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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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converted into the corresponding vi'c-dihydroxy-bacteriochlorins 144 and
isobacteriochlorins 145, respectively. Acid-catalyzed pinacol-pinacolone
rearrangement converts the vi'c-dihydroxy-bacteriochlorins 144 into the
corresponding ketobacteriochlorins, as an isomeric mixture containing
146a and 146b, in a reasonable yield (Scheme 41). Bonnett et al. employed
this approach to prepare bacteriochlorins related to 147. Some of these
compounds showed considerable PDT efficacy in vitro.193 A few years later
Pandey et al. extended this methodology to the pheophorbide a and chlorin
eb pigments and prepared a series of v/c-dihydroxy- and keto-
bacteriochlorins 148-151,220'221 (Scheme 42). Though the stable
bacteriochlorins prepared from mesochlorin <?<-, trimethyl ester and
methyl pyropheophorbide a had strong absorptions in the red region of
their electronic spectra (730-750 nm), these compounds did not show any
significant in vivo photosensitizing activity.222
C. BACTERIOCHLORINS VIA A DIELS-ALDER
REACTION APPROACH
Pandey et al.148 and Dolphin and coworkers223 reported the synthesis of
new bacteriochlorins which involved the double
186
Pandey and Zheng
Scheme 42. Stable bacteriochlorins from chlorins.
Methyl mesopyropheophorbide a
148
149
Mesochlorin e5 trimethyl ester
151
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
187
Scheme 43. Synthesis of bacteriochlorins by the double Diels-Alder
approach.
DMAD
DBU
Me2^ Me02C ,C02Me
152
C02Me
C02Me
153
155
Diels-Alder reaction on divinylporphyrins 152 and 153 (Scheme 43). Such
bacteriochlorins 154 and 155 show long-wavelength absorption maxima near
800 nm with limited PDT efficacy.224
Morgan et al.225 have shown that bacteriochlorin-like macrocycles 157
can be generated through cyclization of either 5,10- or 5,15-
bis[(ethoxycarbonyl)vinyl]-porphyrins (e.g., 156). However, the resulting
products are rapidly decomposed upon exposure to air, thus precluding
their use as photosensitizers for PDT. To achieve more stable
bacteriochlorins, they modified the pinacol rearrangement conditions of
vi'c-dihydroxy-ketobacteriochlorin 147 to generate a conjugated diene
system. Starting from a mixture of vinylchlorins 158 and 159, they
obtained the corresponding DMAD adducts, via Diels-Alder reaction, as an
isomeric mixture of bacteriochlorins 160 and 161 (Scheme 44). The mixture
derived from the DMAD reaction showed some activity in a mouse tumor
model. About 75% of the mice treated at a dose of 1 mg/kg were found to
be free from palpable tumor 12 days after the light treatment.
D. Wc-DIHYDROXYBACTERIOCHLORINS AND THEIR KETO-ANALOGUES
Osmium-mediated hydroxylation of carbon-carbon double bonds has been
known about for many years. However, using 0s04, two alternative
mechanisms which lead to the first stable product - an osmium complex
with two carbon-oxygen single bonds - are still under scrutiny. As shown
in Scheme 45,226 in one possible mechanism a concerted cycloaddition
forms the two new bonds simultaneously, while in another the two new
bonds are formed
stepwise. Although the latest data favor the concerted mechanism [(3 + 2)
cycloaddition], this debate is still far from over.
As discussed previously, Chang and Sotiriou189 were the first to show
that free-base and metalated octaethylpor-phyrin (without any electron-
withdrawing substituents) can be converted into the corresponding vi'c-
dihydroxy-bacteriochlorins and isobacteriochlorins on reacting with 0s04.
In general, the syntheses of such vi'c-dihydroxy derivatives are achieved
by reacting chlorins with 0s04. The intermediate osmate ester is
hydrolyzed either reduc-tively, to give insoluble osmium salts, or
oxidatively, to regenerate osmium tetroxide. In both cases, the
corresponding vicinal cis- diol is formed selectively in good yield.
There are several methods to hydrolyze the osmate ester. In the case of
the porphyrin macrocycle, reductive cleavage with hydrogen sulfide gave
the best results. As in other alicyclic systems, addition of pyridine to
hydroxylation reactions led to a marked increase in the rate of formation
of the intermediate ester complexes. The dihydroxy derivatives, under
acidic conditions, can be converted into the corresponding ketochlorins
via pinacol-pinacolone rearrangements.181 The most interesting
observation in the pinacol rearrangement is the migratory aptitude of the
side chain substituted at the peripheral position(s) of the macrocycle.
Chang et al. have shown that unsymmetrical porphyrins (e.g.,
deuteroporphyrin IX dimethyl ester 162a and mesoporphyrin IX dimethyl
ester 162b), on reacting individually with 0s04, gave all four possible
(rings , , and D) vi'c-dihydroxychlorins 163-166 (Scheme 46) from the
corresponding porphyrins, without any selectivity. The subsequent
pinancol rearrangement of these diols gave the
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