Part 1. Studies towards total synthesis of enfumafungin. Part 2. Synthesis of C8 to C13 building block of discodermolide. Part 3. Studies on LAH-mediated regioselective hydroalumination of homopropargyl alcohols. Part 4. Studies towards total synthesis of bielschowskysin.

摘要

Part 1. Enfumafungin belongs to a class of antifungal agents that specifically inhibit 1.3-beta-glucan synthesis in cells and in vitro. Our study focuses on the control of cascade methyl and hydride groups migration by using modified steroids as models. Four types of substrates have been synthesized and tested. The presence of methyl groups and electron-withdrawing groups were found to affect the migration greatly. Part 2. Discodermolide is an antitumor agent that stabilizes microtubules, promoting cell cycle arrest. We tested a consecutive epoxidation-ring opening strategy in the synthesis of the C8-C13 building block of discodermolide. All the intermediate compounds were successfully prepared except for the final product. This unexpected result leads us to consider the role of protective groups in the synthesis of the stereotriads. Part 3. Up to date, only very few studies on hydroalumination of homopropargyl alcohols were reported. Our study aimed at making cis vinyl iodide via iodinolysis of the hydroaluminated homopropargyl alcohols. Different types of homopropagyl alcohols were used and the desired products were obtained with good regioselectivity. Part 4. Bielschowskysin is a recently isolated natural product Pseudopterogorgia kallos. It showed significant antiplasmodial activity against Plasmodium falciparum and strong cytotoxicity against cell lung and renal cancer cell. We employed a cascade 8pi/6pi electrocyclization strategy and obtained the four membered core with the desired stereochemistry in the model study.