A strategic approach for the synthesis of new porphyrin rings, attractive for heme model purpose

Article abstract of DOI:10.1016/j.tet.2007.01.036

Novel complexes have been efficiently synthesized with a facile route using two different atropisomers of the same porphyrin. These compounds feature a tridentate binding site, a tyrosine molecule, and a proximal base, all bound to the porphyrin ring in different fashions, making them attractive for heme modeling purposes.

Full text of DOI:10.1016/j.tet.2007.01.036

Tetrahedron 63 (2007) 2882–2887
A strategic approach for the synthesis of new porphyrin rings,
attractive for heme model purpose
*
Kalliopi Ladomenou, Georgios Charalambidis and Athanassios G. Coutsolelos
Laboratory of Bioinorganic Chemistry, Department of Chemistry, University of Crete, PO Box 2208,
Voutes, 710 03 Heraklion, Crete, Greece
Received 31 August 2006; revised 9 January 2007; accepted 18 January 2007
Available online 21 January 2007
Abstract—Novel complexes have been efficiently synthesized with a facile route using two different atropisomers of the same porphyrin.
These compounds feature a tridentate binding site, a tyrosine molecule, and a proximal base, all bound to the porphyrin ring in different fash-
ions, making them attractive for heme modeling purposes.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
atropisomers of the same porphyrin. All complexes have
the same porphyrin base and differ in three ways: (i) the co-
ordination environment of a second metallic center; (ii) the
presence or absence of a proximal base; (iii) the existence,
or not, of a tyrosine molecule as well as the mode by which
the tyrosine is linked to the porphyrin. Finally, various phys-
icochemical studies of these molecules can give an insight
into whether one of the above features will influence the
catalytic activity of these compounds.
Cytochrome c oxidase (CcO) is an important metalloenzyme
of the respiratory chain in many aerobic organisms. It cataly-
ses the four electron, four proton reduction, of oxygen to
water, without releasing toxic, reactive intermediates (e.g.,
H2O2), conserving the energy required for the biosynthesis
of ATP.1 The catalytic active site of the enzyme consists of
a heme (heme a3) and a tricoordinated copper (CuB) in close
˚
proximity (w4.4–5.3 A), depending on the protein and its ox-
idation state.2 Recent X-ray crystallographic studies revealed
that one of the copper-bound histidines (H240) is covalently
connected to a tyrosine residue (Y244).3 The presence of
a phenol residue is proposed to act either as an electron and
proton donor to the oxygen reduction cycle3a,4 or to help
the enzyme to adopt a favorable structural conformation.5
Despite all the above detailed information derived from the
natural enzyme, the precise role of CuB in mediating O2
reduction remains unresolved. Therefore, in order to eluci-
date the mechanism of O2 reduction, a number of synthetic
heme-based binuclear complexes have been prepared.6 De-
spite the large number of catalysts that have been synthesized
so far, it is not clear which elements influence the selective
reduction of O2 to H2O over H2O2.
Complex 1 is based on the a,a-atropisomer of porphyrin 11a
and has a tridentate ligand covalently attached on one site of
the porphyrin ring and a tyrosine molecule on the opposite
site. In compounds 2–4, tyrosine and bis(2-(pyridin-2-yl)-
ethyl)amine (BPEA) 5 are covalently linked to the porphyrin.
The hydroxyl group of all compounds can be protected/
deprotected in order to investigate the role of this tyrosine
mimic. Moreover, in complexes 3 and 4 an axial pyridine li-
gand is covalently attached to the porphyrin in order to block
the lower face of the porphyrin ring.
The synthesis of tridentate ligands is shown in Scheme 1.
