Parallel combinatorial synthesis of glycodendrimers and their hydrogelation properties

Article abstract of DOI:10.1002/1099-0690(200107)2001:13<2535::AID-EJOC2535>3.0.CO;2-V

A series of glycodendrons has been assembled using a parallel combinatorial approach, and it has been shown that subtle structural variations between dendrons give rise to significant differences in their hydrogelation behavior.

Full text of DOI:10.1002/1099-0690(200107)2001:13<2535::AID-EJOC2535>3.0.CO;2-V

FULL PAPER
Parallel Combinatorial Synthesis of Glycodendrimers and Their Hydrogelation
Properties
Martin McWatt[a] and Geert-Jan Boons*[a]
Keywords: Carbohydrates / Combinatorial chemistry / Dendrimers / Hydrogelation
A series of glycodendrons has been assembled using a paral-
lel combinatorial approach, and it has been shown that subtle
structural variations between dendrons give rise to signific-
ant differences in their hydrogelation behavior.
Introduction
variations possible between structurally related but consti-
tutionally different branched macromolecules.
Recently, Hirsch and co-workers reported the construc-
tion of a series of ‘‘depsipeptide’’ dendrimers up to the third
generation.[16] Their synthetic strategy involved the assem-
bly of a sample of dendrons from enantiomerically pure
peptide-tartaric acid conjugate building blocks, by parallel
synthetic methodology. The potential for the generation of
an enormous number of compounds stemmed from the
variety of peptides and tartaric acid isomers available.
Concurrently, a similar strategy, the ‘‘parallel monomer
Recent advances in dendrimer research have focussed on
the discovery of specific properties and functions that are a
direct consequence of the dendritic architecture.[1] It has
been proposed that the pronounced branching of higher
generation dendrimers may result in three-dimensional
structures possessing cavities with distinct microenviron-
ments. Such cavities may function as specific hosts for par-
ticular guest molecules.[2Ϫ5] Dendritic architectures can
modulate physical properties such as the reduction poten-
tial of encapsulated redox-active metal centers[6,7] and UV/
Vis absorption of central chromophores.[8,9] These unique
properties of dendrimers may be exploited for chromato-
graphy additives,[10] new materials, unimolecular micelles,
catalysts, therapeutics, liquid crystals, and electrically con-
ducting materials.[5]
´
combination approach’’, was being developed by Frechet
and co-workers.[17] Their methodology combined the syn-
thetic power of double-exponential dendrimer growth with
the efficiency of classical parallel synthesis, generating a di-
verse series of dendrons, all of which were derivable from
two common building blocks.
Given these precedents, we report here the synthesis of a
series of novel third generation glycodendrons 14aϪf
(Scheme 3), obtained by the parallel combination of the
three universal building blocks 5aϪc (Scheme 1). Our strat-
egy illustrates the suitability of the parallel monomer com-
bination approach for the investigation and optimization of
structure-property relationships of interest. Monomers
5aϪc represent homologous compounds differing from
each other only in the length of their alkyl chains (n ϭ 3, 4
or 5). A key aspect of the synthetic approach is that the tier
length (n) of each dendritic layer may be tuned in such a
The iterative approach fundamental to dendrimer con-
struction has traditionally involved the manipulation of
building blocks derived from a single monomer unit.[1]
Hence, the only structural variations possible by this pro-
cedure stem from the rudimentary differences between one
generation and the next. On the other hand, the use of a
small number of structurally related building blocks, which
could be assembled in a parallel manner, would give access
to a multitude of structurally related dendrimers.[11Ϫ14]
Such libraries would provide an ideal opportunity for the
systematic study of biological or physical characteristics un-
der scrutiny, and would lay the foundation for rational op-
timization of any given targeted feature.
A few examples of such macromolecular ‘‘fine-tuning’’
have been reported. Newkome and co-workers described
the synthesis and characterization of two-directional
arborols in which branched domains were connected by al-
kyl spacer units of differing lengths.[15] It was observed that
several of these arborols formed thermally reversible aque-
ous gels, one of which was able to gelate at concentrations
as low as 1.0 wt%. This early work illustrated the physical
[a]
Complex Carbohydrate Research Center, University of
Georgia,
220 Riverbend Road, Athens, GA 30602, USA
Fax: (internat.) ϩ 1-706/542-4412
E-mail: gjboons@ccrc.uga.edu
Scheme 1. Reagents and conditions: i) AllBr, Cs2CO3, DMF; ii)
NaOH, MeOH/H2O; iii) EDC, HOBT, iPr2NEt, DMF/CH2Cl2
Eur. J. Org. Chem. 2001, 2535Ϫ2545
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0713Ϫ2535 $ 17.50ϩ.50/0
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M. McWatt, G.-J. Boons
FULL PAPER
way that any combination is readily accessible. Moreover,
Thus, treatment of phenol 1 with allyl bromide in the
the synthesized materials were shown to exhibit gelation presence of Cs2CO3 gave dimethyl diester 2, which upon
properties, revealing that subtle structural variations be- saponification afforded diacid 3 in 90% overall yield
tween glycodendrons may give rise to significant differences (Scheme 1). Building blocks 5aϪc were obtained in excel-
in their physical behavior. A striking feature of these low lent yields, using standard peptide coupling conditions,[24]
molecular weight dendrons[18,19] is that they are monodis- by treatment of diacid 3 with amines 4aϪc, respectively.
perse and it is evident that the rational synthesis and study
Orthogonally protected dendrons 5aϪc were converted in
of structurally related molecules will enhance efforts to- 90Ϫ100% yields either into the corresponding phenols
wards the design of improved hydrogelators, compounds 6aϪc by palladium-catalyzed deallylation,[25] or into their
that have already proven useful in a variety of medical ap- corresponding chloroacetamides 7aϪc by removal of Boc
plications ranging from drug delivery[20Ϫ22] to tissue engin- protecting groups with TFA in CH2Cl2, followed by treat-
eering.[23]
ment with pentafluorophenyl chloroacetate (Scheme 2).[26]
The homologous sets 6aϪc and 7aϪc represent focally and
peripherally activated first generation dendrons from which
32 ϭ 9 fully protected second generation molecules can be
assembled. Thus, second generation building blocks 8aϪc
were prepared in ca. 90% yield by base-mediated condensa-
tion of chloroacetamide 7b with phenols 6aϪc, respectively.
Mass-spectrometric analysis of the crude reaction products
showed that they were free both of starting material 7b and
of any partially substituted derivatives. The compounds
were purified by silica gel or LH-20 size exclusion column
chromatography.
Results and Discussion
The synthesis of the dendrimers is based on the activa-
tion of 5aϪc either at the focal point, by removal of the
allyl protecting group to give a phenol, or at the surface, by
cleavage of the Boc groups and subsequent reaction with
pentafluorophenyl chloroacetate to give a chloroacetamide
derivative (Scheme 2). Dendrimer growth can be achieved
by the efficient nucleophilic substitution of the chloroacetyl
groups with the phenol moiety to give ether linkages.
Higher generation dendrimers can be obtained by repetition
of the activation and condensation reaction sequence. In
the final stage of the synthesis, different groups can be at-
tached to the exterior to give functionalized dendrimers.
The same synthetic strategy was employed for the effici-
ent construction of model third generation dendrons
10aϪc. Thus, focally activated phenol 9a, obtained quantit-
atively from second generation building block 8a, was con-
densed with chloroacetamides 7aϪc to give the correspond-
ing third generation subset 10aϪc in excellent yields (ca.
90%) (Scheme 3). The process of activation and condensa-
tion can in principle be repeated to produce higher genera-
tion dendrimers. However, the exteriors of the dendrimers
can also be modified with other functionalities. In this case,
saccharides were attached in a divergent manner, to pro-
duce water-soluble glycodendrimers.[27,28] Thus, the Boc
protecting groups of the wedges 10aϪc were cleaved with
TFA in dichloromethane and the resulting amino func-
tionalities of 11aϪc activated by treatment with pentafluor-
ophenyl chloroacetate to give dendrons 12aϪc, each bear-
ing eight reactive chloroacetyl functionalities at the exterior.
Termini of other dendrimers have been N-chloroacetylated
by using chloroacetic anhydride;[26] however, it was found
that pentafluorophenyl chloroacetate yielded equally good
results without the necessity for aqueous extraction of chlo-
roacetic acid. Fully protected melibiose hemithioacetal,
conveniently generated in situ from peracetylated thioglyco-
side in ammoniacal DMF (Ϫ60 °C), was coupled with key
precursors 12aϪc to afford the protected glycodendron
family 13aϪc. It was found that deprotection in situ and
condensation at ambient temperature yielded dendrimers
containing α/β-mixed S-linkages (ca. 1:9). The same re-
agents, when combined at Ϫ60 °C and brought slowly to
room temperature, gave β-S-linked products only. The com-
pounds were isolated in yields of ca. 85% for three steps
starting from 10aϪc. The structural homogeneity of these
new materials was established by high-resolution NMR
spectroscopy and MALDI-TOF mass spectrometry after
purification by size-exclusion chromatography on Sephadex
Scheme 2. Reagents and conditions: i) Pd(PPh3)4, EtOH, 80 °C; ii)
TFA/CH2Cl2; iii) pentafluorophenyl chloroacetate, Et3N, DMF; iv)
K2CO3, acetone, ∆Τ
2536
Eur. J. Org. Chem. 2001, 2535Ϫ2545

Parallel Combinatorial Synthesis of Glycodendrimers and Their Hydrogelation Properties
FULL PAPER
Scheme 3. Reagents and conditions: i) K2CO3, acetone, ∆Τ; ii) TFA, CH2Cl2; iii) pentafluorophenyl chloroacetate, Et3N, DMF; iv) acetyl
2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-α--galactopyranosyl)-1-thio-β--glucopyranose, DMF saturated with NH3, Ϫ60 °C to 0
°C; v) 0.5  NaOMe in methanol
LH-20. In particular, it was established that eight disacchar- 7aϪc to give precursors 10dϪf. The target molecules 14dϪf
ide moieties had indeed been incorporated. Removal of the were obtained from these in excellent yields (Scheme 3). Gel
acetyl protecting groups of 13aϪc was easily accomplished transition behavior of the extended analogs 14dϪf par-
by treatment with NaOMe in methanol to afford the target alleled the trends observed earlier for the original subset
molecules 14aϪc in quantitative yields.
14aϪc, relating thermal stability (Tgel) with internal tier
Compounds 14aϪc formed thermally reversible aqueous length (n1), (Table 1). Moreover, comparison of 14a with
gels. Dissolution in water at 80 °C followed by rapid cooling 14d, 14b with 14e, and 14c with 14f reveals that an increase
to 4 °C induced hydrogelation (Table 1). Gel transition in external tier length (n3) also produces an elevation of
(Tgel) experiments revealed that an increase in thermal transition temperatures. However, it is clear that the dimen-
stability was concomitant with a decrease in the internal sions of the innermost tiers (n1) have the most pronounced
tier length, n1 (Scheme 3). This implies that the observed impact on the gel transition behavior of these three-tier
variations in Tgel were the result of differences in innermost dendrons (Table 1). The relative water solubility of the hy-
tier length (n1), which is the only structural element distin- drogelators is noteworthy. For example, when heated solu-
guishing glycodendrons 14a from 14b, and 14b from 14c. tions (80 °C) of 14aϪf were each allowed to come to ambi-
This motivated us to examine the influence on hydrogela- ent temperature, solutions of 14a, 14b, 14d, and 14e formed
tion of the external tier length, n3, in greater detail. For this hydrogels, whereas those of 14c and 14f formed precipitates,
purpose we required the new subset 14dϪf (n3 ϭ 5), dif- which could only be redissolved by heating. Furthermore,
fering from subset 14aϪc (n3 ϭ 3) only with respect to the replacement of peripheral melibiose moieties with galacto-
additional methylene units in their outermost tiers. Thus, in side units resulted in water-insoluble glycodendrons, high-
an application of our established route, phenol 9c, prepared lighting the dramatic influence of the bulk structural topo-
quantitatively from 8c, was treated with building blocks logy of these materials on their solution properties. It
Eur. J. Org. Chem. 2001, 2535Ϫ2545
2537

M. McWatt, G.-J. Boons
FULL PAPER
should also be noted that critical hydrogel concentrations
occurred at 0.33 wt%, with the notable exception of 14d,
which formed a viscous liquid below 0.5 wt%. The concen-
tration of glycodendrons had little effect on gel solution
transitions above these critical values (Figure 1).
