The Synthesis of the Dimethyl Ester of Quino[4,4a,5,6‐efg]‐Annulated 7‐Demethyl‐8‐deethylmesoporphyrin and Three of Its Isomers with Unprecedented peri‐Condensed Quinoline Porphyrin Structures. Molecules with Outstanding Properties as Sensitizers for Photodynamic Therapy in the Far‐Red Region of the Visible Spectrum

Abstract

The mesoporphyrin dimethyl ester nickel complex has been formylated via the Vilsmeier method. The four possible mono meso-formyl derivatives were isolated and characterized. Wadsworth−Emmons coupling with the anion of (diethylphosphono)acetonitrile converted these aldehydes into the four novel meso acrylonitriles. Brief treatment of these acrylonitrile systems in hot trichloroacetic acid resulted in the formation of four achiral porphyrin derivatives with unprecedented nickel complexes of quino-fused porphyrins. Subsequent removal of the nickel gave four quino-porphyrin free bases: quino[4,4a,5,6-efg]-annulated 7-demethyl-8-deethylmesoporphyrin dimethyl ester 6a, 2Ј-(methoxycarbonyl)quino-[4,4a,5,6-jkl]-annulated 12-demethyl-13-de[2Ј-(methoxycarbonyl)ethyl]mesoporphyrin dimethyl ester 6b, 2Ј-(methoxycarbonyl)quino [4,4a,5,6-qrs]-annulated 18-demethyl-17-de(2Ј-methoxycarbonylethyl)mesoporphyrin dimethyl ester 6c and quino [4,5,6,7-abt]-annulated 2-demethyl-3-deethylmesoporphyrin dimethyl ester 6d. The structures of these systems were unambiguously determined via mass spectroscopy and a plethora of NMR techniques. In the same way, etioporphyrin and octaethylporphyrin were converted into the corresponding peri-condensed quinoporphyrins as products, which shows that the formation of novel peri-

Synthesis of the Dimethyl Ester of 2'‐Cyano‐8'‐formyl‐N'‐methyl‐1',1a',5a',6'‐tetrahydroacrido[4,5,5a,6‐bcd]‐Annulated 2,3‐Dihydromesoporphyrin – A Novel System with Outstanding Properties as Basis for Photodynamic Therapy in the Far‐Red Region of the Visible Spectrum

“…This mixture shows a strong absorption in the visible spectrum at 633 nm. The HR-FAB mass spectrum shows two parent peaks, one large signal at m/z = 684.2134 corresponding with an elemental composition 12 1 H NOESY NMR spectroscopy and comparing this with the analytical properties of 2 [1] we found that the structure of the main compound is 7 as depicted in Figure 7. The minor compound has one carbon and two hydrogen atoms more than 7.…”

“…The signals that point downwards are those of car- Figure 2A it can be seen that the aromatic carbon atom at position 2 1 only has unique 3 J( 13 C-1 H) interactions with the protons at positions 2 1 Ј and 2 5 . The only carbon signal that shows these interactions in the 2D 1 H-13 C HMBC spectrum is that at δ = 126.3 ppm, which is therefore ascribed to carbon atom 2 1 . The carbon resonance at δ = 149.2 ppm shows 3 J( 13 C-1 H) interactions with the protons at positions 2 2 , 2 4 , 2 7 Ј and 2 8 .…”

“…From 2D 1 H NOESY NMR spectroscopy and comparison with the analytical properties of 2 this compound turns out to be the 5 6 -methyl-substituted quinoporphyrin 8 as depicted in Figure 7. Based on our earlier detailed structure elucidation of peri-annulated quinoporphyrin systems [1] and the 600 MHz 1 H NMR spectrum of the mixture of 7 and 8, the assignment of all signals could be performed and the structures of 7 and 8 established without any ambiguity.…”

“…The [5-(2Ј-Cyanovinyl)mesoporphyrin dimethyl ester]-nickel complex was prepared according to our earlier paper [1] and treated with a sixfold excess of Vilsmeier-Haack reagent prepared from N-methylformanilide and phosphorus oxychloride After hydrolysis and purification on silica gel, 130 mg (22 %) of a novel green compound 4 with a strong absorption at 650 nm ( Figure 1) was obtained along with a mixture of the expected meso-formylated products. From the latter mixture the pure [20-formyl-5-(2 Ј -cyanovinyl)mesoporphyrin dimethyl ester]nickel complex 6 could be isolated.…”

“…[1] This reaction is unique, because in a series of steps two aromatic rings are annulated to the porphyrin system. We also found system of the Vilsmeier reagent is intimately involved in this reaction.…”