BPEA 5 and axial ligand 6 were prepared by the reaction
of 2-vinylpyridine and ammonium chloride in 50 and 30%,
respectively.7 Reaction of commercially available protected
tyrosine 7 and BPEA 5, followed by deprotection of the
9-fluorenylmethoxycarbonyl (Fmoc) group afforded ligand
9 in good yield.8
2. Results and discussion
In this new synthetic approach, we have developed new com-
plexes in which it is easy to modify possible factors that are
responsible for the reduction of oxygen. These new com-
pounds 1–4 are easily made, based on the two different
After preparation of compounds 5 and 9, a suitable trans-
substituted porphyrin such as 11 was desired in order to pro-
ceed with the synthesis of superstructured porphyrins9
(Scheme 2). Dipyrromethane 10 was synthesized by reacting
2,4,6-trimethyl-benzaldehyde,pyrrole,andtrifluoroaceticacid
in 70% yield. A mixture of two porphyrin atropisomers 11
* Corresponding author. Tel.: +30 2810545045; fax: +30 2810545001;
e-mail: coutsole@chemistry.uoc.gr
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.01.036

K. Ladomenou et al. / Tetrahedron 63 (2007) 2882–2887
2883
NH2
N
H
NH4Cl
MeOH, reflux
4
3
N
1
N
+
N
N
50% for 5
30% for 6
2
5
6
O
O
O
O
N
5, HOBT, DCC
THF, -10 °C to rt
73%
N
N
piperidine
DMF, rt
N
O
O
N
1
N
NH2
HN
O
94%
2
NH
O
4
O
3
O
OH
7
8
9
Scheme 1. Synthesis of ligands 5 and 9.
was prepared in 20% yield by the reaction of dipyrromethane
10 with 2-nitrobenzaldehyde, in the presence of TFA,
followed by oxidation of the resulting porphyrinogen with
DDQ. The two atropisomers were separated by column chro-
matography. The a,a-atropisomer was used for the synthesis
of 1, while for 2 the a,b-atropisomer was required. Interest-
ingly, compound 12a can be selectively reduced by SnCl2
in the presence of concentrated HCl in CH2Cl2 at 0 ꢀC, to
give a,a-monoaminoporphyrin 12a in 65% yield. Acylation
of 12a with chloroacetyl chloride gave 13 (93%). Condensa-
tion of ligand 5 in the presence of DIPEA gave 14 (88%),10
followed by reduction to give 15 in 94% yield. Then 15
was coupled with protected tyrosine molecule 7 in the pres-
ence of DCC, yielding 16 (75%). The synthesis of compound
1 is completed with deprotection of the Fmoc group in the
presence of piperidine in DMF (92%), and deprotection of
the tert-butyl group using TFA affording 1 in 90% yield.
The synthesis of these molecules was achieved by reduction
of a,b-dinitroporphyrin 11b to obtain diaminoporphyrin 19
in 99% yield. Therefore, selective reaction of amine 6 or
3-(2-aminoethyl)pyridine hydrobromide with porphyrin 19
afforded compounds 20 and 21 in 35 and 48% yield, respec-
tively. According to the above reaction, the isocyanate was
generated in situ by reacting diaminoporphyrin 19 with 1/3
of an equivalent of triphosgene in the presence of Et3N at
room temperature in dry dichloromethane. When the
pyridine amine 6 was added 2 equiv of Et3N was needed to
neutralize the HCl generated, but in case of 3-(2-amino-
ethyl)pyridine hydrobromide, 4 equiv was used. Compounds
20 and 21 were also prepared following an alternative route.
Porphyrin 11b was selectively reduced to give 12b and then
reacted with 6 or 3(2-aminoethyl)pyridine hydrobromide.
Finally, the nitro group was reduced to afford the desired mol-
ecules 20 and 21. Following this route the overall yield was
much lower compared to the overall yield obtained when re-
duced porphyrin 11b selectively reacted with the substituted
pyridines. The overall yield following the above route (selec-
tive reduction) was 16% for 20 and 17% for 21, while the
overall yield of the route that was finally followed (selective
reaction) was 35 and 48%, respectively. Subsequently, reac-
tion of aminoporphyrins 20 and 21 with triphosgene in the
presence of Et3N and addition of amine 9 afforded urea-
linked porphyrins 22 and 23. Finally, the compounds were
obtained by deprotection of the tert-butyl group with TFA
to produce 3 and 4 in 97% yield.