Experimental Section
General Procedures: Chemicals were purchased from Aldrich and
Fluka and used without further purification. Molecular sieves were
activated at 350 °C in vacuo for 3 h. All solvents were distilled from
the appropriate drying agents; dichloromethane and toluene were
˚
distilled from P2O5 and stored over 4 A molecular sieves. Diethyl
ether and THF were distilled from CaH2, redistilled from LiAlH4,
and stored over sodium wire. Pyridine and acetonitrile were dis-
Table 1. Gel transition data for glycodendrons 14aϪf at 1.0 wt%
concentration; the matrix displays compound identity and associ-
ated Tgel
˚
tilled from CaH2 and stored over 4 A molecular sieves. Methanol
˚
was distilled from sodium and stored over 4 A molecular sieves.
Tier length, n
n1 ϭ 3
n1 ϭ 4
n1 ϭ 5
All reactions were performed under anhydrous conditions and
monitored by TLC on 60 F254 Kieselgel (Merck). Detection was by
examination under UV light (254 nm) and by charring with 10%
sulfuric acid in methanol. Column chromatography was performed
on silica gel (Merck, mesh 70Ϫ230). Extracts were concentrated
under reduced pressure at Ͻ 40 °C (bath). Ϫ 1H NMR and 13C
NMR spectra were recorded with a Varian Merc300 spectrometer
and a Varian Inova500 spectrometer equipped with Sun worksta-
tions. 1H and 13C NMR spectra were recorded in CDCl3, chemical
shifts (δ) are given in ppm relative to solvent peaks (1H: δ ϭ 7.26;
13C: δ ϭ 77.3) as internal standard. Ϫ Positive-ion matrix-assisted
laser-desorption ionizationϪtime of flight (MALDIϪTOF) mass
spectra were recorded using an HP-MALDI instrument, using
gentisic acid as a matrix. Ϫ Optical rotations were measured with
a Jasco P-1020 polarimeter, and [α]D values are given in units of
n3 ϭ 3
n3 ϭ 5
14a (34 °C)
14d (37 °C)
14b (17 °C)
14e (24 °C)
14c (15 °C)
14f (19 °C)
deg cm3 gϪ1
.
Synthesis of 2: Allyl bromide (8.2 mL, 95 mmol) was added to a
stirred solution of cesium carbonate (39.0 g, 119 mmol) and di-
methyl 5-hydroxyisophthalate (1) (10.0 g, 48 mmol) in N,N-di-
methylformamide (150 mL). After stirring for 1 h, the reaction mix-
ture was poured into ice-cold water (200 mL) and extracted with
ethyl acetate (500 mL). The organic phase was dried (MgSO4), fil-
tered, and concentrated in vacuo. The yellow residue was redis-
solved in ethyl acetate, preabsorbed onto silica gel under reduced
pressure, and purified by silica gel column chromatography (ethyl
acetate/hexane, 0:1 Ǟ 1:5, v/v). Crystallization from ethyl acetate
and hexane (1:3, v/v) afforded 2 as a white crystalline solid (11.9 g,
99%): Rf ϭ 0.45 (ethyl acetate/hexane, 1:5, v/v); m.p. 68.4Ϫ69.2 °C.
Ϫ 1H NMR (CDCl3, 300 MHz): δ ϭ 8.28 (s, 1 H, CH Ar), 7.76 (s,
2 H, 2 CH Ar), 6.12Ϫ5.97 (m, 1 H, OCH2CHCH2), 5.47Ϫ5.30 (m,
2 H, OCH2CHCH2), 4.63Ϫ4.62 (m, 2 H, OCH2CHCH2), 3.94 (s,
6 H, 2 CH3). Ϫ 13C NMR (CDCl3, 75 MHz): δ ϭ 166.1 (2 CO-
Figure 1. Tgel values of glycodendrimers 14aϪf
Conclusion
In summary, we have demonstrated that a series of glyco-
dendrons can be assembled in a parallel combinatorial
manner from a relatively small number of mutually compat-
ible building blocks. An important aspect of the methodo-
logy is that the process of material discovery is accelerated
by the reiterative use of first- and second-generation build-
ing blocks. A key step in the assembly is the condensation OMe), 158.6 (Cq, Ar), 132.4 (OCH2CHCH2), 131.7 (2 Cq, Ar),
123.1 (CH Ar), 120.1 (2 CH Ar), 118.2 (OCH2CHCH2), 69.2
of chloroacetamides with phenols, which has proven to be
an efficient method for generation growth, and to the best
of our knowledge has not been reported for dendrimer syn-
thesis. The range of dendrons obtained has allowed a sys-
tematic study to be made of their hydrogelation behavior,
and has for the first time revealed that subtle structural
(OCH2CHCH2), 52.5 (2 CH3). Ϫ FAB MS; m/z ϭ 251 [M ϩ H]ϩ.
Synthesis of 3: Compound 2 (11.9 g, 48 mmol) was added to a sat-
urated solution of sodium hydroxide in water (10 mL) and meth-
anol (80 mL) and refluxed for 18 h. The resultant white slurry was
neutralized with Dowex-50 (Hϩ) resin until the precipitate disap-
variations have a profound influence on bulk physical prop- peared, and was then concentrated to dryness under reduced pres-
sure. Subsequent redissolution in methanol was only partial and
the remaining precipitate was stirred a second time with Dowex-50
(Hϩ) resin until all the material had dissolved. Compound 3 was
precipitated from acetone, collected by filtration, and isolated as a
white solid (9.6 g, 90%): Rf ϭ 0.33 (methanol/dichloromethane, 1:9,
erties. A wide range of small organic molecules has been
found to gel a variety of organic solvents.[29Ϫ35] On the
other hand, there are only a few examples of nonpolymeric
molecules that form hydrogels.[36,37] Only one other report
deals with dendritic hydrogelators; however, these arborols
were unable to gelate below concentrations of 1.0 wt%.[15]
It is to be expected that the parallel combinatorial synthesis
of dendrimers will accelerate the design and evaluation of
dendrimers targeted for other applications, and could un-
derpin rational attempts to modulate desired features.
1
v/v and 1 drop of acetic acid). Ϫ H NMR (CD3OD, 300 MHz):
δ ϭ 8.23 (s, 1 H, CH Ar), 7.75 (s, 2 H, 2 CH Ar), 6.15Ϫ6.00 (m,
1
H, OCH2CHCH2), 5.46Ϫ5.27 (m,
4.67Ϫ4.65 (m, 2 H, OCH2CHCH2). Ϫ 13C NMR (CD3OD,
75 MHz): 169.7 (COOH), 160.7 (Cq, Err), 134.9
2 H, OCH2CHCH2),
δ
ϭ
(OCH2CHCH2), 134.8 (Cq, Ar), 124.9 (CH Ar), 121.4 (2 CH Ar),
2538
Eur. J. Org. Chem. 2001, 2535Ϫ2545

Parallel Combinatorial Synthesis of Glycodendrimers and Their Hydrogelation Properties
FULL PAPER
118.7 (OCH2CHCH2), 70.8 (OCH2CHCH2). Ϫ CI MS; m/z ϭ 240 Compound 5b: This compound was synthesized under the same
[M ϩ NH4]ϩ.
conditions as described for the preparation of 5a, employing 4b in
place of 4a to yield a white foam (8.7 g, 91%): Rf ϭ 0.39 (methanol/
dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD, 300 MHz): δ ϭ
7.82 (s, 1 H, CH Ar), 7.51 (s, 2 H, 2 CH Ar), 6.12Ϫ5.99 (m, 1 H,
OCH2CHCH2), 5.47Ϫ5.23 (m, 2 H, OCH2CHCH2), 4.67Ϫ4.60 (m,
2 H, OCH2CHCH2), 3.44Ϫ3.33, 3.12Ϫ2.99 (2 m, 8 H, 4 NHCH2),
1.69Ϫ1.46 (m, 8 H, 2 CH2(CH2)2CH2), 1.42 (s, 18 H, 6 CH3). Ϫ
13C NMR (CD3OD, 75 MHz): δ ϭ 169.1, 160.2, 137.6 (4 NHCO,
Synthesis of 4a: A solution of Boc-ON (20.0 g, 82 mmol) in tetrahy-
drofuran (250 mL) was added dropwise to a stirred solution of 1,3-
diaminopropane (6.8 mL, 82 mmol) in tetrahydrofuran (250 mL) at
0 °C. After stirring for 10 min, the reaction mixture was concen-
trated in vacuo and preabsorbed onto silica gel under reduced pres-
sure. The dry powder was applied to a silica gel column (triethylam-
ine/methanol/dichloromethane, 1:5:94 Ǟ 1:50:49, v/v/v) and 4a was
isolated as a viscous yellow oil (7.7 g, 54%): Rf ϭ 0 Ǟ 0.1 (meth-
3
Cq Ar), 134.3 (OCH2CHCH2), 119.4 (CH Ar), 118.0
(OCH2CHCH2), 117.5 (2 CH Ar), 80.0 [2 C(CH3)3], 70.3
(OCH2CHCH2), 41.2, 40.9 (4 NHCH2), 29.0 (6 CH3), 28.7, 27.9
[CH2(CH2)2CH2]. Ϫ FAB MS; m/z ϭ 585 [M ϩ Na]ϩ. Ϫ
C29H47N4O7: m/z calcd. 563.3445, found 563.3458.
anol/dichloromethane, 13:87, v/v).
Ϫ
1H NMR (CD3OD,
300 MHz): δ ϭ 3.22Ϫ3.11, 3.00Ϫ2.91 (2 m, 4 H, 2 NHCH2),
1.91Ϫ1.77 (m, 2 H, CH2CH2CH2), 1.45 (s, 9 H, 3 CH3). Ϫ 13C
NMR (CD3OD, 75 MHz): δ ϭ 158.9 (NHCO), 80.4 [C(CH3)3],
38.5, 38.1 (2 NHCH2), 29.3 (CH2CH2CH2), 28.9 (CH3). Ϫ FAB
MS; m/z ϭ 175 [M ϩ H]ϩ.
Compound 5c: This compound was synthesized under the same
conditions as described for the preparation of 5a, employing 4c in
place of 4a to yield a white foam (4.9 g, 98%): Rf ϭ 0.39 (methanol/
dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD, 300 MHz): δ ϭ
7.83 (s, 1 H, CH Ar), 7.51 (s, 2 H, 2 CH Ar), 6.16Ϫ5.99 (m, 1 H,
OCH2CHCH2), 5.47Ϫ5.23 (m, 2 H, OCH2CHCH2), 4.67Ϫ4.61 (m,
2 H, OCH2CHCH2), 3.42Ϫ3.32, 3.08Ϫ2.99 (2 m, 8 H, 4 NHCH2),
1.70Ϫ1.40 [m, 12 H, 2 CH2(CH2)3CH2], 1.40 (s, 18 H, 6 CH3). Ϫ
13C NMR (CD3OD, 75 MHz): δ ϭ 169.1, 160.2, 137.6 (4 NHCO,
Compound 4b: This compound was synthesized under the same
conditions as described for the preparation of 4a, employing 1,4-
diaminobutane in place of 1,3-diaminopropane to yield a viscous
yellow oil (8.0 g, 52%): Rf ϭ 0 Ǟ 0.1 (methanol/dichloromethane,
13:87, v/v). Ϫ 1H NMR (CDCl3, 300 MHz): δ ϭ 3.19Ϫ3.08,
2.78Ϫ2.70 (2 m,
4 H, 2 NHCH2), 1.59Ϫ1.50 [m, 4 H,
CH2(CH2)2CH2], 1.47 (s, 9 H, 3 CH3). Ϫ 13C NMR (CDCl3,
75 MHz): δ ϭ 156.3 (NHCO), 79.2 [C(CH3)3], 39.9, 39.7 (2
NHCH2), 28.5 (CH3), 27.0, 24.8 [CH2(CH2)2CH2]. Ϫ FAB MS; m/
z ϭ 189 [M ϩ H]ϩ.
