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The porphyrin handbook - Kadish K.M.

Kadish K.M. The porphyrin handbook - Academic press, 2000. - 368 p.
Download (direct link): kadishsmishgulilard2000.djvu
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dimethylpyridi-niumpurpurin 95175 (Scheme 26).
3. Verdins
Many years ago Fischer and Orth176 discovered that treatment of
mesoporphyrin IX 96 with oleum afforded the cyclized anhydro compounds,
the so-called rhodins 97. Since that time, several groups have further
investigated the
Pandey and Zheng
Scheme 20. Naphthalochlorin via intramolecular cyclization.
Scheme 21. Naphthochlorins from 2-nitro-5,10,15,20-tetraphenylporphyrin.
R = Et, Pr, Benzyl or t-Bu
Scheme 22. Intramolecular cyclization of b-formyl-tetra-(methoxyphenyl)-
porphyrin under acidic conditions.
Scheme 23. Some novel benzochlorins from 5,15-diphenylporphyrin. (
(i) Me2N(CH2)2CHO, POCI3; (ii) BF3.Et20; (iii) TFA/H2S04.
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 24. Synthesis of chlorins with fused nitrogen-containing rings.
(i) ямнямн, THF/EtOH,A ; (ii) Montmorillonite K10, toluene, A.
Scheme 25. Preparation of purpurins.
meso-Formyl OEP
88a M = 2H 88b M = Sn
meso-Formyl etioporphyrin
89a M = 2H 89b M = Sn
chemistry of these compounds.177-179 Morgan's group, in particular,
evaluated the PDT efficacy of rhodins and their oxidation products, the
verdins 98 (Scheme 27). Verdins in general were found to be more
effective than their related rhodin analogues.
A new class of long-wavelength photosensitizers (738-798 nm) named
verdinochlorins 100 were recently reported by Pandey and coworkers.180
These compounds were obtained by the reaction of 132-oxopyropheophorbide
a 99 with diazomethane which produces the isomeric verdinochlorins 100
via expansion of the cyclopentanedione ring E (Scheme 28). These long-
wavelength photosensitizers represent the first example of verdins with a
reduced pyrrolic-ring system.
Among synthetic porphyrins, me.vo-tetraphenylporphyrin [H2(TPP)] is the
most easily accessible porphyrin.
Converting the meso-hydroxytetraphenylporphyrin derivatives 101 into
me.vo-tetraphenylchlorin 102 derivatives generated chlorins with
favorable photophysical properties. Bonnett et a/.181 used the diimide-
reduction method introduced by Whitlock et al.182 and synthesized a
series of meso-tetra(hydroxyphenyl)chlorins [H2(THPC)] and investigated
their PDT efficacy (Scheme 26).183 184 Among these analogues, the m-
isomer [H2(m-THPC)] 102b appeared to be the most promising candidate for
PDT.185 Interestingly, in combination with mitomycin, the H2(m-THPC)
showed enhanced PDT efficacy (Scheme 29).186
In the early 1940s Fischer et al. reported that the octa-alkylporphyrins
can be oxidized with OsC>4 to yield the corresponding vi'c-
dihydroxychlorins 103.187 188 This approach was later extended to prepare
ketochlorins via
Pandey and Zheng
Scheme 26. Preparation of purpurins from 5,15-disubstituted H2(OEP).
Et Et
Et Et
Scheme 27. Preparations of rhodins and verdins. (Only one of the isomers
is shown.)
PMe = CH2CH2C02CH3
acid-catalyzed pinancol-pinacolone rearrangement 104 (Scheme 30).189-192
In recent years, it has been shown that some of the ketochlorins and
their vic-dihydroxy precursors show in vivo photosensitizing properties.
Bonnett etal. demonstrated that the dihydroxychlorin 103 possesses quite
effective in vivo activity when dissolved in dimethyl sulfoxide.193
Kessel and coworkers194 reported a dioctyl-substituted ketochlorin 105
(C8KC) that, due to its low water solubility, could be formulated using
various solvents. It is interesting to note that the use of Cremophor EL
(CRM) for C8KC formulation was associated with longer tissue persistence
and enhanced
PDT efficacy, while Tween 80 did not show such an effect. These results
indicate that the delivery vehicles also play an important role in PDT
From the in vivo biological data obtained from the photo sensitizers
related to phthalocyanines, it has been suggested that in this class of
compounds there is a possibilty that the nitrogen atoms present at the
meso positions of the macrocycle might have an important role in
localization of the drug in tumor cells. However, it is still not
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 28. A new approach to the preparation of verdinochlorins.
clear if all four meso nitrogens are necessary to achieve the otimum
efficacy. Montforts et al,'95 aimed at improving the photophysical
properties of chlorins and reported the preparation by photo-oxygenation
of 5-azachlorins 109a
and 109b from 5-azaprotoporphyrin IX dimethyl ester 108. The 5-
Azaprotoporphyrin IX dimethyl ester, in turn, was prepared from naturally
occurring bilirubin using Fuhrhop and coworkers' procedure.196 The 5-
azachlorins (e. g., 109) exhibit enhanced absorption at 674 nm (e =
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