Expeditious synthesis of glycosylated phthalocyanines

Article abstract of DOI:10.1055/s-2007-983753

3,4-Dicyanophenyl O- and S-glycosides in the gluco, galacto, lacto, and cellobiose series were prepared in virtually quantitative yield through nucleophilic aromatic substitution of 4-nitrophthalonitrile with acetyl-protected glycoses and 1-thio-glycoses. Similarly, 2-(3,4-dicyanophenoxy) ethyl 2,3,4,6-tetra-O-acetyl-β-D-gluco- and galacto-pyranosides were obtained by nucleophilic substitution of 2-(tosyloxy)ethyl 2,3,4,6-tetra-O- acetyl-β-D-gluco- and -galactopyranoside with 3,4-dicyanophenol in 82% and 94% yields, respectively. All glycosides were deacetylated and tetramerized to the corresponding glycosylated zinc(II) phthalocyanines without further purification using a template condensation in 42-54% yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983753

2186
PAPER
Expeditious Synthesis of Glycosylated Phthalocyanines
Expeditious
Synth
a
esis of Glyc
v
osylated Pht
i
haloc
y
e
anine
s
r Álvarez-Micó, Mario J. F. Calvete, Michael Hanack, Thomas Ziegler*
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany
Fax +49(7071)295244; E-mail: thomas.ziegler@uni-tuebingen.de
Received 23 February 2007; revised 9 May 2007
ing advantage of the excellent leaving group character of
fluoride in substituted fluorinated nitro- or dinitroben-
zenes. Mainly b-O-aryl glucosides are obtained in fairly
good yields in this way. Recently, we reported a new
Abstract: 3,4-Dicyanophenyl O- and S-glycosides in the gluco, ga-
lacto, lacto, and cellobiose series were prepared in virtually quanti-
tative yield through nucleophilic aromatic substitution of 4-
nitrophthalonitrile with acetyl-protected glycoses and 1-thio-gly-
coses. Similarly, 2-(3,4-dicyanophenoxy)ethyl 2,3,4,6-tetra-O- method for the synthesis of O-aryl glycosides through nu-
acetyl-b-D-gluco- and galacto-pyranosides were obtained by nu-
cleophilic substitution of 2-(tosyloxy)ethyl 2,3,4,6-tetra-O-acetyl-
b-D-gluco- and -galactopyranoside with 3,4-dicyanophenol in 82%
and 94% yields, respectively. All glycosides were deacetylated and
tetramerized to the corresponding glycosylated zinc(II) phthalocya-
nines without further purification using a template condensation in
42–54% yields.
cleophilic substitution of nitrite in nitroarenes by anomer-
ic glycosyl oxides.9 The nucleophilic displacement of a
nitro group from an activated aromatic substrate has been
shown to proceed effectively for a variety of strong nu-
cleophiles under dipolar aprotic solvent conditions. For
example, at room temperature in N,N-dimethylform-
amide, dimethyl sulfoxide, or hexamethyphosphoramide,
hydroxy or alkoxy anions,10,11 the thiol anion,10,12 and sul-
finate anions10 effect a synthetically practical displace-
ment of a nitro group from carbonyl,10–13 nitro,10,13
cyano,10–13 sulfone,10 and aryl12 activated substrates. In
addition, as it has been previously demonstrated, nitrite is
comparable to fluoride as leaving group in SNAr reac-
tions.14 The cyano-substituted aryl glycosides prepared by
this novel anomeric O-arylation strategy were used for the
template synthesis of phthalocyanines.9
Key words: carbohydrate, phthalocyanine, glycoside, cellular up-
take
Carbohydrates habitually exist on cell surfaces as glyco-
proteins or glycolipids and are engaged in various impor-
tant biological recognition processes, for example, cancer
metastasis, inflammatory response, innate and adaptive
immunity, viral and bacterial infection, and many other
receptor-mediated signaling processes.1 Moreover, a large
number of natural products require glycosylation in order
to exhibit biological activity.2,3 However, the effect of
glycosylation on the structure and function of glycosylat-
ed natural products is not well understood, mostly due to
the lack of efficient synthetic methods to cover all the
structural features.
Phthalocyanines (Pcs) have been known for more than
seven decades. These compounds have been widely inves-
tigated as advanced materials for diverse applications,15
including photobiological and medical applications.16 Ph-
thalocyanines possess characteristic absorption spectra,17
with a Soret band at approximately 350 nm and a usually
narrow but very strong Q band around 675 nm, with a mo-
lar extinction coefficient in the range of 105 M–1 cm–1. In
addition to being red shifted compared to porphyrins, light
absorption of phthalocyanines is approximately two or-
ders of magnitude stronger than the highest Q band ab-
sorption of a porphyrin. The photophysical properties of
the phthalocyanine dyes are strongly influenced by the
presence and nature of the coordinated central metal.
Closed shell, diamagnetic ions, such as Zn2+, Al3+ and
Ga3+, give phthalocyanine complexes with both high trip-
let yields and long lifetimes of the excited triplet state.18
Thus, these complexes are expected to exhibit strong pho-
tochemical and photodynamic activities, due to a higher
efficiency in generating reactive oxygen species than por-
phyrins.19 By possessing low dark toxicity,20 these com-
pounds appeared to be a very promising kind of second
generation photosensitizer for biological purposes.
Selective glycoside bond formation for the chemical syn-
thesis of well-defined oligosaccharides based on highly
reactive glycosyl donors, on versatile building block strat-
egies, and on advanced protective-group design4,5 is prob-
ably the most significant challenge of carbohydrate
chemistry. Thus, a variety of useful methods have been
developed over the last few decades, most noteworthy
several efficient Koenigs–Knorr type glycosylation proto-
cols, using various leaving groups at the anomeric cen-
ter.4–6
In contrast, the anomeric O-alkylation or O-arylation has,
as yet, been applied less widely for the synthesis of glyco-
conjugates.7 Nevertheless, this methodology is superior to
Koenigs–Knorr type glycosylations for the preparation of
aryl glycosides.
Base-promoted direct anomeric O-arylation of protected
sugars has been investigated by several authors,8 by tak-
Phthalocyanine–carbohydrate conjugates are remarkably
uncommon.21 Recently, we reported for the first time the
synthesis of peripherally substituted zinc(II) phthalocya-
nines linked anomerically to glucose moieties, which
SYNTHESIS 2007, No. 14, pp 2186–2192
x
x.
x
x
.
2
0
0
7
Advanced online publication: 03.07.2007
DOI: 10.1055/s-2007-983753; Art ID: T04207SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Expeditious Synthesis of Glycosylated Phthalocyanines
2187
were thought to provide new biologically active photosen- formamide afforded phthalonitrile glycosides 2a–e in vir-
sitizers.22
tually quantitative yield. As was observed previously,9
glycosyl oxide 1a gave predominantly the a-glycoside 3a
whereas all glycosyl thiolates 1b–e afforded solely the
corresponding b-thioglycosides 3b–e. Therefore, it is rec-
ommended to use 1-thio-glycoses as nucleophiles for the
preparation of 3,4-dicyanophenyl-carbohydrate deriva-
tives since anomerically pure aryl 1-thio-glycosides are
obtained in this case.
