Long wavelength photosensitizers related to chlorins and bacteriochlorins for use in photodynamic therapy

A series of long wavelength photosensitizers related to chlorins and bacteriochlorins has been synthesized from the Diels–Alder reaction of protoporphyrin III dimethyl ester 6, or protoporphyrin II dimethyl ester 29. These porphyrins were prepared either by copper(II)-promoted cyclization of the corresponding a,c-biladienes or by following the modified MacDonald dipyrromethane approach. To eliminate the possibility of isomer formation in synthesis of so-called ‘benzoporphyrin derivatives’ and also to understand structure–activity relationships among various photosensitizers, Diels–Alder reactions were also performed on 13,17-bis(2-methoxycarbonylethyl)-2,3,8,12,18-pentamethyl-7-vinylporphyrin 21 and 3-(1-hydroxyethyl)-13,17-bis(2-methoxycarbonylethyl)-2,7,12,18-tetra-methyl-8-vinylporphyrin 22.

[1]  T. Dougherty,et al.  Fast atom bombardment mass spectral analyses of Photofrin II and its synthetic analogs. , 1990, Biomedical & environmental mass spectrometry.

[2]  S. F. Macdonald,et al.  Pyrromethanes and Porphyrins Therefrom1 , 1960 .

[3]  Ian K. Morris,et al.  The synthesis of dihematoporphyrin ether and related porphyrin dimers , 1988 .

[4]  R. Pandey,et al.  Reactions on solid supports part II: a convenient method for synthesis of pyrromethanes using a montmorillonite clay as catalyst , 1985 .

[5]  B W Henderson,et al.  Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor. , 1987, Cancer research.

[6]  Kevin M Smith,et al.  Syntheses of isomers of protoporphyrin-IX with permuted propionic side-chains , 1985 .

[7]  T. Dougherty,et al.  Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue. , 1979, Cancer research.

[8]  T J Dougherty,et al.  Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. , 1976, Cancer research.

[9]  D. Dolphin,et al.  A convenient synthetic route to the bacteriochlorin chromophore , 1991 .

[10]  T J Dougherty,et al.  STUDIES ON THE STRUCTURE OF PORPHYRINS CONTAINED IN PHOTOFRIN® II , 1987, Photochemistry and photobiology.

[11]  R. Dinello,et al.  Reactions of protoporphyrin with tetracyanoethylene , 1980 .

[12]  Kevin M Smith,et al.  Total syntheses of derivatives of protoporphyrin IX regioselectively labeled with carbon-13 in the methyls , 1986 .

[13]  Albert W. Giroti,et al.  MECHANISMS OF PHOTOSENSITIZATION , 1983 .

[14]  P. Clezy,et al.  The chemistry of pyrrolic compounds. LV: 13C chemical shift data for the isomeric protoporphyrins , 1984 .

[15]  D. Kessel,et al.  Fast atom bombardment mass spectrometry of high-molecular-weight fraction of porphyrin-based photodynamic therapy drugs. , 1988, Biomedical & environmental mass spectrometry.

[16]  T. Dougherty,et al.  Syntheses and photosensitizing activity of porphyrins joined with ester linkages. , 1989, Cancer research.

[17]  S. Britton,et al.  Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light. , 1984, Cancer research.

[18]  Kevin M. Smith,et al.  Efficient synthesis of porphyrin dimers with carbon-carbon linkages , 1990 .

[19]  R. Chong,et al.  The chemistry of pyrrolic compounds. VII. Synthesis of 5,5'-diformyldipyrryl-methanes , 1969 .

[20]  J. Parrish,et al.  Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. , 1974, The New England journal of medicine.

[21]  W. Star,et al.  Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. , 1986, Cancer research.

[22]  A. Richter,et al.  THE PLASMA DISTRIBUTION OF BENZOPORPHYRIN DERIVATIVE and THE EFFECTS OF PLASMA LIPOPROTEINS ON ITS BIODISTRIBUTION , 1990, Photochemistry and photobiology.

[23]  D. Dolphin,et al.  Preliminary studies on a more effective phototoxic agent than hematoporphyrin. , 1987, Journal of the National Cancer Institute.

[24]  Kevin M Smith,et al.  New efficient total syntheses of derivatives of protoporphyrin-IX bearing deuteriated methyl groups , 1983 .