3
Cq Ar), 134.3 (OCH2CHCH2), 119.4 (CH Ar), 118.0
(OCH2CHCH2), 117.5 (2 CH Ar), 80.0 [2 C(CH3)3], 70.3
(OCH2CHCH2), 41.4, 41.2 (4 NHCH2), 29.0 (6 CH3), 30.9, 30.3,
25.4 [2 CH2(CH2)3CH2]. Ϫ FAB MS; m/z ϭ 591 [M ϩ H]ϩ.
Compound 4c: This compound was synthesized under the same
conditions as described for the preparation of 4a, employing 1,5-
diaminopentane in place of 1,3-diaminopropane to yield a viscous
yellow oil (4.2 g, 52%): Rf ϭ 0 Ǟ 0.1 (methanol/dichloromethane,
13:87, v/v). Ϫ 1H NMR (CDCl3, 300 MHz): δ ϭ 3.19Ϫ3.07,
Synthesis of 6a: A solution of 5a (8.5 g, 16 mmol) and tetrakis(tri-
phenylphosphane)palladium(0) (900 mg, 0.8 mmol) in deoxygen-
ated ethanol (50 mL) was refluxed for 1 h. The resultant black
slurry was filtered through Celite and washed with hot methanol
(200 mL). The filtrate was repeatedly boiled (3 times) and filtered
to reduce and remove black palladium metal. The precipitate
formed on cooling was collected by filtration (6.0 g). The filtrate
was concentrated under reduced pressure, purified by silica gel col-
umn chromatography (methanol/dichloromethane, 1:49 Ǟ 1:19,
v/v), and combined with the precipitate to afford 6a as a white
foam (7.1 g, 90%): Rf ϭ 0.31 (acetone/hexane, 1:1, v/v). Ϫ 1H NMR
(CD3OD, 300 MHz): δ ϭ 7.71 (s, 1 H, CH Ar), 7.38 (s, 2 H, 2 CH
Ar), 3.45Ϫ3.38, 3.18Ϫ3.08 (2 m, 8 H, 4 NHCH2), 1.82Ϫ1.72 (m,
4 H, 2 CH2CH2CH2), 1.46 (s, 18 H, 6 CH3). Ϫ 13C NMR (CD3OD,
75 MHz): δ ϭ 169.6, 159.1, 158.6, 137.6 (4 NHCO, 3 Cq Ar), 118.2,
117.8 (3 CH Ar), 80.2 [2 C(CH3)3], 39.0, 38.6 (4 NHCH2), 31.0 (2
CH2CH2CH2), 29.0 (6 CH3). Ϫ FAB MS; m/z ϭ 495 [M ϩ H]ϩ.
Ϫ C24H39N4O7: m/z calcd. 495.2819, found 495.2807.
2.77Ϫ2.68 (2 m,
4 H, 2 NHCH2), 1.58Ϫ1.32 [m, 6 H,
CH2(CH2)3CH2], 1.48 (s, 9 H, 3 CH3). Ϫ 13C NMR (CDCl3,
75 MHz): δ ϭ 156.0 (NHCO), 79.0 [C(CH3)3], 41.9, 40.6 (2
NHCH2), 33.0, 30.1, 24.2 [CH2(CH2)3CH2], 28.6 (CH3). Ϫ FAB
MS; m/z ϭ 203 [M ϩ H]ϩ.
Synthesis of 5a: 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide
hydrochloride (11.9 g, 62 mmol) and N,N-diisopropylethylamine
(7.7 mL, 44 mmol) were added to an ice-cold solution of 4a (7.7 g,
44 mmol), diacid 3 (3.9 g, 18 mmol), and 1-hydroxybenzotriazole
(6.0 g, 44 mmol) in N,N-dimethylformamide/dichloromethane
(100 mL, 3:1, v/v). The mixture was stirred for 18 h at room tem-
perature. The dichloromethane present in the solvents was evapor-
ated under reduced pressure, and the remaining slurry was diluted
with ethyl acetate (500 mL). The resultant organic solution was
washed with ice-cold water (1 ϫ 100 mL), aqueous ammonium
chloride (saturated, 1 ϫ 100 mL), and aqueous sodium bicarbonate
(saturated, 1 ϫ 100 mL). The organic phase was dried (MgSO4)
and concentrated in vacuo, and the residue was purified by silica
gel chromatography (acetone/hexane, 1:9 Ǟ 3:7, v/v) to afford 5a
as a white foam (9.3 g, 99%): Rf ϭ 0.39 (methanol/dichlorome-
Compound 6b: This compound was synthesized under the same
conditions as described for the preparation of 6a, employing 5b in
place of 5a to yield a white foam (1.4 g, 98%): Rf ϭ 0.31 (acetone/
1
hexane, 1:1, v/v). Ϫ H NMR (CD3OD, 300 MHz): δ ϭ 7.68 (s, 1
H, CH Ar), 7.37 (s, 2 H, 2 CH Ar), 3.42Ϫ3.35, 3.12Ϫ3.03 (2 m, 8
H, 4 NHCH2), 1.70Ϫ1.48 [m, 8 H, 2 CH2(CH2)2CH2], 1.42 (s, 18
H, 6 CH3). Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ 168.3, 157.9,
157.3, 136.5 (4 NHCO, 3 Cq Ar), 116.9, 116.5 (3 CH Ar), 78.7
[2 C(CH3)3], 40.0, 39.7 (4 NHCH2), 27.8 (6 CH3), 27.4, 26.7 [2
1
thane, 2:23, v/v). Ϫ H NMR (CD3OD, 300 MHz): δ ϭ 7.84 (s, 1
H, CH Ar), 7.53 (s, 2 H, 2 CH Ar), 6.19Ϫ6.00 (m, 1 H,
OCH2CHCH2), 5.48Ϫ5.24 (m, 2 H, OCH2CHCH2), 4.69Ϫ4.61 (m,
2 H, OCH2CHCH2), 3.47Ϫ3.34, 3.19Ϫ3.07 (2 m, 8 H, 4 NHCH2),
1.83Ϫ1.69 (m, 4 H, 2 CH2CH2CH2), 1.43 (s, 18 H, 6 CH3). Ϫ 13C
NMR (CD3OD, 75 MHz): δ ϭ 169.1, 160.3, 137.5 (4 NHCO, 3 Cq
CH2(CH2)2CH2].
C26H43N4O7: m/z calcd. 523.3132, found 523.3083.
Ϫ FAB MS; m/z ϭ 523 [M ϩ Ϫ
H]ϩ.
Ar), 134.3 (OCH2CHCH2), 119.4 (CH Ar), 118.0 (OCH2CHCH2), Compound 6c: This compound was synthesized under the same
117.6 (2 CH Ar), 80.0 [2 C(CH3)3], 70.3 (OCH2CHCH2), 39.0, 38.6 conditions as described for the preparation of 6a, employing 5c in
(4 NHCH2), 30.9 (2 CH2CH2CH2), 29.0 (6 CH3). Ϫ FAB MS; place of 5a to yield a white foam (330 mg, 100%): Rf ϭ 0.31 (acet-
1
m/z ϭ 535 [M ϩ H]ϩ. Ϫ C27H43N4O7: m/z calcd. 535.3132, found
535.3116.
one/hexane, 1:1, v/v). Ϫ H NMR (CD3OD, 300 MHz): δ ϭ 7.67
(s, 1 H, CH Ar), 7.36 (s, 2 H, 2 CH Ar), 3.42Ϫ3.34, 3.08Ϫ3.00 (2
Eur. J. Org. Chem. 2001, 2535Ϫ2545
2539

M. McWatt, G.-J. Boons
FULL PAPER
m, 8 H, 4 NHCH2), 1.68Ϫ1.40 [m, 12 H, 2 CH2(CH2)3CH2], 1.42 Synthesis of 8a: A solution of 6a (3.6 g, 7.3 mmol), 7b (2.1 g,
(s, 18 H, 6 CH3). Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ 167.7, 3.5 mmol), and potassium carbonate (2.42 g, 17.5 mmol) in acetone
157.4, 156.7, 135.9 (4 NHCO, 3 Cq Ar), 116.4, 116.0 (3 CH Ar), (150 mL) was stirred under reflux for 18 h. The white slurry was
78.1 [2 C(CH3)3], 39.6, 39.3 (4 NHCH2), 29.1, 28.5, 23.6 [2 filtered rapidly through a column of silica gel (methanol/dichloro-
CH2(CH2)3CH2], 27.2 (6 CH3). Ϫ FAB MS; m/z ϭ 551 [M ϩ H]ϩ. methane, 1:1, v/v) and the eluted solution concentrated and preab-
Ϫ C28H47N4O7:m/z calcd. 551.3445, found 551.3434.
sorbed onto silica gel (25 g) under reduced pressure. The immobil-
ized crude material was purified by silica gel column chromato-
graphy (acetone/dichloromethane, 2:3 Ǟ 4:1, v/v) to afford 8a as a
white foam (4.5 g, 91%): Rf ϭ 0.15 (acetone/dichloromethane, 3:2,
v/v). Ϫ 1H NMR (CD3OD, 300 MHz): δ ϭ 7.87 (s, 2 H, 2 CH Ar),
7.83 (s, 1 H, CH Ar), 7.55 (s, 4 H, 4 CH Ar), 7.50 (s, 2 H, 2
CH Ar), 6.12Ϫ5.98 (m, 1 H, OCH2CHCH2), 5.46Ϫ5.22 (m, 2 H,
OCH2CHCH2), 4.65Ϫ4.56 (m, 6 H, OCH2CHCH2; 2 OCH2CO),
3.44Ϫ3.30, 3.18Ϫ3.06 (2 m, 24 H, 12 NHCH2), 1.81Ϫ1.55 [m, 16
H, 8 CH2(CH2)nCH2], 1.42 (s, 36 H, 12 CH3). Ϫ 13C NMR
(CD3OD, 75 MHz): δ ϭ 170.3, 169.0, 168.8, 160.2, 159.2, 137.7,
137.5 (12 NHCO, 9 Cq Ar), 134.3 (OCH2CHCH2), 120.2, 119.4 (3
CH Ar), 118.1 (OCH2CHCH2), 117.7, 117.6 (6 CH Ar), 80.1 [4
C(CH3)3], 70.3 (OCH2CHCH2), 68.6 (2 OCH2CO), 40.9, 40.0, 39.0,
38.6 (12 NHCH2), 30.9, 28.1, 27.9 [8 CH2(CH2)nCH2], 29.0 (12
CH3). Ϫ FAB MS; m/z ϭ 1354 [M ϩ Na]ϩ.
Synthesis of 7a: Trifluoroacetic acid (4 mL) was added dropwise to
a suspension of 5a (267 mg, 0.5 mmol) in dichloromethane (2 mL).
The solution was stirred for 30 min, coevaporated under reduced
pressure with 1,2 dichloroethane/toluene (3 ϫ 10 mL, 1:1, v/v), and
stored under vacuum (1.5 mbar) for 3 h. The crude residue was
dissolved in N,N-dimethylformamide (4 mL) and triethylamine was
added dropwise (ca. 20 drops) until basic conditions were reached
(pH ഠ 8). A solution of pentafluorophenyl chloroacetate (287 mg,
1.1 mmol) in N,N-dimethylformamide (0.5 mL) was rapidly added,
followed by a further 15 drops of triethylamine. The reaction mix-
ture was stirred for 5 min, concentrated to dryness, coevaporated
with toluene (5 ϫ 10 mL), dissolved in methanol (20 mL), and pre-
absorbed onto silica gel under reduced pressure. The immobilized
solid was purified by silica gel chromatography (acetone/dichloro-
methane, 0 Ǟ 2:3, v/v) to yield 7a as a white powder (203 mg,
Compound 8b: This compound was synthesized under the same
conditions as described for the preparation of 8a, employing 6b in
place of 6a to yield a white foam (930 mg, 89%): Rf ϭ 0.15 (acet-
1
84%): Rf ϭ 0.32 (acetone/dichloromethane, 1:1, v/v). Ϫ H NMR
(CDCl3, 300 MHz): δ ϭ 7.78 (s, 1 H, CH Ar), 7.46 (s, 2 H, 2 CH
Ar), 6.02Ϫ5.87 (m, 1 H, OCH2CHCH2), 5.39Ϫ5.18 (m, 2 H,
OCH2CHCH2), 4.55Ϫ4.50 (m, 2 H, OCH2CHCH2), 3.98 (s, 4 H,
2 CH2Cl), 3.42Ϫ3.28 (m, 8 H, 4 NHCH2), 1.77Ϫ1.65 (m, 4 H, 2
CH2CH2CH2). Ϫ 13C NMR (CDCl3, 75 MHz): δ ϭ 167.2, 167.1,
159.2, 136.1 (4 NHCO, 3 Cq Ar), 132.7 (OCH2CHCH2), 118.3 (CH
Ar), 117.5 (OCH2CHCH2), 116.9 (2 CH Ar), 69.4 (OCH2CHCH2),
42.9 (2 CH2Cl), 36.9, 36.8 (4 NHCH2), 29.6 (2 CH2CH2CH2). Ϫ
FAB MS; m/z ϭ 487 [M ϩ H]ϩ. Ϫ C21H2935Cl2N4O5: m/z calcd.