The key point for biological effectiveness in such materi-
als is the balance between hydrophobicity and hydrophi-
licity in the cellular uptake, that is acknowledged as an
important aspect for the design of new biological active
photosensitizers,23 A novel therapeutic antitumor ap-
proach termed photothermal therapy relies on the uptake
of such type of chromophores by diseased tissues.24 These
chromophores can then be excited by laser pulses, thereby Phthalonitrile glycosides 3f and 3g were prepared by nu-
locally generating heat which eventually leads to the lysis cleophilic substitution of 2-(tosyloxy)ethyl glycosides 1f
of tumor cells. Several research groups synthesized a va- and 1g, respectively with 4-hydroxyphthalonitrile (2b)
riety of new porphyrin–carbohydrate conjugates,25 assum- (Table 1). The latter procedure was chosen because per-
ing that the presence of the carbohydrate moiety could acetylated hydroxyethyl glycosides turned out to be insuf-
improve the membrane interaction and thus, increasing ficiently nucleophilic to induce nucleophilic substitution
their tumor selectivity. Moreover, since various types of in the case of 4-nitrophthalonitrile (2a) (no further exper-
glucose transporters are specific for different monosac- imental details shown).
charides in cancer cells,26 it is logical to expect a cellular
Synthesis of peripherally glycosylated zinc(II) phthalocy-
uptake improvement of the complexes through glycocon-
anines was performed according to the method described
jugation, which may increase the biological activity. Here
earlier.22 Glycosides 3 were first Zemplén deacetylated,28
and the resulting deprotected 3,4-dicyanophenyl glyco-
we report on the expeditious synthesis of several novel
phthalocyanine glycoconjugates linked anomerically to
sides and 1-thio-glycosides were directly cyclotetramer-
the glycoses, for which classical phthalocyanine template
ized by a template reaction without further purification, to
afford phthalocyanines 4 (Scheme 1, Table 1). The choice
of the solvent was crucial for this step because both sub-
chemistry with the corresponding unprotected phthaloni-
trile glycosides was used.9
3,4-Dicyanophenyl-carbohydrate derivatives 3a–e (see strates and products should be kept in solution during the
Scheme 1 and Table 1) were synthesized by nucleophilic cyclotetramerization in order to achieve good yields of
displacement of the nitro group in 4-nitrophthalonitrile phthalocyanines. As previously found,22 a 2:1 mixture of
(2a), a method otherwise widely used for the synthesis of 2-(dimethylamino)ethanol and butanol proved to be the
oxoaryl phthalonitriles.27 Thus, treatment of glycosides best choice.
1a–e and 2a with potassium carbonate in N,N-dimethyl-
CN
CN
K2CO3, DMF
60 °C, 24 h
O
O
AcO
AcO
1a–e
+
X
CN
XH
O2N
CN
3a–e
2a
Glc, Gal, Lac, Cel
(X = O, S)
O
CN
CN
O
AcO
CN
CN
K2CO3, DMF
60 °C, 12 h
O
O
AcO
O
OTs
+
2
2
HO
3f,g
1f,g
Glc, Gal
2b
O
HO
Y
1) NaOMe, MeOH
r.t., 1 h
N
N
N
N
O
3a–g
HO
Y
N
Zn
Y
2) Zn(OAc)2
OH
O
Me2NCH2CH2OH,
n-BuOH, 100 °C, 24 h
N
Y
N
N
4a–g
Glc, Gal, Lac, Cel
(Y = O, S, O(CH2)2O)
O
HO
Scheme 1
Synthesis 2007, No. 14, 2186–2192 © Thieme Stuttgart · New York

2188
X. Álvarez-Micó et al.
PAPER
Table 1 Yields of Phthalonitrile Glycosides 3 and Phthalocyanines 4
Glycose 1
Phthalonitrile 2
Glycosylated phthalonitrile 3
Yield (%)
3
4
CN
CN
OAc
O
OAc
CN
AcO
AcO
O
99a
99a
98
51
54
48
AcO
AcO
OH
SH
O
O2N
CN
OAc
OAc
2a
1a
3a
CN
CN
OAc
O
OAc
AcO
AcO
O
AcO
AcO
2a
2a
2a
2a
S
OAc
OAc
1b
3b
CN
AcO
OAc
AcO
OAc
O
O
SH
AcO
S
CN
AcO
OAc
OAc
1c
3c
AcO
AcO
CN
CN
OAc
OAc
OAc
O
OAc
O
O
O
O
AcO
99
99
46
42
O
AcO
AcO
AcO
SH
S
OAc
OAc
OAc
OAc
1d
3d
CN
OAc
O
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
AcO
O
AcO
O
AcO
SH
CN
S
OAc
OAc
OAc
OAc
1e
3e
OAc
O
OAc
O
CN
CN
CN
CN
AcO
AcO
82
94
48
45
O
O
AcO
AcO
HO
OTs
O
OAc
OAc
2b
1f
AcO
3f
AcO
OAc
OAc
CN
O
O
2b
O
O
AcO
AcO
O
CN
OTs
OAc
OAc
3g
1g
a See ref. 9.
Spectroscopic data of all compounds are in full agreement Our findings show that the aromatic nitro displacement is
with common substituted phthalocyanines. Although all a very useful method to form phenyl glycosides owing to
phthalocyanines prepared here are mixtures of isomers,29 such important features as bearing electron-withdrawing
they show typical chemical shifts in their 1H and 13C NMR groups, namely cyano or nitro, and using a dipolar aprotic
spectra. However, the phthalocyanine protons appear usu- solvent like N,N-dimethylformamide. Moreover, this type
ally at slightly lower fields when compared to other oxo- of carbohydrate is a very versatile building block for the
substituted phthalocyanines.29 This low-field shift of the preparation of anomerically linked carbohydrate-substi-
phthalocyanine protons is probably due to the deshielding tuted phthalocyanines, which can have an important role
effect caused by the carbohydrate moieties. The chemical in some biological processes, displaying very high solu-
shifts of the protons at the anomeric carbons are also af- bility in water.
fected by the electron-rich core of the phthalocyanine and,
therefore, also appear at lower fields. All UV/Vis spectra
are very similar to zinc-substituted phthalocyanines,
showing the Q-band maxima at around 690 nm.
