Bio-inspired acetal induced polyene cyclization : the development and applications

• Main Author: Li, Bin
• Other Authors: Loh Teck Peng
• Format: Theses and Dissertations
• Language: English
• Published: 2013
• Subjects: DRNTU::Science::Chemistry::Organic chemistry
• Online Access: https://hdl.handle.net/10356/51034
• Institution: Nanyang Technological University

The development of a bio-inspired acetal induced intermolecular polyene cyclization is described. This process has been successfully applied to construct terpenoids skeletons and the core structure of Cortistatin A between chiral acetals and silyl enol ethers. On the other hand, a direct method to construct 2-functionalized terpenoids was developed by using isobutene as the other component. In addition, this strategy was further extended to construct 7-6-6 fused rings. Interestingly, TiCl4 and SnCl4 gave different diastereomers. Another InBr3 catalyzed Prins reaction initiated polyene cyclization also has been developed, which allowed for the rapid synthesis of 3-oxaterpenoids. The first total synthesis of (±)-moluccanic acid methyl ester has been achieved using the current method as the key step. By exploiting the acetal induced intermolecular polyene cyclization, a highly efficient method to construct 8-oxabicyclo[3,2,1]octanes was discovered. Interestingly, an opposite diasteroselectivity product was obtained, which depended on whether aldehydes or corresponding acetals were used. The investigation of the reaction of acetal with relatively stable (TIPS-, TBS-, Me-) enol ethers disclosed that the reaction undertook another pathway compared with classical Mukaiyama-aldol reaction. Switching the protecting group of acetal, mono and double Mukaiyama-aldol/[1,5]-H shift cascade products were obtained. The reaction mechanism was studied in great detail through deuterium labelling experiments. Based on this method, a novel synthetic route for the synthesis of commercial analgesics drug Sufentanil also has been developed.