Synthesis of some oligopyridine-galactose conjugates and their metal complexes: A simple entry to multivalent sugar ligands

Article abstract of DOI:10.1016/j.tet.2005.08.018

Some galactose-oligopyridine conjugates were readily assembled by combining differently functionalized oligopyridines with peracetylated galactose derivatives. Variation in the structure of the components and of the linkers employed for their connection a

Full text of DOI:10.1016/j.tet.2005.08.018

Tetrahedron 61 (2005) 10048–10060
Synthesis of some oligopyridine–galactose conjugates and their
metal complexes: a simple entry to multivalent sugar ligands
a,b,
Simonetta Orlandi,a Rita Annunziata,a Maurizio Benaglia,a, Franco Cozzi
*
*
and Leonardo Manzonib
aDipartimento di Chimica Organica e Industriale, Centro di Eccellenza CISI, Universita’ degli Studi di Milano, Via Golgi 19,
20133 Milano, Italy
bDipartimento di Chimica Organica e Industriale, CNR-ISTM, Universita’ degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy
Received 9 May 2005; revised 20 July 2005; accepted 4 August 2005
Available online 25 August 2005
Abstract—Some galactose–oligopyridine conjugates were readily assembled by combining differently functionalized oligopyridines with
peracetylated galactose derivatives. Variation in the structure of the components and of the linkers employed for their connection afforded
adducts of different size, shape, and conformational mobility. Complexation of the bipyridine ligands with CuOTf and of the terpyridine
ligand with Zn(OTf)2 afforded the corresponding peracetylated 2:1 and 1:1 complexes, respectively, as single species. Their structures were
determined to be tetrahedral (Cu complexes) and trigonal-bipyramidal (Zn complex), on the basis of spectroscopic evidence. Removal of the
acetyl protecting groups from the ligands afforded the corresponding polyols. The terpyridine–Zn(II) complex, unlike the bipyridine–Cu(I)
complexes maintained their structures upon removal of the acetyl protecting groups.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
almost at will by changing the structure of the ligand and the
nature of the metal.
Protein–carbohydrate interactions control a variety of
fundamental biological processes.1 In many instances
several carbohydrate units are involved in the binding
event,2 to take advantage of the so-called ‘glycoside cluster
effect’.3,4 Artificial multivalent glycoside ligands have been
synthesized with the aim of better understanding the
protein–carbohydrate interaction processes and of develop-
ing inhibitors of these phenomena when they are involved in
infectious cycles.
As a part of a project devoted to explore the potential of
metal saccharide–ligand conjugates in the field of multi-
valent sugar presentation, we wish to report some
preliminary results on the synthesis of galactose-containing
oligopyridine derivatives and their complexes with metal
ions.
2. Results and discussion
The vast majority of the multivalent sugar ligands reported
so far have been assembled around dendritic or polymeric
frameworks to exploit the high number of functional groups
presented by these scaffolds.3 Among the studied systems
falling outside these classes of compounds, examples of
metal saccharide–ligand conjugates have been particularly
scarce.5–7 This is surprising, because the metal-assisted
association of carbohydrate components modified with a
metal-binding ligand can open a straightforward access to
carbohydrate clusters in which the number and the relative
orientation of the carbohydrate residues can be modulated
Synthesis of the modified galactose residues. On the basis of
its ubiquitous involvement in protein–carbohydrate inter-
actions,1–3 galactose was selected as the sugar component of
the designed oligopyridine–carbohydrate conjugates.
Derivatives 2–4, featuring different spacers and handles
for the connection to the oligopyridine ligands, were
synthesized starting from O-(2,3,4,6-O-tetracetyl-D-galacto-
pyranosyl) trichloroacetimidate 18 and using trimethylsilyl
triflate promoted glycosidation reactions (Scheme 1). In
particular, amine 2 was obtained as a single b-isomer in
50% overall yield by reaction with benzyl N-(2-hydroxy-
ethyl)carbamate followed by reductive cleavage of
the nitrogen-protecting group; phenol 3 was prepared in
33% overall yield by b-selective glycosidation with
Keywords: Carbohydrates; N-ligand; Metal complexes.
*
Corresponding authors. Tel.: C39 0250314171; fax: C39 0250314159;
e-mail: maurizio.benaglia@unimi.it
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.018

S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
10049
Scheme 1. Synthesis of galactose derivatives 2–4. Reagents and conditions:
(a) TMSOTf, HOCH2CH2NHCOBn, DCM, 0 8C, 2 h; (b) 10% Pd/C, 1 atm
H2, EtOH, rt, 2 h; (c) TMSOTf, 4-BnO–C6H4–(CH2)3OH, DCM, 0 8C, 2 h;
(d) TMSOTf, 4-I-C6H4OH, DCM, 0 8C, 2 h.
3-(4-benzyloxyphenyl)-1-propanol,9 followed by hydro-
genolysis of the benzyl group; reaction of 1 with
4-iodophenol afforded (85% yield) a 78:22 mixture of
anomers, from which the pure b-isomer 4 was readily
obtained by chromatography in 66% yield.
Synthesis of the oligopyridines. Oligopyridines 5, 6, 8, 9,
and 10 carrying functional groups of different size and
conformational mobility were selected for this study
(Scheme 2). Compounds 5,10 6,11 and 1012 were prepared
according to literature procedures. Bis-aldehyde 8a was
obtained in two steps involving first Suzuki-type coupling of
2,6-dibromopyridine with 3-formylphenylboronic acid to
afford compound 7 (56% yield),13 and then nickel promoted
homocoupling of the latter (47% yield).14 From 8a,
dibromide 9 was readily prepared by reduction to the
corresponding diol 8b with NaBH4 (96% yield) and
bromination with PBr3 (82% yield).
Scheme 2. Structure of oligopyridines 5, 6, and 10 and synthesis of
bipyridines 8 and 9. Reagents and conditions: (a), 3-formylphenyboronic
acid, Pd(OAc)2, PPh3, DME, NaHCO3, reflux, 22 h; (b), NiCl2 hexahydrate,
PPh3, Zn, DMF, 50 8C, 22 h; (c), NaBH4, EtOH, 0 8C, 5 h; (d), PBr3, DCM,
0 8C to rt, 16 h.
acetonitrile/CHCl3 to afford, after solvent evaporation, dark
red solids. Cu(11)2–Cu(13)2 were purified by filtration
through a short silica gel column. Mass spectroscopy (MS-
FAB) indicated the formation of adducts containing two
ligands for each copper cation.
Synthesis of the oligopyridine–galactose conjugates and
their metal complexes. By combining bipyridines 5, 6, 8a,
and 9 with functionalized galactose derivatives 2-4, acetates
11–14 were obtained (Scheme 3).
The assignment of structures to these complexes was based
on NMR evidence. For instance, in all cases the 13C NMR
signals of the bipyridine carbons in positions 5/50 and 3/30
were shifted downfield by 4.3–4.6 and 1.1–1.9 ppm,
respectively, upon complexation. An opposite shift was
experienced by the quaternary 2/20 carbons of bipyridine,
that were shifted upfield by 2.8–3.7 ppm. These trends are i0n
agreement with those generally observed when two 6,6 -
disubstituted bipyridine units complex a Cu(I) cation to
afford a tetrahedral adduct.15,16
Reaction of phenol 3 with dibromides 5 and 9, carried out in
the presence of cesium carbonate, afforded adducts 11 and
13 in 55 and 30% yields, respectively. The bis-acetylene
derivative 12 was obtained in 33% yield by coupling
bipyridine 6 with aryliodide 4 under standard Sonogashira
conditions.
Further support in favor of the formation of tetrahedrally
arranged complexes Cu(11)2–Cu(14)2 also came from the
variation in the chemical shift observed for the protons of
the residues in the vicinity of the bipyridine nuclei.
Inspection of molecular models showed that upon formation
of a tetrahedral complex protons of one ligand molecule fell
in the shielding cone of the bipyridine moiety of the other
ligand molecule (Fig. 1). As a consequence, strong upfield
shifts were expected and indeed observed. For instance, the
signal of the methylene groups bound to bipyridine C-6 and
C-60 in ligand 11 were shifted by about 0.5 ppm upfield in
Imine 14 was synthesized in 90% yield by adding 6 equiv of
amine 2 to a 5 mM solution of bis-aldehyde 8a in 80:20
CH2Cl2/MeOH. Terpyridine 15 was obtained in 60% yield
by combining galactose derivative 4 with 200,6-diethynyl-
2,20:60,600-terpyridine 10 following the procedure employed
for the preparation of conjugate 12.
Formation of complexes Cu(11)2–Cu(14)2 was performed
in 92–98% yields by addition of 1 mol equiv of
CuOTf$0.5C6H6 to 2 mol equiv of ligands 11–14 in 50:50

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S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
Scheme 3. Synthesis of oligopyridine–galactose conjugates 11–20. Reagents and conditions: (a), Cs2CO3, MeCN, rt, 18 h; (b), 0.1 M MeONa, MeOH, rt, 15 h;
(c), CuI, PdCl2(PPh3)2, i-Pr2NH, THF, reflux, 24 h; (d), Cs2CO3, DMF/MeCN 80:20, rt, 18 h; (e), MeOH/DCM 20:80, rt, 18 h.
complex Cu(11)2. Similarly, the protons of the phenyl
rings connected to the same bipyridine carbons in ligands 13
and 14 experienced large upfield shifts (up to more than
1 ppm) upon formation of Cu(13)2 and Cu(14)2 (see
Section 4).
upon complex formation. This showed that these
residues, being isolated from the bipyridine nucleus by
the spacer, were not affected by the complexation event
and maintained their conformational freedom. This
observation is important because it suggests that the
galactose units in Cu(11)2–Cu(14)2 were not limited by
the complexation in their potential ability to interact with a
biological target.
On the other hand, the chemical shifts of the the H and C
atoms of the glactose units remained virtually unchanged

