Download (direct link):
coworkers,309 Comia et al.,310 Momenteau and coworkers,311 and Ono et
al3X2 (Schemes 77 and 78). The highest activity was observed for a
derivative having four OH-protected glucose moieties. Krausz and
coworkers reported the preparation of glycosylated peptide porphyrins
391-398 as shown in Scheme 79. Maillard et al.313 reported the synthesis
and in vitro photosensitizing efficacy of a glycoconjugated meso mono-
arybenzochlorin 403. This compound was obtained by first reacting
monoarylporphyrin 399 with 3-(dimethylamino) acrolein. The
formylvinylporphyrin 400 thus obtained produced the desired benzochlorin
(Scheme 80) upon regiospecific cyclization under acidic conditions and
subsequent glycosylation. This compound displayed good in vitro
phototoxicity on tumor cell lines after irradiation with light.
Bonnett and coworkers314 reported the synthesis, starting with jS-
hydroxyoctaethylchlorin 404, and the in vitro photosensitizing efficacy
of the related glycosylated chlorin 405. This product was found to be
more effective than the unconjugated analogue (Scheme 81).
Montforts et al.315 further explored this approach by attaching
hydrophilic carbohydrate structural units to certain chlorins (e.g.,
406). Such conjugation increased the water solubility of the parent
chlorins 407 and 408. By introducing an estradiol with a diethyl spacer,
the chlorin-estrogen conjugate was then prepared in the hope that it
would bind to an estrogen receptor which could induce selective
destruction of mammalian carcinoma (Scheme 82).
Frank et al. reported the preparation of isohematopor-phyrin
diglycosides 410 that exhibit excellent water solubility (Scheme 83).316
The isohematoporphyrin 409 used as a starting material was obtained from
protoporphyrin IX by following the methodology developed by Smith and
B. BARBITURIC ACID FUNCTIONALIZED PORPHYRINS AND CHLORINS
Porphyrins and chlorin derivatives bearing a thiobarbaturic acid
functionality at the meso- and Ä-pyrrole positions have been synthesized
by Morgan et al.3ls and Pandey et al.319 from a series of chlorins 411-
416. All these free-base metallo derivatives show highly perturbed
electronic spectra, with major absorptions observed in the range of 700-
870nm (Scheme 84).
C. NUCLEOSIDE ADDUCTS OF PORPHYRINS AND CHLORINS
Porphyrins coupled with nucleosides have attracted attention owing to
their strong tumoricidal activity against human malignant melanoma320
Czuchajowski et al. reported the first representatives of porphyrin
nucleosides.321 Smith and coworkers322"323 have reported a facile
approach for the preparation of ethene-linked nucleoside derivatives 419,
420, 422 and 423 by palladium-catalyzed coupling (Heck-type reactions)
between acetylated 5-chloromercuriuridine 418 and various vinylporphyrins
(e.g., 417) and vinylchlorins (e.g., 421) (see Scheme 85).
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 69. Chlorin dimers from w'c-dihydroxy bacteriochlorins.
333b R = CH=CH2
338a, 338b 339a, 339b
a R = C2H5
b R = CH(CH3)OC7H15
D. PORPHYRINS CONTAINING SIX-MEMBERED RINGS
The first synthesis of a porphyrin containing a pyridine ring was
reported by Bonnett and coworkers.324 Recently Lash et a/.,325-326 and
Breitmour et al,327 independently synthesized similar structures named
oxypyriporphyrin and pyr-iporphyrinone (424 and 425) via the 3 + 1
approach (Scheme 86) [see Chapters X by Lash and Chapter by X Smith].
These novel 18 ë; aromatic porphyrinoides exhibit spectroscopic
properties similar to porphyrin-type systems but with a significantly
red-shifted Soret band. Two examples of secochlorins 426 and 427 have
also been reported by Bonnet et al.328 and Dolphin and coworkers.329 Both
secochlorins were derived from the oxidative cleavage of the
corresponding Ni-v/c-dihydroxyoctaethylchlorin and
Ni-v/c-dihydroxy tetraphenylchlorin. Reaction of 426 and 427 with
methanolic HC1 afforded the corresponding cyclized oxybenziporphyrins 428
and 429, respectively, in high yield (Scheme 87).
Following the successful synthesis of verdinochlorins by reaction of
13-oxypyropheophorbide a with diazomethane, Pandey and coworkers330
explored the utility of this methodology in synthesizing porphyrin
derivatives containing diketo- and tetraketo-pyrrole ring systems.
Reaction of diketo-chlorin 430 with diazomethane gave a mixture of 2-oxy-
3-epoxymethylene-TPC 432 (minor product) and methoxypyridinoporphyrins
433 and 434. The ring-enlarge-ment reaction was extended to
tetraoxobacteriochlorin 435, which produced 436 and 437 as isomeric
mixtures. This reaction represents a novel approach for porphyrin
modification (Scheme 88).
Pandey and Zheng
Scheme 70. Mechanism for the formation of the carbon-carbon dimer via o-
XI. Endogeneous Porphyrins from ALA
Most forms of photodynamic therapy involve the administration of