Synthetic Studies Towards Calixanthomycin A And IB-00208

Part 1:construction of ABCD rings of polycyclic xanthone natural productsPolycyclic xanthone natural products normally share the similar structural features of A-B-C-D tetracyclic rings,its efficient preparation will facilitate the total synthesis of this family of natural products.The major difference of the tetracyclic rings relies on the substituted groups on the lactam ring.We tried to construct the tetracyclic rings using a C-H bond functionalization strategy,wherein the directing group can act as internal oxidant.After surveying the reaction conditions and reactants,including alkyne and alkene,methyl acrylate was successfully introduced without formation the desired A-B-C-D tetracyclic rings.Part 2:synthesis of aglycone of Calixanthomycin A.Calixanthomycin A and IB-00208,the phenolic O-glycosides,are polycyclic xanthones which exhibit potent anticancer properties.For the construction of A-B ring,we developed a reaction sequence involving the Claisen rearrangement,Wacker oxidation and NaBH₄ reduction.The C ring was built through a photo-induced intramolecular radical cyclization.Then we used the nucleophilic aromatic substitution reaction?S_NAr reaction?to couple the tetracyclic ring with F ring,which was followed by the intramolecular Friedel-Crafts reaction to form the xanthone ring?E-F ring?.Finally,the methoxy protection group was removed by BCl₃.We finished the synthesis of aglycone of Calixanthomycin A.