S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
10051
Zn(15) resulted in complex decomposition to afford the
deprotected ligand 20.
3. Conclusions
In conclusion, this work has demonstrated that galactose–
oligopyridine conjugates could readily be assembled by
combining four differently functionalized bipyridines and
one terpyridine with three peracetylated galactose deriva-
tives. Variation in the structure of the components and of the
linkers employed for their connection afforded adducts of
different size, shape, and conformational mobility, thus
showing the generality of this approach.
Complexation of the bipyridine ligands with CuOTf and of
the terpyridine ligand with Zn(OTf)2 afforded the corre-
sponding peracetylated 2:1 and 1:1 complexes, respectively,
as single species. Their structures were determined to be
tetrahedral (Cu complexes) and trigonal-bipyramidal (Zn
complex), on the basis of NMR and mass spectroscopic
evidence. Removal of the acetyl protecting groups from the
ligands was possible, affording polyols that turned out to be
poorly soluble in most organic solvents and in water. In
contrast to the terpyridine–Zn(II) complex, the bipyridine/
Cu(I) complexes survived the removal of the acetyl
protecting groups and maintained their structure.
Figure 1. Schematic representation of copper(I)- and zinc(II)-complexes.
Reaction of ligand 15 with 1 mol equiv of Zn(OTf)2 in
chloroform afforded the corresponding 1:1 complex Zn(15),
to which, on the basis of literature data collected for related
complexes17 and of NMR and mass spectroscopic evidence,
the trigonal bipyramidal structure reported in Figure 1 was
assigned.
Studies dedicated to assess the binding ability21 of these
multivalent glycosylated ligands on macromolecular
receptors such as lectins22 by turbidimetric analysis23 will
be reported in due course.
Having performed the synthesis of the acetylated
complexes, we turned our attention to the preparation of
their unprotected analogs required for biological evaluation.
In principle these compounds could be obtained by two
different approaches: (i) by deprotection of the acetylated
complexes, and (ii) by complexation of the deacetylated
ligands.
4. Experimental
4.1. General methods
1H NMR spectra were recorded on Bruker instruments at
300 or 500 MHz in chloroform-d (CDCl3) unless otherwise
stated, and were referenced to tetramethylsilane (TMS) at
0.00 ppm; 13C NMR spectra were recorded at 75 or
125 MHz and were referenced to 77.0 ppm in CDCl3.
13C{1H} NMRspectra were obtained using Waltz decoup-
ling and were exponentially multiplied to give 0.8 Hz line
broadening before Fourier transformation. All two dimen-
sional experiments were acquired with a Bruker inverse
5 mm z-gradient probe. The 908 pulse widths were 9.2 and
13.1 ms for 1H and 13C, respectively. The gradient was
shaped by a waveform generator and amplified by a Bruker
B-AFPA-10 amplifier. A sinusoidal gradient of 1 ms length
and a recovery time of 0.1 ms was used. The 2D COSY
spectra were recorded with a 1024!1024 data matrix and
512 increments of 1 scan each, in magnitude mode, with a
relaxation delay of 1.0 s and using a 1:1 gradient
combination, then processed with zero-filling in f1 and
unshifted sine-bell apodization function. The HMQC and
HMBC spectra were recorded using standard Bruker
software sequences inv4gs and inv4gslplrnd, respectively.
The following acquisition parameters were applied in both
experiments: spectral widths in f1 (13C) and f2 (1H)
dimensions 16,000 and 3000 Hz, respectively, a 1024!
1024 data matrix, 512 time increments of 200 scans each
Reaction of ligands 11–15 with excess sodium methoxide in
methanol readily gave the corresponding fully deprotected,
crude polyols 16–20 that were isolated by simple
evaporation of the reaction solvent. The extremely poor
solubility of these compounds in most organic solvents18
made their purification very difficult. Removal of sodium
methoxide was only achieved by stirring a suspension of the
crude polyols in water. Filtration of the mixture, however,
afforded products containing large and undetermined
amounts of water. These products were fully characterized
1
by H and 13C NMR analysis and mass spectroscopy.18
The poor solubility of the polyhydroxylated ligands 16–20
made quite unpractical the synthesis of their complexes by
reaction with metal triflates, requiring the use of very dilute
methanol solution of the ligands.19 However, by deacetyla-
tion of the corresponding adducts Cu(11)2, Cu(12)2, and
Cu(14)2 (see above) unprotected complexes Cu(16)2,
Cu(17)2, and Cu(19)2 were obtained and fully character-
ized.20 The trends in the chemical shift difference between
the polyhydroxylated ligands and their complexes observed
1
in the H and 13C NMR spectra in combination with mass
spectroscopy data (MS-ESI) indicated that Cu(16)2,
Cu(17)2, and Cu(19)2 maintained the tetrahedral structure
of their parent species. However, deacetylation of complex

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S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
and a 5:3:4 gradient combination. We set D1Z3.5 ms in
both experiments and D2Z60 ms only in HMBC, as
interpulse delay for the evolution of long-range coupling.
The Fourier transformations were performed with shifted
and unshifted sine-bell apodization functions in f1 (13C) and
f2 (1H) dimension, respectively.
filtrate was concentrated under vacuum to afford the pure
product 2 (0.195 g, 0.5 mmol, 99% yield) as a thick oil.
(Found: C, 48.9; H, 6.2; N, 3.8. C16H25NO10 requires C,
49.1; H, 6.4; N, 3.6%); [a]2D2 C13.1 (c 0.6 in CH2Cl2); IR:
nmax(film)/cmK1 3320, 1751; 1H NMR: d 1.75 (2H, bs,
NH2), 1.92 (3H, s, Me), 1.98 (3H, s, Me), 2.00 (3H, s, Me),
2.09 (3H, s, Me), 2.70–2.85 (2H, m, CH2N), 3.53–3.60 (1H,
m, one H of CH2CH2O), 3.80–3.90 (2H, m, H-C5 and one H
of CH2CH2O), 4.06–4.14 (2H, m, H-C6), 4.46 (1H, d, JZ
7.9 Hz, H-C1), 4.97 (1H, dd, JZ3.2, 7.1 Hz, H-C3), 5.14
(1H, dd, JZ8.1, 8.3 Hz, H-C2), 5.33 (1H, d, JZ3.2 Hz,
H-C4); 13C NMR: d 20.4 (Me), 20.5 (2 Me), 20.6 (Me), 41.6
(CH2–N), 61.2 (galactose C-6), 67.0 (galactose C-4), 68.9
(galactose C-2), 69.3 (CH2 bound to anomeric O), 70.6
(galactose C-5), 70.8 (galactose C-3), 101.4 (galactose C-1),
169.3 (C]O), 169.9 (C]O), 170.0 (C]O), 170.2 (C]O);
MS-ESIC: m/z 392 [MCH]C.
Optical rotations were measured at the Na-D line in a 1 dm
cell at 22 8C. IR spectra were recorded on thin film or as
solution in CH2Cl2 or as KBr pellets. 3-(4-Benzyloxyphe-
nyl)-1-propanol,9 and compounds 1,9 5,10 6,11 and 10 were
prepared according to literature procedures. 3-(4-Benzyloxy-
phenyl)-1-propanol had mp 63–65 8C (lit.,9 64–65 8C); the b-
and a-anomers of imidate 1 had mp 145–146 and 121–123 8C,
respectively (lit.,8 146–147 and 122–123 8C); 6,60-bis(bro-
momethyl)-2,20-bipyridine had mp 180–181 8C (lit.,10 180–
181 8C); 6,60-diethynyl-2,20-bipyridine had mp 190–192 8C
(lit.,11 192–193 8C); 200,6-diethynyl-2,20:60,600-terpyridine
(mp 220 8C, decomposition) had NMR data identical to
those reported in the literature.14
4.2.2. O-[3-(4-Hydroxyphenyl)-1-propyl)]-(2,3,4,6-O-tet-
racetyl)-b-D-galactopyranose (3). Glycosidation reaction.
To a solution of a 2:1 mixture of b and a anomers of
O-(2,3,4,6-O-tetracetyl-D-galactopyranosyl) trichloroaceti-
midate 1 (0.49 g, 1.0 mmol) and 3-(4-benzyloxy-phenyl)-1-
propanol (0.36 g, 1.5 mmol) in dry CH2Cl2 (8 mL) stirred
under nitrogen and cooled at 0 8C, a solution of trimethylsi-
lyl triflate (0.08 mL, 0.46 mmol) in dry CH2Cl2 (1 mL) was
added dropwise. After 2 h stirring at 0 8C, the reaction was
quenched by the addition of triethylamine (0.5 mL), and the
resulting mixture was concentrated under vacuum. The
residue was purified by flash chromatography with a 70:30
hexane/ethyl acetate mixture as eluant. The product O-[3-
(4-phenylmethoxyphenyl)-1-propyl)]-(2,3,4,6-O-tetrace-
tyl)-b-D-galacto-pyranose (0.19 g, 0.33 mmol, 33% yield)
was obtained as a thick oil. (Found: C, 63.2; H, 6.5.
C30H36O11 requires C, 62.9; H, 6.3%); [a]2D2 K4.4 (c 0.6 in
4.2. Synthesis of the galactose dendrons 2–4
4.2.1. O-(2-Aminoethyl)-(2,3,4,6-O-tetracetyl)-b-D-galac-
topyranose (2). Glycosidation reaction. To a solution of a
2:1 mixture of b and a anomers of O-(2,3,4,6-O-tetracetyl-
D-galactopyranosyl) trichloroacetimidate
1 (1.40 g,
2.84 mmol) and benzyl N-(2-hydroxyethyl)carbamate
(0.98 g, 4.76 mmol) in dry CH2Cl2 (30 mL) stirred under
nitrogen and cooled at 0 8C, a solution of trimethylsilyl
triflate (0.25 mL, 1.30 mmol) in dry CH2Cl2 (2 mL) was
added dropwise. After 1 h stirring at 0 8C, the reaction was
quenched by the addition of triethylamine (2 mL), and the
resulting mixture was concentrated under vacuum. The
residue was purified by flash chromatography with a 50:50
hexane/ethyl acetate mixture as eluant. The product O-(2-N-
carbobenzyloxyaminoethyl)-(2,3,4,6-O-tetracetyl)-b-D-
galactopyranose (0.75 g, 1.43 mmol, 50% yield) was
obtained as a thick pale yellow oil. (Found: C, 55.0; H,
6.0; N, 2.5. C24H31NO12 requires C, 54.8; H, 5.9; N, 2.7%);
[a]2D2 C4.4 (c 1.2 in CH2Cl2); IR: nmax (film)/cmK1 3250,
1751, 1722, 1230; 1H NMR: d 2.00 (3H, s, Me), 2.02 (3H, s,
Me), 2.05 (3H, s, Me), 2.17 (3H, s, Me), 3.35–3.50 (2H, m,
CH2NH), 3.68–3.77 (2H, m, CH2CH2O), 3.85–3.95 (1H, m,
H-C5), 4.16 (2H, d, JZ6.6 Hz, H-C6), 4.47 (1H, d, JZ
7.9 Hz, H-C1), 5.03 (1H, dd, JZ3.4, 7.1 Hz, H-C3), 5.12
(2H, s, CH2Ar), 5.17-5.22 (1H, m, H-C2), 5.40 (1H, d, JZ
3.4 Hz, H-C4), 7.32–7.40 (5H, m, aromatic H); 13C NMR: d
20.4 (2!Me), 20.5 (2!Me), 40.8 (CH2–NH), 61.2
(galactose C-6), 66.7 (CH2–Ar), 66.9 (galactose C-4), 68.8
(galactose C-2), 69.3 (CH2 bound to anomeric O), 70.5
(galactose C-3), 70.8 (galactose C-5), 101.5 (galactose C-1),
128.0 (2 ortho C of aryl ring), 128.1 (para C of aryl ring),
128.4 (2, meta C of aryl ring), 136.5 (quaternary C of aryl
ring), 169.5 (C]O), 170.0 (2 C]O), 170.1 (C]O), 170.2
(C]O).
1
CH2Cl2); IR: nmax (film)/cmK1 1752, 1224; H NMR: d
1.80–2.00 (2H, m, CH2CH2CH2), 2.02 (3H, s, Me), 2.05
(3H, s, Me), 2.08 (3H, s, Me), 2.17 (3H, s, Me), 2.57–2.70
(2H, m, CH2CH2Ar), 3.45–3.60 (1H, m, one H of CH2
bound to anomeric O), 3.87–3.99 (2H, m, H-C5 and one H
of CH2 bound to anomeric O), 4.10–4.25 (2H, m, H-C6),
4.48 (1H, d, JZ7.9 Hz, H-C1), 5.00–5.10 (3H, m, H-C3 and
OCH2Ar), 5.26 (1H, dd, JZ7.9, 9.3 Hz, H-C2), 5.41 (1H, d,
JZ3.4 Hz, H-C4), 6.92 (2H, A part of AB system, JZ
8.5 Hz, aromatic H ortho to O), 7.10 (2H, B part of AB
system, JZ8.5 Hz, aromatic H meta to O); 7.25–7.40 (5H,
m, aromatic H of benzyloxy group); 13C NMR: d 20.4 (2!
Me), 20.5 (2 Me), 30.9 (CH2–C–CH2), 31.2 (Ar–C–CH2),
61.2 (galactose C-6), 67.0 (d, galactose C-4), 68.9 (d,
galactose C-2), 69.0 (CH2 bound to anomeric O), 70.0
(O–C–Ar), 70.6 (galactose C-3), 70.9 (galactose C-5), 101.3
(galactose C-1), 114.8 (2!aromatic C ortho to O), 127.4
(para C of benzyloxy ring), 127.8 (2!meta C of benzyloxy
ring), 128.5 (2!ortho C of benzyloxy ring), 129.3 (2!C of
aryl ring meta to O), 133.9 (quaternary aromatic C para to
O), 137.0 (quaternary C of benzyloxy ring), 158.0
(quaternary aromatic C bound to O), 169.0 (C]O), 170.2
(2!C]O), 170.5 (C]O).
Removal of the Cbz group. To a solution of O-(2-N-
carbobenzyloxyaminoethyl)-(2,3,4,6-O-tetracetyl)-b-D-
galactopyranose (0.26 g, 0.50 mmol) in absolute EtOH
(20 mL), 10% Pd/C (0.03 g) was added. The resulting
slurry was shaken under a hydrogen atmosphere for 2 h. The
mixture was then filtered through a Celite cake and the
Removal of the benzyl group. To a solution of O-[3-(4-
phenylmethoxyphenyl)-1-propyl)]-(2,3,4,6-O-tetracetyl)-b-
D-galactopyranose (0.30 g, 0.52 mmol) in absolute EtOH
(20 mL), 10% Pd/C (0.02 g) was added. The resulting slurry

