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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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43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 14. Various BPD analogue from methyl pheophorbide a
42b X = S
48a R = H
48b R = C02Me
49a R = H
49b R = C02Me
47 R = -NCH2CH2C02Bu
Scheme 15. Preparation of benzochlorins from OEP. Et Et
ii, in
i- 51. M = Ni, R = CH=CH-C02Et
p" 52. M = 2H, R = CH=CHC02Et
v L"- 53, M = 2H, R = CH=CHCH2OH
. POCI3, 3-(dimethylamino)acroiein; ii, POCI3, DMF; ii. Carboxyethylene
triphenyiphosphorane; v, H2S04; v, Di-bal
Pandey and Zheng
Scheme 16. Free-base benzochlorins from 5,15-diphenyl-TPP.
Et R1 Et-
R = Phenyl or substituted phenyl,
a. TFA _
b. H2S04
R1 = - CH=CH-CHO
1X1 ,Et
Et- yYi)
V-NH N-/ 4Et
R- JT -R
Et- -Et

Scheme 17. Ni(ll) isobacteriochlorin from chlorin-e6 trimethyl ester.
1. Naphthochlorins
Cavaleiro and coworkers163 have shown that treatment of Ni(II) (j-vinyl- 75 with a dilute solution of sulfuric acid
affords naphthochlorin 76 via an intramolecular cyclization involving the
vinyl group and the ortho position of the adjacent phenyl ring. These
stable naphthochlorins exhibit long wavelength absorptions near 670 nm
(Scheme 20).
Smith and coworkers164 also reported a novel synthesis of
naphthochlorins. In their approach, reactions of 2-nitro-5, 10,15,20-
tetraphenylporphyrin 77 with alkyl a-isocyano acetate afforded
naphthochlorin 78 (in addition to the expected pyrroloporphyrin) which
underwent free radical dimerization (Scheme 21).
The work of Barloy et al.165 has demonstrated that in the H2(TPP)
series, the formyl group present at the peripheral position in 79 in
acidic conditions undergoes an intramolecular cyclization to produce
benzochlorin-type compounds 80 (Scheme 22).
Sternberg et al.i6b showed that the vinylogous Vilsmeyer formylation
of 5,10-diphenylporphyrin 81 gives 82 which, followed by cyclization,
resulted in the formation of both the fused-ring system 83 and an
oxidized form 84 of the expected primary cyclization product, (Scheme
Johnson and Dolphin167 also reported the preparation of
octaethylbenzochlorin 87 via an intramolecular cyclization of the meso-
acrylaldehyde-substituted porphyrin 86 under the acidic conditions. The
outcome of the ring-forming reaction was dependent on whether the
intermediate was metalated or metal free (Scheme 24).
2. Purpurins, Rhodins and Verdins
Since the early 1940s, purpurins 88 have been known as degradation
products of chlorophyll; the synthesis of 88 was first reported by
Woodward et al.168 The chemistry of purpurins169 has been ignored for
quite some time, presumably because no biological role had been found for
this macrocycle. It was only recently that the utility of this class of
compounds as photosensitizer was reported by Morgan and coworkers.170
Among purpurins, the etiopurpurin derivative 89 appeared to be more
active when compared with the related octaethylpurpurin 88. Insertion of
metal increased the in vivo PDT efficacy of the molecule, with tin(IV)
being superior to zinc(II) (Scheme 25). Among all the purpurins evaluated
so far, the Sn etiopurpurin (SnEt2) 89 is considered to be the best
photosensitizer; it absorbs at 650 nm and has high singlet oxygen quantum
yield. Complete tumor cures in the rat tumor model were obtained at doses
of 1.3 /kg for SnEt2. Similar to Photofrin-based PDT, vascular damage
seems to be the most important mechanism for SnEt2-PDT.I7I~173
Gunter and Robinson reported the synthesis and spectroscopic
properties of purpurins bearing functionality starting from 5,15-
disubstituted meso - [/Hethoxycarbonyl) vi nyl] porphyrins 91.174 The
meso-acrylate porphyrins were efficiently converted into the so-called
type-A purpurins 92 under basic conditions. Type- purpurins 93 were also
formed, and the relative yields of types A and are temperature and
solvent dependent, but independent of the presence of oxygen. These
results are in contrast with those
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 18. Benzochlorin analogues from
9-deoxy-mesopyropheophorbide a.
Et Me
C02Me 61
62. X = CH=CH-CHO
65. M = 2H
66. M = Zn
67. M = 2H, R = H2
68. M = Zn, R = H2
69. M = 2H, R =
70. M = 2H
71. M = Zn
Reagents: a, TFA; b, H2S04; o, DDQ/MeOH
Scheme 19. Benzochlorins from rhodins.
Coproporphyrin I
PMe = CH2CH2CO2CH3, Me=CH3
reported for the formation of octaethylpurpurin derivatives. This
approach (base catalyzed) was later extended by Smith and coworkers for
the preparation of the 5,15-bis (4-pyridyl)purpurin 94. Quatemization
with methyl iodide yielded the corresponding cationic N,N'-
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