487.1515, found 487.1528.
1
one/dichloromethane, 3:2, v/v). Ϫ H NMR (CD3OD, 300 MHz):
δ ϭ 7.85 (s, 2 H, 2 CH Ar), 7.83 (s, 1 H, CH Ar), 7.53 (s, 4 H, 4
CH Ar), 7.50 (s,
2 H, 2 CH Ar), 6.13Ϫ5.98 (m, 1 H,
OCH2CHCH2), 5.46Ϫ5.22 (m, 2 H, OCH2CHCH2), 4.65Ϫ4.56 (m,
6 H, OCH2CHCH2, 2 OCH2CO), 3.44Ϫ3.30, 3.12Ϫ3.00 (2 m, 24
H, 12 NHCH2), 1.68Ϫ1.50 [m, 24 H, 6 CH2(CH2)2CH2], 1.41 (s,
36 H, 12 CH3). Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ 169.1, 167.8,
167.5, 159.0, 158.0, 157.2, 136.6, 136.3 (12 NHCO, 9 Cq Ar), 133.1
(OCH2CHCH2), 119.0, 118.2 (3 CH Ar), 116.9 (OCH2CHCH2),
116.5, 116.3 (6 CH Ar), 78.7 [4 C(CH3)3], 69.1 (OCH2CHCH2),
67.4 (2 OCH2CO), 40.0, 39.8, 39.7, 38.7 (12 NHCH2), 27.8, 27.5,
26.9, 26.7 [6 CH2(CH2)2CH2], 29.0 (12 CH3). Ϫ FAB MS; m/z ϭ
1488 [M ϩ H]ϩ.
Compound 7b: This compound was synthesized under the same
conditions as described for the preparation of 7a, employing 5b in
place of 5a to yield a white powder (1.2 g, 85%): Rf ϭ 0.32 (acet-
1
one/dichloromethane, 1:1, v/v). Ϫ H NMR (CD3OD, 300 MHz):
δ ϭ 7.83 (s, 1 H, CH Ar), 7.51 (s, 2 H, 2 CH Ar), 6.14Ϫ5.99 (m,
Compound 8c: This compound was synthesized under the same
conditions as described for the preparation of 8a, employing 6c in
place of 6a to yield a white foam (220 mg, 89%): Rf ϭ 0.15 (acet-
one/dichloromethane, 3:2, v/v). Ϫ H NMR (CD3OD, 300 MHz):
δ ϭ 7.86 (s, 2 H, 2 CH Ar), 7.84 (s, 1 H, CH Ar), 7.53 (s, 4 H, 4
1
H, OCH2CHCH2), 5.47Ϫ5.24 (m, 2 H, OCH2CHCH2),
4.65Ϫ4.60 (m, 2 H, OCH2CHCH2), 4.02 (s, 4 H, 2 CH2Cl),
3.42Ϫ3.34, 3.33Ϫ3.20 (2 m, 8 H, 4 NHCH2), 1.72Ϫ1.52 [m, 8 H,
2 CH2(CH2)2CH2]. Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ 168.0,
167.9, 159.0, 136.4 (4 NHCO, 3 Cq Ar), 133.1 (OCH2CHCH2),
118.2 (CH Ar), 116.8 (OCH2CHCH2), 116.3 (2 CH Ar), 69.1
(OCH2CHCH2), 42.2 (2 CH2Cl), 39.6, 39.4 (4 NHCH2), 26.7 [2
1
CH Ar), 7.50 (s,
2 H, 2 CH Ar), 6.12Ϫ5.99 (m, 1 H,
OCH2CHCH2), 5.46Ϫ5.22 (m, 2 H, OCH2CHCH2), 4.64Ϫ4.57 (m,
6 H, OCH2CHCH2, 2 OCH2CO), 3.40Ϫ3.28, 3.08Ϫ2.98 (2 m, 24
H, 12 NHCH2), 1.68Ϫ1.40 [m, 32 H, 16 CH2(CH2)nCH2], 1.40 (s,
36 H, 12 CH3). Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ 169.1, 167.8,
167.5, 159.0, 158.0, 157.2, 136.6, 136.3 (12 NHCO, 9 Cq Ar), 133.1
(OCH2CHCH2), 119.0, 118.3 (3 CH Ar), 116.9 (OCH2CHCH2),
116.5, 116.4 (6 CH Ar), 78.7 [4 C(CH3)3], 69.1 (OCH2CHCH2),
67.4 (2 OCH2CO), 40.2, 40.0, 39.7, 38.7 (12 NHCH2), 29.7, 29.1,
26.9, 26.7, 24.2 [12 CH2(CH2)nCH2], 27.8 (12 CH3). Ϫ FAB MS;
m/z ϭ 1567 [M ϩ Na]ϩ.
CH2(CH2)2CH2].
Ϫ FAB MS; m/z ϭ 515 [M ϩ Ϫ
H]ϩ.
C23H3335Cl2N4O5: m/z calcd. 515.1828, found 515.1813.
Compound 7c: This compound was synthesized under the same
conditions as described for the preparation of 7a, employing 5c in
place of 5a to yield a white powder (240 mg, 88%): Rf ϭ 0.32 (acet-
1
one/dichloromethane, 1:1, v/v). Ϫ H NMR (CD3OD, 300 MHz):
δ ϭ 7.82 (s, 1 H, CH Ar), 7.51 (s, 2 H, 2 CH Ar), 6.15Ϫ6.00 (m,
1
H, OCH2CHCH2), 5.47Ϫ5.24 (m, 2 H, OCH2CHCH2),
4.67Ϫ4.62 (m, 2 H, OCH2CHCH2), 4.00 (2 CH2Cl), 3.42Ϫ3.33, Synthesis of 9a: A solution of 8a (7.5 g, 5.2 mmol) and tetrakis(tri-
3.29Ϫ3.20 (2 m, 8 H, 4 NHCH2), 1.71Ϫ1.52, 1.50Ϫ1.38 [2 m, 12 phenylphosphane)palladium(0) (303 mg, 0.26 mmol) in deoxygen-
H, 2 CH2(CH2)3CH2]. Ϫ 13C NMR (CD3OD/CDCl3, 3:1, v/v,
ated ethanol (75 mL) was refluxed for 1 h. The resultant black
75 MHz): δ ϭ 167.9, 167.8, 159.0, 136.3 (4 NHCO, 3 Cq Ar), 132.9 slurry was filtered through Celite and washed with hot methanol
(OCH2CHCH2), 118.1 (CH Ar), 117.2 (OCH2CHCH2), 116.5 (2 (200 mL). The filtrate was repeatedly boiled (3 times) and filtered
CH Ar), 69.2 (OCH2CHCH2), 42.3 (2 CH2Cl), 40.0, 39.7 (4 to reduce and remove black palladium metal, concentrated under
NHCH2), 29.0, 28.9, 24.3 [2 CH2(CH2)3CH2]. Ϫ FAB MS; m/z ϭ reduced pressure, and the residue purified by silica gel column
543 [M ϩ H]ϩ. Ϫ C25H3735Cl2N4O5: m/z calcd. 543.2141, found chromatography (methanol/dichloromethane, 1:24 Ǟ 1:9, v/v) to
543.2125.
afford 9a as a white foam (7.0 g, 96%): Rf ϭ 0.10 (methanol/dichlo-
2540
Eur. J. Org. Chem. 2001, 2535Ϫ2545

Parallel Combinatorial Synthesis of Glycodendrimers and Their Hydrogelation Properties
FULL PAPER
1
romethane, 2:23, v/v). Ϫ H NMR (CD3OD, 300 MHz): δ ϭ 7.87
CDCl3, 3:1, v/v, 300 MHz): δ ϭ 7.89Ϫ7.81 (m, 7 H, 7 CH Ar),
H,
(s, 2 H, 2 CH Ar), 7.67 (s, 1 H, CH Ar), 7.55 (s, 4 H, 4 CH Ar), 7.55Ϫ7.46 (m, 14 H, 14 CH Ar), 6.10Ϫ5.96 (m,
1
7.35 (s, 2 H, 2 CH Ar), 4.60 (s, 4 H, 2 OCH2CO), 3.44Ϫ3.30, OCH2CHCH2), 5.44Ϫ5.22 (m, 2 H, OCH2CHCH2), 4.62Ϫ4.52 (m,
3.18Ϫ3.09 (2 m, 24 H, 12 NHCH2), 1.81Ϫ1.70, 1.69Ϫ1.58 [2 m, 16 14 H, OCH2CHCH2, 6 OCH2CO), 3.45Ϫ3.10 (m, 56 H, 28
H, 8 CH2(CH2)nCH2], 1.42 (s, 36 H, 12 CH3). Ϫ 13C NMR NHCH2), 1.82Ϫ1.53 [m, 40 H, 20 CH2(CH2)nCH2], 1.40 (s, 72 H,
(CD3OD, 75 MHz): δ ϭ 169.1, 168.2, 167.6, 158.1, 157.8, 136.5,
24 CH3). Ϫ 13C NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ
136.4 (12 NHCO, 9 Cq Ar), 119.0, 117.0, 116.5 (9 CH Ar), 78.9 [4 168.9, 167.8, 167.5, 167.4, 157.9, 157.3, 136.4, 136.2 (28 NHCO, 21
C(CH3)3], 67.4 (2 OCH2CO), 39.6, 38.8, 37.8, 37.4 (12 NHCH2), Cq Ar), 132.9 (OCH2CHCH2), 119.1 (7 CH Ar), 117.4
29.7, 26.8, 26.7 [8 CH2(CH2)nCH2], 27.8 (12 CH3). Ϫ FAB MS; (OCH2CHCH2), 116.7 (14 CH Ar), 79.2 [8 C(CH3)3], 69.2
m/z ϭ 1415 [M ϩ Na]ϩ.
(OCH2CHCH2), 67.4 (6 OCH2CO), 39.8, 38.9, 37.8, 37.5 (28
NHCH2), 30.3, 29.7, 26.9, 26.7, 23.4 [20 CH2(CH2)nCH2], 28.2 (24
CH3). Ϫ MALDI TOF MS; m/z ϭ 3247 [M ϩ Na]ϩ.
Compound 9b: This compound was synthesized under the same
conditions as described for the preparation of 9a, employing 8b
in place of 8a: white foam (500 mg, 98%): Rf ϭ 0.10 (methanol/
dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD, 300 MHz): δ ϭ
7.82 (s, 2 H, 2 CH Ar), 7.64 (s, 1 H, CH Ar), 7.51 (s, 4 H, 4 CH
Ar), 7.32 (s, 2 H, 2 CH Ar), 4.58 (s, 4 H, 2 OCH2CO), 3.40Ϫ3.30,
3.08Ϫ2.98 (2 m, 24 H, 12 NHCH2), 1.68Ϫ1.40 [m, 24 H, 6
CH2(CH2)2CH2], 1.38 (s, 36 H, 12 CH3). Ϫ 13C NMR (CD3OD,
75 MHz): δ ϭ 171.1, 170.1, 169.5, 159.9, 159.2, 138.4, 138.3 (12
NHCO, 9 Cq Ar), 120.8, 118.8, 118.4, 118.3 (9 CH Ar), 80.5 [4
C(CH3)3], 69.1 (2 OCH2CO), 41.7, 41.5, 41.3, 40.4 (12 NHCH2),
30.2 (12 CH3), 29.5, 29.1, 28.4, 28.3 [6 CH2(CH2)2CH2]. Ϫ FAB
MS; m/z ϭ 1470 [M ϩ Na]ϩ.
