Divergent total synthesis of conidiogenones and mechanistic studies of Au(I)- and Cu(II)-mediated transformations

Abstract

1. The diverse and complex structures and biological activities of the natural products made that many organic synthesis researchers have targeted. Conidiogenones have highly congested 6/5/5/5-fused tetracyclic framework with up to 8 contiguous stereogenic centers of which 4 of them are quaternary carbon centers and biological activities as the secondary metabolites including cytotoxic, anti-inflammatory, anti-microbial, and anti-allergic effects. Although they have been attractive targets, there was not reported any divergent total synthesis of conidiogenones because of the their highly congested and complex structures. Divergent synthetic strategy is very useful, effective and challenging strategy when total synthesis of the natural products which have the same frameworks. Using trimethylenemethane (TMM) diyl cycloaddition reaction of the allenyl diazo compound produced desired tetracyclic skeleton. Through the selective oxidation from the common intermediate, collective synthesis of six conidiogenones, including three first total synthesis was achieved. 2. Phorbaketal A and Alotaketal A are the natural products which have spiroketal framework. In the previous total synthesis of the phorbaketal A and toward synthesis of the phorbaketal A, the rearrangement of the epoxide to the allylic alcohol were very challenging step. To improve this issue and for the asymmetric total synthesis of the alotaketal A, development of the Au(I)-mediated spiroketalization of epoxy-alkyne-diol and mechanistic studies were achieved. 3. In the previous researches for the modification of dehydroalanine unit in proteins, undesired side products were obtained. To improve the requirement of oxygen-free reaction condition and dialkylated undesired product issues, optimization of the Zn/Cu-promoted 1,4-addition reaction condition and mechanistic studies were achieved.