All reagents were commercially obtained at highest commercial
quality and used without further purification. Air- and moisture-
sensitive liquids and solns were transferred via syringe or stainless
steel cannula. Organic solns were concentrated by rotary evapora-
tion below 45 °C. Reactions were carried out under anhydrous con-
ditions using flame-dried glassware within an argon atmosphere in
anhydrous, freshly distilled solvents, unless otherwise noted. Yields
refer to chromatographically and spectroscopically (1H NMR,13C
NMR) homogeneous materials, unless otherwise stated. Analytical
In conclusion, we have prepared by template condensa-
tion and fully characterized several novel peripherally
glycosylated zinc(II) phthalocyanines, where the sugar
moieties are linked glycosidically through O or S.
Synthesis 2007, No. 14, 2186–2192 © Thieme Stuttgart · New York

PAPER
Expeditious Synthesis of Glycosylated Phthalocyanines
2189
TLC was performed on glass plates precoated with a 0.25 mm thick-
ness of Macherey & Nagel Polygram SIL G/UV254 with UV light
as the visualizing agent and 5% H2SO4 in EtOH soln and heat as de-
tecting agents. Silica gel 60 (particle size 0.040–0.063 mm) was
used for flash chromatography. NMR spectra were recorded on a
Bruker Advance 250 (250 MHz) spectrometer and calibrated using
the deuterated solvent as an internal reference. IR spectra were re-
corded on a Bruker Tensor 27; solid substances were ground with
KBr and pressed to pellets, liquid compounds were measured di-
rectly. UV spectra were recorded on a Shimadzu UV 2102 PC using
a 1 cm quartz cell. Melting points were recorded on a Büchi B-540
and are uncorrected. MS spectra were recorded on a MALDI-TOF
Bruker Autoflex, the spectra were measured with a-cyano-m-hy-
droxycinnamic acid for phthalocyanines and 2-(4-hydroxyphenyl-
azo)benzoic acid for other compounds as matrixes, a Finnigan MAT
TSQ 70 with direct inlet, temperature of ion source 200 °C, electron
energy 70 eV (EI) or a Finnigan MAT TSQ 70 using xenon atoms
for the ionization and 3-nitrobenzyl alcohol as the matrix (FAB). El-
emental analysis was performed on Hekatech GmbH Euro EA 3000
analyzer. Preparative RP-HPLC was performed on an aqueous sys-
tem using a GROM SIL 120 ODS-4HE;10 mm; 250 × 20 mm (C-8
column); the eluents used were H2O and MeCN.
1H NMR (250 MHz, CDCl3): d = 1.93, 2.01, 2.02, 2.04, 2.11, 2.13
(21 H, CH3), 3.72–3.75 (m, 2 H, H4, H5), 3.82–3.87 (m, 1 H, H5¢),
4.04–4.13 (m, 3 H, H6a, H6¢), 4.46 (d, J1¢-2¢ = 7.8 Hz, 1 H, H1¢), 4.52
(br d, J6b-6a = 11.8 Hz, 1 H, H6b), 4.79 (d, J1-2 = 9.9 Hz, 1 H, H1),
4.85–4.97 (m, 2 H, H2, H3¢), 5.04–5.11 (dd, J2¢-3¢ = 10.6, J2¢-1¢ = 7.8
Hz, 1 H, H2¢), 5.18–5.25 (dd, J = 8.8, J = 8.6 Hz, 1 H, H3), 5.31–
5.32 (m, 1 H, H4¢), 7.68–7.69 (m, 2 H, H5¢¢, H6¢¢), 7.83–7.85 (m, 1
H, H2¢¢).
13C NMR (62.9 MHz, CDCl3): d = 20.5, 20.6, 20.7, 20.8 (CH3), 60.7
(C6¢), 62.0 (C6), 66.6 (C4¢), 69.1 (C2¢), 69.7 (C2), 70.8 (C3¢), 70.9
(C5¢), 73.3 (C3), 75.7 (C4), 77.2 (C5), 83.7 (C1), 101.1 (C1¢), 114.2
(C4¢¢), 114.9 (C3¢¢-CN), 115.0 (C4¢¢-CN), 116.4 (C3¢¢), 133.3 (C5¢¢),
134.6 (C2¢¢), 134.8 (C6¢¢), 141.2 (C1¢¢), 169.0, 169.4, 169.5, 169.9,
170.0, 170.2, 170.3 (C-CO).
MS-MALDI-TOF: m/z [M + Na]+ calcd for C34H38N2NaO17S:
801.73; found: 801.38.
Anal. Calcd for C34H38N2O17S: C, 52.44; H, 4.92; N, 3.60; S, 4.12.
Found: C, 52.82; H, 4.90; N, 3.60; S, 3.92.
3,4-Dicyanophenyl 2,3,6,2¢,3¢,4¢,6¢-Hepta-O-acetyl-1-thio-b-cel-
lobiose (3e)
Prepared from 2,3,6,2¢,3¢,4¢,6¢-hepta-O-acetyl-1-thio-b-cello-
biose30,31 (1e, 12.50 g, 19.18 mmol) as described for compound 3c.
Amorphous white powder; yield: 14.96 g (99%).
[a]D20 –48.6 (c 1, CHCl3).
3,4-Dicyanophenyl 2,3,4,6-tetra-O-acetyl-D-glucopyranoside (3a),
and 3,4-dicyanophenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyr-
anoside (3b) were prepared as previously described.9
3,4-Dicyanophenyl 2,3,4,6-Tetra-O-acetyl-1-thio-b-D-galacto-
pyranoside (3c); Typical Procedure
1H NMR (250 MHz, CDCl3): d = 1.95, 1.97, 1.98, 2.00, 2.03, 2.05,
2.14 (21 H, CH3), 3.60–3.69 (m, 1 H, H5¢), 3.70–3.73 (m, 2 H, H4,
H5), 3.99–4.12 (m, 2 H, H6a, H6a¢), 4.30–4.37 (dd, J6b¢-6a¢ = 12.5,
K2CO3 (5.60 g, 40.2 mmol) was added at r.t. to a stirred soln of
2,3,4,6-tetra-O-acetyl-1-thio-b-D-galactopyranose30,31 (1c, 7.00 g,
19.2 mmol) and 4-nitrophthalonitrile (2a, 1.28 g, 7.4 mmol) in an-
hyd DMF (25 mL), and the mixture was stirred overnight. At the
end of this period, the mixture was poured into H2O (200 mL), and
CH2Cl2 (100 mL) was added. The organic layer was separated and
the aqueous layer was extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic layers were washed with H2O (3 × 50 mL), dried
(Na2SO4), filtered, and concentrated in vacuo. Chromatography of
the crude product (silica gel, toluene–acetone, 10:1) gave 3c as an
amorphous white powder; yield: 9.24 g (98%).
J6b¢-5¢ = 4.1 Hz, 1 H, H3), 4.49 (d, J1¢-2¢ = 7.8 Hz, 1 H, H1¢), 4.49 (br
d, J6b-6a = 12.1 Hz, 1 H, H6b), 4.78 (d, J1-2 = 10.1 Hz, 1 H, H1),
4.86–4.93 (m, 2 H, H2, H2¢), 4.99–5.24 (m, 3 H, H3, H3¢, H4¢),
7.66–7.68 (m, 2 H, H5¢¢, H6¢¢), 7.84–7.85 (m, 1 H, H2¢¢).