Compound 10c: This compound was synthesized under the same
conditions as described for the preparation of 10a, employing 7c
in place of 7a to yield a white foam (437 mg, 94%): Rf ϭ 0.08
(methanol/dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD/
CDCl3, 3:1, v/v, 300 MHz): δ ϭ 7.90Ϫ7.79 (m, 7 H, 7 CH Ar),
7.56Ϫ7.43 (m, 14 H, 14 CH Ar), 6.08Ϫ5.94 (m,
1 H,
OCH2CHCH2), 5.43Ϫ5.21 (m, 2 H, OCH2CHCH2), 4.62Ϫ4.50 (m,
14 H, OCH2CHCH2, 6 OCH2CO), 3.45Ϫ3.04 (m, 56 H, 28
NHCH2), 1.84Ϫ1.51 [m, 44 H, 22 CH2(CH2)nCH2], 1.40 (s, 72 H,
24 CH3). Ϫ 13C NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ
169.8, 168.6, 168.4, 158.8, 158.1, 137.3, 137.1 (28 NHCO, 21 Cq
Ar), 133.7 (OCH2CHCH2), 119.9 (7 CH Ar), 118.1
(OCH2CHCH2), 117.5 (14 CH Ar), 80.0 [8 C(CH3)3], 70.0
(OCH2CHCH2), 68.3 (6 OCH2CO), 40.9, 40.6, 39.9, 39.7, 38.6,
38.3 (28 NHCH2), 30.6, 30.0, 29.8, 27.8, 27.5, 25.1 [22
CH2(CH2)nCH2], 29.0 (24 CH3). Ϫ MALDI TOF MS; m/z ϭ 3276
[M ϩ Na]ϩ.
Compound 9c: This compound was synthesized under the same
conditions as described for the preparation of 9a, employing 8c in
place of 8a to yield a white foam (1.4 g, 97%): Rf ϭ 0.10 (methanol/
dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD, 300 MHz): δ ϭ
7.86 (s, 2 H, 2 CH Ar), 7.69 (s, 1 H, CH Ar), 7.54 (s, 4 H, 4 CH
Ar), 7.36 (s, 2 H, 2 CH Ar), 4.60 (s, 4 H, 2 OCH2CO), 3.40Ϫ3.29,
3.08Ϫ2.98 (2 m, 24 H, 12 NHCH2), 1.68Ϫ1.40 [m, 32 H, 16
CH2(CH2)nCH2], 1.40 (s, 36 H, 12 CH3). Ϫ 13C NMR (CD3OD,
75 MHz): δ ϭ 169.2, 168.2, 167.6, 158.0, 157.8, 157.3, 136.5, 136.3
(12 NHCO, 9 Cq Ar), 119.0, 117.1, 116.7, 116.5 (9 CH Ar), 78.9 [4
C(CH3)3], 67.3 (2 OCH2CO), 40.2, 40.1, 39.7, 38.8 (12 NHCH2),
29.6, 29.0, 26.8, 26.7, 24.2 [16 CH2(CH2)nCH2], 27.8 (12 CH3). Ϫ
FAB MS; m/z ϭ 1504 [M ϩ H]ϩ.
Compound 10d: This compound was synthesized under the same
conditions as described for the preparation of 10a, employing 9c
in place of 9a to yield a white foam (109 mg, 88%): Rf ϭ 0.08
(methanol/dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD/
CDCl3, 3:1, v/v, 300 MHz): δ ϭ 7.90Ϫ7.81 (m, 7 H, 7 CH Ar),
7.58Ϫ7.46 (m, 14 H, 14 CH Ar), 6.10Ϫ5.94 (m,
1 H,
OCH2CHCH2), 5.44Ϫ5.22 (m, 2 H, OCH2CHCH2), 4.62Ϫ4.53 (m,
14 H, OCH2CHCH2, 6 OCH2CO), 3.45Ϫ2.96 (m, 56 H, 28
NHCH2), 1.67Ϫ1.35 [m, 68 H, 34 CH2(CH2)nCH2], 1.39 (s, 72 H,
24 CH3). Ϫ 13C NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ
169.0, 167.4, 157.9, 157.2, 136.5, 136.1 (28 NHCO, 21 Cq Ar), 132.8
(OCH2CHCH2), 119.0 (7 CH Ar), 117.3 (OCH2CHCH2), 116.5 (14
CH Ar), 78.9 [8 C(CH3)3], 69.2 (OCH2CHCH2), 67.4 (6 OCH2CO),
40.3, 40.1, 39.8, 38.9 (28 NHCH2), 29.7, 29.1, 26.9, 26.7, 24.3 [34
CH2(CH2)nCH2], 28.1 (24 CH3). Ϫ MALDI TOF MS; m/z ϭ 3443
[M ϩ Na]ϩ.
Synthesis of 10a: A solution of 9a (612 mg, 0.44 mmol), 7a (100 mg,
0.21 mmol), and potassium carbonate (3.4 g, 25 mmol) in acetone
(50 mL) was stirred under reflux for 18 h. The white slurry was
filtered rapidly through a column of silica gel (methanol/dichloro-
methane, 1:1, v/v) and the eluted solution concentrated and preab-
sorbed onto silica gel (25 g) under reduced pressure. The immobil-
ized crude material was purified by silica gel column chromato-
graphy (methanol/ dichloromethane, 7:93 Ǟ 7:43, v/v) to afford
10a as a white foam (603 mg, 92%): Rf ϭ 0.08 (methanol/dichloro-
methane, 2:23, v/v). Ϫ 1H NMR (CD3OD/CDCl3, 3:1, v/v,
300 MHz): δ ϭ 7.92Ϫ7.82 (m, 7 H, 7 CH Ar), 7.58Ϫ7.46 (m, 14
H, 14 CH Ar), 6.10Ϫ5.94 (m, 1 H, OCH2CHCH2), 5.44Ϫ5.22 (m,
2 H, OCH2CHCH2), 4.64Ϫ4.54 (m, 14 H, OCH2CHCH2, 6
OCH2CO), 3.43Ϫ3.04 (m, 56 H, 28 NHCH2), 1.84Ϫ1.51 [m, 36 H,
18 CH2(CH2)nCH2], 1.40 (s, 72 H, 24 CH3). Ϫ 13C NMR (CD3OD/
CDCl3, 3:1, v/v, 75 MHz): δ ϭ 169.2, 168.9, 167.9, 167.5, 157.9,
157.3, 136.4, 136.1 (28 NHCO, 21 Cq Ar), 132.9 (OCH2CHCH2),
119.1 (7 CH Ar), 117.3 (OCH2CHCH2), 116.7 (14 CH Ar), 79.2 [8
C(CH3)3], 69.2 (OCH2CHCH2), 67.5 (6 OCH2CO), 39.8, 38.9, 37.8,
37.5 (28 NHCH2), 29.7, 29.2, 26.9, 26.7 [18 CH2(CH2)nCH2], 28.1
(24 CH3). Ϫ MALDI TOF MS; m/z ϭ 3220 [M ϩ Na]ϩ.
Compound 10e: This compound was synthesized under the same
conditions as described for the preparation of 10a, employing 7b
in place of 7a, and 9c in place of 9a to yield a white foam (105 mg,
89%): Rf ϭ 0.08 (methanol/dichloromethane, 2:23, v/v). Ϫ 1H
NMR (CD3OD/CDCl3, 3:1, v/v, 300 MHz): δ ϭ 7.80Ϫ7.72 (m, 7
H, 7 CH Ar), 7.47Ϫ7.40 (m, 14 H, 14 CH Ar), 6.02Ϫ5.85 (m, 1 H,
OCH2CHCH2), 5.36Ϫ5.14 (m, 2 H, OCH2CHCH2), 4.54Ϫ4.43 (m,
14 H, OCH2CHCH2, 6 OCH2CO), 3.35Ϫ2.91 (m, 56 H, 28
NHCH2), 1.61Ϫ1.35 [m, 72 H, 36 CH2(CH2)nCH2], 1.32 (s, 72 H,
24 CH3). Ϫ 13C NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ
169.0, 167.4, 157.9, 157.2, 136.5, 136.4 (28 NHCO, 21 Cq Ar), 132.9
(OCH2CHCH2), 119.1 (7 CH Ar), 117.3 (OCH2CHCH2), 116.6 (14
CH Ar), 79.0 [8 C(CH3)3], 69.2 (OCH2CHCH2), 67.4 (6 OCH2CO),
40.3, 40.2, 38.9 (28 NHCH2), 29.7, 29.1, 27.0, 26.7, 24.3 [36
CH2(CH2)nCH2], 28.1 (24 CH3). Ϫ MALDI TOF MS; m/z ϭ 3472
Compound 10b: This compound was synthesized under the same
conditions as described for the preparation of 10a, employing 7b
in place of 7a to yield a white foam (281 mg, 87%): Rf ϭ 0.08
(methanol/dichloromethane, 2:23, v/v). Ϫ 1H NMR (CD3OD/ [M ϩ Na]ϩ.
Eur. J. Org. Chem. 2001, 2535Ϫ2545
2541

M. McWatt, G.-J. Boons
FULL PAPER
Compound 10f: This compound was synthesized under the same
20.3, 20.2, 20.1 (56 CH3CO). Ϫ MALDI TOF MS; m/z ϭ 7967 [M
conditions as described for the preparation of 10a, employing 7c ϩ Na]ϩ.
in place of 7a, and 9c in place of 9a to yield a white foam (100 mg,
Compound 13b: This compound was synthesized under the same
91%): Rf ϭ 0.08 (methanol/dichloromethane, 2:23, v/v). Ϫ 1H
NMR (CD3OD/CDCl3, 3:1, v/v, 300 MHz): δ ϭ 7.82Ϫ7.70 (m, 7
H, 7 CH Ar), 7.47Ϫ7.38 (m, 14 H, 14 CH Ar), 6.00Ϫ5.76 (m, 1 H,
OCH2CHCH2), 5.36Ϫ5.14 (m, 2 H, OCH2CHCH2), 4.54Ϫ4.42 (m,
14 H, OCH2CHCH2, 6 OCH2CO), 3.35Ϫ2.91 (m, 56 H, 28
NHCH2), 1.61Ϫ1.35 [m, 76 H, 38 CH2(CH2)nCH2], 1.32 (s, 72 H,
24 CH3). Ϫ 13C NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ
169.0, 168.9, 167.4, 157.9, 157.2, 136.5, 136.3 (28 NHCO, 21 Cq
Ar), 132.9 (OCH2CHCH2), 119.1, 118.1 (7 CH Ar), 117.3
(OCH2CHCH2), 116.6 (14 CH Ar), 79.0 [8 C(CH3)3], 69.2
(OCH2CHCH2), 67.4 (6 OCH2CO), 40.3, 40.2, 39.8, 39.1, 38.9 (28
NHCH2), 29.7, 29.2, 29.0, 27.0, 26.7, 24.3 [38 CH2(CH2)nCH2],
28.2 (24 CH3). Ϫ MALDI TOF MS; m/z ϭ 3501 [M ϩ Na]ϩ.
