Synthetic methodology of carbohydrates : access to carbohydrate-linked heterocycles and dimycolyl diarabinoglycerol ; Synthetic methodology development of carbohydrates : quick access to carbohydrate-integrated heterocycles and arabinosylated glycerol dimycolate
Date of Issue2014
School of Physical and Mathematical Sciences
Carbohydrates have always attracted large interests in their synthesis and applications. Due to their diversified roles, they have been employed in many synthetic methodologies as well as building blocks of numerous natural products. The different roles of carbohydrates and successful examples of their applications would be demonstrated. Part 1: In the first part, pyrrolidine derivatives were constructed in high diastereoselectivities and good yields through a [3 + 2] cycloaddition of a tert-butyldimethylsilyl protected carbohydrate allene with a range of imines. Following which, the carbohydrate auxiliary was removed and pyrrolidines were afforded with excellent enantioselectivities of up to 99% ee. The potential of this strategy was further demonstrated by the selective reduction of the pyrrolidines. Part 2: In the second part, carbohydrate-integrated isoxazolines were synthesized from 2-nitroglycals and sulfur ylides in the presence of 1-phenylthiourea catalyst. The reactions underwent [4 + 1] annulations and rearrangement to afford the corresponding carbohydrate-integrated isoxazolines in high yields with excellent diastereoselectivities of up to 95% de. Part 3: In the final chapter, protected dimycolyl-diarabino-glycerol (purified from Mycobacterium marinum) was successfully synthesized by using Mitsunobu reaction and selective arabinofuranosylation. This glycolipid was found to stimulate a pro-inflammatory response in macrophages and investigation of this cell wall glycoconjugate in driving host-pathogen interactions and contributing to the immunopathogenesis of mycobacterial infections is currently underway.