13C NMR (62.9 MHz, CDCl3): d = 20.41, 20.49, 20.58, 20.61, 20.8
(CH3), 61.5 (C6¢), 61.9 (C6), 67.7 (C3¢), 69.6 (C2¢), 71.6 (C2), 72.1
(C5¢), 72.8 (C4¢), 73.1 (C3), 75.9 (C5), 77.3 (C4), 83.7 (C1), 100.8
(C1¢), 114.1 (C4¢¢), 114.9 (C3¢¢-CN), 115.0 (C4¢¢-CN), 116.4 (C3¢¢),
133.3 (C5¢¢), 134.6 (C2¢¢), 134.8 (C6¢¢), 141.2 (C1¢¢), 169.0, 158.3,
169.4, 169.5, 170.1, 170.2, 170.4 (C-CO).
[a]D20 –13.7 (c 1, CHCl3).
MS-MALDI-TOF: m/z [M + Na]+ calcd for C34H38N2NaO17S:
801.73; found: 801.74.
1H NMR (250 MHz, CDCl3): d = 1.96 (s), 2.06 (s), 2.09 (s), 2.17 (s)
(12 H, H-CH3), 4.01–4.06 (m, 1 H, H5), 4.14–4.18 (m, 2 H, H6),
4.80 (d, J1-2 = 9.1 Hz, 1 H, H1), 5.05–5.11 (dd, J3-2 = 9.9, J3-4 = 3.2
Hz, 1 H, H3), 5.19–5.27 (dd, J2-3 = 9.9, J2-1 = 9.1 Hz, 1 H, H2), 5.47
(d, J4-3 = 3.2 Hz, 1 H, H4), 7.68 (d, J5¢-6¢ = 8.4 Hz, 1 H, H5¢), 7.70–
7.74 (dd, J6¢-5¢ = 8.1, J6¢-2¢ = 1.7 Hz, 1 H, H6¢), 7.94 (d, J2¢-6¢ = 1.7 Hz,
1 H, H2¢).
13C NMR (62.9 MHz, CDCl3): d = 20.5, 20.62, 20.64, 20.7 (CCH3),
61.9 (C6), 66.3 (C2), 67.1 (C4), 71.5 (C3), 75.3 (C5), 83.9 (C1),
113.8 (C4¢), 114.9 (C3¢-CN), 115.0 (C4¢-CN), 116.4 (C3¢), 133.2
(C5¢), 134.1 (C2¢), 134.2(C6¢), 141.7 (C1¢), 169.3, 169.8, 169.9,
170.4 (C-CO).
Anal. Calcd for C34H38N2O17S: C, 52.44; H, 4.92; N, 3.60; S, 4.12.
Found: C, 52.27; H, 4.82; N,3.45; S, 3.92.
2-Hydroxyethyl 2,3,4,6-Tetra-O-acetyl-b-D-galactopyranoside
Powdered molecular sieves (3Å) and ethylene glycol (13.4 mL, 243
mmol) were added to a-D-acetobromogalactose30 (10.00 g, 24.3
mmol) in anhyd CH2Cl2 (100 mL). After 15 min, HgBr2 (8.75 g,
24.3 mmol) was added and the mixture was stirred overnight. The
mixture was diluted with CH2Cl2 (300 mL) and filtered over a pad
of Celite. The organic phase was washed with 5% aq soln of KI (3
× 50 mL) and H2O (3 × 50 mL), dried (Na2SO4), and the solvent was
evaporated to afford the product as a slightly yellowish oil (7.47 g,
78%) that was sufficiently pure for the next step. The spectroscopic
data were in accordance with those in the literature.32
MS-MALDI-TOF: m/z [M + Na]+ calcd for C22H22N2NaO9S:
513.47; found: 513.73.
Anal. Calcd for C22H22N2O9S: C, 53.87; H, 4.52; N, 5.71; S, 6.54.
Found: C, 54.04; H, 4.55; N, 5.75; S, 6.34.
2-(Tosyloxy)ethyl 2,3,4,6-Tetra-O-acetyl-b-D-galactopyrano-
side (1g)
3,4-Dicyanophenyl 2,3,6,2¢,3¢,4¢,6¢-Hepta-O-acetyl-1-thio-b-lac-
TsCl (5.83 g, 30.6 mmol) was added at 0 °C in small portions to 2-
hydroxyethyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranoside (6.00 g,
15.3 mmol) in CH2Cl2 (75 mL) and pyridine (6.75 mL) and the soln
was stirred overnight at r.t. The mixture was diluted with CH2Cl2 to
a volume of 300 mL and washed with aq 1 M HCl (3 × 50 mL), sat.
aq NaHCO3 (50 mL), and H2O (50 mL). After drying (Na2SO4), fil-
tration, and removal of the solvent in vacuo, the crude product was
toside (3d)
Prepared
from
2,3,6,2¢,3¢,4¢,6¢-hepta-O-acetyl-1-thio-b-
lactoside30,31 (1d, 12.50 g, 19.15 mmol) as described for compound
3c. Amorphous white powder; yield: 14.90 g (99%).
[a]D20 –37.5 (c 1, CHCl3).
Synthesis 2007, No. 14, 2186–2192 © Thieme Stuttgart · New York

2190
X. Álvarez-Micó et al.
PAPER
purified by chromatography (silica gel, toluene–acetone, 10:1) to
give compound 1g; yield: 7.98 g (95%).
119.4 (C6¢), 119.8 (C2¢), 135.3 (C5¢), 161.8 (C1¢), 169.2, 169.3,
170.2, 170.5 (C-CO).
[a]D20 –9.1 (c 1, CHCl3).
MS-MALDI-TOF: m/z [M + Na]+ calcd for C24H26N2NaO11: 541.5;
found: 541.4.
1H NMR (250 MHz, CDCl3): d = 1.95 (s), 2.01 (s), 2.04 (s), 2.11
(s) (12 H, CH3), 2.42 (s, 3 H, H-CH3), 3.72–3.82 (m, 1 H, H7a),
3.83–3.90 (m, 1 H, H5), 3.93–4.15 (m, 5 H, H6, H7b, H8), 4.46 (d,
J1-2 = 7.9 Hz, 1 H, H1), 4.94–5.00 (dd, J3-2 = 10.6, J3-4 = 2.8 Hz, 1
H, H3), 5.12–5.20 (dd, J2-3 = 10.6, J2-1 = 7.9 Hz, 1 H, H2), 5.05–
5.11 (dd, J4-3 = 2.8, J4-5 = 1 Hz, 1 H, H4), 7.33 (d, J2¢-3¢/6¢-5¢ = 8.4 Hz,
2 H, H2¢, H6¢), 7.75 (d, J3¢-2¢/5¢-6¢ = 8.4 Hz, 2 H, H3¢, H5¢).
13C NMR (62.9 MHz, CDCl3): d = 20.5, 20.59, 20.61, 20.7 (CH3),
21.6 (CCH3), 61.2 (C6), 66.9 (C4), 67.1 (C7), 68.4 (C2), 68.5 (C8),
70.7 (C3), 70.8 (C5), 101.4 (C1), 127.9 (C2¢, C6¢), 129.9 (C3¢, C5¢),
132.8 (C1¢), 145.0 (C4¢), 169.6, 170.0, 171.1, 170.3 (C-CO).