conditions as described for the preparation of 13a, employing 10b
in place of 10a to yield a white foam (37 mg, 76%): Rf ϭ 0.50
(methanol/dichloromethane, 3:22, v/v); [α]2D5 ϭ ϩ33.1 (c ϭ 1, meth-
anol/dichloromethane, 3:1, v/v). Ϫ 1H NMR (CD3OD/CDCl3, 3:1,
v/v, 600 MHz): δ ϭ 7.89, 7.84, 7.79 (3 s, 7 H, 7 CH Ar), 7.56, 7.51,
7.47 (3 s, 14 H, 14 CH Ar), 6.05Ϫ5.96 (m, 1 H, OCH2CHCH2),
5.40 (d, 8 H, 8 H-4Ј, J3Ј,4Ј ϭ 3.0 Hz), 5.40Ϫ5.22 (m, 2 H,
OCH2CHCH2), 5.29 (dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 10.7 Hz), 5.24 (t, 8
H, 8 H-3, J2,3J3,4 ϭ 9.5 Hz), 5.20 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz),
5.14 (t, 8 H, 8 H-4, J4,5 ϭ 9.5 Hz), 5.02 (dd, 8 H, 8 H-2Ј), 4.90 (t,
8 H, 8 H-2, J1,2 ϭ 10.3 Hz), 4.80 (d, 8 H, 8 H-1), 4.60Ϫ4.55 (m,
14 H, 6 OCH2CO, OCH2CHCH2), 4.23Ϫ4.18 (m, 8 H, 8 H-5Ј),
4.10Ϫ4.02 (m, 16 H, 8 H-6aЈ, 8 H-6bЈ), 3.82Ϫ3.78 (m, 8 H, 8 H-
5), 3.72 (dd, 8 H, 8 H-6a, J5,6a ϭ 3.9, J6a,6b ϭ 12.2 Hz), 3.67 (dd,
8 H, 8 H-6b, J5,6b ϭ 2.0 Hz), 3.45Ϫ3.22 (m, 72 H, 8 SCH2, 28
NHCH2), 2.13, 2.10, 2.00, 1.99, 1.95, 1.94 (6 s, 168 H, 56 CH3CO),
1.82Ϫ1.76, 1.62Ϫ1.57 [2 m, 40 H, 20 CH2(CH2)nCH2]. Ϫ 13C
NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ 171.0, 170.9, 170.7,
170.5, 170.4, 169.9, 168.9, 167.7, 167.4, 167.3, 158.9, 158.0, 157.9,
136.5, 136.4, 136.3 (56 CH3CO, 28 NHCO, 21 Cq Ar), 132.9
(OCH2CHCH2), 119.1, 118.2 (7 CH Ar), 117.4 (OCH2CHCH2),
116.7 (14 CH Ar), 96.4 (8 C-1Ј), 82.9 (8 C-1), 76.9 (8 C-5), 74.2 (8
C-3), 70.4 (8 C-2), 69.2 (OCH2CHCH2), 68.7 (8 C-4), 68.5 (8 C-
2Ј), 68.3 (8 C-4Ј), 67.9 (8 C-3Ј), 67.5 (6 OCH2CO), 66.6 (8 C-5Ј),
65.6 (8 C-6), 61.8 (8 C-6Ј), 39.9, 38.9, 37.4, 37.2 (28 NHCH2), 33.3
(8 SCH2), 29.2, 27.0, 26.7 [20 CH2(CH2)nCH2], 20.5, 20.3, 20.2,
20.1 (56 CH3CO). Ϫ MALDI TOF MS; m/z ϭ 7992 [M ϩ Na]ϩ.
Synthesis of 13a: Trifluoroacetic acid (6 mL) was added dropwise
to a suspension of 10a (202 mg, 63 µmol) in dichloromethane
(3 mL). The solution was stirred for 30 min, coevaporated under
reduced pressure with 1,2-dichloroethane/toluene (3 ϫ 10 mL, 1:1,
v/v), and stored under vacuum (1.5 mbar) for 3 h. The crude res-
idue was dissolved in N,N-dimethylformamide (4 mL) and triethyl-
amine was added dropwise (ca. 20 drops) until the solution was
basic (pH ഠ 8). A solution of pentafluorophenyl chloroacetate
(197 mg, 760 µmol) in N,N-dimethylformamide (0.5 mL) was
rapidly added, followed by a further 15 drops of triethylamine. The
reaction mixture was stirred for 5 min and concentrated under re-
duced pressure to a smaller volume (ca. 0.3 mL). The lower mo-
lecular weight chlorides were removed by size exclusion chromato-
graphy (LH-20, N,N-dimethylformamide). A fraction of the yellow
residue 12a (6 µmol) and peracetylated melibiose thioacetal (45 mg,
64 µmol) was dissolved in N,N-dimethylformamide (2 mL) and
stirred at Ϫ60 °C. To this mixture was added dropwise a cooled
(Ϫ60 °C), saturated solution of ammonia in N,N-dimethylformam-
ide (3 mL). The mixture was allowed to come to room temperature
over a period of 2 h, concentrated under reduced pressure, and
purified by size exclusion chromatography (LH-60, methanol/
dichloromethane, 1:1, v/v) to afford 13a as a white foam (43 mg,
Compound 13c: This compound was synthesized under the same
conditions as described for the preparation of 13a, employing 10c
in place of 10a to yield a white foam (43 mg, 85%): Rf ϭ 0.50
(methanol/dichloromethane, 3:22, v/v); [α]2D5 ϭ ϩ29.4 (c ϭ 1, meth-
anol/dichloromethane, 3:1, v/v). Ϫ 1H NMR (CD3OD/CDCl3, 3:1,
v/v, 600 MHz): δ ϭ 7.90, 7.84, 7.77 (3 s, 7 H, 7 CH Ar), 7.56, 7.51,
7.44 (3 s, 14 H, 14 CH Ar), 6.03Ϫ5.95 (m, 1 H, OCH2CHCH2),
5.40 (d, 8 H, 8 H-4Ј, J3Ј,4Ј ϭ 3.4 Hz), 5.40Ϫ5.23 (m, 2 H,
OCH2CHCH2), 5.29 (dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 10.7 Hz), 5.24 (t, 8
H, 8 H-3, J2,3J3,4 ϭ 9.5 Hz), 5.20 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz),
5.14 (t, 8 H, 8 H-4, J4,5 ϭ 9.5 Hz), 5.02 (dd, 8 H, 8 H-2Ј), 4.90 (t,
8 H, 8 H-2, J1,2 ϭ 9.8 Hz), 4.80 (d, 8 H, 8 H-1), 4.60Ϫ4.52 (m,
14 H, 6 OCH2CO, OCH2CHCH2), 4.23Ϫ4.18 (m, 8 H, 8 H-5Ј),
4.10Ϫ4.02 (m, 16 H, 8 H-6aЈ, 8 H-6bЈ), 3.82Ϫ3.78 (m, 8 H, 8 H-
5), 3.72 (dd, 8 H, 8 H-6a, J5,6a ϭ 3.9, J6a,6b ϭ 12.2 Hz), 3.67 (dd,
8 H, 8 H-6b, J5,6b ϭ 2.0 Hz), 3.45Ϫ3.22 (m, 72 H, 8 SCH2, 28
NHCH2), 2.12, 2.10, 2.00, 1.99, 1.95, 1.94 (6 s, 168 H, 56 CH3CO),
1.82Ϫ1.76, 1.64Ϫ1.52, 1.39Ϫ1.31 [3 m, 44 H, 22 CH2(CH2)nCH2].
86%): Rf ϭ 0.50 (methanol/dichloromethane, 3:22, v/v); [α]D25
ϭ
ϩ36.4 (c ϭ 1, methanol/dichloromethane, 3:1, v/v). Ϫ 1H NMR
(CD3OD/CDCl3, 3:1, v/v, 600 MHz): δ ϭ 7.89, 7.85, 7.81 (3 s, 7 H,
7 CH Ar), 7.56, 7.54, 7.47 (3 s, 14 H, 14 CH Ar), 6.05Ϫ5.96 (m, 1
H, OCH2CHCH2), 5.40 (d, 8 H, 8 H-4Ј, J3Ј,4Ј ϭ 2.9 Hz), 5.40Ϫ5.22
(m, 2 H, OCH2CHCH2), 5.29 (dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 11.0 Hz),
5.24 (t, 8 H, 8 H-3, J2,3/J3,4 ϭ 9.5 Hz), 5.20 (d, 8 H, 8 H-1Ј, J1Ј,2Ј
ϭ
3.4 Hz), 5.14 (t, 8 H, 8 H-4, J4,5 ϭ 9.5 Hz), 5.02 (dd, 8 H, 8 H-2Ј),
4.90 (t, 8 H, 8 H-2, J1,2 ϭ 10.3 Hz), 4.80 (d, 8 H, 8 H-1), 4.60Ϫ4.55
(m, 14 H, 6 OCH2CO, OCH2CHCH2), 4.23Ϫ4.18 (m, 8 H, 8 H-
5Ј), 4.10Ϫ4.02 (m, 16 H, 8 H-6aЈ, 8 H-6bЈ), 3.82Ϫ3.77 (m, 8 H, 8
H-5), 3.72 (dd, 8 H, 8 H-6a, J5,6a ϭ 3.9, J6a,6b ϭ 11.7 Hz),
3.69Ϫ3.65 (m, 8 H, 8 H-6b), 3.45Ϫ3.20 (m, 72 H, 8 SCH2, 28
NHCH2), 2.12, 2.09, 2.00, 1.99, 1.95, 1.94 (6 s, 168 H, 56 CH3CO),
1.83Ϫ1.76, 1.62Ϫ1.58, [2 m, 36 H, 18 CH2(CH2)nCH2]. Ϫ 13C
NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ 171.0, 170.9, 170.7,
170.5, 170.4, 169.9, 169.8, 169.1, 168.9, 167.9, 167.4, 167.3, 159.0,
158.0, 157.9, 136.5, 136.4, 136.2 (56 CH3CO, 28 NHCO, 21 Cq Ar),
132.9 (OCH2CHCH2), 119.2, 119.1 (7 CH Ar), 117.5
(OCH2CHCH2), 116.7 (14 CH Ar), 96.4 (8 C-1Ј), 82.9 (8 C-1), 76.9
(8 C-5), 74.2 (8 C-3), 70.4 (8 C-2), 69.2 (OCH2CHCH2), 68.7 (8 C-
Ϫ
13C NMR (CD3OD/CDCl3, 3:1, v/v, 75 MHz): δ ϭ 171.0, 170.9,
170.7, 170.5, 170.4, 169.9, 169.8, 168.9, 167.7, 167.4, 167.3, 158.9,
158.0, 157.9, 136.5, 136.4, 136.3 (56 CH3CO, 28 NHCO, 21 Cq Ar),
132.9 (OCH2CHCH2), 119.1, 118.2 (7 CH Ar), 117.4
(OCH2CHCH2), 116.7, 116.5 (14 CH Ar), 96.4 (8 C-1Ј), 82.9 (8 C-
1), 76.9 (8 C-5), 74.2 (8 C-3), 70.4 (8 C-2), 69.2 (OCH2CHCH2),
68.7 (8 C-4), 68.5 (8 C-2Ј), 68.3 (8 C-4Ј), 67.9 (8 C-3Ј), 67.5 (6
OCH2CO), 66.6 (8 C-5Ј), 65.6 (8 C-6), 61.8 (8 C-6Ј), 40.1, 39.9,
39.1, 38.9, 37.4, 37.2 (28 NHCH2), 33.3 (8 SCH2), 29.2, 29.1, 27.0,
26.8, 24.3 [22 CH2(CH2)nCH2], 20.5, 20.3, 20.2, 20.1 (56 CH3CO).
Ϫ MALDI TOF MS; m/z ϭ 8019 [M ϩ Na]ϩ.
