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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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282 both generate singlet oxygen efficiently ( = 0.58 and 0.48,
respectively). Therefore, from a pure photophysical perspective,
hemiporphycene 281 and also corrphycene 282 are potential PDT
photosensitizers.241
Scheme 58. Preparation of inverted or "N-confused" porphyrins.
ArCHO
287

N
H
288
1. HBr/HOAc CH2CI2/THF
2. NEt3; DDQ
N=i
1. BF3. Et20, N2
2. p-chloranil
Porphyrin - 20%
289
-5%
biladiene 294 with an inverted pyrrole unit, which was converted into
the corresponding inverted biliverdin 295. However, cyclization of these
biladienes did not produce the expected inverted porphyrins (Scheme 60).
The "N-confused" porphyrins reported so far exhibit long-wavelength
absorption near 700 nm, which makes them suitable candidates for use in
PDT. However, their low yield limits their application as
photosensitizing agents.
VIII. Porphyrin Dimers and Higher
Oligomers
B. INVERTED PORPHYRINS
The inverted porphyrins (also called "N-confused" porphyrins) 289 were
discovered accidentally as by-products of the well-known acid-catalyzed
pyrrole aldehyde cyclocon-densation route to porphyrins (Scheme 58)253
254 (see Chapter 14 by Latos-Grazynski). Rational multistep synthetic
approaches to inverted porphyrins have appeared recently. Dolphin and
coworkers.255 have reported a method for the preparation of porphyrin 292
involving acid-catalyzed MacDonald-type (2 + 2) condensation of an a,/?-
dipyrromethane 291 and a,a-dipyrromethane dialdehyde 290. Lee and
coworkers256 have reported a (3 + 1) approach to porphyrin analogues with
an inverted pyrrole and a thiphene, or a furan ring system 293 (Scheme
59). Pandey et al.251 reported the preparation of dibromo-a, c-
A. PORPHYRIN DIMERS WITH ETHER, ESTER AND CARBON-CARBON LINKAGES
Photofrin, a mixture of porphyrin oligomers, is currently the most widely
used photosensitizer in PDT. Despite numerous studies with Photofrin,
little is known about its mode of action, principally due to its complex
chemical composition. Thus, establishing the chemical nature of Photofrin
has been difficult. The commercial method for preparation of Photofrin is
depicted in Scheme 61.258 The aqueous solution of HpD is separated by
size exclusion gel chromatography into two main fractions. The higher
molecular-weight fraction contained the material which is active in vivo
(the so-called Photofrin) and a lower molecular-weight fraction
containing mainly the monomers, which are not retained in tumors.
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
199
Scheme 59. Inverted porphyrins: other synthetic approaches. ^
Me Me
Me Me
290

1. n-BuLi
S 2. CBH=CHi
Ph
Ph
293 ~ 8%
-3%
Scheme 60. Inverted biliverdins from 1,19-dibromo-a,c-biladienes.
INVERTED
PORPHYRIN
200
Pandey and Zheng
Scheme 61. Commercial preparation of Photofrin. Me
Ac20/pyridine
0.1 NNa OH
BR3 = R8 = CH(OAc)Me CR3 = CH(OAc)Me;
R6= CH(0H)Me D R3 = CH(OH)Me;
R6 = CH(0Ac)Me E R3 = CH=CH2;
R8 = CH(0Ac)Me FR3 = CH(0Ac)Me;
R8 = CH=CH2 G R3 = CH=CH2;
R8 = CH(OH)Me H R3 = CH(OH)Me;
R6 = CH=CH2
,3
, mainly
0.1 N NaOH
Hpd
I R =R = CH=CH2 Size-exclusion gel
chromatography
monomers (E-l), dimers, and higher oligomers with ether ester and/or C-C
linkages
Photofrin
Mainly dimers and higher oligomers
Scheme 62. Rationalization of oligomer formation during the commercial
prepation of Photofrin.
Ether Formation
C-C Bond Formation

N-/

\

HN\
H
It was originally postulated that Photofrin consists mainly of a mixture
of porphyrin dimers and oligomers involving ether, ester and carbon-
carbon interporphyrin linkages.259-264 The formation of these linkages is
rationalized in Scheme 62.265 However, Ward and coworkers later
identified one of the regioisomers of a carbon-carbon linked dimer 296,
and suggested the presence of other possible carbon-carbon bridges in the
Photofrin mixture as shown in Scheme 63.266 The data obtained from fast
bombardment (FAB) mass spectroscopy indicates that the
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
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