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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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mono-vinyl-mono-acetyl- intermediates has synthetic advantages, but this
methodology still requires the separation of the individual mono-acetyl
deuteroporphyrin IX isomers at the
early stage of the synthesis. To completely eliminate the problem of
isomer formation, Pandey et al. synthesized the BPD analogues with
symmetrically substituted divinyl porphyrins.148 Thus, significant
simplification in the regio-selectivity of the Diels-Alder reaction of
divinylporphyrins with dienophiles was achieved by use of protoporphyrin
II and protoporphyrin III dimethyl ester. Interestingly, among all the
BPD-type derivatives, the ring-A-modified isomers were found to be most
In order to avoid the formation of various isomers, Pandey et al.149
extended the Diels-Alder approach to certain porphyrin systems such as 3-
vinylphylloerythrin methyl ester 42 and rhodoporphyrin XV dimethyl ester
43, derived from methylpheophorbide a. In the 3-vinylphylloerythrin
series, it was observed that the presence of the 131 keto- group in ring
E inhibits the Diels-Alder reaction with DMAD, but with more reactive
dienophiles, the related adduct was isolated in modest yield. Protection
of the keto- group (before reacting with DMAD) as the ketal or thioketal
afforded the benzoporphyrin derivative 44 which upon deprotection gave
the desired BPD analog 45. Among these compounds, the cis- isomer
obtained from rhodoporphyrin XV di-/err-butyl aspartate 47 showed the
best in vivo activity. This approach was later extended by
Pandey and Zheng
Scheme 13. Preparation of benzoporphyrin derivatives from isomerically
pure mono-acetyl-mono-vinyl deuteroporphyrin dimethyl esters.
Me02C-Me H

HBr/AoOH Me hexanol Me V.
Me02C C02Me H"
41 R1 = R2 =C02Me R3 = Hexyl
37a R1 = H, R2 = Me 37b R1 = Me, R2 =H
38a R1 = H, R2 = Me 38b R1 = Me, R2 =H
Dolphin and Ma150 to prepare the related benzoporphyrin derivatives 49
from the methyl 9-deoxyphylloerythin 48 (Schemel4).
Benzochlorin 50 consists of a benzene ring fused to the tetrapyrrolic
structure and was first reported by Arnold et al.151 from
octaethylporphyrin H2(OEP) in several steps such as, formylation, Wittig
reaction, reduction and oxidation. Morgan et al. followed this approach
and benzochlorins 54 and 55, as major and minor products, respectively,
were obtained (Scheme 15).152
A very similar type of benzochlorin 50 was also synthesized by Smith's
group as a result of the cyclization of the product obtained after
Vilsmeier formylation reaction of Ni or Cu(OEP) using
dimethylaminoacrolein and phosphorous oxychloride.153,154 The utility of
this class of compounds as photosensitizers for PDT was first shown by
Morgan et al.155 in a mouse tumor model. With a few exceptions, most of
the benzochlorins derivatives prepared by Morgan's group are based on
symmetrical porphyrins (Scheme 15).
One of the major problems associated with benzochlorin preparation is
the difficulty in demetalation at the final step of the synthesis. Gunter
et al.156 converted a series of Ni(II) 5,15-diphenylporphyrins 56 into
the corresponding benzochlorins, which upon acid treatment produced the
corresponding free-base analogue 57 in excellent yield.
X-ray analyses of Ni(II) 5,15-diarylbenzochlorins showed a remarkable
distortion in the ring, which possibly helped in the removal of the
central metal ion. This methodology was later followed by Osuka et al.151
for preparation of several meso-substituted analogues. Among the H2(OEP)-
based benzochlorins, the Zn(II) complex was found to be quite effective
in the mouse tumor model (Scheme 16).
Unfortunately, benzochlorins derived from H2(OEP) have some
disadvantages due to their insoluble nature in most useful injectable
solvents. It is also difficult to chemically modify these benzochlorins.
In order to avoid this problem, Vicente and Smith158 converted
mesochlorin e6 58 to the corresponding 20-(2-formylvinyl) analogue 59,
which, upon acid-mediated cyclization, produced isobacteriochlorin 60
(Scheme 17). However, attempts to prepare the corresponding free-base
analogue were unsuccessful.
Pandey and coworkers159 reported an efficient regiose-lective
synthesis of benzochlorins from the Ni(II) methyl 9-
deoxymesopyropheophorbide a 61. Among these compounds, Zn(II)
benzochlorin 71 (^max = 753nm) showed a 42-nm red shift compared with its
free-base analogue 70 and it also possessed a good singlet oxygen quantum
yield (0.5) (see Scheme 18).
It has been shown by Fischer160 and Clezy et al.161 that the porphyrin
containing tetrapropionic ester functionalities 72 can be converted into
rhodin 73 which, upon treament with fuming sulfuric acid in the presence
of air, can beconverted into benzochlorin 74162 in modest yield (Scheme
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