Synthesis Of Antitumor Natural Product Cytosporone B And Its Analogues

Malignant tumor disease threatens human life and health seriously. In the near future, it would become the number one killer followed by cardio-cerebral vascular diseases. Recently, researches on antitumor drugs have acheived much progress. Among them, small organic molecule drugs are receiving more and more attention.Cytosporone B, a polyketides compound which was isolated from endophytic fungi dothiorella sp. (HTF3), exhibited great antifungal and cytotoxin activities with the potential of pharaiaceutic value. In this dissertation, the synthsis of cytosporone B and its analogues were investigated. The main results are listed as follows:1. Starting from the wildly available 3,5-dihydroxybenzoic acid 2, cytosporone B 1 was synthesized in night steps with an overall yield of 32%. The key step is the activation of the primary alcohol followed by nucleophilic displacement with the elongation of carbon chain. TFAA catalyzed Friedel-Crafts acylation and subsequential deprotection afforded the target molecular.2. Based on the procedure for the synthesis of cytosporone B, twenty-one analogues were prepared with the modification on the carbonyl and the ester functional groups. 3. Cytosporone B analogue 46 with three hydroxyl groups was prepared. 3,4,5-Trihydroxybenzoic acid 33 was first transformed to compound 44 via esterification and hydrolyzation, followed by Wolff rearrangement. Finally, acylation of compound 44 mediated by PPA with n-octanoic acid gave the desired product 46 in 9% total yield.4. Prepared compounds, including cytosporone B 1 and its analogues 1a-1u were evaluated for their potential activities toward the cancer cell line BGC-823 and Saccharomyces cerevisiae. The results showed that an analogue 1r exhibited significant activity in both assays.