Asymmetric Total Synthesis And Structure Determination Of The Polyketide Natural Product Calixanthomycin A

This dissertation focuses on the synthesis and structural determination of calixanthomycin A.Calixanthomycin A,isolated from S.albus BAC-AB1692/916/170,belongs to the family of polycyclic xanthone-type natural products.It shows a strong inhibitory activity against HCT-116 cells(IC₅₀=0.43 n M).A modular strategy was developed to achieve the first asymmetric synthesis and structural determination of calixanthomycin A.oxa-Pictet-Spengler cyclization,regioselective oxidation construct the lactone A ring.S_NAr reaction and intramolecular Friedel Crafts acylation synthesize the xanthone skeleton.Sonogashira cross-coupling and oxidative cyclization construct the six-ring skeleton.Stereoselective glycosylation of the angular hexacyclic framework and a monosaccharide fragment to afford calixanthomycin A and its stereoisomers.This enables us to determine the absolute configuration of C-25（S）and monosaccharide（derivative of L-glucose）.