S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
10053
was shaken under a hydrogen atmosphere for 2 h. The
4.3. Synthesis of oligopyridines
mixture was then filtered through a Celite cake and the
filtrate was concentrated under vacuum to afford the pure
product 3 (0.25 g, 0.52 mmol, 99% yield) as a gum-like
4.3.1. 2-Bromo-6-(3-formylphenyl)pyridine (7). To a
solution of 2,6-dibromopyridine (2.00 g, 8.44 mmol),
triphenylphosphine (0.44 g, 1.67 mmol), and palladium
acetate (0.19 g, 0.83 mmol) in dry DME (100 mL) stirred
under nitrogen at room temperature, 3-formylphenylboronic
acid (1.37 g, 9.17 mmol) was added followed by a 2 M
aqueous solution of sodium carbonate (25 mL, 40.8 mmol).
The resulting mixture was refluxed for 22 h, and the solvent
was evaporated under vacuum. The remaining aqueous
phase was extracted with CH2Cl2 (3!50 mL), and the
combined organic phases were washed with water and dried
over sodium sulfate. Filtration and evaporation of the
solvent under vacuum afforded the crude product that was
purified by flash chromatography with a 80:20 hexane/ethyl
acetate mixture as eluant. The product 7 (1.24 g, 4.72 mmol,
56% yield) was a white solid, mp 90–91 8C. (Found: C,
55.3; H, 2.9; N, 5.5. C12H8BrNO requires C, 55.0; H, 3.1; N,
5.3%); IR: nmax(KBr)/cmK1 1688, 1552, 1430, 1188, 1125;
1H NMR: d 7.50 (1H, d, JZ7.8 Hz, pyridine H–C3), 7.64–
7.70 (2H, m, pyridine H–C4 and H meta to CHO), 7.79 (1H,
d, JZ7.8 Hz, pyridine H–C5), 7.98 (1H, dt, JZ1.4, 7.8 Hz,
H para to CHO), 8.31 (1H, dd, JZ1.4, 7.9 Hz, H ortho to
CHO), 8.52 (1H, t, JZ1.4 Hz, H between pyridine and
CHO), 10.15 (1H, s, CHO); 13C NMR: d 119.1 (pyridine
C-5), 127.1 (pyridine C-3), 128.2 (C between pyridine ring
and CHO), 129.6 (C meta to pyridine ring), 130.6 (C para to
CHO), 132.7 (C ortho to CHO and para to pyridine ring),
137.0 (quaternary C bound to pyridine ring), 138.6
(quaternary carbon bound to CHO), 139.2 (pyridine C-4),
142.2 (pyridine C-2), 157.0 (pyridine C-6) 191.9 (CHO).
MS-ESIC: m/z 263.9 [MCH]C.
material. (Found: C, 57.0; H, 6.1. C23H30O11 requires C,
57.2; H, 6.3%); [a]D22 0.0, [a] C0.8 (c 1 in CH2Cl2); IR:
22
436
1
nmax(film)/cmK1 3436, 1751, 1225; H NMR: d 1.83–1.96
(2H, m, CH2CH2CH2), 2.00 (3H, s, Me), 2.04 (3H, s, Me),
2.07 (3H, s, Me), 2.16 (3H, s, Me), 2.55–2.70 (2H, m,
CH2CH2Ar), 3.41–3.55 (1H, m, one H of CH2 bound to
anomeric C), 3.80–3.95 (2H, m, H-C5 and one H of CH2
bound to anomeric O), 4.10–4.25 (2H, m, H-C6), 4.47 (1H,
d, JZ7.8 Hz, H-C1), 5.04 (1H, dd, JZ3.4, 10.5 Hz, H-C3),
5.25 (1H, dd, JZ7.8, 8.3 Hz, H-C2), 5.40 (1H, d, JZ3.4 Hz,
H-C4), 5.70 (1H, b s, OH), 6.77 (2H, A part of AB system,
JZ8.5 Hz, aromatic H ortho to O), 7.03 (2H, B part of AB
system, JZ8.5 Hz, aromatic H meta to O); 13C NMR: d 20.4
(2!Me), 20.7 (2!Me), 30.8 (CH2–C–CH2), 31.2 (t, Ar–C–
CH2), 61.2 (galactose C-6), 67.1 (galactose C-4), 68.9
(methylene bound to anomeric O), 69.0 (galactose C-2),
70.6 (galactose C-3), 70.9 (galactose C-5), 101.3 (galactose
C-1), 115.2 (2!C of aryl ring ortho to O), 129.4 (2!C of
aryl ring meta to O), 132.0 (quaternary aromatic C para to
O), 154.0 (quaternary aromatic C bound to O), 170.1 (2!
C]O), 170.2 (2!C]O). MS-ESIC: m/z 505.6 [MCNa]C.
4.2.3. O-(4-Iodophenyl)-(2,3,4,6-O-tetracetyl)-b-D-galac-
topyranose (4). To a solution of a 2:1 mixture of b and a
anomers of O-(2,3,4,6-O-tetracetyl-D-galactopyranosyl) tri-
chloroacetimidate 1 (0.49 g, 1.0 mmol) and 4-iodophenol
(0.22 g, 1.0 mmol) in dry CH2Cl2 (8 mL) stirred under
nitrogen and cooled at 0 8C, a solution of trimethylsilyl
triflate (0.08 ml, 0.46 mmol) in dry CH2Cl2 (1 mL) was
added dropwise. After 2 h stirring at 0 8C, the reaction was
quenched by the addition of triethylamine (0.5 mL), and the
resulting mixture was concentrated under vacuum. The
residue was purified by flash chromatography with a 70:30
hexane/ethyl acetate mixture as eluant. The first eluted
product (0.104 g, 0.19 mmol, 19% yield) was a pale yellow
solid with mp 88–90 8C, [a]2D2 C23.0 (c 1 in CH2Cl2). On
the basis of the H–C1/H–C2 coupling constant value (JZ
3.4 Hz) the a-anomeric configuration was assigned to this
compound. The second eluted product (0.363 g, 0.66 mmol,
66% yield) was the b-anomer. It was obtained as a white
solid with mp 44–45 8C. (Found: C, 43.3; H, 4.5.
C20H23IO10 requires C, 43.6; H, 4.2%); [a]2D2 C8.7 (c 0.7
in CH2Cl2); IR: nmax(KBr)/cmK1 1752, 1227, 1087; 1H
NMR: d 2.00 (3H, s, Me), 2.05 (6H, s, 2 Me), 2.17 (3H, s,
Me), 4.02–4.10 (1H, m, H-C5), 4.15–4.25 (2H, m, H-C6),
5.02 (1H, d, JZ7.9 Hz, H–C1), 5.13 (1H, dd, JZ3.5,
10.5 Hz, H–C3), 5.43–5.51 (2H, m, H–C4 and H–C2), 6.80
(2H, A part of AB system, JZ8.8 Hz, aromatic H ortho to
O), 7.60 (2H, B part of AB system, JZ8.8 Hz, aromatic H
meta to O); 13C NMR: d 20.4 (2!Me), 20.5 (2!Me), 61.3
(galactose C-6), 66.8 (galactose C-4), 68.5 (galactose C-2),
70.7 (galactose C-3), 71.1 (galactose C-5), 86.0 (quaternary
aromatic C bound to iodine) 99.5 (galactose C-1), 119.2
(2!C of aryl ring ortho to O),138.4 (2!C of aryl ring
meta to O), 156.7 (quateranry aromatic C bound to O), 170.1
(2!C]O), 170.2 (2!C]O). MS-ESIC: m/z 573.2 [MC
Na]C.
4.3.2. 6,60-Bis(3-formylphenyl)-2,20-bipyridine (8a). A
suspension of nickel dichloride hexahydrate (1.06 g,
3.87 mmol), triphenylphosphine (4.06 g, 15.47 mmol), and
zinc powder (0.38 g, 5.8 mmol) in dry DMF (30 mL) was
stirred at 60 8C under nitrogen for 1 h. A DMF (10 mL)
solution of 2-bromo-6-(3-formylphenyl)pyridine (1.01 g,
3.86 mmol) was then added and the mixture was stirred at
60 8C for 23 h. After addition of diluted aqueous ammonia
(50 mL) to the cooled mixture, this was extracted with
CH2Cl2 (3!20 mL). The combined organic phases were
washed twice with brine and dried over sodium sulfate.
Filtration and evaporation of the solvent under vacuum,
afforded the crude product as a cream-colored solid. This
was purified by several washings with a 90:10 hexane/ethyl
acetate mixture to remove the unreacted aldehyde, excess
triphenylphosphine, and some triphenylphosphineoxide.
The resulting solid 8a (0.70 g, 1.9 mmol, 47% yield), mp
197–198 8C, was pure enough for analysis and subsequent
manipulation. (Found: C, 78.9; H, 4.2; N, 7.9. C24H16N2O2
requires C, 79.1; H, 4.4; N, 7.7%); IR: nmax(KBr)/cmK1
1680, 1589, 1437, 1199; 1H NMR: d 7.73 (2H, t, JZ8.5 Hz,
H meta to CHO), 7.91 (2H, d, JZ7.8 Hz, pyridine H-5),
8.00–8.05 (4H, m, H para to CHO and pyridine H-4), 8.50
(2H, d, JZ8.5 Hz, H ortho to CHO and para to pyridine
ring), 8.67 (2H, d, JZ7.8 Hz, pyridine H-3), 8.72 (2H, s, H
between CHO and pyridine ring), 10.20 (2H, s, CHO); 13C
NMR: d 121.0 (2!pyridine C-3), 121.5 (2!pyridine C-5),
128.2 (2!C between CHO and pyridine ring), 129.8 (2!C
meta to CHO and to pyridine ring), 130.8 (2!C ortho to

