Model studies for the synthesis of the marine hepatotoxin cylindrospermopsin. Preparation of a bicyclic guanidine with the hydroxymethyluracil side chain

Abstract

Ketone 13 was prepared by coupling acetylene 7b with aldehyde 9 in a convergent six-step sequence. In the key step, hydrogenation of bromo ketone 14 afforded 81% of an 81:14:4.5:0.5 mixture of 15–18. Hydrolysis of the major product 15 in concentrated hydrochloric acid at reflux afforded cylindrospermopsin model 5 in 95% yield.