For the preparation of porphyrin 2, the a,b-atropisomer 11b
was selectively reduced with SnCl2 in the presence of con-
centrated HCl in CHCl3 at room temperature yielding 12b
(21%). Urea-substituted porphyrin 18 was synthesized by
a useful method introduced by Collman and co-workers in
which the amino group of the monoaminoporphyrin 12b is
converted to isocyanate under mild conditions using triphos-
gene.11 The intermediate porphyrin can then be reacted with
a nucleophile, such as amine 9, to form 18 in 62% yield. The
reason that ligand 9 is attached on the porphyrin ring via urea
link is because the affinity of dioxygen might be stronger
compared to an amide link, as observed for other oxyhemo-
globin models.12 Finally, compound 2 was obtained by de-
protection of the tert-butyl group, using TFA in 96% yield.
Structural information from the above compounds in solu-
tion was obtained by comparison of the H NMR spectra
1
of the free ligands and final molecules. In the first simple ap-
proach, a comparison of the chemical shifts was performed
between ligands 5 and 1 (Table 1).
The synthesis of complexes 3 and 4 is shown in Scheme 3
and they both bear groups attached to the porphyrin via
urea linkers. A tridentate ligand is directly attached to a tyro-
sine molecule and a proximal base. The only difference be-
tween them is the coordinating base that will be used later as
a fifth ligand for the iron atoms of porphyrin. Thus, two dif-
ferent substituted pyridine molecules were used in order to
investigate which one will better coordinate to the iron.
Protons H1–H4 of compound 1 are found to be shifted upfield
in comparison to BPEA 5, with values varying from
Dd¼2.6 ppm for H4 to Dd¼0.3 ppm for H2. This upfield shift
observed is due to the porphyrin ring current, which means
that the tridentate ligand is well situated on top of the por-
phyrin plane. On the other hand, comparison of chemical

2884
K. Ladomenou et al. / Tetrahedron 63 (2007) 2882–2887
a) 2-nitrobenzaldehyde,
TFA, CH2Cl2, rt
NO2
O
H
N
NO2
H
b) DDQ, rt
7% for 11a
13% for 11b
O2N
TFA, rt
70%
H
NH
NH
+
N
N
+
N
65%
NH
N
HN
NH
NH
NH
O2N
10
11a
11b
SnCl2, HCl
CHCl3, rt
SnCl2, HCl
CH2Cl2, 0 °C
21%
Cl
O
ClCH2COCl
NH
NH2
NH2
CH2Cl2, 0 °C to rt
O2N
O2N
N
NH
N
NH
N
NH
93%
N
N
N
NH
NH
O2N
13
12b
12a
a) triphosgene
Et3N, CH2Cl2, rt
b) 8, rt
5, DIPEA
CH2Cl2, 40 °C
88%
62%
N
N
O
O
OH
O
N
N
N
N
N
N
N
1
NH
NH
2
4
O
3
O
O
NH
TFA
NH
NH
R
CH2Cl2, rt
NH
N
NH
NH
N
N
N
96%
NH
N
N
NH
NH
O2N
O2N
2
18
R
R
NO2
NH2
14
15
SnCl2, HCl
CH2Cl2, rt
94%
7, DCC
75%
O
CH2Cl2, 5 °C
N
HO
N
O
3
N
4
2
1
N
N
N
N
N
N
NH2
O
NH2
NHFmoc
O
O
O
TFA
CH2Cl2, rt
90%
NH
NH
piperidine
NH
O
HN
HN
O
DMF, rt
HN
NH
NH
N
N
NH
N
N
N
92%
NH
N
NH
NH
1
17
16
Scheme 2. Synthesis of compounds 1 and 2.
shifts of free ligand 9 and porphyrin 2 showed a slight upfield
shift. This indicates that the tridentate ligand is not sus-
pended over the porphyrin plane. However, the structures
shown in Schemes 2 and 3 are not a good representation of
2–4. This is due to the small Dd values of the phenol protons
between free ligand 9 and porphyrins 18, 22, and 23. More-
over, in order to investigate the stereo orientation of the
proximal base attached on 3 and 4, the non-porphyrin ana-
logs 24 and 25 were synthesized and their chemical shifts
were compared (Scheme 4 and Table 2).13
Compounds 24 and 25 were synthesized following Coll-
man’s isocyanate method.11 Reaction of aniline with triphos-
gene in the presence of triethylamine in dry dichloromethane,
followed by the addition of 6 or 3-(2-aminoethyl)pyridine
hydrobromide and stirring for 1 h at room temperature,
afforded 24 and 25 in 78 and 76% yield, respectively.
