Studies On The Synthesis Of Rubriflordilactone B

This dissertation mainly describes our total synthesis approach of rubriflordilactone B, which shows an anti-HIV bioactivity. The artical includes two chapters: Chapter 1 The recent development of Schisandra triterpenoids.Schisandra triterpenoids were isolated from the Schisandra, widely used in traditional chinese medicine, which posess a fused ring system and highly oxygenated structure. In this Chapter, we describe the isolation, framework, bioactivities of Schisandra triterpenoids. Preliminary biological assays indicated these compounds shows a variety of bioactivities, antihepatitis, modulate the immune system, anti-HIV etc. And the biosynthetic route of these compounds were also described in this article. In this part, we mainly introduce the total synthesis work of schindilactone A and propindilactone G presented by Yang’s group, the total synthesis of rubriflordilactone A by the research groups of Li and Edward A. Anderson, and the total synthesis of schilancitrilactone B and C by the research group of Tang. Chapter 2 Studies on the total synthesis of Rubriflordilactone B.Rubriflordilactone B was isolated from the leaves and stems of Schisandra rubriflora by Sun et al. in 2006, Preliminary biological assays indicated that rubriflordilactone B exhibited a fairly strong bioactivity against HIV-1 replication with an EC50 value of 9.75 μg/m L(SI = 12.39) and low cytotoxicity. Rubriflordilactone B contains rarely tetra-substituted arene and seven rings with eight chiral centers. Because of it’s novel structures and diverse biological activities, we choose rubriflordilactone B as the target molecular.From the easily obtained material 2-82 and 2-176, we designed a convergent synthetic strategy. Through Mukaiyama-Michael additon, oxo-Micheal addtion, we completed the synthesis of C-5-epi AB moiety in moderate yield, 97% ee value. The compound 2-182 and 2-227 undertook coupling reaction followed by deprotection and [2+2+2] cycloaddion. Finally, we disclosed the C-5-epi ABCDE-ring system of the target molecule in the longest linear sequence of 10 steps.This article also describes the synthesis of the F ring via the polar-radical-crossover cycloaddition(PRCC) as a key step. From the commercial available starting materials 2-239 and 2-242, we forged the four consecutive chiral centers of F ring in single step. Thus, the compound 2-241 was obtained in four steps. A concise and efficient synthesis route of racemic synthesis DEFG ring of rubriflordilactone B was bulid.