Synthesis of a membrane-spanning lipophilic porphyrin with links to two alamethicin fragments on each face

We have successfully synthesised alpha,beta,alpha,beta-tetrakis(2-amino-5-d odecyloxyphenyl)porphyrin in high yield. Its porphyrin precursor with nitro groups was synthesised without the use of high dilution. The dodecyloxy gr oups of this precursor increased its solubility. The yield of the desired a lpha,beta,alpha,beta-atropisomer of the nitro-precursor could be enriched t o 60% by treatment in hot toluene. The reduction of the nitro groups to the amino groups was carried out at room temperature. Thus, alpha,beta,alpha,b eta-tetrakis(2-amino-5-dodecyloxyphenyl)porphyrin was synthesized under mil d conditions on a multigram scale. This porphyrin possesses two amino group s and two dodecyloxy groups on each face of the porphyrin plane. It was com bined with a fragment of alamethicin, a typical membrane peptide, to give a porphyrin-polypeptide hybrid, in which two hydrophobic polypeptides existe d on each face of the porphyrin. This conjugate was successfully embedded i nto the lipid bilayer membrane. The resulting mixed vesicle showed the CD p rofile of a helical peptide. Thus, a membrane-penetrating columnar structur e of alpha,beta,alpha,beta-tetrakis(2-peptidyl-5-dodecyloxyphenyl)porphyrin in the lipid bilayer membrane was suggested.