10054
S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
CHO and para to pyridine ring), 132.8 (2!C para to CHO),
137.1 (2!pyridine C-4), 139.0 (2!quaternary C bound to
CHO), 139.1 (2!quaternary C meta to CHO), 154.8 (2!
pyridine C-6), 155.7 (2!pyridine C-2), 192.1 (2!C of
CHO). MS-ESIC: m/z 387.1 [MCNa]C.
CH2Br), 8.65 (2H, d, JZ8.5 Hz, pyridine H–C3); 13C NMR:
d 33.6 (2!CH2Br), 120.5 (2!pyridine C-3), 120.8 (2!
pyridine C-5), 127.2 (2!C ortho to CH2Br and para to
pyridine ring), 127.9 (2!C between CH2Br and pyridine
ring), 129.3 (2!C meta to CH2Br and meta to pyridine
ring), 129.7 (2!C para to CH2Br), 138.2 (2!pyridine C-4,
and 2!quaternary C meta to CH2Br), 139.8 (2!quaternary
C bound to CH2Br), 155.7 (4!pyridine C-2 and C-6).
MS-ESIC: m/z 495.1 [MCH]C.
4.3.3. 6,60-Bis(3-hydroxymethylphenyl)-2,20-bipyridine
(8b). To a sirred suspension of dialdehyde 8a (0.365 g,
1 mmol) in absolute EtOH (10 mL) cooled at 0 8C, NaBH4
(0.08 g, 2 mmol) was added in one portion. The reaction
mixture was warmed up to room temperature and stirring
was continued until a clear solution was obtained (about
3 h). A few drops of water were then added and the solvent
was evaporated under vacuum. The residue was dissolved in
water (10 mL) and the aqueous phase was extracted with
CH2Cl2 (2!20 mL). The combined organic phases were
dried over sodium sulfate. Filtration and evaporation of the
solvent under vacuum, afforded the crude product as a
cream-colored solid that was purified by flash chromato-
graphy with a 98:2 CH2Cl2:MeOH mixture as eluant to give
the product 8b (0.353 g, 0.96 mmol, 96% yield), as a white
solid, mp 142 8C. (Found: C, 78.0; H, 5.6; N, 7.9.
C24H20N2O2 requires C, 78.2; H, 5.5; N, 7.6%); IR:
nmax(KBr)/cmK1 3270, 1568, 1437, 1039; 1H NMR: d
3.60 (2H, bs, OH), 4.26 (4H, s, CH2O), 7.48 (2H, d, JZ
8.5 Hz, H ortho to CH2OH and para to pyridine ring), 7.55
(2H, t, JZ8.4 Hz, H meta to CH2OH), 7.83 (2H, d, JZ
8.5 Hz, pyridine H-C5), 7.95 (2H, t, JZ8.5 Hz, pyridine H-
C4), 8.11 (2H, d, JZ8.5 Hz, H para to CH2OH), 8.23 (2H,
s, H between CH2OH and pyridine ring), 8.63 (2H, d, JZ
8.5 Hz, pyridine H–C3); 13C NMR: d 65.1 (2!CH2–O),
119.8 (2!pyridine C-3), 120.5 (2!d, pyridine C-5), 125.6
(2!C para to CH2OH), 126.3 (2!C between CH2OH and
pyridine ring), 127.6 (2!C meta to CH2OH), 129.0 (2!C
ortho to CH2OH and para to pyridine ring), 137.7 (2!
pyridine C-4 and 2!quaternary C meta to CH2OH), 141.8
(2!quaternary C bound to CH2OH), 155.7 (2!pyridine
C-6), 156.0 (2!pyridine C-2). MS-ESIC: m/z 391.1 [MC
Na]C.
4.4. Synthesis of oligopyridine–galactose conjugates
4.4.1. 6,60-Bis-[4-[3-[(2,3,4,6-O-tetracetyl)-b-D-galacto-
pyranosyl]-prop-1-yl]-phenyloxy-methyl]-2,20-bipyri-
dine (11). To a stirred solution of bipyridine 5 (51 mg,
0.15 mmol) and phenol 3 (166 mg, 0.34 mmol) in dry
acetonitrile (4 mL), cesium carbonate (0.3 g, 0.84 mmol)
was added. The mixture was stirred at room temperature for
18 h. The solvent was then evaporated under vacuum and
the residue was purified by flash chromatography with a
50:50 hexane/ethyl acetate mixture as eluant to give 11 as a
light brown, gum-like material (95 mg, 0.083 mmol, 55%
yield). (Found: C, 60.5; H, 5.7; N, 2.7. C58H68N2O22
requires C, 60.8; H, 6.0; N, 2.4%); [a]2D2 K2.5 (c 0.8 in
CH2Cl2); IR: nmax(film)/cmK1 2932, 1746, 1510, 1223,
1
1048; H NMR (CD3OD): d 1.83–1.95 (4H, m, CH2CH2-
CH2O), 2.00 (6H, s, Me), 2.04 (6H, s, Me), 2.07 (6H, s, Me),
2.17 (6H, s, Me), 2.56–2.72 (4H, m, CH2CH2CH2O), 3.50
(2H, A part of an AB system, JZ6.0, 10.0 Hz, one H of
CH2CH2CH2O), 3.86–3.95 (4H, m, one H of CH2CH2CH2O
and galactose H-5), 4.17 (4H, AB system, JZ6.2 Hz,
galactose H-6), 4.48 (2H, d, JZ8.0 Hz, galactose H-1), 5.04
(2H, dd, JZ3.4, 10.4 Hz, galactose H-3), 5.23 (2H, dd, JZ
8.0, 10.4 Hz, galactose H-2), 5.30 (4H, s, PyCH2O), 5.41
(2H, d, JZ3.4 Hz, galactose H-4), 6.97 (4H, A part of an
AB system, JZ8.5 Hz, H ortho to O), 7.11 (4H, B part of an
AB system, JZ8.5 Hz, H meta to O), 7.57 (2H, d, JZ
7.6 Hz, pyridine H-5), 7.87 (2H, t, JZ7.6 Hz, pyridine H-4),
8.37 (2H, d, JZ7.6 Hz, pyridine H-3); 13C NMR (CD3OD):
d 20.5 (4!Me), 20.6 (2!Me), 20.8 (2!Me), 30.9 (2!
CH2–C–CH2), 31.2 (2!Ar–C–CH2), 61.3 (2!galactose
C-6), 67.1 (2!galactose C-4), 69.0 (2!galactose C-2, and
2!CH2 bound to anomeric O), 70.6 (2!galactose C-5),
71.0 (2!galactose C-3), 77.0 (2!CH2 bound to pyridine),
101.3 (2!galactose C-1), 114.8 (4!aromatic C ortho to
O), 120.3 (2!pyridine C-3), 121.4 (2!pyridine C-5),
129.4 (4!aromatic C meta to O), 134.1 (2!quaternary
aromatic C of phenyl ring bound to CH2), 137.9 (2!
pyridine C-4), 155.0 (2!pyridine C-2), 156.8 (2!
quaternary aromatic C of phenyl ring bound to O), 157.0
(2!pyridine C-6), 170.1 (8!C]O); MS-ESIC: m/z 1145
[MCH]C, 1167 [MCNa]C.
4.3.4. 6,60-Bis(3-bromomethylphenyl)-2,20-bipyridine
(9). To a stirred solution of the diol 8b (0.30 g,
0.81 mmol) in dry CH2Cl2 (10 mL) cooled at 0 8C, a
solution of PBr3 (0.46 mL) in dry CH2Cl2 (2 mL) was
slowly added. After 30 min stirring at 0 8C the reaction
mixture was warmed up to room temperature, and stirring
was continued for 16 h. The reaction was quenched by the
addition of a 0.1 M solution of sodium hydroxide until
neutrality of the aqueous phase was obtained. The organic
phase was separated and the aqueous phase was extracted
with CH2Cl2 (2!10 mL). The combined organic phases
were dried over sodium sulfate. Filtration and evaporation
of the solvent under vacuum, afforded the crude product that
was purified by flash chromatography with CH2Cl2 as eluant
to give the product 9 (0.33 g, 0.66 mmol, 82% yield), as a
white solid, mp 209–211 8C. (Found: C, 58.1; H, 3.6; N, 5.4.
C24H18Br2N2 requires C, 58.3; H, 3.7; N, 5.7%); IR:
nmax(KBr)/cmK1 1568, 1437, 1218; 1H NMR: d 4.66 (4H, s,
CH2Br), 7.45–7.60 (4H, m, H ortho to CH2Br and para to
pyridine ring, and H meta to CH2Br and meta to pyridine
ring), 7.84 (2H, d, JZ8.5 Hz, pyridine H-C5), 7.98 (2H, t,
JZ8.5 Hz, pyridine H-C4), 8.11 (2H, d, JZ8.5 Hz, H para
to CH2Br), 8.24 (2H, s, H between pyridine ring and
4.4.2. 6,60-Bis-[2-[4-[(2,3,4,6-O-tetracetyl)-b-D-galacto-
pyranosyl]-phenyl]-ethynyl]-2,20-bipyridine (12). In a
stirred mixture of dry THF (4.4 mL) and diisopropylamine
(3.1 mL) kept under a nitrogen atmosphere, bipyridine 6
(47 mg, 0.23 mmol) and iodide 4 (251 mg, 0.46 mmol)
were added. After 10 min stirring at room temperature,
PdCl2(PPh3)2 (5 mg, 0.007 mmol) and CuI (4 mg,
0.02 mmol) were added in this order. The mixture was
refluxed for 24 h. Evaporation of the solvent under vacuum
afforded a residue that was purified by flash chromatography

