Application of new synthetic methodologies to access 2,6-anti-tetrahydropyrans : towards the total synthesis of apicularen A
Chua, Sin Siu
Date of Issue2014
School of Physical and Mathematical Sciences
This dissertation is intended to be a comprehensive research progress report of my pursuit towards a PhD degree in Chemistry at Nanyang Technology University under the tutelage of Dr. Motoki Yamane and Prof. Loh Teck Peng. It would be my honour and pleasure if this dissertation of mine could be of any help to fellow PhD aspirants, undergraduates as well as practitioners of synthetic organic chemistry, who are doing related research. This dissertation consists of four chapters. The first chapter aims to provide a general idea of what total synthetic chemistry is as well as its significance and relevance to both the chemical society and general public. The motif of interest, 2,6-anti-tetrahydropyran was then introduced and its prevalence in natural products was illustrated alongside with a discussion on the construction of the 2,6-anti-tetrahydropyran motif in total syntheses of three different natural products, namely Swinholide A, Irciniastatin A and (-)-Aspergillide B. Thereafter, the development of our group’s methodologies to construct cyclic ethers was showcased in a chronological order. In the second chapter, the target molecule, Apicularen A, was introduced, briefly describing its isolation, structural elucidation as well as its biological significance. We then delved into previously reported synthetic efforts towards the synthesis of Apicularen A by various research groups, highlighting the three key reactions, which are the construction of 2,6-anti-tetrahydropyran ring, the formation of 12-membered ring macrolactone and the installation of highly unsaturated side chain. The third chapter consists of our group’s synthetic studies towards Apicularen A. The progress from preliminary retrosynthetic analysis, alongside with its synthetic route, to the revised versions, was described and elaborated to the best of the author’s knowledge. Experimental procedures and structural data, complete with supporting spectra and other data analysis, can be found in the last chapter.