Carbohydrate-derived molecular diversity : synthesis and application in cell biology

• Main Author: Ma, Jimei
• Other Authors: Liu Xuewei
• Format: Theses and Dissertations
• Language: English
• Published: 2010
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: https://hdl.handle.net/10356/42235
• Institution: Nanyang Technological University

Tamiflu is currently the most effective drug for the treatment of influenza. In this part, a practical synthesis of Tamiflu was developed using novel synthetic route, cheap reagents, and abundantly available starting material D-glucal. This strategy features Claisen rearrangement of hexose to obtain the cyclohexene backbone and introduction of diamino groups through tandem intramolecular aziridination and ring opening. In addition, our synthetic protocol allows late-stage functionalization for facile and flexible synthesis of Tamiflu analogues. Using the synthesized Tamiflu and its active metabolite (oseltamivir carboxylate), we investigated their influence on morphology, proliferation, differentiation and vesicular exocytosis (regulated secretion) of neuroendocrine PC12 cells. It was found that oseltamivir carboxylate significantly inhibited the vesicular exocytosis of PC12 cells, postulating a mechanism underlying the Tamiflu side-effects, particularly, its possible adverse influences on neurotransmitter release in the central nervous system.