Asymmetric Total Synthesis Of Natural Products Jaspine B And Its Isomers

Polysubstitutedtetrahydrofurans are important structural motifs that are found in natural products that exhibit useful biological properties. The research work presented in this thesis describes the total synthesis of the tetrahydrofuran-containing natural product pachastrissamine(Jaspine B), as well as the development of new synthesis methods towards all three of its diastereomers.Jaspine B, the first naturally occurring anhydrosphingosine derivative, was isolated in 2001 by Higa and co-workers from an Okinawan marine sponge Pachastrissa sp.. Later in 2003 Debitus and co-workers isolated the same compound from a Vanuatuan marine sponge genus Jaspis. It was found to possess marked cytotoxicity at a level of IC50 lOng/mL against P388, A549, HT29 and Mel 28 cell lines.A divergent novel and effective route for the stereoselective synthesis of Jaspine B and all three of its diastereomerswere achieved. The route consists of 17 steps from the commercially available L-serine as the sole chiral source. The furan framework is formed by use of Silver nitrate catalyze intramolecular cyclization. With this cyclization as the key step, Natural Jaspine B was synthesized by stereospecific reduction reaction through stereo-hindrance effect.3-epi-Pachastrissamine was obtained after the key step through Hydroboration-oxidation reaction.2-epi-and 2,3-epi-pachastrissamines were synthesized by hydrogen induced effect with the selectivity was 3:1 (syn/anti). the synthesis route also involves an important nitrogen-containing organic bases, the diisopropylethylamine, which can be efficient and convenient to change the configuration of the long alkyl side chain.