TOTAL SYNTHESIS OF DESOXOPROSOPHYLLINE - APPLICATION OF A LACTAM-DERIVED ENOL TRIFLATE TO NATURAL PRODUCT SYNTHESIS

The total synthesis of desoxoprosophylline 1 from a piperidinone-deriv ed enol triflate 8 has been realized and is one of the first applicati ons of such lactam-derived triflates to natural product synthesis. Pal ladium-catalyzed methoxycarbonylation of 8 followed by 1,2-reduction a nd protection introduces the required C2 hydroxymethyl group, affordin g 10. The C3 hydroxy function is stereoselectively added by a novel N- tosylenamide hydroboration (de 88%), and the final C6 dodecyl chain is incorporated with complete stereocontrol, in a single step, via an N- tosyliminium ion-allylsilane coupling. Deprotection gives the natural product in an efficient 7.5% yield over nine steps.