In porphyrin 3, protons Ha–d and Hf,g are shifted upfield in
comparison to 24 with a maximum value of Dd¼0.9 ppm
for Ha. This indicates that the proximal base is situated close

K. Ladomenou et al. / Tetrahedron 63 (2007) 2882–2887
2885
a) triphosgene
Et3N, CH2Cl2,rt
b) 6, rt for 20
.
3-(2-aminoethyl)pyridine HBr
SnCl2, HCl
CH2Cl2, rt
NH2
NH2
NO2
rt, for 21
NH
NH
NH
N
N
N
35% for 20
48% for 21
99%
N
N
N
NH
NH
NH
R
H2N
O2N
19
11b
20 R1
21 R2
a) triphosgene
Et3N, CH2Cl2, rt
b) 6, rt
57% for 22
52% for 23
O
O
OH
O
N
N
N
N
N
N
NH
NH
O
O
TFA
NH
NH
CH2Cl2, rt
HN
NH
NH
N
NH
N
97% for 3
97% for 4
O
a
N
f
N
N
NH
3
R1
e
d
b
NH
g
c
R
R
22 R1
23 R2
HN
e
d
N
c
a
O
f
R2
4
NH
b
g
Scheme 3. Synthesis of porphyrins 3 and 4.
Table 1. Chemical shifts of pyridine protons
3-pyridine base is oriented closer under the porphyrin ring
compared to 2-pyridine.
H1
H2
H3
H4
5
1
9
2
8.37
7.91
8.49
8.38
6.96
6.68
7.08
6.81
7.43
6.43
7.55
7.24
7.02
4.45
7.00, 7.14
6.76
3. Conclusion
In conclusion, a new series of porphyrins 1–4 have been effi-
ciently synthesized, featuring covalently attached tridentate
ligand sites, a tyrosine molecule, and a proximal base. Urea
and amide linkers have been used to build-up the superstruc-
tures, in order to examine whether different linkers can affect
binding and reduction of oxygen. Furthermore, protection or
deprotection of tyrosine molecule can be used as a switch to
probe the role of tyrosine in these compounds. Finally a
preliminary structural investigation has been attempted com-
paring the 1H NMR chemical shifts offree and bound ligands.
All chemical shifts are in parts per million; 1H NMR 500 MHz, 300 K.
to the porphyrin ring. In addition, for compounds 4 and 25
there is a more pronounced upfield trend for all protons
with a maximum value of Dd¼1.2 ppm for He, implying that
O
a) triphosgene
N
H
N
H
Et3N, CH2Cl2, rt
NH2
e
b) aniline, rt
d
c
N
N
N
78%
a
4. Experimental section
4.1. General
b
d
24
6
O
a) triphosgene
Et3N, CH2Cl2, rt
b) aniline, rt
NH2
1H and 13C NMR spectra were recorded unless otherwise
specified, as deuteriochloroform solutions using the solvent
peak as internal standard on a Bruker AMX-500 MHz
spectrometer. UV–vis spectra were recorded on a Shimadzu
Multispec-1501 instrument. All electrospray mass spectro-
metric experiments were performed using an LCQ Advan-
tage (ThermoElectron, San Jose, CA) mass spectrometer.
High-resolution mass spectra were performed on a MS/MS
ZABSpec TOF spectrometer at the University of Rennes I
(C.R.M.P.O.). Thin layer chromatography was preformed
on silica gel 60 F254 plates. Chromatography refers to flash
chromatography and was carried out on SiO2 (silica gel
60, SDS, 70–230 mesh ASTM). All dry solvents used were
dried by the appropriate technique. Organic extracts were
dried over magnesium sulfate unless indicated otherwise.
N
N
H
H
e
c
76%
N
b
a
25
Scheme 4. Synthesis of pyridine analogs 24 and 25.
Table 2. Chemical shifts of proximal base protons
Ha
Hb
Hc
Hd
He
Hf
Hg
24
3
25
4
8.44
7.53
8.41
7.42
7.14
6.42
7.23
6.11
7.62
6.91
7.61
6.42
7.19
6.51
—
—
—
8.41
7.20
3.03
2.43
2.85
1.68
3.68
3.08
3.46
2.69
—
All chemical shifts are in parts per million; 1H NMR 500 MHz, 300 K.