Anal. Calcd for C24H26N2O11: C, 55.60; H, 5.05; N, 5.40. Found: C,
56.50; H, 5.11; N, 5.33.
2-(3,4-Dicyanophenoxy)ethyl 2,3,4,6-Tetra-O-acetyl-b-D-galac-
topyranoside (3g)
Treatment of 1g (7.5 g, 13.7 mmol), 3,4-dicyanophenol (2b, 2.37 g,
16.4 mmol), and K2CO3 (5.68 g, 41.1 mmol) in DMF (75 mL) as de-
scribed for the preparation of compound 3f gave 3g; yield: 6.71 g
(94%).
[a]D20 –5.8 (c 0.25, CHCl3).
MS-MALDI-TOF: m/z [M + Na]+ calcd for C23H30NaO13S: 569.53;
found: 569.64.
1H NMR (250 MHz, CDCl3): d = 1.94 (s), 1.96 (s), 2.02 (s), 2.13 (s)
(12 H, CH3), 3.88–3.96 (m, 2 H, H5, H7a), 4.06–4.25 (m, 5 H, H6,
H7b, H8), 4.55 (d, J1-2 = 7.9 Hz, 1 H, H1), 4.98–5.03 (dd, J3-
2 = 10.6, J3-4 = 3.4 Hz, 1 H, H3), 5.15–5.22 (dd, J2-3 = 10.6, J2-
1 = 7.9 Hz, 1 H, H2), 5.37–5.39 (dd, J4-3 = 3.4, J4-5 = 1 Hz, 1 H, H4),
7.15–7.25 (m, 2 H, H2¢,H6¢), 7.69 (d, J5¢-6¢ = 8.6 Hz, 1 H, H5¢).
13C NMR (62.9 MHz, CDCl3): d = 20.5, 20.61, 20.64 (CH3), 61.2
(C8), 66.9 (C4), 67.4 (C7), 68.2 (C6), 68.5 (C2), 70.7 (C3), 70.9
(C5), 101.3 (C1), 107.7 (C4¢), 115.1 (C3¢-CN), 115.6 (C4¢-CN),
117.5 (C3¢), 119.5 (C2¢), 119.8 (C6¢), 135.3 (C5¢), 161.8 (C1¢),
169.3, 170.0, 170.1, 170.3 (C-CO).
Anal. Calcd for C23H30O13S: C, 50.54; H, 5.53. Found: C, 50.24; H,
5.59.
3,4-Dicyanophenol (2b)
K2CO3 (41.00 g, 300 mmol) was added to a soln of benzyl alcohol
(6.20 mL, 60 mmol) and 4-nitrophthalonitrile (7.00 g, 40 mmol) in
DMF (100 mL). The mixture was heated and stirred at 80 °C for 6
h. At the end of this period, the mixture was cooled to r.t. and poured
into ice-water (1 L). The product, 4-(benzyloxy)phthalonitrile, was
filtered off and recrystallized (EtOH). A soln of 4-(benzyloxy)ph-
thalonitrile (8.9 g, 38 mmol) in EtOAc (200 mL) was added to a sus-
pension of 10% Pd/C (300 mg) in EtOAc (100 mL) and the resulting
slurry was stirred in an atmosphere of H2 for 6 h. The catalyst was
removed from the soln by filtration over Celite and the solvent was
evaporated in vacuo. The residue was dissolved in 5% aq NaOH, the
soln was filtered, and the filtrate was neutralized with concentrated
HCl whereupon 2b crystallized. Filtration and drying afforded of
2b; yield: 4.6 g (85%).
MS-MALDI-TOF: m/z [M + Na]+ calcd for C24H26N2NaO11: 541.5;
found: 541.9.
Anal. C, 55.60; H, 5.05; N, 5.40. Found: C, 55.43; H, 4.92; N, 5.41.
[2(3),9(10),16(17),23(24)-Tetrakis(a/b-D-glucopyranosyl-
oxy)phthalocyaninato]zinc (4a); Typical Procedure
An a/b mixture (10:1) of 3,4-dicyanophenyl 2,3,4,6-tetra-O-acetyl-
D-glucopyranoside (3a, 1.0 g, 2.0 mmol) was suspended in anhyd
MeOH (25 mL). NaOMe (100 mmol) was added and the soln was
stirred for 1 h. Dowex 50WX8-400 ion-exchange resin was added
to neutralize the soln. The resin was filtered off and the solvent
evaporated in vacuo. To the deprotected phthalonitrile dissolved in
a mixture of 2-(dimethylamino)ethanol (1 mL) and BuOH (0.5 mL),
Zn(OAc)2 (183 mg, 1 mmol) was added. The mixture was stirred
under argon for 24 h at 100 °C. After cooling, the residue was dis-
solved in a minimal amount of H2O and crude 4a was precipitated
from the resulting soln by adding acetone. The solid was filtered off,
redissolved in a minimal amount of H2O, precipitated again by add-
ing acetone, and collected by filtration. Purification was achieved
by preparative RP-HPLC chromatography (H2O–MeCN, 10:1) to
afford 4a as a green solid; yield: 320 mg (51%).
1H NMR (250 MHz, DMSO-d6): d = 7.16–7.22 (dd, J5-3 = 2.5, J5-6
=
8.6 Hz, 1 H, H5), 7.37 (d, 1 H, J3-5 = 2.5 Hz, 1 H, H3), 7.89 (d, 1 H,
J6-5 = 8.6 Hz, 1 H, H6).
13C NMR (62.9 MHz, CD3OD): d = 107.74 (C4), 118.17 (C6),
118.82 (C3, C5), 119.64 (C2), 123.38 (C1-CN), 128.11 (C2-CN),
164.57 (C1).
EI-MS: m/z [M]+ calcd for C8H4N2O: 144.1; found: 143.9.
2-(3,4-Dicyanophenoxy)ethyl 2,3,4,6-Tetra-O-acetyl-b-D-gluco-
pyranoside (3f); Typical Procedure
Glucopyranoside 1f33 (4.00 g, 7.3 mmol), K2CO3 (2.00 g, 15 mmol),
and 3,4-dicyanophenol (2b, 1.44 g, 10 mmol) in DMF (25 mL) were
heated overnight at 60 °C. After cooling, the mixture was diluted
with H2O (500 mL), extracted with CH2Cl2 (3 × 100 mL), and the
combined organic extracts were dried (Na2SO4). After evaporation
of the solvent, the crude product was purified by chromatography
(silica gel, toluene–acetone, 10:1); yield: 3.12 g (82%).