S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
10055
with a 50:50 hexane/ethyl acetate mixture as eluant to give
12 as a light brown, gum-like material (80 mg, 0.076 mmol,
33% yield). (Found: C, 62.0; H, 5.3; N, 2.4. C54H52N2O20
requires C, 61.8; H, 5.0; N, 2.7%); [a]2D2 C18.6 (c 0.2 in
CH2Cl2); IR: nmax(film)/cmK1 2925, 2217, 1747, 1260,
(CD3OD): 19.5 (8!Me), 30.9 (2!CH2–C–Ar), 31.6 (2!
CH2–C–CH2), 61.6 (2!galactose C-6), 67.9 (2!galactose
C-4, and 2!CH2–CH2–O–anomeric C), 69.6 (2!galactose
C-2), 70.0 (2!Ar–C–O), 70.7 (2!galactose C-5), 71.4
(2!galactose C-3), 101.2 (2!galactose C-1), 115.1 (4!
aromatic C ortho to O), 119.8 (2!pyridine C-3), 120.6 (2!
pyridine C-5), 126.1 (2!aromatic C of phenyl ring between
pyridine ring and CH2–OAr), 126.3 (2!aromatic C meta to
pyridine ring and CH2–OAr), 128.2 (2!aromatic para to
pyridine ring), 129.0 (2!aromatic C para to CH2–OAr),
129.5 (4!aromatic C meta to O), 134.0 (2!quaternary
aromatic C para to O), 138.2 (2!quaternary aromatic C
bound to CH2–OAr, and 2!pyridine C-4), 138.5 (2!
quaternary C bound to pyridine ring), 156.8 (2!quaternary
aromatic C bound to O),157.0 (4!pyridine C-2 and C-6),
170.0 (4!C]O), 171.0 (4!C]O); MS-ESIC: m/z 1297
[MCH]C, 1319 [MCNa]C.
1
1043; H NMR (CD3OD): d 1.97 (6H, s, Me), 2.04 (6H, s,
Me), 2.06 (6H, s, Me), 2.17 (6H, s, Me), 4.13 (4H, d, JZ
6.2 Hz, galactose H-6), 4.49 (2H, t, JZ6.2 Hz, galactose
H-5), 5.26 (2H, A part of an AB system, JZ8.0, 10.0 Hz,
galactose H-2), 5.31 (2H, B part of an AB system, JZ3.0,
10.0 Hz, galactose H-3), 5.38 (2H, d, JZ3.0 Hz, galactose
H-4), 5.61 (2H, d, JZ8.0 Hz, galactose H-1), 7.10 (4H, A
part of an AB system, JZ8.6 Hz, H ortho to O), 7.68 (4H, B
part of an AB system, JZ8.6 Hz, H meta to O), 7.74 (2H, d,
JZ7.7 Hz, pyridine H-3), 8.04 (2H, t, JZ7.7 Hz, pyridine
H-4) and 8.39 (2H, d, JZ7.7 Hz, pyridine H-5); 13C NMR
(CD3OD): 19.0 (8!Me), 61.1 (2!galactose C-6), 67.3
(2!galactose C-4), 68.7 (2!galactose C-2), 70.8 (2!
galactose C-3, and 2!galactose C-5), 87.6 (2!s, one
acetylenic C), 88.3 (2!s, other acetylenic C), 98.2 (2!
galactose C-1), 116.5 (4!aromatic C ortho to O, and 2!
quaternary phenyl C bound to acetylenic C), 120.4
(2!pyridine C-3), 127.1 (2!pyridine C-5), 133.2 (4!
aromatic C meta to O), 137.4 (2!pyridine C-4), 142.6 (2!
pyridine C-6), 155.7 (2!pyridine C-2), 157.4 (2!aromatic
C bound to O), 169.9 (4!C]O), 170.5 (4!C]O);
MS-ESIC: m/z 1049 [MCH]C, 1071 [MCNa]C.
4.4.4. 6,60-Bis-[3-[N-2-[(2,3,4,6-O-tetracetyl)-b-D-galac-
topyranosyl]-ethyl]-imminomethyl] phenyl]-2,20-bipyri-
dine (14). A solution of dialdehyde 8a (35 mg, 0.09 mmol)
and amine 2 (241 mg, 0.61 mmol) in a mixture of CH2Cl2
(14 mL) and MeOH (3.5 mL) was stirred overnight at room
temperature. The solvent was then evaporated under
vacuum and water (2 mL) and Et2O (10 mL) were then
added. The organic phase was separated and the aqueous
phase was extracted with Et2O (2!10 mL). The combined
organic phases were dried over sodium sulfate. Filtration
and evaporation of the solvent under vacuum, afforded the
product 14 as a light brown solid (87 mg, 0.081 mmol, 90%
yield) that softened into a very thick oil when heated at
48 8C and remained like that up to 220 8C. (Found: C, 60.2;
H, 5.5; N, 5.3. C56H62N4O20 requires C, 60.5; H, 5.6; N,
5.0%); [a]2D2 C2.3 (c 0.4 in CH2Cl2); IR: nmax(CH2Cl2)/
cmK1 2925, 1747, 1651, 1370, 1226, 1060; 1H NMR
(CD3CN): d 1.97 (6H, s, Me), 2.07 (12H, s, Me), 2.16 (6H, s,
Me), 3.75–3.84 (2H, m, one H of NCH2CH2O), 3.89–3.97
(6H, m, galactose H-5, one H of NCH2CH2O, and one H of
NCH2CH2O), 4.12–4.22 (6H, m, one hydrogen of NCH2-
CH2O and galactose H-6), 4.56 (2H, d, JZ8.0 Hz, galactose
H-1), 5.00 (2H, dd, JZ3.5, 11.5 Hz, galactose H-3), 5.20
(2H, dd, JZ8.0, 11.5 Hz, galactose H-2), 5.50 (2H, br s,
galactose H-4), 7.60 (2H, t, JZ7.7 Hz, aromatic H meta to
pyridine ring), 7.86 (2H, dt, JZ1.1, 7.7 Hz, aromatic H para
to pyridine ring), 7.89 (2H, dd, JZ0.8, 7.2 Hz, pyridine
H-5), 7.98 (2H, t, JZ7.2 Hz, pyridine H-4), 8.33 (2H, dt,
JZ1.1, 7.7 Hz, aromatic H para to CH]N), 8.42 (2H, s,
CH]N), 8.50 (2H, t, JZ1.1 Hz, aromatic H ortho to
CH]N and ortho to pyridine ring), 8.66 (2H, dd, JZ0.8,
7.2 Hz, pyridine H-3); 13C NMR (CD3CN): d 20.3 (2!Me),
20.5 (2!Me), 20.6 (4!Me), 60.5 (2!CH2–N), 61.2 (2!
galactose C-6), 67.0 (2!galactose C-4), 68.6 (2!galactose
C-2), 68.9 (2!CH2–O–galactose C-1), 70.6 (2!galactose
C-5), 70.8 (2!galactose C-3), 101.3 (2!galactose C-1),
119.9 (2!pyridine C-3), 120.4 (2!pyridine C-5), 126.8
(2!aromatic C between pyridine ring and CH]N), 128.5
(2!aromatic C para to pyridine ring), 129.0 (2!aromatic
C meta to pyridine ring and meta to CH]N), 129.3 (2!
aromatic C para to CH]N), 136.4 (2!quaternary C bound
to CH]N), 137.7 (2!pyridine C-4), 139.7 (2!aromatic C
bound to pyridine ring), 155.5 (2!pyridine C-6), 155.8
(2!pyridine C-2), 163.3 (2!CH]N), 170.0 (4!C]O),
4.4.3. 6,60-Bis-[3-[4-[3-[(2,3,4,6-O-tetracetyl)-b-D-galac-
topyranosyl]-prop-1-yl]-phenyloxy-methyl]phenyl]-2,20-
bipyridine (13). To a stirred solution of bipyridine 9
(74 mg, 0.15 mmol) and phenol 3 (166 mg, 0.34 mmol) in a
mixture of dry DMF (4 mL) and dry acetonitrile (1 mL),
cesium carbonate (0.3 g, 0.84 mmol) was added. The
mixture was stirred at room temperature for 18 h. Water
(5 mL) was then added and the organic phase was separated.
The aqueous phase was extracted with CH2Cl2 (2!10 mL).
The combined organic phases were dried over sodium
sulfate. Filtration and evaporation of the solvent under
vacuum, afforded the crude product that was purified by
flash chromatography with a 50:50 hexane/ethyl acetate
mixtures as eluant to give 13 as a light brown, gum-like
solid (58 mg, 0.045 mmol, 30% yield). (Found: C, 64.5; H,
5.6; N, 2.5. C70H76N2O22 requires C, 64.8; H, 5.9; N, 2.2%);
[a]2D2 K3.4 (c 0.15 in CH2Cl2); nmax(CH2Cl2)/cmK1 2948,
1
1747, 1510, 1223, 1050; H NMR (CD3OD): d 1.85 (4H,
quintet, JZ6.5 Hz, CH2CH2CH2O), 1.95 (6H, s, Me), 1.99
(6H, s, Me), 2.08 (6H, s, Me), 2.17 (6H, s, Me), 2.63 (4H, t,
JZ6.5 Hz, CH2CH2CH2O), 3.52 (2H, A part of an AB
system, JZ6.5, 9.8 Hz, one H of CH2CH2CH2O), 3.83 (2H,
B part of an AB system, JZ6.5, 9.8 Hz, one H of
CH2CH2CH2O), 4.04 (2H, quartet, JZ6.2 Hz, galactose
H-5), 4.12 (4H, AB system, JZ3.6, 6.2 Hz, galactose H-6),
4.58 (2H, d, JZ4.4 Hz, galactose H-1), 5.04–5.14 (4H, m,
galactose H-2 and H-3), 5.23 (4H, s, ArCH2O), 5.38 (2H, br
s, galactose H-4), 6.99 (4H, A part of an AB system, JZ
8.6 Hz, H ortho to OCH2Ar), 7.14 (4H, B part of an AB
system, JZ8.6 Hz, H meta to OCH2Ar), 7.55 (4H, d, JZ
5.1 Hz, H para to CH2OAr and H para to pyridine ring),
7.95 (2H, d, JZ7.2 Hz, pyridine H-5), 8.02 (2H, t, JZ
7.5 Hz, pyridine H-4), 8.16 (2H, t, JZ5.1 Hz, H meta to
pyridine ring), 8.31 (2H, br s, H between pyridine ring and
OCH2Ar), 8.54 (2H, d, JZ7.5 Hz, pyridine H-3); 13C NMR

