Acetals - Exploring reactivity for improved carbohydrate synthesis

Abstract: In my research, I have explored various aspects of acetals and their reactivity. Acetals have a central role in carbohydrate chemistry as an inherent functionality and as versatile protecting groups. The first part of the thesis summarizes results on regioselective reductive openings of benzylidene acetals. We thus used deuterium substituted benzylidene acetals and boranes, to investigate stereoselectivity and kinetic isotope effects. In addition, we explored the electronic requirements using p-bromo benzylidene acetals. Our results show that the regioselective reductive opening reactions of benzylidene acetal rings with boranes, and aluminum trichloride progress via three distinctly different mechanisms. The intermediates range from ntimate ion pairs to solvent separated oxocarbenium ions in a mechanistic continuum depending on borane ligand, Lewis acid strength, and solvent polarity. The second part of thesis is focused on synthetic routes towards daunosamine donors. We thus used the equilibrium between the anomeric hemiacetal and the corresponding aldehyde, and improved the 1,4-Michael additions of azides, without advanced catalysts. We present an efficient synthesis of a versatile donor which was used to synthesize anthracycline analogs. These anthracyline analogs were tested for anti-tumor activity but initial biological evaluations were inconclusive.