1H NMR (250 MHz, DMSO-d6): d = 6.05 (br, 4 H, H1¢), 7.95 (br, 4
H, H6), 9.08 (br, 4 H, H3), 9.35 (s, 4 H, H5).
13C NMR (62.9 MHz, DMSO-d6): d = 61.3 (C6¢), 70.5 (C5¢), 72.3
(C4¢), 73.8 (C2¢), 74.8 (C3¢), 98.9 (C1¢), 109.8 (C3), 120.2 (C5),
124.2 (C6), 132.5 (C7), 140.1 (C2), 153 (C1, C8), 159 (C4).
[a]D20 –22.0 (c 1, CHCl3).
MS-MALDI-TOF: m/z [M + H]+ calcd for C56H57N8O24Zn:
1H NMR (250 MHz, CDCl3): d = 1.93 (s), 1.98 (s), 2.00 (s), 2.06 (s)
(12 H, CH3), 3.65–3.74 (m, 1 H, H5), 3.86–3.97 (m, 1 H, H8), 4.10–
4.27 (m, 5 H, H6, H7, H8), 4.59 (d, J1-2 = 7 9 Hz, 1 H, H1), 4.94–
5.01 (dd, J2-1 = 7.9, J2-3 = 9.3 Hz, 1 H, H2), 5.02–5.11(dd, J4-3 = 9.4,
J4-5 = 9.8 Hz, 1 H, H4), 5.14–5.24 (dd, J4-5 = 9.3, J3-4 = 9.4 Hz, 1 H,
H3), 7.15–7.22 (dd, J6¢-2¢ = 2.5, J6¢-5¢ = 8.6 Hz, 1 H, H6¢), 7.25 (d,
1289.2777; found: 1289.2690.
UV-Vis (DMSO): l (% rel. int.) = 354 (41, B band), 613 (17, sh),
681 nm (100, Q band).
[2(3),9(10),16(17),23(24)-Tetrakis(b-D-glucopyranosylsulfa-
nyl)phthalocyaninato]zinc (4b)
3,4-Dicyanophenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyrano-
side (3b, 1.5 g, 3.1 mmol) was deacetylated with a catalytic amount
of NaOMe in MeOH and condensed with ZnCl2 as described for the
preparation of compound 4a. RP-HPLC chromatography (H2O–
MeCN, 10:1) afforded 4b as a green solid; yield: 565 mg (54%).
J
2¢-6¢ = 2.6 Hz, 1 H, H2¢), 7.69 (d, J5¢-6¢ = 8.6 Hz, 1 H, H5¢).
13C NMR (62.9 MHz, CDCl3): d = 20.5, 20.7 (CH3), 61.7 (C6), 67.4
(C8), 68.1 (C7), 68.3 (C4), 71.1 (C2), 72.1 (C5), 72.6 (C3), 100.8
(C1), 107.7 (C4¢), 115.1 (C3¢-CN), 115.5 (C4¢-CN), 117.5 (C3¢),
Synthesis 2007, No. 14, 2186–2192 © Thieme Stuttgart · New York

PAPER
Expeditious Synthesis of Glycosylated Phthalocyanines
2191
1H NMR (250 MHz, DMSO-d6): d = 8.3 (br, 4 H, H6), 9.3 (br, 4 H,
H5), 9.5 (br, 4 H, H3).
UV-Vis (DMSO): l (% rel. int.) = 360 (32, B band), 621 (17, sh),
690 nm (100, Q band).
13C NMR (62.9 MHz, DMSO-d6): d = 61.6 (C6¢), 70.3 (C4¢), 73.1
(C2¢), 78.8 (C5¢), 81.7 (C3¢), 88.0 (C1¢), 123.0 (C3), 123.6 (C6),
130.9 (C4), 136.5 (C7), 137.8 (C2), 139 (C4), 153 (C1, C8).
MS-MALDI-TOF: m/z [M + H]+ calcd for C56H57N8O20S4Zn:
1353.18634; found: 1353.14486.
{2(3),9(10),16(17),23(24)-Tetrakis[2-(b-D-glucopyranosyl-
oxy)ethoxy]phthalocyaninato}zinc (4f)
2-(3,4-Dicyanophenoxy)ethyl 2,3,4,6-tetra-O-acetyl-b-D-glucopy-
ranoside (3f, 1.08 g, 2 mmol) was deacetylated with a catalytic
amount of NaOMe in MeOH and condensed with ZnCl2 as de-
scribed for the preparation of compound 4a. RP-HPLC chromatog-
raphy (H2O–MeCN, 10:1) afforded 4f as a green solid; yield: 367
mg (48%).
UV-Vis (DMSO): l (% rel. int.) = 362 (33, B band), 622 (16, sh),
691 nm (100, Q band).
1H NMR (250 MHz, DMSO-d6): d = 7.8 (br, 4 H, H6), 8.9 (br, 4 H,
H5), 9.2 (br, 4 H, H3).
[2(3),9(10),16(17),23(24)-Tetrakis(b-D-galactopyranosylsulfa-
nyl)phthalocyaninato]zinc (4c)
3,4-Dicyanophenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-galactopyra-
noside (3c, 1.0 g, 2.0 mmol) was deacetylated with a catalytic
amount of NaOMe in MeOH and condensed with ZnCl2 as de-
scribed for the preparation of compound 4a. RP-HPLC chromatog-
raphy (H2O–MeCN, 10:1) afforded 4c as a green solid; yield: 325
mg (48%).
13C NMR (62.9 MHz, DMSO-d6): d = 61.6 (C6¢), 67.8 (C8¢), 68.7
(C7¢), 70.6 (C4¢), 74.0 (C2¢), 77.3 (C5¢), 77.5 (C3¢), 103.8 (C1¢)
106.3 (C3), 118.7 (C5), 124.1 (C6), 131.6 (C7), 140.5 (C2), 153
(C1, C8), 160.9 (C4).
MS-MALDI-TOF: m/z [M]+ calcd for C64H72N8O28Zn: 1464.375;
found: 1464.347.
1H NMR (250 MHz, DMSO-d6): d = 8.3 (br, 4 H, H6), 9.2 (br, 4 H,
H5), 9.4 (br, 4 H, H3).
UV-Vis (DMSO): l (% rel. int.) = 357 (46, B band), 613 (17, sh),
682 nm (100, Q band).
13C NMR (62.9 MHz, DMSO-d6): d = 61.3 (C6¢), 69.1 (C4¢), 70.2
(C2¢), 75.3 (C5¢), 79.9 (C3¢), 88.6 (C1¢), 123.3 (C3), 123.7 (C6),
130.8 (C4), 136.1 (C7), 138.4 (C2), 138.8 (C4), 153 (C1, C8).