10056
S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
170.1 (2!C]O), 170.3 (2!C]O); MS-ESIC: m/z 1111
[MCH]C, 1133 [MCNa]C.
phenyloxymethyl]-2,20-bipyridine (16). White solid. 1H
NMR (CD3OD): d 1.91 (4H, quintet, JZ7.0 Hz, CH2CH2-
CH2O), 2.68 (4H, t, JZ7.0 Hz, CH2CH2CH2O), 3.45–3.60
(6H, m, galactose H-5, H-2, and H-3), 3.57 (2H, A part of an
AB system, JZ6.4, 9.7 Hz, one H of CH2CH2CH2O), 3.74
(4H, AB system, JZ6.0 Hz, galactose H-6), 3.85 (2H, d,
JZ3.4 Hz, galactose H-4), 3.92 (2H, B part of an AB
system, JZ6.4, 9.7 Hz, one H of CH2CH2CH2O), 4.22 (2H,
d, JZ7.4 Hz, galactose H-1), 5.27 (4H, s, PyCH2O), 6.97
(4H, A part of an AB system, JZ8.5 Hz, aromatic H ortho
to O), 7.17 (4H, B part of an AB system, JZ8.5 Hz,
aromatic H meta to O), 7.60 (2H, d, JZ7.6 Hz, pyridine
H-5), 7.94 (2H, t, JZ7.6 Hz, pyridine H-4), 8.33 (2H, d, JZ
7.6 Hz, pyridine H-3); 13C NMR (CD3OD): d 31.2 (2!
CH2–C–Ar), 31.8 (2!CH2–C–CH2Ar), 61.4 (2!galactose
C-6), 68.9 (2!CH2 bound to anomeric O), 69.3 (2!
galactose C-4), 70.8 (2!PyCH2O), 71.6 (2!galactose
C-2), 74.0 (2!galactose C-3), 75.5 (2!galactose C-5),
104.1 (2!galactose C-1), 114.9 (4!aromatic C of phenyl
ring ortho to O), 120.3 (2!pyridine C-3), 121.7 (2!
pyridine C-5), 129.6 (4!aromatic C of phenyl ring meta to
O), 135.0 (2!quaternary C of phenyl ring bound to CH2),
138.0 (2!pyrdine C-4), 156.0 (2!pyridine C-2), 156.8
(2!quaternary C of phenyl ring bound to O), 157.7 (2!
pyridine C-6); MS-ESIC: m/z 831 [MCNa]C. HRMS m/z
808.34278.
4.4.5. 200,6-Bis-[2-[4-[(2,3,4,6-O-tetracetyl)-b-D-galacto-
pyranosyl]-phenyl]-ethynyl]-2,20:60,600-terpyridine (15).
In a stirred mixture of dry THF (4.6 mL) and diisopropyl-
amine (3.1 mL) kept under a nitrogen atmosphere,
terpyridine 10 (63 mg, 0.22 mmol) and iodide 4 (260 mg,
0.47 mmol) were added. After 10 min stirring at room
temperature, PdCl2(PPh3)2 (5 mg, 0.007 mmol) and CuI
(4 mg, 0.02 mmol) were added in this order. The mixture
was refluxed for 24 h. Evaporation of the solvent under
vacuum afforded a residue that was purified by flash
chromatography with a 50:50 hexane/ethyl acetate mixture
as eluant to give 15 as a light brown solid (150 mg,
0.13 mmol, 60%) that softened into a very thick oil when
heated at 145 8C and remained like that up to 220 8C.
(Found: C, 62.6; H, 4.6; N, 4.0. C59H55N3O20 requires C,
62.9; H, 4.9; N, 3.7%); [a]2D2 C11.0 (c 0.4 in CH2Cl2); IR:
nmax(CH2Cl2)/cmK1 2936, 2220, 1752, 1229, 1077; 1H
NMR (CD3OD): d 2.00 (6H, s, Me), 2.08 (6H, s, Me), 2.07
(6H, s, Me), 2.09 (6H, s, Me), 4.20 (4H, d, JZ6.4 Hz,
galactose H-6), 4.14 (2H, t, JZ6.4 Hz, galactose H-5), 5.30
(2H, dd, JZ3.2, 10.0 Hz, galactose H-3), 5.35–5.45 (4H, m,
galactose H-1 and H-2), 5.50 (2H, d, JZ3.2 Hz, galactose
H-4), 7.10 (4H, A part of an AB system, JZ8.8 Hz,
aromatic00H ortho to O), 7.55–7.65 (6H, m, terpyridine H-5
and H-3 , and aromatic H meta to O), 7.98 (2H, t, JZ
7.9 Hz, terpyridine H-4 and H-400), 8.08 (1H, t, JZ7.9 Hz,
terpyridine H-40), 8.47 (2H, d, JZ7.9 Hz, terpyridine H-30
and H-50), 8.57 (2H, d, JZ7.9 Hz, terpyridine H-3 and
H-500); 13C NMR (CD3OD): 20.5 (8!Me), 61.0 (2!
galactose C-6), 66.8 (2!galactose C-4), 68.5 (2!galactose
C-2), 70.7 (2!galactose C-3), 71.2 (2!galactose C-5),
88.2 (4!acetylenic C), 99.0 (2!galactose C-1), 116.8 (4!
aromatic C ortho to O and 2!quaternary phenyl C 0b0 ound to
acetylenic C), 120.6 (2!terpyridine C-3 and C-5 ), 121.8
(2!terpyridine C-30 and C-50), 127.4 (2!terpyridine C-5
and C-300), 133.2 (4!aro0m0 atic C meta to O), 137.6 (2!
terpyridine C-4 and C-4 ), 138.1 (1!terpyridine C-40),
143.0 (2!terpyridine C-6 and C-200), 155.0 (2!terpyridine
C-20 and C-60), 156.7 (2!terpyridine C-2 and C-600), 158.0
(2!aromatic C bound to O), 170.5 (8!C]O); MS-ESIC:
m/z 1126 [MCH]C.
4.5.2. 6,60-Bis-[2-[4-(b-D-galactopyranosyl)-phenyl]-
ethynyl]-2,20-bipyridine (17). White solid 1H NMR
(CD3OD): d 3.63 (2H, dd, JZ3.4, 9.8 Hz, galactose H-3),
3.71–3.79 (2H, m, galactose H-5), 3.81 (4H, AB system, JZ
5.0, 8.0 Hz, galactose H-6), 3.85 (2H, dd, JZ7.8, 9.9 Hz,
galactose H-2), 3.95 (2H, d, JZ3.4 Hz, galactose H-4), 4.97
(2H, d, JZ7.8 Hz, galactose H-1), 7.18 (4H, A part of an
AB system, JZ8.6 Hz, aromatic H ortho to O), 7.60 (4H, B
part of an AB system, JZ8.6 Hz, aromatic H meta to O),
7.65 (2H, d, JZ7.7 Hz, pyridine H-3), 7.97 (2H, t, JZ
7.7 Hz, pyridine H-4), 8.35 (2H, d, JZ7.7 Hz, pyridine H-
5); 13C NMR (CD3OD): d 61.0 (2!galactose C-6), 68.8
(2!galactose C-4), 70.8 (2!galactose C-2), 73.4 (2!
galactose C-3), 75.7 (2!galactose C-5), 87.2 (2!ace-
tylenic C bound to pyridine), 88.8 (2!acetylenic C bound
to ArO), 101.2 (2!galactose C-1), 115. (2!quaternary
aromatic C bound to acetylenic C), 116.6 (4!aromatic C
ortho to O), 120.4 (2!pyridine C-3), 127.1 (2!pyridine
C-5), 133.1 (4!aromatic C meta to O), 137.5 (2!pyridine
C-4), 143.0 (2!pyridine C-6), 155.0 (2!pyridine
C-2),158.0 (2!quaternary aromatic C bound to O);
MS-ESIC: m/z 735 [MCNa]C. HRMS m/z 712.22595.
4.5. Deprotection of the acetylated ligands 11-14 to
polyols 16-19
General procedure. A solution of ligand (typical amount
0.015 mmol) in 0.1 M MeONa in MeOH (2 mL, 0.2 mmol)
was stirred overnight under nitrogen. The solvent was
evaporated under vacuum from the resulting suspension,
and the residue was shaken with water (2 mL) for 3 h. The
solid was filtered and washed with water until the filtered
water was neutral. All the crude products obtained by
filtration were insoluble in most organic solvents and
soluble in DMSO. The solubility in MeOH was enough to
record NMR spectra on very diluted solutions of these
4.5.3. 6,60-Bis-[3-[4-[3-(b-D-galactopyranosyl)-prop-1-
yl]-phenyloxymethyl]phenyl]-2,20-bipyridine (18). White
1
solid. H NMR (CD3OD): d 1.91 (4H, quintet, JZ8.0 Hz,
CH2CH2CH2O), 2.69 (4H, t, JZ8.0 Hz, CH2CH2CH2O),
3.45–3.60 (6H, m, galactose H-3, H-5, and H-2), 3.57 (2H,
A part of an AB system, JZ8.0, 9.8 Hz, one H of
CH2CH2CH2O), 3.76 (4H, d, JZ6.6 Hz, galactose H-6),
3.86 (2H, d, JZ3.5 Hz, galactose H-4), 3.92 (2H, B part of
an AB system, JZ8.0, 9.8 Hz, one H of CH2CH2CH2O),
4.22 (2H, d, JZ7.6 Hz, galactose H-1), 5.20 (4H, s,
ArCH2O), 6.98 (4H, A part of an AB system, JZ8.6 Hz,
aromatic H ortho to O), 7.18 (4H, B part of an AB system,
JZ8.6 Hz, aromatic H meta to O), 7.55 (4H, d, JZ5.1 Hz,
1
compounds. H NMR (CD3OD) showed the presence of
large but difficult to determine amount of water in the
samples. Satisfactory analytical data could not be obtained.
4.5.1. 6,60-Bis-[4-[3-(b-D-galactopyranosyl)-prop-1-yl]-