4), 68.5 (8 C-2Ј), 68.3 (8 C-4Ј), 67.9 (8 C-3Ј), 67.5 (6 OCH2CO), Compound 13d: This compound was synthesized under the same
66.6 (8 C-5Ј), 65.7 (8 C-6), 61.8 (8 C-6Ј), 39.9, 38.9, 37.4, 37.2 (28 conditions as described for the preparation of 13a, employing 10d
NHCH2), 33.3 (8 SCH2), 29.2, 27.0, 26.8 [18 CH2(CH2)nCH2], 20.5, in place of 10a to yield a white foam (44 mg, 85%): Rf ϭ 0.50
2542
Eur. J. Org. Chem. 2001, 2535Ϫ2545

Parallel Combinatorial Synthesis of Glycodendrimers and Their Hydrogelation Properties
FULL PAPER
(methanol/dichloromethane, 3:22, v/v); [α]2D5 ϭ ϩ27.1 (c ϭ 1, meth-
anol/dichloromethane, 3:1, v/v). Ϫ H NMR (CD3OD, 600 MHz):
8 H, 8 H-1), 4.62Ϫ4.56 (m, 14 H, 6 OCH2CO, OCH2CHCH2),
4.26Ϫ4.22 (m, 8 H, 8 H-5Ј), 4.12Ϫ4.04 (m, 16 H, 8 H-6aЈ, 8 H-
1
δ ϭ 7.86Ϫ7.81 (m, 7 H, 7 CH Ar), 7.54Ϫ7.45 (m, 14 H, 14 CH 6bЈ), 3.83Ϫ3.79 (m, 8 H, 8 H-5), 3.74 (dd, 8 H, 8 H-6a, J5,6a ϭ 3.9,
Ar), 6.07Ϫ5.96 (m, 1 H, OCH2CHCH2), 5.41 (d, 8 H, 8 H-4Ј, J6a,6b ϭ 12.2 Hz), 3.70Ϫ3.66 (m, 8 H, 8 H-6b), 3.44Ϫ3.13 (m, 72
J3Ј,4Ј ϭ 3.4 Hz), 5.40Ϫ5.22 (m, 2 H, OCH2CHCH2), 5.29 (dd, 8 H, H, 8 SCH2, 28 NHCH2), 2.12, 2.10, 2.01, 2.00, 1.95, 1.94 (6 s, 168
8 H-3Ј, J2Ј,3Ј ϭ 10.7 Hz), 5.24 (t, 8 H, 8 H-3, J2,3J3,4 ϭ 9.5 Hz), H, 56 CH3CO), 1.64Ϫ1.50, 1.41Ϫ1.35 [2 m, 76 H, 38
5.20 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz), 5.14 (t, 8 H, 8 H-4, J4,5
9.8 Hz), 5.02 (dd, 8 H, 8 H-2Ј), 4.89 (t, 8 H, 8 H-2, J1,2 ϭ 9.8 Hz),
4.80 (d, H, H-1), 4.62Ϫ4.56 (m, 14 H, 6 OCH2CO, 28 NHCO, 21 Cq Ar), 132.9 (OCH2CHCH2), 119.1 (7 CH Ar),
ϭ
CH2(CH2)nCH2]. Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ 170.8,
170.7, 170.4, 170.2, 169.9, 169.1, 167.4, 158.1, 136.6 (56 CH3CO,
8
8
OCH2CHCH2), 4.26Ϫ4.22 (m, 8 H, 8 H-5Ј), 4.12Ϫ4.04 (m, 16 H,
8 H-6aЈ, 8 H-6bЈ), 3.83Ϫ3.79 (m, 8 H, 8 H-5), 3.74 (dd, 8 H, 8 H-
117.1 (OCH2CHCH2), 116.5 (14 CH Ar), 96.5 (8 C-1Ј), 83.0 (8 C-
1), 76.9 (8 C-5), 74.3 (8 C-3), 70.3 (8 C-2), 69.2 (OCH2CHCH2),
6a, J5,6a ϭ 3.9, J6a,6b ϭ 12.2 Hz), 3.70Ϫ3.66 (m, 8 H, 8 H-6b), 68.7 (8 C-4), 68.4 (8 C-2Ј, 8 C-4Ј), 68.0 (8 C-3Ј), 67.5 (6 OCH2CO),
3.44Ϫ3.13 (m, 72 H, 8 SCH2, 28 NHCH2), 2.11, 2.10, 2.01, 2.00, 66.7 (8 C-5Ј), 65.6 (8 C-6), 61.7 (8 C-6Ј), 40.0, 39.7, 38.8 (28
1.95, 1.94 (6 s, 168 H, 56 CH3CO), 1.64Ϫ1.50, 1.41Ϫ1.35 [2 m, 68 NHCH2), 33.3 (8 SCH2), 29.1, 27.0, 26.7, 24.4 [38 CH2(CH2)nCH2],
H, 34 CH2(CH2)nCH2]. Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ
20.0, 19.8, 19.6 (56 CH3CO). Ϫ MALDI TOF MS; m/z ϭ 8237 [M
171.3, 171.2, 170.8, 170.7, 170.4, 169.7, 169.6, 167.9, 158.5, 137.1 ϩ Na]ϩ.
(56 CH3CO, 28 NHCO, 21 Cq Ar), 132.9 (OCH2CHCH2), 119.6 (7
Synthesis of 14a: A methanolic solution of sodium methoxide (1.0
CH Ar), 117.5 (OCH2CHCH2), 117.0 (14 CH Ar), 96.9 (8 C-1Ј),
83.4 (8 C-1), 77.4 (8 C-5), 74.7 (8 C-3), 70.8 (8 C-2), 69.6
(OCH2CHCH2), 69.2 (8 C-4), 68.8 (8 C-2Ј, 8 C-4Ј), 68.4 (8 C-3Ј),
67.9 (6 OCH2CO), 67.1 (8 C-5Ј), 66.1 (8 C-6), 62.2 (8 C-6Ј), 40.5,
40.2, 39.3 (28 NHCH2), 33.8 (8 SCH2), 29.5, 27.4, 27.2, 24.8 [34
CH2(CH2)nCH2], 20.5, 20.3, 20.2, 20.1 (56 CH3CO). Ϫ MALDI
TOF MS; m/z ϭ 8185 [M ϩ Na]ϩ.
, 2 mL) was added to a solution of 13a (17.4 mg, 2.1 µmol) in
methanol (1 mL). The mixture was stirred for 1 h and neutralized
with Dowex-50 (Hϩ) resin. The resin was extracted repeatedly with
water/methanol/N,N-dimethylformamide (5 ϫ 6 mL, 1:1:1, v/v/v).
The washings were combined, concentrated under reduced pres-
sure, and purified by size exclusion chromatography (G-25, water)
to afford 13a as a white glass (11.4 mg, 97%): [α]2D5 ϭ ϩ17.8 (c ϭ
1
1, water). Ϫ H NMR (D2O, 600 MHz): δ ϭ 7.46, 7.43, 7.31 (3 s,
Compound 13e: This compound was synthesized under the same
conditions as described for the preparation of 13a, employing 10e
in place of 10a to yield a white foam (50 mg, 82%): Rf ϭ 0.50
(methanol/dichloromethane, 3:22, v/v); [α]2D5 ϭ ϩ39.9 (c ϭ 1, meth-
7 H, 7 CH Ar), 7.11, 6.95, 6.84 (3 s, 14 H, 14 CH Ar), 5.79Ϫ5.70
(m, 1 H, OCH2CHCH2), 5.20Ϫ5.09 (m, 2 H, OCH2CHCH2), 4.77
(d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.3 Hz), 4.42 (d, 8 H, 8 H-1, J1,2 ϭ 9.9 Hz),
4.36Ϫ4.07 (m, 14 H, 6 OCH2CO, OCH2CHCH2), 3.84Ϫ3.74 (m,
24 H, 8 H-6a, 8 H-4Ј, 8 H-5Ј), 3.70 (dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 10.3,
J3Ј,4Ј ϭ 2.6 Hz), 3.63 (dd, 8 H, 8 H-2Ј), 3.58Ϫ3.51 (m, 24 H, 8 H-
6b, 8 H-6aЈ, 8 H-6bЈ), 3.45Ϫ3.37 (m, 16 H, 8 H-4, 8 H-5),
3.36Ϫ3.30 (m, 16 H, 8 H-3, 8 SCHaHb), 3.25Ϫ3.05 (m, 72 H, 8
H-2, 8 SCHaHb, 28 NHCH2), 1.68Ϫ1.58, 1.44Ϫ1.32 [2 m, 36 H,
18 CH2(CH2)nCH2]. Ϫ 13C NMR (D2O, 125 MHz): δ ϭ 172.2,
170.0, 168.2, 167.7, 157.4, 157.1, 135.7, 135.5, 135.2 (28 NHCO,
21 Cq Ar), 132.6 (OCH2CHCH2), 119.2, 116.7, 116.2 (21 CH Ar,
OCH2CHCH2), 98.4 (8 C-1Ј), 85.9 (8 C-1), 78.7 (8 C-5), 77.7 (8 C-
3), 72.6 (8 C-2), 71.3 (8 C-5Ј), 69.9 (8 C-3Ј), 69.6 (8 C-4Ј), 69.5 (8
C-4), 68.8 (8 C-2Ј), 67.1 (OCH2CHCH2, 6 OCH2CO), 65.9 (8 C-
6), 61.4 (8 C-6Ј), 40.1, 39.1, 38.0, 37.8, (28 NHCH2), 33.9 (8 SCH2),
28.5, 26.5, 26.3 [18 CH2(CH2)nCH2].
1
anol/dichloromethane, 3:1, v/v). Ϫ H NMR (CD3OD, 600 MHz):
δ ϭ 7.86Ϫ7.81 (m, 7 H, 7 CH Ar), 7.54Ϫ7.46 (m, 14 H, 14 CH
Ar), 6.07Ϫ5.96 (m, 1 H, OCH2CHCH2), 5.41 (d, 8 H, 8 H-4Ј,
J3Ј,4Ј ϭ 3.4 Hz), 5.40Ϫ5.22 (m, 2 H, OCH2CHCH2), 5.29 (dd, 8 H,
8 H-3Ј, J2Ј,3Ј ϭ 10.7 Hz), 5.24 (t, 8 H, 8 H-3, J2,3J3,4 ϭ 9.5 Hz),
5.20 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz), 5.14 (t, 8 H, 8 H-4, J4,5
9.5 Hz), 5.02 (dd, 8 H, 8 H-2Ј), 4.89 (t, 8 H, 8 H-2, J1,2 ϭ 9.3 Hz),
4.80 (d, H, H-1), 4.62Ϫ4.56 (m, 14 H, OCH2CO,
ϭ
8
8
6
OCH2CHCH2), 4.26Ϫ4.22 (m, 8 H, 8 H-5Ј), 4.12Ϫ4.04 (m, 16 H,
8 H-6aЈ, 8 H-6bЈ), 3.83Ϫ3.79 (m, 8 H, 8 H-5), 3.74 (dd, 8 H, 8 H-
6a, J5,6a ϭ 3.9, J6a,6b ϭ 12.2 Hz), 3.70Ϫ3.66 (m, 8 H, 8 H-6b),
3.44Ϫ3.13 (m, 72 H, 8 SCH2, 28 NHCH2), 2.12, 2.10, 2.01, 2.00,
1.95, 1.94 (6 s, 168 H, 56 CH3CO), 1.64Ϫ1.50, 1.41Ϫ1.35 [2 m, 72
H, 36 CH2(CH2)nCH2]. Ϫ 13C NMR (CD3OD, 75 MHz): δ ϭ
170.8, 170.7, 170.3, 170.2, 169.9, 169.1, 167.4, 158.0, 136.6 (56
CH3CO, 28 NHCO, 21 Cq Ar), 132.9 (OCH2CHCH2), 119.1 (7 CH
Ar), 117.0 (OCH2CHCH2), 116.5 (14 CH Ar), 96.5 (8 C-1Ј), 83.0
(8 C-1), 76.9 (8 C-5), 74.3 (8 C-3), 70.3 (8 C-2), 69.1
(OCH2CHCH2), 68.8 (8 C-4), 68.4 (8 C-2Ј, 8 C-4Ј), 68.0 (8 C-3Ј),
67.5 (6 OCH2CO), 66.7 (8 C-5Ј), 65.6 (8 C-6), 61.7 (8 C-6Ј), 40.0,
39.7, 38.8 (28 NHCH2), 33.3 (8 SCH2), 29.1, 27.0, 26.7, 24.4 [36
CH2(CH2)nCH2], 20.0, 19.8, 19.6 (56 CH3CO). Ϫ MALDI TOF
MS; m/z ϭ 8212 [M ϩ Na]ϩ.