2886
K. Ladomenou et al. / Tetrahedron 63 (2007) 2882–2887
Evaporation of the solvents was accomplished on a rotary
evaporator.
N,N-diisopropylethylamine (0.6 mL, 3.5 mmol) and BPEA
5 (0.57 g, 2.5 mmol). The resulting mixture was stirred for
18 h at 40 ꢀC under argon. Then CH2Cl2 (30 mL) was added
to the mixture and washed with water (4ꢁ30 mL). The or-
ganic layer was dried over magnesium sulfate, filtered, con-
centrated, and the residue was chromatographed on a silica
gel column (CH2Cl2/ethanol 50:3) to obtain 14 as a purple
4.1.1. Synthesis of ligands 5 and 6. A solution of 2-vinyl-
pyridine (25.4 mL, 0.23 mmol) and ammonium chloride
(24.6 g, 0.46 mmol) in water (70 mL) and methanol (10 mL)
was heated for 8 h under reflux. Then the reaction mixture
was cooled at 0 ꢀC and basified with 30% w/w aqueous
NaOH solution (60 mL). The water layer was then washed
with chloroform (5ꢁ20 mL). The combined organic extracts
were dried over sodium sulfate, filtered, and the solvent was
evaporated to obtain a yellow oil. The resulting mixture was
then distilled under reduced pressure (w0.07 Torr) to give
first at 100–120 ꢀC 2-(pyridin-2-yl)ethanamine 6 (8.43 g,
30%) as a colorless oil and then at 130–150 ꢀC bis(2-(pyri-
din-2-yl)ethyl)amine (BPEA) 5 (26.1 g, 50%) as a pale
1
solid (45 mg, 88%). H NMR (500 MHz, CDCl3): d 9.59
(s, 1H), 8.86 (d, J¼8 Hz, 1H), 8.77 (d, J¼4.5 Hz, 2H),
8.66 (d, J¼4.5 Hz, 2H), 8.63 (m, 4H), 8.50 (d, J¼8.5 Hz,
1H), 8.20 (d, J¼7 Hz, 1H), 8.00 (t, J¼7 Hz, 1H), 7.94
(m, 2H), 7.85 (m, 3H), 7.46 (t, J¼7.5 Hz, 1H), 7.20 (s,
2H), 7.15 (s, 2H), 6.47 (m, 2H), 5.91 (t, J¼7.5 Hz, 2H),
3.67 (d, J¼7.5 Hz, 2H), 2.70 (s, 2H), 2.58 (s, 6H), 1.70 (s,
6H), 1.41 (s, 6H), 1.37 (m, 4H), 0.50 (br s, 4H), ꢂ2.40 (s,
2H). 13C NMR (125 MHz, CDCl3): d 170.3 (C), 158.0 (C),
152.2 (C), 148.7 (CH), 139.9 (C), 139.4 (C), 139.0 (C),
138.4 (C), 138.1 (C), 137.8 (CH), 136.8 (C), 135.7 (CH),
135.2 (CH), 131.7 (C), 131.5 (CH), 130.1 (CH), 128.2
(CH), 124.4 (CH), 123.0 (CH), 122.1 (CH), 120.9 (CH),
120.6 (CH), 119.6 (C), 114.8 (C), 114.4 (C), 58.9 (CH2),
54.7 (CH2), 35.3 (CH2), 22.0 (CH3), 21.8 (CH3), 21.7
(CH3). Rf (CH2Cl2/MeOH 9:1): 0.57. MS (EI): m/z¼
1026.3 [M+H]+ (100%) for C66H59N9O3. Anal. Calcd for
C66H59N9O3: C, 77.24; H, 5.79; N, 12.28. Found: C,
77.18; H, 5.82; N, 12.27. UV–vis: labs (CH2Cl2)
(3, mMꢂ1 cmꢂ1) 419 (304.6), 514 (16.5), 548 (4.8), 590
(4.9), 647 (2.4).