S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
10057
aromatic H para to CH2OAr and aromatic H para to
pyridine ring), 7.95 (2H, d, JZ7.8 Hz, pyridine H-5), 8.03
(2H, t, JZ7.8 Hz, pyridine H-4), 8.16 (2H, t, JZ5.1 Hz,
aromatic H meta to pyridine ring), 8.31 (2H, br s, aromatic
H between pyridine ring and CH2OAr), 8.55 (2H, d, JZ
7.8 Hz, pyridine H-3); 13C NMR (CD3OD): d 30.9 (2!
CH2–C–Ar), 31.4 (2!CH2–C–CH2), 61.1 (2!galactose
C-6), 68.6 (2!CH2–CH2–C), 69.0 (2!galactose C-4), 69.8
(2!Ar–CH2–O), 71.3 (2!galactose C-2), 73.7 (2!
galactose C-3), 75.2 (2!galactose C-5), 103.0 (2!
galactose C-1), 114.7 (4!aromatic C ortho to O), 119.4
(2!pyridine C-3), 120.2 (2!pyridine C-5), 125.8 (2!
aromatic C between pyridine ring and CH2OAr), 126.0
(2!aromatic C meta to pyridine ring and CH2OAr), 128.0
(2!aromatic C para to pyridine ring), 128.5 (2!aromatic
C para to CH2OAr), 129.1 (4!aromatic C meta to O),
135.0 (2!quaternary aromatic C para to O), 137.7 (2!
pyridine C-4), 138.0 (2!s, quaternary aromatic C meta to
pyridine ring), 156.0 (4!pyridine C-2 and C-6) and 157.5
(2!quaternary aromatic C bound to O); MS-ESIC: m/z 983
[MCNa]C. HRMS m/z 960.40331.
product). In all cases the recovery of the complex was
virtually quantitative.
Compound Cu(11)2. Red solid. 1H NMR (CD3OD): d 1.75–
1.86 (8H, m, 2!CH2CH2CH2O), 1.98 (12H, s, Me), 2.01
(12H, s, Me), 2.07 (12H, s, Me), 2.16 (12H, s, Me), 2.45–
2.61 (8H, m, CH2CH2CH2O), 3.52 (4H, A part of an AB
system, JZ6.0, 10.0 Hz, one H of CH2CH2CH2O), 3.82
(4H, B part of an AB system, JZ6.0, 10.0 Hz, H of
CH2CH2CH2O), 4.06–4.22 (12H, m, galactose H-5 and
H-6), 4.64 (4H, d, JZ7.8 Hz, galactose H-1), 4.82 (8H, s,
2!ArCH2O), 5.08–5.19 (8H, m, galactose H-2 and H-3),
5.41 (4H, br s, galactose H-4), 6.25 (8H, A part of an AB
system, JZ8.3 Hz, aromatic H ortho to O), 6.80 (8H, B part
of an AB system, JZ8.3 Hz, aromatic H meta to O), 7.78
(4H, d, JZ7.6 Hz, pyridine H-5), 8.09 (4H, t, JZ7.6 Hz,
pyridine H-4), 8.20 (4H, d, JZ7.6 Hz, pyridine H-3); 13C
NMR (CD3OD): d 19.0 (8!Me), 19.4 (8!Me), 30.3 (4!
Ar–C–CH2), 31.3 (4!CH2–C–CH2), 61.1 (4!galactose
C-6), 67.4 (4!galactose C-4), 68.4 (4!CH2 bound to
anomeric O), 69.2 (4!galactose C-2), 70.3 (4!galactose
C-5), 70.4 (4!ArO–CH2), 70.9 (4!galactose C-3), 100.8
(4!galactose C-1), 113.2 (8!aromatic C ortho to O),
121.4 (4!pyridine C-3), 125.7 (4!pyridine C-5), 128.9
(8!aromatic C meta to O), 134.3 (4!quaternary aromatic
C para to O), 138.9 (4!pyridine C-4), 151.5 (4!pyridine
C-2), 155.0 (4!pyridine C-6), 155.8 (4!quaternary
aromatic C bound to O), 169.9 (8!C]O), 170.5 (8!
C]O); MS-FAB: m/z 2353 [MKOTf]C; HRMS m/z
2351.79451 [MKOTf]C.
4.5.4. 6,60-Bis-[3-[N-2-(b-D-galactopyranosyl)-ethyl]-
imminomethyl]-phenyl]-2,20-bipyridine (19). White
solid. H NMR (CD3OD): d 3.41–3.60 (6H, m, galactose
1
H-2, H-3, and H-5), 3.72–3.78 (4H, m, galactose H-6), 3.85
(2H, br d, JZ3.0 Hz, galactose H-4), 3.90–4.00 (6H, m,
NCH2CH2O and one H of NCH2CH2O), 4.20–4.30 (2H, m,
one H of NCH2CH2O), 4.35 (2H, d, JZ8.0 Hz, galactose H-
1), 7.63 (2H, t, JZ7.8 Hz, aromatic H meta to pyridine ring
and meta to CH]N), 7.85 (2H, d, JZ7.7 Hz, aromatic H
para to pyridine ring), 8.01 (2H, d, JZ7.2 Hz, pyridine
H-5), 8.06 (2H, t, JZ7.2 Hz, pyridine H-4), 8.34 (2H, d, JZ
7.8 Hz, aromatic H para to CH]N), 8.57 (2H, s, CH]N),
8.65 (2H, br s, aromatic C between pyridine ring and
CH]N), 8.76 (2H, d, JZ7.2 Hz, pyridine H-3); 13C NMR
(CD3OD): d 60.3 (2!CH2–N), 61.2 (2!galactose C-6),
68.8 (2!N–CH2CH2–O), 69.1 (2!galactose C-4), 71.2
(2!galactose C-2), 73.6 (2!galactose C-3), 75.3 (2!
galactose C-5), 103.8 (2!galactose C-1), 119.7 (2!
pyridine C-3), 120.2 (2!pyridine C-5), 126.3 (2!aromatic
C between pyridine ring and CH]N), 128.8 (4!aromatic
C para to pyridine ring and aromatic C meta to pyridine
ring and meta to CH]N), 129.2 (2!aromatic C para to
CH]N), 136.2 (2!quaternary aromatic C bound to
CH]N), 137.9 (2!pyridine C-4), 139.7 (2!quaternary
aromatic C bound to pyridine ring), 155.5 (2!pyridine
C-2), 156.0 (2!pyridine C-6), 164.8 (2!CH]N);
MS-ESIC: m/z 797 [MCNa]C. HRMS m/z 774.31085.
1
Compound Cu(12)2. Red solid. H NMR (CD3OD): d 2.00
(12H, s, Me), 2.06 (12H, s, Me), 2.08 (12H, s, Me), 2.21
(12H, s, Me), 4.20–4.26 (8H, m, galactose H-6), 4.34 (4H, t,
JZ6.5 Hz, galactose H-5), 5.25–5.41 (12H, m, galactose
H-3, H-2, and H-1), 5.51 (4H, d, JZ3.2 Hz, galactose H-4),
6.73 (8H, A part of an AB system, JZ8.7 Hz, aromatic H
meta to O), 6.85 (8H, B part of an AB system, JZ8.6 Hz,
aromatic H meta to O), 7.77 (4H, d, JZ7.6 Hz, pyridine
H-5), 8.00 (4H, t, JZ7.8 Hz, pyridine H-4), 8.12 (4H, d, JZ
8.0 Hz, pyridine H-3); 13C NMR (CD3OD): d 19.1 (8!Me),
19.3 (8!Me), 61.1 (4!galactose C-6), 67.3 (4!galactose
C-4), 68.7 (4!galactose C-2), 70.7 (4!galactose C-3),
70.9 (4!galactose C-5), 86.4 (4!acetylenic C bound to
pyridine), 92.0 (4!acetylenic C bound to phenyl ring), 98.0
(4!galactose C-1), 115.0 (4!quaternary aromatic C bound
to acetylenic C), 116.3 (8!aromatic C ortho to O), 121.1
(4!pyridine C-3), 128.4 (4!pyridine C-5), 132.5 (8!
aromatic C meta to O), 137.7 (4!pyridine C-4), 141.4
(4!pyridine C-6), 151.6 (4!pyridine C-2), 157.5
(4!aromatic C bound to O), 169.8 (4!C]O), 170.0
(4!C]O), 170.5 (4!C]O), 170.6 (2!C]O); MS-FAB:
m/z 2161 [MKOTf]C; HRMS m/z 2159.56450
[MKOTf]C.
4.6. Synthesis of Cu(I) and Zn(II) complexes
4.6.1. Synthesis of the Cu(I) complexes. General pro-
cedure. To a stirred solution of ligand (typical amount
0.01 mmol) in CHCl3 (0.5 mL), kept under nitrogen at room
temperature, CuOTf$0.5C6H6 (0.36 mL of a 0.01 M
solution in acetonitrile, 0.005 mmol) was added. The red
solution was stirred at room temperature for 24 h. The
solvent was then evaporated under vacuum to afford a red
solid that was purified by a filtration on a short column of
silica gel for flash chromatography with a 95:5 CH2Cl2/
MeOH mixture as eluant (when attempted, this purification
degraded complex Cu(14)2 that was isolated as crude
1
Compound Cu(13)2. Red solid. H NMR (CD3OD): d 1.71
(8H, quintet, JZ6.5 Hz, CH2CH2CH2O), 1.95 (12H, s, Me),
1.99 (12H, s, Me), 2.00 (12H, s, Me), 2.14 (12H, s, Me),
2.47 (8H, t, JZ6.5 Hz, CH2CH2CH2O), 3.43 (4H, A part of
an AB system, JZ6.5, 9.8 Hz, one H of CH2CH2CH2O),
3.75 (4H, B part of an AB system, JZ6.5, 9.8 Hz, one H of
CH2CH2CH2O), 4.04 (4H, q, JZ6.2 Hz, galactose H-5),
4.12 (8H, AB system, JZ3.6, 6.2 Hz, galactose H-6), 4.39

