Total Synthesis Of Dendrodolide A,B And Their Derivatives

In the past 50 years, macrolide compounds have attracted the attention of synthetic chemists. There are two reasons: first macrolides have good biological activity, and have been widely used in clinical medicine; second, the unique structure of macrolide compounds, are also meaningful for synthesis. Accordingly, this thesis focused on the total synthesis of several macrolide compounds and their biological activity exploration, and the contens could be divided into the following two parts.Chapter 1. Research progressing on macrolide compoundsWe brief ly introduced the classification, biologically activity and the synthetic method of macrolide compounds, We also expounded the source, research purpose and the main contents of this research.Chapter 2.Total Synthesis of Dendrodolide A, B and Their DerivativesStarting from 1,3-propanediol, the efficient synthesis of acid fragment was achieved in 8 steps with 48.1% over yield and 91% ee. using Wittig reaction and Sharpless Asymmetric Epoxidation as the key steps. Then we successful synthesized the alchol fragment in 10 steps with 18.5% over yield, using(R)-3-hydroxybutyrate as starting material. Finally, we completed the synthesis of Dendrodolide A, B in 5 steps, using Yamaguchi esterification and RCM reaction as the key steps.Anther research emphasis of our research is to explore the biological activity of these natural macrolides derivatives. Therefore, we further modified the structure of macrolide Dendrodolide A, B and successfully synthesized four new natural macrolide derivatives. We denoted them as: Dendrodolide X?Compound-1?Compound-2?and Compound-3. Dendrodolide X is the epimer of the Dendrodolide A and Compound(1,2,3) are derivatives of Dendrodolide A, B&X. Next we'll test the biological activity of these compounds, and this work is in progress.