Synthesis of methyl pyropheophorbide-a substituted with mono(di)-long chain alkyl group at 3-position

From methyl pyropheophorbide-a (1), the aldehyde chlorin 2 was obtained by the protection of ring-E and oxidation of vinyl group at 3-position. Grignard reaction with long chain alkyl magnesium bromide converted the formyl group into the acyl group. The hydroxyl group of sec-alcohol chlorin 3 was oxidized by mixed oxidizing agent consisting of tetrapropylammonium perruthenate and N-methylmorpholine N-oxide to generate 3-acyl pyropheophorbide-a derivative 4. The Grignard reaction of which with long chain alkyl magnesium bromide was carried out to yield tertiary alcohol chlorin 5 as nucleophilic adduct and chlorin 3 as reduced product. The following dehydration of alcohol chlorin 3 or 5 was performed in the dry benzene at reflux to form trans-form methyl pyropheophorbide-a substituted with mono- or di-long chain alkyl group at 3-position 6 or 7, respectively. The structures of all new compounds were characterized by elemental analysis, UV, IR and H-1 NMR spectra.