1
yellow oil. Compound 5. H NMR (500 MHz, CDCl3): d
8.37 (m, 2H), 7.43 (td, J1¼7.5 Hz, J2¼2 Hz, 2H), 7.02 (d,
J¼8 Hz, 2H), 6.96 (td, J1¼5 Hz, J2¼1 Hz, 2H), 2.94 (t, J¼
6.5 Hz, 4H), 2.85 (t, J¼6.5 Hz, 4H), 1.64 (br s, 1H). 13C
NMR (125 MHz, CDCl3): d 160.6 (C), 149.6 (CH), 136.6
(CH), 123.6 (CH), 121.5 (CH), 49.6 (CH2), 38.8 (CH2). Rf
(CH2Cl2/MeOH/Et3N 9:1:0.3): 0.37. Anal. Calcd for
C14H17N3: C, 73.98; H, 7.54; N, 18.49. Found: C, 73.91;
H, 7.58; N, 18.88. Compound 6. 1H NMR (500 MHz,
CDCl3): d 8.40 (d, J¼5.0 Hz, 1H), 7.46 (td, J1¼7.5 Hz, J2¼
2.0 Hz, 1H), 7.03 (d, J¼7.5 Hz, 1H), 6.98 (m, 1H), 2.97
(t, J¼7.0 Hz, 2H), 2.79 (t, J¼7.0 Hz, 2H), 1.24 (br s, 2H).
13C NMR (125 MHz, CDCl3): d 160.4 (C), 149.7 (CH),
136.6 (CH), 123.7 (CH), 121.5 (CH), 42.4 (CH2), 42.3
(CH2). Rf (CH2Cl2/MeOH/Et3N 9:1:0.3): 0.48. Anal. Calcd
for C7H10N2: C, 68.82; H, 8.25; N, 22.93. Found: C,
68.89; H, 8.21; N, 22.97.
4.1.4. Synthesis of porphyrin 18. A mixture of a,b-mono-
aminoporphyrin 12b (89 mg, 0.2 mmol), triethylamine
(56 mL, 0.4 mmol), and triphosgene (20 mg, 0.07 mmol) in
dry dichloromethane (150 mL) was stirred for 1 h under
argon at room temperature, after which ligand 9 (89 mg,
0.2 mmol) was added and the stirring continued overnight.
The reaction was monitored by thin layer chromatography
(4% methanol in dichloromethane). The residue was purified
by column chromatography (1–3% methanol in dichloro-
methane). The desired porphyrin was eluted with 2% meth-
anol in dichloromethane to give a purple solid (153 mg,
4.1.2. Synthesis of ligand 9. Piperidine (9.5 mL, 96 mmol)
was added to a solution of 8 (0.4 g, 0.6 mmol) in DMF
(20 mL) at room temperature. The resulting solution was
stirred for an hour and the reaction was monitored by thin
layer chromatography (CH2Cl2/MeOH 9:1). The solvent
was then removed under vacuum and the mixture was
dissolved in CH2Cl2 (40 mL) and extracted with water
(2ꢁ20 mL), dried over sodium sulfate, filtered, and con-
centrated under vacuum. The resulting crude product was
purified by chromatography (2–20% methanol in dichloro-
methane). The product was eluted with 10% methanol in di-
chloromethane to give 9 as a pale yellow oil (253 mg, 94%).
1H NMR (500 MHz, CDCl3): d 8.49 (m, 2H), 7.55 (m, 2H),
7.14 (d, J¼7.5 Hz, 1H), 7.08 (m, 4H), 7.00 (d, J¼8.0 Hz,
1H), 6.85 (d, J¼8.5 Hz, 2H), 3.82 (m, 2H), 3.46 (m, 2H),
3.23 (m, 1H), 3.00 (m, 1H), 2.89 (m, 3H), 2.84–2.70 (m,
2H), 2.62 (br s, 2H), 1.25 (s, 9H). 13C NMR (125 MHz,
CDCl3): d 175.4 (C), 159.5 (C), 158.4 (C), 154.4 (C),
150.1 (CH), 149.6 (CH), 136.9 (CH), 133.1 (C), 130.2
(CH), 124.6 (CH), 124.0 (CH), 123.9 (CH), 122.1 (CH),
121.9 (CH), 78.6 (C), 53.2 (CH), 47.5 (CH2), 46.8 (CH2),
42.4 (CH2), 37.8 (CH2), 36.4 (CH2), 29.2 (CH3). Rf
(CH2Cl2/MeOH 9:1): 0.29. MS (EI): m/z¼469.9 [M+Na]+
(100%) for C27H34N4O2. Anal. Calcd for C27H34N4O2: C,
72.62; H, 7.67; N, 12.55. Found: C, 72.69; H, 7.73; N,
12.51.
