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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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position 17) with an aspartic-acid residue enhanced the in vivo efficacy.
Keeping these results in mind, the aspartic-acid analogue of 3-devinyl-3-
v/c-dihydroxy-bacteriopurpurin 216 was converted into its isoimide and
imide analogues 217 and 218, both with long-wavelength absorption near
?imax 825 nm 235 (Scheme 52).
Another approach to improve the tumor affinity of the vic-dihydroxy-
bacteriochlorins is by the introduction of a hydrophobic alkyl ether side
chain at position 3 (ring A) of the molecule. Such a modification had
proven to be successful in the pyropheophorbide a, BPD and purpurin-18-N-
alkyl-imide series. In order to investigate the effect of ether alkyl
chain length in this series of compounds, the 3-(l-heptyloxy)ethyl-
purpurin-18-N-hexylimide was converted into the corresponding vi'c-
dihydroxy-bacteriochlorin 218 with a long-wavelength absorption at 111
Scheme 54. Bacteriochlorins from chlorins containing a vinyl group at the
diagonal position of the reduced ring.
Me02C ! C02Me Et
Pandey and Zheng Scheme 55. Vogel and coworkers'
synthesis of porphycene.
H H V-N N-^"
L v--- \ il
f" N H

/ !
Us-/ VssJ
TiCI4 / Zn
Morgan and coworkers237 have reported the synthesis of a series of
long-wavelength-absorbing chlorins (690-860 nm) on reaction of
organolithiums with ketochlorins. For example, reaction of l-lithio-3,3-
dimethyl allene with ketochlorin 219 gave the corresponding hydroxy
compound, which upon cyclization in TFA gave a purpurin-type product 220
with a long-wavelength absorption at 694 nm. The reaction of l-lithio-3-
trimethyl silyl allene with ketopor-phyrin afforded the hydroxy product
221 and the cyclized purpurins 222 and 223 in a 40% combined yield.
Interestingly, reaction of the same ketoporphyrin with 4-lithio
tetrahydropyranyl phenol and 4-lithio-N,N-dimethylaniline afforded the
corresponding hydroxy derivatives 224 and 225, which upon cyclization
produced quinone 226 (727 nm) and ammonium salt 227 (857 nm),
respectively (Scheme 53). No biological results have been reported with
these long-wavelength-absorbing chlorin analogues.
The transformation of the vic-dihydroxyoctaethylchlorin to
vinyloctaethylporphyrins had previously been reported by Chang and
Sotiriou;238 the reaction involved refluxing the diol in bezene solution
containing /-toluene sulfonic acid. Several methods, published by
various investigators, introduced a vinyl group to ring in chlorin
systems (diagonal to the reduced pyrrole subunit) so that Diels-Alder
cycloaddition reactions could lead to new classes of bacteriochlorins.
The Diels-Alder reaction for facile conversion of vinyl porphyrins to
chlorins has been studied in depth by several groups.143-148 A few years
ago, this methodology was used independently by Pandey et al.149 and Ma
and Dolphin150 for preparing bacteriochlorins by a "double" Diels-Alder
reaction of 8,18-divinylporphyrins with various dienophiles. Depending
upon the nature of dienophiles, these bacteriochlorins exhibit long-
wavelength absorptions at 720 nm (with TCNE-tetracyanoethylene) and 782
nm (with DMAD-dimethylacetylenedicarboxylate).
However, due to their multistep syntheses, the overall yields of the
final products were low.
Pandey and coworkers239 showed that 3-ethyl-vic-dihydroxy-purpurin-18
methyl ester on refluxing alone in o-dichlorobenzene at 160 C for 1 hour
produces 8-vinyl-3-ethyl-purpurin-18 methyl ester 228 (?imax 684 nm) in
60% yield (another product from this reaction was identified as 8-
ketobacteriopurpurin (^max 711 nm; yield 20%), in which the ethyl group
had preferentially migrated over the methyl substituent). Reaction of 228
with various dienophiles (TCNE, DMAD) afforded bacteriopurpurins 229-232
with long-wavelength absorptions at 762 and 795 nm, respectively. The
reaction sequence is summarized in Scheme 54.
Following a similar approach, 8-vinyl-3-ethyl-chlorin p6 trimethyl
ester 233, obtained from the pyrolysis of 3-ethyl-vic-dihydroxy-
bacteriochlorin p6 trimethyl ester, was also converted into the TCNE
adduct 234, the trans isomer of DMAD adduct 236, and the cis- isomer 237
(Scheme 55).240
VII. Isomeric Porphyrins
The synthesis of porphycenes 239 from diformylbipyrrole 238 by Vogel et
al.241 marked the beginning of a promising new direction of research for
the quest of new PDT photosensitizers (Scheme 56). The formally simple
construction principle of porphycene involved the reorganization of the
structural elements of porphyrin (four pyrrole and four methine units)
while maintaining the N4 coordination site. Vogel et al 242 found that
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