer.; Secondly, we attempted the preparation of highly substituted cyclobutene and cyclobutene derivatives.; Part B. Antifreeze glycoproteins are biological antifreezes found predominantly in Arctic and Northern cod fishes. The antifreeze glycoproteins generally consist of a repeating sequence of a simple glycotripeptide monomer, (alanine-alanine-threonine)n, with the disaccharide beta-D-galactosyl-(1 → 3)-alpha-N-acetyl-D-galactosamine attached to the threonyl residue. In some Arctic and northern codfishes alanine and threonine are replaced with proline and arginine, respectively, in their peptide backbone. AFGPs exhibit a number of unique properties, which protect biological systems in vitro and have been investigated for potential applications in medicine, biotechnology and food industry. However, their full application has yet to be realized due to difficulties in isolation from the natural sources in analytically pure quantities for commercial development, as well as the fact harvesting of fish is an expensive undertaking. Furthermore most of the native AFGPs are unstable in both chemical and enzymatic media.; Therefore chemical synthesis of AFGP and AFGP analogs is an attractive alternative to the difficult isolation of AFGPs from natural sources. Consequently, a rational design of a facile and efficient synthesis of chemically and biologically stable AFGP analogs is urgently required. In an attempt to address these challenges, we have developed a model, that allows the preparation of structurally diverse C-linked glycosylated tripeptide building units useful for the solid-phase synthesis of chemically and biologically stable antifreeze glycoprotein analogs. (Abstract shortened by UMI.)... |