Compound 14b: This compound was synthesized under the same
conditions as described for the preparation of 14a, employing 13b
in place of 13a to yield a white glass (11.6 mg, 95%): [α]2D5 ϭ ϩ18.2
1
(c ϭ 1, water). Ϫ H NMR (D2O, 600 MHz): δ ϭ 7.47, 7.36, 7.28
(3 s, 7 H, 7 CH Ar), 7.11, 6.99, 6.92 (3 s, 14 H, 14 CH Ar),
5.83Ϫ5.73 (m,
OCH2CHCH2), 4.77 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz), 4.42 (d, 8 H,
H-1, J1,2 9.8 Hz), 4.36Ϫ4.17 (m, 14 H, OCH2CO,
1 H, OCH2CHCH2), 5.22Ϫ5.09 (m, 2 H,
8
ϭ
6
OCH2CHCH2), 3.84Ϫ3.74 (m, 24 H, 8 H-6a, 8 H-4Ј, 8 H-5Ј), 3.70
(dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 10.3, J3Ј,4Ј ϭ 3.4 Hz), 3.63 (dd, 8 H, 8 H-
2Ј), 3.58Ϫ3.51 (m, 24 H, 8 H-6b, 8 H-6aЈ, 8 H-6bЈ), 3.45Ϫ3.37 (m,
Compound 13f: This compound was synthesized under the same
conditions as described for the preparation of 13a, employing 10f 16 H, 8 H-4, 8 H-5), 3.36Ϫ3.30 (m, 16 H, 8 H-3, 8 SCHaHb),
in place of 10a to yield a white foam (42 mg, 82%): Rf ϭ 0.50
(methanol/dichloromethane, 3:22, v/v); [α]2D5 ϭ ϩ50.0 (c ϭ 1, meth-
anol/dichloromethane, 3:1, v/v);1H NMR (CD3OD, 600 MHz): δ ϭ
3.25Ϫ3.05 (m, 72 H, 8 H-2, 8 SCHaHb, 28 NHCH2), 1.68Ϫ1.58,
1.44Ϫ1.32 [2 m, 40 H, 20 CH2(CH2)nCH2]. Ϫ 13C NMR (D2O,
125 MHz): δ ϭ 172.2, 170.0, 168.2, 167.7, 158.3, 157.4, 135.7 (28
7.87Ϫ7.79 (m, 7 H, 7 CH Ar), 7.53Ϫ7.43 (m, 14 H, 14 CH Ar), NHCO, 21 Cq Ar), 132.6 (OCH2CHCH2), 119.2, 116.7, 116.2 (21
6.07Ϫ5.96 (m, 1 H, OCH2CHCH2), 5.41 (d, 8 H, 8 H-4Ј, J3Ј,4Ј
3.4 Hz), 5.40Ϫ5.21 (m, 2 H, OCH2CHCH2), 5.29 (dd, 8 H, 8 H-
ϭ
CH Ar, OCH2CHCH2), 98.4 (8 C-1Ј), 85.9 (8 C-1), 78.7 (8 C-5),
77.7 (8 C-3), 72.6 (8 C-2), 71.3 (8 C-5Ј), 69.9 (8 C-3Ј), 69.6 (8 C-
3Ј, J2Ј,3Ј ϭ 10.7 Hz), 5.24 (t, 8 H, 8 H-3, J2,3J3,4 ϭ 9.5 Hz), 5.20 (d, 4Ј), 69.5 (8 C-4), 68.8 (8 C-2Ј), 67.1 (OCH2CHCH2, 6 OCH2CO),
8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.9 Hz), 5.14 (t, 8 H, 8 H-4, J4,5 ϭ 9.5 Hz), 65.9 (8 C-6), 61.4 (8 C-6Ј), 40.0, 39.1, 37.9, 37.8 (28 NHCH2), 33.9
5.02 (dd, 8 H, 8 H-2Ј), 4.89 (t, 8 H, 8 H-2, J1,2 ϭ 9.8 Hz), 4.80 (d, (8 SCH2), 28.5, 26.5, 26.3 [20 CH2(CH2)nCH2].
Eur. J. Org. Chem. 2001, 2535Ϫ2545
2543

M. McWatt, G.-J. Boons
FULL PAPER
Compound 14c: This compound was synthesized under the same
conditions as described for the preparation of 14a, employing 13c
in place of 13a to yield a white glass (14.0 mg, 100%): [α]2D5 ϭ ϩ19.0
Compound 14f: This compound was synthesized under the same
conditions as described for the preparation of 14a, employing 14f
in place of 14a to yield a white glass (14.8 mg, 100%): [α]2D5 ϭ ϩ50.1
1
1
(c ϭ 1, water). Ϫ H NMR (D2O, 500 MHz): δ ϭ 7.49, 7.45, 7.27
(c ϭ 1, water). Ϫ H NMR (D2O, 600 MHz): δ ϭ 7.50Ϫ7.28 (m,
(3 s, 7 H, 7 CH Ar), 7.14, 6.99, 6.84 (3 s, 14 H, 14 CH Ar), 7 H, 7 CH Ar), 7.15Ϫ6.84 (m, 14 H, 14 CH Ar), 5.78Ϫ5.68 (m, 1
5.82Ϫ5.70 (m, H, OCH2CHCH2), 5.20Ϫ5.08 (m, H, H, OCH2CHCH2), 5.17Ϫ5.05 (m, 2 H, OCH2CHCH2), 4.80 (s, 8
OCH2CHCH2), 4.78 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz), 4.42 (d, 8 H, H, 8 H-1Ј), 4.40 (d, 8 H, 8 H-1, J1,2 ϭ 9.3 Hz), 4.36Ϫ4.08 (m, 14
H-1, J1,2 9.8 Hz), 4.38Ϫ4.08 (m, 14 H, OCH2CO, H, 6 OCH2CO, OCH2CHCH2), 3.86Ϫ3.76 (m, 24 H, 8 H-6a, 8 H-
1
2
8
ϭ
6
OCH2CHCH2), 3.84Ϫ3.74 (m, 24 H, 8 H-6a, 8 H-4Ј, 8 H-5Ј), 3.71
(dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 10.3, J3Ј,4Ј ϭ 3.4 Hz), 3.64 (dd, 8 H, 8 H-
4Ј, 8 H-5Ј), 3.72Ϫ3.64 (m, 16 H, 8 H-3Ј, 8 H-2Ј), 3.63Ϫ3.51 (m, 24
H, 8 H-6b, 8 H-6aЈ, 8 H-6bЈ), 3.45Ϫ3.37 (m, 16 H, 8 H-4, 8 H-5),
2Ј), 3.61Ϫ3.52 (m, 24 H, 8 H-6b, 8 H-6aЈ, 8 H-6bЈ), 3.45Ϫ3.31 (m, 3.35Ϫ3.27 (m, 16 H, 8 H-3, 8 SCHaHb), 3.25Ϫ2.96 (m, 72 H, 8
32 H, 8 H-3, 8 H-4, 8 H-5, 8 SCHaHb), 3.25Ϫ3.00 (m, 72 H, 8 H- H-2, SCHaHb, 28 NHCH2), 1.48Ϫ1.00 [m, 76 H, 38
2, 8 SCHaHb, 28 NHCH2), 1.68Ϫ1.60, 1.45Ϫ1.28, 1.10Ϫ1.02 [3 CH2(CH2)nCH2]. Ϫ 13C NMR (D2O, 125 MHz): δ ϭ 172.1, 170.2,
m, 44 H, 22 CH2(CH2)nCH2]. Ϫ 13C NMR [(CD3)2SO, 125 MHz]:
168.3, 157.8, 136.4 (28 NHCO, 21 Cq Ar), 133.1 (OCH2CHCH2),
8
δ ϭ 171.9, 169.9, 168.3, 160.4, 138.9 (28 NHCO, 21 Cq Ar), 136.1 119.5, 118.8, 117.0 (21 CH Ar, OCH2CHCH2), 98.9 (8 C-1Ј), 86.0
(OCH2CHCH2), 121.7, 120.4, 118.9 (21 CH Ar, OCH2CHCH2), (8 C-1), 79.1 (8 C-5), 78.0 (8 C-3), 72.9 (8 C-2), 71.5 (8 C-5Ј), 70.3
101.4 (8 C-1Ј), 87.3 (8 C-1), 81.6 (8 C-5), 80.9 (8 C-3), 75.9 (8 C-
(8 C-3Ј), 69.9 (8 C-4Ј, 8 C-4), 69.1 (8 C-2Ј), 67.7 (OCH2CHCH2, 6
2), 73.9 (8 C-5Ј), 73.1 (8 C-3Ј), 72.5 (8 C-4Ј), 71.8 (8 C-4), 71.3 (8 OCH2CO), 66.5 (8 C-6), 61.7 (8 C-6Ј), 40.6, 40.2, 39.3 (28
C-2Ј), 70.1 (OCH2CHCH2, 6 OCH2CO), 69.6 (8 C-6), 63.5 (8 C- NHCH2), 33.9 (8 SCH2), 28.8, 28.7, 26.7, 26.5, 24.3 [38
6Ј), 41.3, 41.0, 40.1, 39.8 (28 NHCH2), 35.1 (8 SCH2), 32.1, 31.9, CH2(CH2)nCH2].
31.8, 29.7, 29.5, 26.9 [22 CH2(CH2)nCH2].
Experimental Procedure for the Study of the Dependence of Tgel
Compound 14d: This compound was synthesized under the same
Values on Hydrogelator Concentration: See Figure 1. The appropri-
conditions as described for the preparation of 14a, employing 13d
ate amount of water was added to each freeze-dried sample, and
in place of 13a to yield a white glass (11.6 mg, 100%): [α]2D5 ϭ ϩ47.0
this was heated with gentle agitation for 2 min at 80 °C. The clear
solutions obtained were rapidly cooled to 4 °C and maintained at
this temperature for 3.5 h. The samples were then heated from 2.0
1
(c ϭ 1, water). Ϫ H NMR (D2O, 600 MHz): δ ϭ 7.46, 7.44, 7.36
(3 s, 7 H, 7 CH Ar), 7.08, 6.99, 6.91 (3 s, 14 H, 14 CH Ar),
5.79Ϫ5.70 (m,
OCH2CHCH2), 4.79 (d, 8 H, 8 H-1Ј, J1Ј,2Ј ϭ 3.4 Hz), 4.39 (d, 8 H,
H-1, J1,2 9.8 Hz), 4.36Ϫ4.12 (m, 14 H, OCH2CO,
1 H, OCH2CHCH2), 5.20Ϫ5.09 (m, 2 H,
°C at a rate of 0.2 °C minϪ1. Tgel was defined as the temperature
range over which the gel phase became liquid, as determined by
test tube tilting method and the ball drop method. The range in all
cases was Ͻ 1.5 °C; curtailed mean values are reported for clarity.
8
ϭ
6
OCH2CHCH2), 3.85Ϫ3.76 (m, 24 H, 8 H-6a, 8 H-4Ј, 8 H-5Ј), 3.72
(dd, 8 H, 8 H-3Ј, J2Ј,3Ј ϭ 10.3, J3Ј,4Ј ϭ 2.9 Hz), 3.66 (dd, 8 H, 8 H-
2Ј), 3.60Ϫ3.51 (m, 24 H, 8 H-6b, 8 H-6aЈ, 8 H-6bЈ), 3.44Ϫ3.37 (m,
16 H, 8 H-4, 8 H-5), 3.35Ϫ3.27 (m, 16 H, 8 H-3, 8 SCHaHb),
3.25Ϫ2.96 (m, 72 H, 8 H-2, 8 SCHaHb, 28 NHCH2), 1.72Ϫ1.11
[m, 68 H, 34 CH2(CH2)nCH2]. Ϫ 13C NMR (D2O, 125 MHz): δ ϭ
172.2, 170.0, 168.3, 167.7, 157.4, 135.8 (28 NHCO, 21 Cq Ar), 132.6
(OCH2CHCH2), 119.2, 116.7, 116.2 (21 CH Ar, OCH2CHCH2),
98.8 (8 C-1Ј), 86.0 (8 C-1), 79.1 (8 C-5), 78.0 (8 C-3), 72.9 (8 C-2),
71.6 (8 C-5Ј), 70.0 (8 C-3Ј), 69.9 (8 C-4Ј, 8 C-4), 69.1 (8 C-2Ј), 67.5
(OCH2CHCH2, 6 OCH2CO), 66.5 (8 C-6), 61.7 (8 C-6Ј), 40.3, 39.4,
38.0 (28 NHCH2), 33.9 (8 SCH2), 28.5, 26.5, 26.3, 24.2 [34
CH2(CH2)nCH2].
Acknowledgments
We thank Dr. Aloysius Siriwardena and Dr. Tong Zhu for valuable
discussions, and Dr. John Glushka for help with recording NMR-
spectroscopic data.
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rahedron 1998, 54, 8543Ϫ8660.
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Received December 11, 2000
[O00632]
Eur. J. Org. Chem. 2001, 2535Ϫ2545
2545