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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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188
Pandey and Zheng
Scheme 44. H2(OEP)-based bacteriochlorins.
156
157

jj -C02Me
"V. | \ C02Me
^-NH N=( Et
160
mixed with
161
Scheme 45. Two possible mechanisms of osmium-mediated hydroxylation of
carbon-carbon double bonds with osmium tetraoxide. [(Note: L=ligand e.g.,
pyridine.)]
'/
Os
+L

/S

O'' \

Concerted cycloaddition (3+2)

;o/=o
V
O^Os-
0V/ +
^Os
0
Os-0
u
+L
ii/1
Os-0
U
o
P
0 = Os-
oO. I
Stepwise cycloaddition (2+2)
respective ketones, and the migratory preference of hydrogen, ethyl,
alkyl groups (including the propionate side chain) over the methyl group
was established.227
Some of the ketobacteriochlorins and their vi'c-dihydroxy precursors
have also been prepared as PDT photosensitizers for the treatment of
cancer by PDT193'220'228 (Scheme 47).
Though most of the stable vi'c-dihydroxy-bacteriochlorins1 exhibit strong
absorptions in the red region of their electronic spectra (710-750 nm),
they did not show any significant in vivo photosensitizing activity.
Among these bacteriochlorins, the corresponding keto-analogues were found
to be more effective PDT sensitizers than were their
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
189
Scheme 46. 0s04 reaction on deuteroporphyrin and mesoporphyrin dimethyl
esters.
Me
R1 Me
n(TbWr2
V-NH
f
/=N

pMe pMe
162a R1 = R2 = H
162b R1 = R2 = C2H5 PMe = CH2CH2CO2CH3
165
Scheme 47. Some examples of w'c-dihydroxy-bacteriochlorinxs and
ketobacteriochlorins prepared as long-wavelength absorbing
photosensitizers for PDT.
C02H
C02Me
167
168
Et
Me
Me02C
Me Et
0 = C
NH-CH-CHj-CC^Bu*

C02Bu'
173
190
Pandey and Zheng
corresponding v/c-diol presursors.228 This might be due to their more
hydrophobic nature, which possibly helps them to be retained in tumor
cells longer, compared with their precursors containing hydrophilic diol
functionalities.
E. EFFECT OF ELECTRON WITHDRAWING SUBSTITUENTS IN 0s04 REACTIONS AND
PINACOL-PINACOLONE REARRANGEMENTS
Pandey et al.229 were the first to study the effect of electron-
withdrawing group(s) in tetrapyrrole subunit reactivity toward 0s04
reaction and pinancol-pinacolone rearrangements. They found that
regiospecificity of pyrrole subunit oxidation in porphyrins is affected
significantly by the presence of electron-withdrawing groups on the
macrocycle, with oxidation taking place at the subunit in the quadrant
opposite to the electronegative group. As discussed earlier, Chang and
coworkers have shown that the metalated chlorins, upon reaction with
0s04, generally produce vic-dihydroxyisobacteriochlorins. This was found
to be also true for various other chlorin systems. However, it was
recently shown that if the 0s04 reaction was performed on chlorins
containing electron-withdrawing groups at the
adjacent pyrrolic ring system of the metalated chlorins, then
dihydroxybacteriochlorins are obtained as the sole product.230 Migratory
aptitudes in subsequent pinacol-pinancolone rearrangements of porphyrin
and pheophorbide vie-diol systems are likewise dependent upon the
presence of electron-withdrawing functionalities. For example (Scheme
48), reaction of 3-acetyldeuteroporphyrin IX dimethyl ester with 0s04
gave mainly the vi'c-diol 174, demonstrating that the electron-
withdrawing acetyl group had directed the oxidation to the opposite
pyrrole subunit. Acid treatment of 174 gave ketochlorin 175 and 176 in
equal ratio. However, the vic-diol 177 obtained from the 8-
acetylporphyrin gave mainly the ketochlorin 178 in which the preferential
migration of propionic ester over the methyl group was observed. The 0s04
reaction on the 3,8-diacetylporphyrin 179 did not show any selectivity
for the formation of Wc-diols 180 and 181. Under pinancol-pinacolone
rearrangement conditions, both diols produced a mixture of the related
ketochlorins without any preferential migration of propionic
functionality over the methyl group.
Similar results were obtained in pheophorbide and chlorin e6 vic-diol
systems (Scheme 49).230 For example, acid treatment of diol 182 obtained
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