1
62%). H NMR (500 MHz, CDCl3): d 8.74–8.67 (m, 6H),
8.59 (m, 2H), 8.48 (dd, J1¼8.0 Hz, J2¼1.5 Hz, 1H), 8.44
(d, J¼8.5 Hz, 1H), 8.30 (m, 2H), 8.22 (d, J¼7.0 Hz, 1H),
7.96 (m, 3H), 7.77 (t, J¼8.0 Hz, 1H), 7.42 (t, J¼7.5 Hz,
1H), 7.35 (m, 2H), 7.27 (m, 2H), 7.24 (m, 2H), 6.88 (m,
4H), 6.77 (d, J¼7.0 Hz, 2H), 6.64 (d, J¼7.5 Hz, 2H), 5.98
(s, 1H), 4.64 (m, 1H), 4.50 (d, J¼7.5 Hz, 1H), 3.41 (m,
1H), 3.18 (m, 1H), 3.09 (m, 2H), 2.68 (m, 2H), 2.61 (m,
6H), 2.45 (m, 4H), 1.87 (s, 3H), 1.84 (s, 3H), 1.82 (s, 6H),
1.16 (s, 9H), ꢂ2.54 (s, 2H). 13C NMR (125 MHz, CDCl3):
d 172.0 (C), 159.1 (C), 158.1 (C), 154.5 (C), 154.3 (C),
152.0 (C), 149.7 (CH), 149.4 (CH), 140.0 (C), 139.9 (C),
139.7 (C), 139.6 (C), 138.3 (C), 137.5 (CH), 136.9 (C),
136.8 (CH), 136.7 (CH), 135.3 (CH), 131.8 (C), 131.4 (C),
131.3 (CH), 130.2 (CH), 130.0 (CH), 129.9 (CH), 128.3
(CH), 128.2 (CH), 124.5 (CH), 124.4 (CH), 123.8 (CH),
123.7 (CH), 122.0 (CH), 121.9 (CH), 121.7 (CH), 120.7
(CH), 119.6 (C), 119.5 (C), 114.5 (C), 114.1 (C), 78.6 (C),
51.5 (CH), 48.0 (CH2), 46.9 (CH2), 39.8 (CH2), 37.5
(CH2), 36.1 (CH2), 29.1 (CH3), 22.3 (CH3), 22.2 (CH3),
21.9 (CH3). Rf (CH2Cl2/MeOH 95:5): 0.32. MS (EI):
m/z¼1232.0 [M+H]+ (100%) for C78H74N10O5. Anal. Calcd
for C78H74N10O5: C, 76.07; H, 6.06; N, 11.37. Found: C,
4.1.3. Synthesis of porphyrin 14. To a solution of porphyrin
13 (45 mg, 0.05 mmol) in dry CH2Cl2 (3 mL) were added

K. Ladomenou et al. / Tetrahedron 63 (2007) 2882–2887
2887
3. (a) Yoshikawa, S.; Shinzawa-Itoh, K.; Nakashima, R.; Yaono,
R.; Yamashita, E.; Inoue, N.; Yao, M.; Fei, M. J.; Libeu,
C. P.; Mizushima, T.; Yamaguchi, H.; Tomizaki, T.;
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mMꢂ1 cmꢂ1) 420 (280.9), 515 (14.6), 549 (4.3), 591 (4.4),
647 (2.1).
Acknowledgements
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We thank Assistant Professor Spiros A. Pergantis for all
electrospray mass spectrometric experiments and Professor
Bernard Boitrel for his assistance in obtaining HRMS data.
This work was supported by the Greek Secretariat of
Research and Technology (‘Pythagoras’ and ‘Heraklitos’).
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13C NMR spectra, for all new compounds. For synthesis of
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the online version, at doi:10.1016/j.tet.2007.01.036.
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