Synthesizing Demanding Tri-substituted E-olefins Through An MBH-RCM Sequence

Autolytimycin is apolyketide natural product isolated from the culture broth of Streptomyces Autolyticus found in Yunnan of China and features a 19-membered ring macrolactam.This macrolactam belongs to ansamycin antibiotics,many members of this family exhibit potent anticancer activities,e.g.This thesis research describe a strategy to synthesize the demanding tri-substituted?E?-double bond throngh the MBH-RCM sequence reactions.The total synthesis of Autolytimycin is based on this model study and hopeful to complete in due course.Chapter 1 briefly introdues the research background as well as main content of this thesis.Besides,the structures and anticancer activity of the ansamycin family were also included.It is followed by an review on synthesis methods of tri-substituted?E?-double bond for ansamycin chains.Chapter 2 briefly introdues the MBH reaction and its mechanism,specially decribing the application of RCM reaction in total synthesis of natual products with an emphasis on constructing trisubstituted?E?-double bond of 17-membered ring,14-membered ring,11-membered ring,8-membered ring and 6-membered ring compounds.Chapter 3 diseusses in detail on the model study on contructing ?,?,unsatured 6-membered lactones,in which the phenyl aldehyde as the starting materials undergoes the reactions of MBH,hydrolysis,Yamaguchi esterification and RCM,and explores and optimizes the condition of RCM reaction.Chapter 4 Chapter 3 diseusses in detail on the model study on contructing trisubstituted?E?-double bond,in which the phenyl aldehyde as the starting materials undergoes the reactions of MBH,Yamaguchi esterification,RCM,reduction,and Barton deoxygen,et al.Chapter 5 firstly describes an review on the difluoromethylation reactions and its applition in the aromatic fragment of autolytimycin as well as piperazine derivantives.The main experimental procedures,the characterization data for the key intermediates and the final product,and the cited references are found at the end of the thesis.Copies of original ¹H and ¹³C NMR spectra are given in the Appendix.