L- Fucose Synthesis And Unexpected Discovery

Carbohydrates, which serve as not only a major source of energy in life process, but also a structural material, are known as one of three biomacromolecules occurring in nature along with protein and nucleic acid. Aside from the above mentioned functions, carbohydrates have been demonstrated to play many important roles in life process, for example, cell adhesion, recognition. Research in glycobiology field has becoming very important to disclose the different functions of carbohydrates in contemporary biological and medical field.In the thesis, we aim at developing a rapid construction of L-fucose and L-fucose building blocks which are used for the synthesis of Globo-H which is a tumor antigen isolated from many different cancer cells.The strategy is that inversion of the C-2and C-4hydroxyl groups of L-rhamnose via SN2or Mitsunobu reaction installs the desired stereo configurations of C-2and C-4hydroxyl groups at L-fucose. We have synthesized L-fucose within6steps from cheap and commonly available L-rhamnose according to literature method. Unfortunately, simultaneous inversion of the C-2and C-4hydroxyl groups did not provide the expected product, but surprising results were discovered when we applied Mitsunobu reaction to the inversion. The Mitsunobu reaction of methyl-α-L-3-O-phenyl-rhamnopyranoside gave unexpected regioselectively and stereoselectively acylated rhamnose product, whose structure is proved by NMR and simple esterification reaction. And we studied the reaction in detail. At last, we introduced a fluorous chain in rhamnose in attempt to help the purification of the Mitsunobu reaction products.In conclusion, the following have been done in this thesis:(a) L-fucose and L-fucose building blocks were synthesized from L-rhamnose via literature method;(b) We have attempted to synthesize L-fucose building blocks from L-rhamnose by one-step inversion of the C-2and C-4hydroxyl groups of L-rhamnose via SN2or Mitsunobu reaction;(c) Unexpected Mitsunobu reaction results were obtained and we explored the reaction in detail.