Asymmetric Synthesis And Activities Study Of Novel Analogues Of Natural Products Jaspine B

Polysubstituted tetrahydrothiophenes are common structural motifs found in natural products and biologically active molecules such as(+)-biotin,tetronothiodin,kotalanol and salacinol.Due to their biological activities including antitumour,antidiabetes,antimicrobial,antimalarial as well as challenging structures,development of methods for synthesizing differently substituted tetrahydrothiophenes have become important.Jaspine B,a marine natural product,which has a tetrahydrofuran ring possessing three contiguous stereogenic centers.Untill now,to the best of our knowledge,there is only one sulfur analogue of jaspine B has been reported,which is known as S-jaspine B.Fortunately,S-jaspine B was found to be much more effective than jaspine B at inhibiting cancer cell growth.This has made us generated a great deal of interest in the synthesis of other sulfur analogue of jaspine B and their activities.In this thesis,we desined a new strategy to synthesize a series of new analogues of jaspine B and(+)-biotin via Sodium carbonate induced intramolecular cyclization.And we used Hydroboration oxidation reaction to form the C-2,C-3 chiral centers.After the successful total synthesis,the cytotoxic activities of analogues 1,2 and 3 and Jaspine B were examined to study the effect of the substituent on antitumor activity of these molecules.We were delighted to find that the anti-prostate activities of analogue 3 was better than Jaspine B,analogue 2 could selectively inhibit the growth of prostate cancer cells,and find that the 14-carbon side chain is important for Jaspine B and its analogues.