The Synthetic Study Of Anti-tumor Compound Phomopsin B

The directed activation and functionalization of carbon-hydrogen bonds of organic compounds has recently emerged as a powerful and ideal method for the formation of different functional groups. In the syntheses of useful molecular entities, this approach not only streamlines existing synthesis strategies, but also broadens retro synthesis with new rational disconnections. Thus, such strategies has been gradually utilizated in total synthesis of natural products. Pursuant to this goal, we explored directed carbon-hydrogen bond functionalization to fulfill the synthesis of Ustiloxin D and Phomopsin B in this thesis.Chapter1briefly introduces carbon-hydrogen bond activation catalytic oxidation. Since the oxidation of carbon-hydrogen still remains as immense challenges, it provides chemists excellent chances to develop different methods for the diversity of substrates. Herein, we summarize several traditional methods and also enumerate some applications in the total and partial synthesis of natural products.Chapter2concerns the reported total synthesis of Ustiloxin D and Phomopsin B. Dr. Joullie’s and Dr. Wandless’s groups have focused on several routes to the total synthesis of these two natural products. Inspired by their work and the methodology study of carbon-hydrogen bond functionalization, we designed new synthetic skills and strategies for these syntheses.Chapter3details our research in carbon-hydrogen functionalization. We explored different transition-metal catalysis, including Pd, Ru, Fe and Cr compounds for tertiary carbon-hydrogen bond oxidation. Finally suitable methods was established for the synthesis of chiral tertiary alcohol, and further optimization of the reactions will be continued for higher yields. Moreover, this part also covers the investigation of tertiary alcohol-SNAr reaction, unactivated primary sp3C-H arylation and unactivated secondary sp3C-H acetoxylation.Chapter4reports our synthetic approaches of Phomopsin B. Based on the results of methodology study we have achieved, we designed two synthetic routes and started our synthesis of Phomopsin B. The coupling of the alkyl-aryl ether bond by S^Ar reaction was employed as a pivotal step in both two routes.Finally, the experimental section, full characterization data for all products, cited references, some copies of selected original1H NMR and13C NMR spectra are found at the end of the thesis.