MS-MALDI-TOF: m/z [M]+ calcd for C56H57N8O20S4Zn: 1352.178;
found: 1352.157.
{2(3),9(10),16(17),23(24)-Tetrakis[2-(b-D-galactopyranosyl-
oxy)ethoxy]phthalocyaninato}zinc (4g)
2-(3,4-Dicyanophenoxy)ethyl 2,3,4,6-tetra-O-acetyl-b-D-galacto-
pyranoside (3g, 1.08 g, 2 mmol) was deacetylated with a catalytic
amount of NaOMe in MeOH and condensed with ZnCl2 as de-
scribed for the preparation of compound 4a. RP-HPLC chromatog-
raphy (H2O–MeCN, 10:1) afforded 4g as a green solid; yield: 343
mg (45%).
1H NMR (250 MHz, DMSO-d6): d = 7.7 (br, 4 H, H6), 8.7 (br, 4 H,
H5), 9.1 (br, 4 H, H3).
13C NMR (62.9 MHz, DMSO-d6): d = 61.1 (C6¢), 67.7 (C8¢), 68.7
(C7¢, C4¢), 71.1 (C2¢), 74.0 (C3¢), 75.9 (C5¢), 104.4 (C1¢) 106.3
(C3), 118.7 (C5), 124.0 (C6), 131.4 (C7), 140.3 (C2), 153 (C1, C8),
160.9 (C4).
UV-Vis (DMSO): l (% rel. int.) = 363 (33, B band), 623 (16, sh),
692 nm (100, Q band).
[2(3),9(10),16(17),23(24)-Tetrakis(b-D-lactosylsulfanyl)phthalo-
cyaninato]zinc (4d)
3,4-Dicyanophenyl 2,3,6,2¢,3¢,4¢,6¢-hepta-O-acetyl-1-thio-b-lacto-
side (3d, 1.95 g, 2.5 mmol) was deacetylated with a catalytic
amount of NaOMe in MeOH and condensed with ZnCl2 as de-
scribed for the preparation of compound 4a. RP-HPLC chromatog-
raphy (H2O–MeCN, 10:1) afforded 4d as a green solid; yield: 576
mg (46%).
MS-MALDI-TOF: m/z [M]+ calcd for C64H72N8O28Zn: 1464.375;
found: 1464.138.
1H NMR (250 MHz, DMSO-d6): d = 8.3 (br, 4 H, H6), 9.1 (br, 4 H,
H5), 9.3 (br, 4 H, H3).
UV-Vis (DMSO): l (% rel. int.) = 355 (40, B band), 614 (21, sh),
684 nm (100, Q band).
13C NMR (62.9 MHz, DMSO-d6): d = 60.9 (C6¢, C6¢¢), 68.6 (C4¢¢),
71.0 (C2¢¢), 73.2 (C2¢), 73.7 (C5¢), 76.0 (C3¢), 76.9 (C3¢¢), 79.6
(C5¢¢), 80.6 (C4¢), 87.6 (C1¢), 104.3 (C1¢¢).
MS-MALDI-TOF: m/z [M + Na]+ calcd for C80H96N8NaO40S4Zn:
2023.403; found: 2023.378.
Acknowledgment
This work was financially supported by the Fonds der Chemischen
Industrie. We thank Dr. B. Kammerer, Clinical Pharmacology, Uni-
versity of Tübingen for performing the MALDI-TOF MS.
UV-Vis (DMSO): l (% rel. int.) = 363 (55, B band), 622 (22, sh),
689 nm (100, Q band).
[2(3),9(10),16(17),23(24)-Tetrakis(b-D-cellobiosylsulfanyl)ph-
thalocyaninato]zinc (4e)
References
3,4-Dicyanophenyl 2,3,6,2¢,3¢,4¢,6¢-hepta-O-acetyl-1-thio-b-cello-
bioside (3e, 1.56 g, 2.0 mmol) was deacetylated with a catalytic
amount of NaOMe in MeOH and condensed with ZnCl2 as de-
scribed for the preparation of compound 4a. RP-HPLC chromatog-
raphy (H2O–MeCN, 10:1) afforded 4e as a green solid; yield: 421
mg (42%).
1H NMR (250 MHz, DMSO-d6): d = 8.3 (br, 4 H, H6), 9.2 (br, 4 H,
H5), 9.3 (br, 4 H, H3).
13C NMR (62.9 MHz, DMSO-d6): d = 60.9 (C6¢), 61.5 (C6¢¢), 70.5
(C3¢¢), 73.1 (C2¢¢), 73.8 (C2¢), 76.9 (C5¢¢,C4¢¢), 77.3 (C3¢), 79.6
(C5¢), 80.3 (C4¢), 87.6 (C1¢), 103.6 (C1¢¢), 123.3 (C3), 123.5 (C6),
131.5 (C4), 136.3 (C7), 137.4 (C2), 138.7 (C4), 153 (C1, C8).
(1) (a) Varki, A. Glycobiology 1993, 3, 97. (b) Sears, P.;Wong,
C.-H. Cell. Mol. Life Sci. 1998, 54, 223.
(2) Gabius, H. J.; Gabius, S. Glycosciences: Status and
Perspectives; Chapman & Hall: Weinheim, 1997.
(3) (a) Paulson, J. C. Trends Biochem. Sci. 1989, 14, 272.
(b) Dwek, R. A. Chem. Rev. 1996, 96, 683.
(4) (a) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25,
212; Angew. Chem., 1986, 98, 213. (b) Schmidt, R. R.;
Kinzy, W. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21.
(c) Schmidt, R. R. Pure Appl. Chem. 1989, 61, 1257.
(5) Schmidt, R. R. Pure Appl. Chem. 1998, 70, 397.
(6) (a) Kazunoho, T.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(b) Jung, K.-H.; Müller, M.; Schmidt, R. R. Chem. Rev.
2000, 100, 4423.
MS-MALDI-TOF: m/z [M]+ calcd for C80H96N8O40S4Zn: 2000.389;
found: 2000.134.
Synthesis 2007, No. 14, 2186–2192 © Thieme Stuttgart · New York

2192
X. Álvarez-Micó et al.
PAPER
(7) Schmidt, R. R. Modern Methods in Carbohydrate Synthesis;
Khan, S. H.; O’Neill, R. A., Eds.; Harwood Academic
Publishers GmbH: Amsterdam, 1996.
(8) (a) Berven, L. A.; Dolphin, D.; Withers, S. G. Can. J. Chem.
1990, 68, 1859. (b) Lindberg, B. Acta Chem. Scand. 1950, 4,
49. (c) Ferrier, R. J. Fortschr. Chem. Forsch. 1970, 14, 389.
(d) Huchel, U.; Schmidt, C.; Schmidt, R. R. Tetrahedron
Lett. 1995, 36, 9457.
(19) Roeder, B.; Naether, D.; Lewald, T.; Braune, M.; Nowak, C.;
Freyer, W. Biophys. Chem. 1990, 35, 303.
