The details of the intramolecular 1,3-diyl trapping reactions are being investigated and the results of the investigations are being applied to the total synthesis of natural products. This proposal describes the use of the intramolecular diyl trapping reaction to complete a total synthesis of the very important and potent antiviral and anticancer agent aphidicolin (1). The key steps of the sequence involve (a) a reverse regiochemical mode of addition of a diylophile to a diyl (18 Greater than 19) to first create the CD ring system, including the """"""""troublesome"""""""" pro C9 quaternary carbon, and (b) an intramolecular Diels-Alder reaction (20 Greater than 21) to add rings A and B onto the CD unit. In addition, total syntheses of the anticancer agents diketocoriolin B (2) and hypnophilin (26) are described. The route outlined utilize a regiochemical mode of intramolecular diyl trapping and can be adapted to allow the synthesis of each in chiral form.
