Reaction of nickel(H) or copper(H) porphyrins with 3-dimethylamino-acroleinlPOC13 gives meso-(2formylvinyl)-porphyrins, which @ier strong acid treatment give the corresponding benzochlorins. Use of nickel(U) or copper(II} chlorine gives benzoisobacteriochlorins; a modification also gives benzobacteriochlorins. Reductive coupling of (2-formylvinyl) derivatives gives carbon-carbon linked dimers.
PHOTOFRIN-II@
is the only drug currently being evaluated in phase III clinical trials for treatment of various tumors using photodynamic therapy (PDT). It is a purified form of "hematoporphyrin derivative" prepared from hematoporphyrin IX dihydrochloride in two steps by modifications of Lipson's pr0cedure.l Photofrin-II@ is a complex mixture of porphyrins, believed to be porphyrin dimers and higher oligomers joined by ether, ester, and/or carbon-carbon linkages, and chemical syntheses of all of these types of linked dimers and oligomers have recently been reported.z-7 Amongst numerous other sensitizers for PDT,8-10 purpurins9 and benzochlorinsto have shown promise. We now outline a new route to benzochlorins using procedures applicable also to purpurin synthesis, and show that intermediates in these approaches can be used IO furnish carbon-carbon linked porphyrin dimers related to one of the active principles7 in Photofrin-II@.