(20) Komatsu, K. Jpn. J. Cancer Res. 1991, 82, 599.
(21) (a) Maillard, P.; Guerquin-Kern, J.-L.; Momenteau, M.;
Gaspard, S. J. Am. Chem. Soc. 1989, 111, 9125. (b) Lee, P.;
Lo, P.-C.; Chan, E.; Fong, W.-P.; Ko, W.-H.; Ng, D.
Tetrahedron Lett. 2005, 46, 1551. (c) Ribeiro, A. O.; Tomé,
J. P. C.; Neves, M. G. P. M. S.; Tomé, A. C.; Cavaleiro, J. A.
S.; Iammoto, Y.; Torres, T. Tetrahedron Lett. 2006, 47,
9177.
(9) Alvarez-Mico, X.; Calvete, M. J. F.; Hanack, M.; Ziegler, T.
h. Carbohydrate Res. 2006, 324, 440.
(10) Kornblum, N.; Cheng, L.; Kerber, R. C.; Kestner, M. M.;
Newton, B. N.; Pinnick, H. W.; Smith, R. G.; Wade, P. A. J.
Org. Chem. 1976, 41, 1560.
(11) (a) Rodimann, E.; Schmidt, W.; Nischk, G. E. Makromol.
Chem. 1969, 130, 45. (b) Mauleon, D.; Granados, R.;
Minguillon, C. J. Org. Chem. 1983, 48, 3105.
(22) Alvarez-Mico, X.; Calvete, M. J. F.; Hanack, M.; Ziegler, T.
h. Tetrahedron Lett. 2006, 47, 3283.
(23) MacDonald, I.; Dougherty, T. J. Porphyrins
Phthalocyanines 2001, 5, 105.
(24) Camerin, M.; Rello, S.; Villanueva, A.; Ping, X.; Kenney,
M.; Rodgers, M.; Jori, G. Eur. J. Cancer 2005, 8, 1203.
(25) (a) Ono, N.; Bougauchi, M.; Maruyama, K. Tetrahedron
Lett. 1992, 33, 1629. (b) Maillard, P.; Guerquin-Kern, J.-L.;
Huel, C.; Momenteau, M. J. Org. Chem. 1993, 58, 2774.
(c) Fujimoto, K.; Miyata, T.; Aoyama, Y. J. Am. Chem. Soc.
2000, 122, 3558. (d) Chen, X.; Hui, L.; Foster, D.; Drain, C.
Biochemistry 2004, 43, 10918. (e) Li, G.; Pandey, S.;
Graham, A.; Dobhal, M.; Ricky, M.; Chen, Y.; Gryshuk, A.;
Rittenhouse-Olson, K.; Oseroff, A.; Pandey, R. J. Org.
Chem. 2004, 69, 158. (f) Chen, X.; Drain, C. Drug Design
Rev. – Online 2004, 1, 215; www.ingentaconnect.com/
content/ben/ddro.
(12) Beck, J. R. J. Org. Chem. 1972, 37, 3224.
(13) Knudsen, R. D.; Snyder, H. R. J. Org. Chem. 1974, 39, 3343.
(14) (a) Idoux, J. P.; Gupton, M. T.; McCurry, C. K.; Crews, A.
D.; Jurss, C. D.; Colon, C.; Rampi, R. J. Org. Chem. 1983,
48, 3771. (b) March, J. Advanced Organic Chemistry;
McGraw-Hill: New York, 1977, 2nd Ed..
(15) (a) Dini, D.; Hanack, M. The Porphyrin Handbook, Vol. 17;
Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.; Academic
Press: New York, 2003, 1. (b) Cook, M.; Chambrier, I. The
Porphyrin Handbook, Vol. 17; Kadish, K. M.; Smith, K. M.;
Guilard, R., Eds.; Academic Press: New York, 2003, 37.
(c) Wöhrle, D.; Schnurpfeil, G. The Porphyrin Handbook,
Vol. 17; Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.;
Academic Press: New York, 2003, 177. (d) Wark, M. The
Porphyrin Handbook, Vol. 17; Kadish, K. M.; Smith, K. M.;
Guilard, R., Eds.; Academic Press: New York, 2003, 247.
(e) Erk, P.; Hengelsberg, H. The Porphyrin Handbook, Vol.
19; Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.;
Academic Press: New York, 2003, 105. (f) Bouvet, M. The
Porphyrin Handbook, Vol. 19; Kadish, K. M.; Smith, K. M.;
Guilard, R., Eds.; Academic Press: New York, 2003, 37.
(16) Ben-Hur, E.; Chan, W.-S. The Porphyrin Handbook, Vol.
19; Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.;
Academic Press: New York, 2003, 1; and references cited
therein.
(26) (a) Chandler, J.; Williams, E.; Slavin, J.; Best, J.; Rogers, S.
Cancer 2003, 97, 2035. (b) Kumamoto, K.; Goto, Y.;
Sekikawa, K.; Takenoshita, S.; Ishida, N.; Kawakita, M.;
Kannagi, R. Cancer Res. 2001, 61, 4620.
(27) Wöhrle, D.; Schnurpfeil, G.; Knothe, G. Dyes Pigments
1992, 18, 91.
(28) Zemplén, G. Ber. Dtsch. Chem. Ges. 1927, 60, 1555.
(29) Sommerauer, M.; Rager, C.; Hanack, M. J. Am. Chem. Soc.
1996, 118, 10085.
(30) (a) Wolfrom, M. L.; Thompson, A. Methods in
Carbohydrate Chemistry, Vol. 2; Whistler, R. L.; Wolfrom,
M. L., Eds.; Academic Press: New York, 1963, 211.
(b) Mikamo, M. Carbohydr. Res. 1989, 191, 150.
(31) (a) Scheurer, P. G.; Smith, F. J. Am. Chem. Soc. 1954, 76,
3224. (b) Matta, K. L.; Girotra, R. N.; Barlow, J. J.
Carbohydr. Res. 1975, 43, 101.
(17) Phthalocyanines, Properties and Applications, Vols. 1-4;
Leznoff, C. C.; Lever, A. B. P., Eds.; VCH: New York,
1989-1996.
(32) Sorg, B. L.; Hull, W. I.; Kleim, H. C.; Mier, W.; Wiessler,
(18) van Lier, J. E.; Spikes, J. D. Photosensitizing Compounds:
Their Chemistry, Biology and Clinical Use (CIBA
Foundation Symposium 146); Dougherty, T. J.; Bock, G.;
Harnett, S., Eds.; Wiley: Chichester, 1989, 17.
M. Carbohydr. Res. 2005, 340, 181.
(33) Petrig, J.; Schibli, R.; Dumas, C.; Alberto, R.; Schubiger, P.
A. Chem. Eur. J. 2001, 7, 1868.
Synthesis 2007, No. 14, 2186–2192 © Thieme Stuttgart · New York