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S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
(8H, s, ArCH2O), 4.53 (4H, d, JZ7.8 Hz, galactose H-1),
5.02–5.13 (8H, m, galactose H-2 and H-3), 5.38 (4H, br s,
galactose H-4), 6.36 (8H, A part of an AB system, JZ
8.6 Hz, aromatic H ortho to OCH2Ar), 6.83 (8H, B part of
an AB system, JZ8.6 Hz, aromatic H meta to OCH2Ar),
7.03–7.09 (8H, m, aromatic H of phenyl ring in meta and
para position to pyridine ring), 7.24 (8H, d, JZ6.7 Hz,
aromatic H of phenyl ring para to CH2OAr), 7.38 (8H, d,
JZ7.7 Hz, pyridine H-5), 7.75 (4H, t, JZ7.7 Hz, pyridine
H-4), 7.97 (4H, d, JZ7.7 Hz, pyridine H-3), 8.06 (4H, br s,
aromatic H of phenyl ring between pyridine and CH2OAr);
13C NMR (CD3OD): d 19.5 (12!Me), 19.8 (4!Me), 30.8
(4!Ar–C–CH2), 31.6 (4!CH2C–CH2), 61.5 (4!galactose
C-6), 67.8 (4!galactose C-4), 68.6 (4!Ar–C–O), 68.8
(4!CH2 bound to anomeric O), 69.6 (4!galactose C-2),
70.7 (4!galactose C-5), 71.4 (4!galactose C-3), 101.2
(4!galactose C-1), 114.5 (8!aromatic C ortho to O),
121.3 (4!pyridine C-3), 125.2 (4!pyridine C-5), 125.6
(4!aromatic C between pyridine and CH2OAr), 127.3
(4!aromatic C meta to CH2OAr), 127.5 (4!aromatic C
para to pyridine), 128.1 (4!aromatic C ortho to pyridine
and para to CH2OAr), 129.2 (4!aromatic C meta to O),
134.0 (4!quaternary aromatic C para to O), 137.4 (4!
quaterrnary C bound to CH2OAr), 138.2 (4!pyridine C-4),
139.0 (4!quaternary aromatic C bound to pyridine), 153.3
(4!pyridine C-2), 156.9 (4!aromatic C bound to O, and
4!pyridine C-6), 170.5 (8!C]O), 171.0 (8!C]O);
MS-FAB: m/z 2658 [MKOTf]C; HRMS m/z 2655.91478
[MKOTf]C.
Compound Cu(16)2. Red solid. 1H NMR (CD3OD): d 1.83–
190 (8H, m, CH2CH2CH2O), 2.56 (8H, t, JZ7.4 Hz,
CH2CH2CH2O), 3.47–3.60 (16H, m, galactose H-3,
galactose H-5, galactose H-2, and one H of CH2CH2CH2O),
3.77 (8H, d, JZ6.0 Hz, galactose H-6), 3.88 (4H, d, JZ
3.3 Hz, galactose H-4), 3.90 (4H, B part of an AB system,
JZ6.4, 9.7 Hz, one H of CH2CH2CH2O), 4.25 (4H, d, JZ
7.7 Hz, galactose H-1), 4.80 (8H, s, PyCH2O), 6.22 (8H, A
part of an AB system, JZ8.5 Hz, aromatic H ortho to O),
6.81 (8H, B part of an AB system, JZ8.5 Hz, aromatic H
meta to O), 7.76 (4H, d, JZ8.1 Hz, pyridine H-3), 8.08 (4H,
t, JZ8.1 Hz, pyridine H-4), 8.18 (4H, d, JZ8.1 Hz,
pyridine H-5); 13C NMR (CD3OD): d 30.6 (4!CH2–C–
Ar), 31.5 (4!CH2–C–CH2), 61.1 (4!galactose C-6), 68.5
(4!CH2–CH2–C–O), 68.9 (4!galactose C-4), 70.5 (4!
PyCH2O), 71.2 (4!galactose C-2), 73.7 (4!galactose
C-3), 75.3 (4!galactose C-5), 103.7 (4!galactose C-1),
113.0 (8!aromatic C ortho to O), 121.5 (4!pyridine C-3),
125.8 (4!pyridine C-5), 128.9 (8!aromatic H meta to O),
134.7 (4!quaternary aromatic C para to O), 139.0 (4!
pyridine C-4), 151.6 (4!pyridine C-2), 155.0 (4!pyridine
C-6), 155.8 (4!quaternary aromatic C bound to O);
MS-ESIC: m/z 1679 [MKOTf]C; HRMS m/z 1679.61973
[MKOTf]C.
1
Compound Cu(17)2. Red solid. H NMR (CD3OD): d 3.63
(4H, dd, JZ3.4, 9.6 Hz, galactose H-3), 3.79–3.90 (16H, m,
galactose H-5, H-6, and H-2), 3.95 (4H, d, JZ3.0 Hz,
galactose H-4), 4.90 (4H, d, JZ7.7 Hz, galactose H-1), 6.70
(8H, A part of an AB system, JZ8.6 Hz, aromatic H ortho
to O), 6.90 (8H, B part of an AB system, JZ8.6 Hz,
aromatic H meta to O), 7.71 (4H, d, JZ7.5 Hz, pyridine
H-3), 7.96 (4H, t, JZ7.7 Hz, pyridine H-4), 8.08 (4H, d, JZ
7.7 Hz, pyridine H-5); 13C NMR (CD3OD): d 61.3 (4!
galactose C-6), 68.9 (4!galactose C-4), 70.6 (4!galactose
C-2), 73.4 (4!galactose C-3), 75.8 (4!galactose C-5),
86.2 (4!acetylenic C bound to pyridine ring), 92.2 (4!
acetylenic C bound to phenyl ring), 100.9 (4!galactose
C-1), 109.0 (4!quaternary aromatic C bound to acetylenic
carbon), 116.2 (8!aromatic C ortho to O), 121.0 (4!
pyridine C-3), 128.0 (4!pyridine C-5), 132.3 (8!aromatic
C meta to O), 137.6 (4!pyridine C-4), 143.0 (4!pyridine
C-6), 152.0 (4!pyridine C-2), 158.0 (4!quaternary
aromatic C bound to O); MS-ESIC: m/z 1487 [MK
OTf]C; HRMS m/z 1487.39145 [MKOTf]C.
1
Compound Cu(14)2. Red solid. H NMR (CD3CN): d 1.80
(12H, s, Me), 1.89 (12H, s, Me), 1.98 (12H, s, Me), 1.99
(12H, s, Me), 3.46–3.57 (4H, m, one H of NCH2CH2O),
3.80–3.96 (8H, m, one H of NCH2CH2O, and one hydrogen
of NCH2CH2O), 4.02–4.12 (12H, m, galactose H-6 and one
hydrogen of NCH2CH2O), 4.48 (4H, d, JZ7.8 Hz, galactose
H-1), 4.90–5.02 (12H, m, galactose H-2, H-3, and H-5), 5.28
(4H, br s, galactose H-4), 7.14 (4H, t, JZ7.5 Hz, aromatic H
meta to pyridine), 7.36 (4H, d, JZ7.5 Hz, aromatic H para to
pyridine), 7.58 (4H, d, JZ7.5 Hz, aromatic H para to
CH]N), 7.65 (4H, d, JZ7.0 Hz, pyridine H-5), 7.72 (4H,
br s, CH]N), 7.95–8.04 (8H, m, pyridine H-4 and H-3),
8.21 (4H, br s, aromatic H between CH]N and pyridine
ring); 13C NMR (CD3CN): d 19.7 (8!Me), 19.8 (8!Me),
60.0 (4!NCH2), 61.2 (4!galactose C-6), 67.3 (4!
galactose C-4), 68.7 (4!galactose C-2), 69.1 (4!CH2
bound to anomeric O), 70.5 (8!galactose C-3 and C-5),
100.8 (4!galactose C-1), 121.5 (4!pyridine C-3), 124.8
(4!pyridine C-5), 126.4 (4!aromatic C between pyridine
ring and CH]N), 128.0 (4!aromatic C meta to pyridine
ring), 128.8 (4!aromatic para to pyridine ring), 130.4 (4!
aromatic C para to CH]N), 135.5 (4!quaternary aromatic
C bound to CH]N), 138.2 (4!pyridine C-4), 138.7
(4!quaternary aromatic C bound to pyridine ring), 152.8
(4!pyridine C-2), 156.0 (4!pyridine C-6), 161.1 (4!
CH]N), 169.7 (8!C]O), 170.0 (8!C]0); MS-FAB: m/z
2284 [M-OTf]C; HRMS m/z 2283.73221 [MKOTf]C.
Compound Cu(19)2. Red solid. 1H NMR (CD3OD): d 3.35–
3.58 (20H, m, galactose H-3, H-5, and H-2, and NCH2CH2-
O), 3.65–3.80 (12H, m, one hydrogen of NCH2CH2O and
galactose H-6), 3.87 (4H, d, JZ3.0 Hz, galactose H-4),
3.90–4.10 (4H, m, one hydrogen of NCH2CH2O), 4.21 (4H,
d, JZ7.2 Hz, galactose H-1), 7.11 (4H, t, JZ7.8 Hz,
aromatic H meta to pyridine ring and meta to CH]N),
7.45 (4H, d, JZ7.8 Hz, aromatic H para to pyridine ring),
7.61 (4H, d, JZ7.8 Hz, aromatic H para to CH]N), 7.73
(4H, d, JZ7.2 Hz, pyridine H-3), 7.82 (4H, s, CH]N),
8.03–8.20 (12H, m, pyridine H-4 and H-5, and aromatic H
between pyridine ring and CH]N); 13C NMR (CD3OD): d
60.0 (4!CH2–N), 61.1 (4!galactose C-6), 68.6 (4!
CH2CH2–O), 68.8 (4!galactose C-4), 71.0 (4!galactose
C-2), 73.5 (4!galactose C-3), 75.2 (4!galactose C-5),
103.7 (4!galactose C-1), 121.6 (4!pyridine C-3), 124.9
(4!pyridine C-5), 127.1 (4!aromatic C between pyridine
4.6.2. Deprotection of the acetylated complexes Cu(11)2,
Cu(12)2, and Cu(14)2 to Cu(16)2, Cu(17)2, and Cu(19)2.
This was performed following the procedure described
above for the deprotection of the acetylated ligands.

S. Orlandi et al. / Tetrahedron 61 (2005) 10048–10060
10059
ring and CH]N), 127.9 (4!aromatic C para to pyridine
ring), 128.4 (4!aromatic C meta to pyridine ring and meta
to CH]N), 130.4 (4!aromatic C para to CH]N), 135.1
(4!aromatic C bound to CH]N), 138.6 (4!pyridine C-4),
138.9 (4!quaternary aromatic C bound to pyridine ring),
152.7 (4!pyridine C-2), 156.1 (4!pyridine C-6), 162.7
(4!CH]N); MS-ESIC: m/z 1611 [MKOTf]C; HRMS m/z
1611.56120 [MKOTf]C.
acetylenic C), 116.7 (4!aromatic C ortho to O), 120.3 (2!
C-5 and C-300 of terpyridine), 121.3 (2!C-30 and C-50 of
terpyridine), 127.5 (2!C-3 and C-500 of terpyridine), 133.0
(4!aromatic C meta to O), 137.4 (2!C-4 and C-400 of
terpyridine),00138.0 (terpyridine C-40), 143.1 (2!terpyridine
C-2 and C-6 ), 155.0 (2!terpyridine C-20 and C-60), 157.0
(2!terpyridine C-6 and C-200), 158.0 (2!aromatic C bound
to O); MS-ESIC: m/z 812 [MCyNa]C.
4.6.3. Synthesis of the Zn(15) complex. To a stirred
solution of ligand 15 (30 mg, 0.026 mmol) in CHCl3
(0.5 mL), kept under nitrogen at room temperature,
Zn(OTf)2 (9.6 mg, 0.026 mmol) was added. The solution
was stirred at room temperature for 15 h. The solvent was
then evaporated under vacuum to afford a pale yellow solid
in quantitative yield. 1H NMR (CD3OD): d 2.02 (6H, s, Me),
2.08 (6H, s, Me), 2.09 (6H, s, Me), 2.23 (6H, s, Me), 4.25
(4H, d, JZ6.4 Hz, galactose H-6), 4.39 (2H, t, JZ6.4 Hz,
galactose H-5), 5.32 (2H, dd, JZ3.2, 10.0 Hz, galactose
H-3), 5.46–5.58 (4H, m, galactose H-1 and H-2), 5.53 (2H,
d, JZ3.2 Hz, galactose H-4), 6.93 (4H, A part of an AB
system, JZ8.7 Hz, aromatic H meta to O), 7.04 (4H, B part
of an AB system, JZ8.7 Hz, aromatic H ortho to O), 7.56
(1H, t, JZ7.9 Hz, terpyridine H-40), 7.75 (2H, d, JZ7.9 Hz,
terpyridine H-50 and H-300), 8.17 (2H, d, JZ7.9 Hz,
terpyridine H-3 and H-50), 8.24 (2H, t, JZ7.9 Hz,
terpyridine H-4 and H-400), 8.55 (2H, d, JZ7.9 Hz, pyridine
H-3 and H-500); 13C NMR (CD3OD): d 19.1 (4!Me), 19.2
(4!Me), 61.0 (2!galactose C-6), 67.2 (2!galactose C-4),
68.6 (2!galactose C-2), 70.7 (2!galactose C-3), 71.0 (2!
galactose C-5), 83.7 (2!acetylenic C bound to terpyridine),
94.9 (2!acetylenic C bound to phenyl), 98.0 (2!galactose
C-1), 114.3 (2!quaternary phenyl C bound to acetylene),
116.6 (4!aromatic C ortho to O), 122.2 (2!terpyridine
C-3 and C-500), 124.1 (2!terpyridine C-30 and C-50), 132.3
(2!terpyridine C-5 and C-300), 133.1 (4!a0r0omatic C meta
to O), 141.1 (2!pyridine C-4 and C-4 ), 142.8 (2!
pyridine C-6 and0 C-200), 142.9 (1!pyridine C-40), 149.7
(2!pyridine C-2 and C-60), 149.9 (2!pyridine C-2 and
C-600), 158.2 (2!aromatic C bound to O), 169.8 (2!
C]O), 169.9 (2!C]O), 170.4 (2!C]O), 170.5 (2!
C]O); MS-FAB: m/z 1339 [MKOTf]C; HRMS m/z
1338.21783 [MKOTf]C.
Acknowledgements
This work was supported by UNIMI, MIUR and CNR. We
want to thank professor Anna Bernardi, Universita’ di
Milano, for helpful suggestions and discussions.
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d6): d 3.44 (2H, dd, JZ3.2, 9.6 Hz, galactose H-3), 3.53-
3.68 (8H, m, galactose H-2, H-5, and H-6), 3.74 (2H, d, JZ
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galactose C-2), 73.5 (2!galactose C-3), 75.7 (2!galactose
C-5), 87.1 (2!acetylenic C bound to terpyridine), 89.0 (2!
acetylenic C bound to phenyl), 101.3 (2!galactose C-1),
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10060
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19. Attempts of running the complexation reaction of 16–20 in
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16. It must be noted that ligand 14 contains two additional nitrogen
atoms as potentially competing binding sites for Cu(I). It has
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bridged olygobipyridine ligands were not involved in the
complexation with Cu(I) cations, that occurred exclusively at
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soluble in CD3OD to obtain NMR data. Cu(18)2 was insoluble
in CD3OD. When the NMR spectra of these complexes were
recorded in DMSO extensive complex decomposition was
observed. As in the case of the polyols, from which they
formally derive, isolation of analytically pure compounds
was not possible. These solubility properties may represent
a problem in the biological studies of such a compounds.
Studies are currently underway in order to solve this
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