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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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the possible isomers is shown).
Me
Me
306a R1 = COCH3 or 306b R1 = CH=CH2
307b R2 = CH(OH)CH3, R3 = COCH3 307c R2 = CH(OH)CH3, R3 = CH=CH2
308 R1 = COCH3, R3= H
309 R1 = COCH3, R3 = CH(OH)CH3
NH ?>R1 310R1 =
CH=CH2, 4 R3 = H
Me 311 R1 =CH=CH2, R3 = CH(OH)CH3 0=c-----C> Me
C02Me
OO2M6
C02Me C02Me 312b R1 = R3 = CH=CH
OO2M6
OO9M6
312a R1 = COCH, R3= CH=CH2
chlorin 333b is obviously due to the cleavage of the 3-(l-heptyloxy)ethyl
functionality at elevated temperatures. Such divinyl derivatives have
great biological significance in that they are reported to be the
intermediates in chloroplast biogenesis in plants,283'284 bacteria,285
and marine organisms.286287 Among divinylchlorins, the 3,8-divinylchlorin
e6288 has attracted more attention because it is believed to be a key
biosynthetic intermediate in chlorophyll biosynthesis. Smith and
coworkers289-291 successfully introduced a new protection/deprotection
methodology for the preparation of 3,8-divinylchlorin e6 through a
multistep synthesis. The o-dichlorobenzene approach288 certainly provides
a mixture of various components, but each product can easily be separated
by chromatography and this process less time consuming for generating
such biologically important intermediates.
C. CHLORIN DIMERS WITH AMIDE LINKAGES
Ando et al. 292-293 reported a series of chlorin e6 dimers 341 and
trimers 342 joined by amide bonds and found that among such oligomers,
dimer 341 (Scheme 71) did show good tumor uptake and selectivity compared
with the hematoporphyrin derivative (HpD). As part of their effort to
improve the in vivo antitumor activity of chlorin-based photosensitizers,
Pandey et al.294 extended this approach for the preparation of a series
of amide-linked symmetrical and unsymmetrical chlorin dimers 345-347
(Scheme 72). For the preparation of unsymmetrical dimer 349, methyl
pheophorbide a was reacted with 1,3-propanediamine and the intermediate
amide 345 was isolated in 80% yield. Reaction of 348 with H2(HPPH)
afforded the unsymmetrical dimer in 70% yield, and was found to be
effective in
204
Pandey and Zheng
Scheme 66. Porphyrin dimers with carbond-carbon linkages.
313 R = H
314 R = COCH3
315 R = CH(OH)CH3
316 R = CH=CH2
317 R = H
318 R = COCH3
PMe = CH2CH2CO2CH3 319 R = CH(OH)CH3
320 R = CH=CH2
vivo at a dose of 5 mg/kg (24 hours postinjection of the drug).
IX. Expanded Porphyrins
A. SAPPHYRINS AND TEXAPHYRINS
In 1966, sapphyrins 350, the first known examples of the expanded
porphyrins, were discovered by Woodward and his colleagues during the
course of their earlier work on the synthesis of vitamin B12.295 Since
then, the search for other expanded pyrrolic macrocycles has ensued. In
recent years, numerous new expanded porphyrins and their heterologues
have been discovered 350-363.296 The increasing knowledge of expanded
porphyrins provides a new direction in developing an ideal
photosensitizer for PDT (see also Chapter 9 by Sessler).
Sessler et al.291 reported a new class of expanded porphyrins, the so-
called texaphyrins 352 that are based on the Schiff base condensation
between a diformyltripyrrane and an aromatic 1,2-diamine. This basic
strategy has since been successfully employed to obtain numerous cadmium
texaphyrin complexes and texaphyrin complexes 364-37 9 298 with a wide
range of metals (Scheme 74).
Photophysical properties of metallotexaphyrins are of particular
interest in photodynamic therapy. Much of the impetus for this attention
is due to the fact that the texaphyrins absorb strongly in the 720-780-nm
spectral
region. High-yield production of long-lived triplet states and their
remarkable efficiency as singlet-oxygen-producing photosensitizers are of
great importance as well. Among all the metallotexaphyrins tested for PDT
so far, lutetium(III) texaphyrin 378 appears to be the most promising.299
It is a pure, water-soluble drug with a large broad absorption band
centered at 732 nm. In a mouse tumor model, lutetium texaphyrin had
significant efficacy in treating neoplasms of moderate size (40 14 mm3)
and in treating larger neoplasms.
Perhaps the most important medical application of texaphyrins lies in
their potential use as MRI contrast agents for the diagnosis and staging
of a variety of diseases and as possible ionizing radiation sensitizers.
Prompted by the selective tumor-targeting properties of porphyrins, much
effort has been made toward the development of paramagnetic porphyrin
complexes as magnetic resonance imaging (MRI) contrast agents.300
Porphyrins cannot complex with gadolinium(III), the single most
paramagnetic atomic cation. The fact that the texaphyrins chelate
gadolinium(III) made them advantageous in MRI. In general, gadolinium-
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