Synthesis of N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine uronic acids

Article abstract of DOI:10.1016/j.carres.2003.10.018

The synthesis of 10 N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine uronic acids that are amenable to solid-phase synthesis is described. The general synthetic strategy involves initial incorporation of the protected amine, followed by selective TEMPO oxidation of C-6 hydroxyl groups to give the corresponding Fmoc-protected sugar amino acids. Amine incorporation may be accomplished from aminolysis of the free sugar or from glycosyl azide reduction. The reactions can be carried out on multigram scale, providing access to unique monomer units for future incorporation into combinatorial library syntheses.

Full text of DOI:10.1016/j.carres.2003.10.018

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 367–375
Synthesis of N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine
uronic acids
Laiqiang Ying and Jacquelyn Gervay-Hague*
Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
Received 18 September 2003; accepted 19 October 2003
Abstract—The synthesis of 10 N-(fluoren-9-ylmethoxycarbonyl)glycopyranosylamine uronic acids that are amenable to solid-phase
synthesis is described. The general synthetic strategy involves initial incorporation of the protected amine, followed by selective
TEMPO oxidation of C-6 hydroxyl groups to give the corresponding Fmoc-protected sugar amino acids. Amine incorporation may
be accomplished from aminolysis of the free sugar or from glycosyl azide reduction. The reactions can be carried out on multigram
scale, providing access to unique monomer units for future incorporation into combinatorial library syntheses.
ꢀ 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Until recently, we focused our studies on the synthesis
of compounds containing analogs of neuraminic acid
(Neu),4 which is a naturally occurring sugar amino acid
(a 5-amino-3,5-dideoxynonulosonic acid). The most
abundant form of neuraminic acid is N-acetylneurami-
nic acid (Neu5Ac), which is commercially available. It
can also be prepared in a simple enzymatic reaction.5
We felt that Neu would be an ideal candidate for
incorporation into oligomeric materials because of the
hydroxylated C-6 side chain. We anticipated this func-
tionality would increase water solubility relative to other
pyranose sugars that were known to precipitate when
more than four monomer subunits were incorporated.6
In order to incorporate Neu into to solid-phase peptide
synthesis, we developed methodologies for converting
Neu into several different N-fluoren-9-ylmethoxy-
carbonylneuraminc acid analogs,7 and indeed, Neu
homooligomers derived from these subunits demon-
strated desirable solubility profiles.8
The design and synthesis of artificial peptides as
molecular scaffolds is a continually growing field of
research.1 Much of the synthetic work in this area has
focused on employing solid-phase peptide synthesis in
the construction of oligomeric materials derived from
a-, b-, or c-amino acids.2 These materials often adopt
stable secondary structures reminiscent of naturally
occurring peptides, which undoubtedly contribute to
their biological activities. Carbohydrates have also been
incorporated into novel structural motifs,3 and here
again amide bond formation between monomeric sub-
units is the most commonly employed synthetic strategy.
N-Acetylneuraminic acid (Neu5Ac)
* Corresponding author. Tel.: +1-530-754-9577; fax: +1-530-752-8995;
e-mail: gervay@chem.ucdavis.edu
Neuraminic acid homooligomers
0008-6215/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2003.10.018

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L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
While our studies centering on synthetic and struc-
ylmethoxycarbonyl (Fmoc) glycosyl amines (Scheme 1).
Two routes were explored: method A involved direct
conversion of the unprotected pyranoses, while method
B employed per-O-acetylated glycosyl azides 2, 6, and
10 as the starting materials.9 The free pyranoses were
first reacted with ammonium hydrogen carbonate
(NH4HCO3) in water to form the corresponding glyco-
syl amines,10 which were directly reacted with fluoren-
9-ylmethoxycarbonyl-O-succinimide (Fmoc-OSu) in
pyridine to give the desired Fmoc-protected amines 3, 7,
and 11.11 Purified yields for the combined reactions
ranged from 24% to 27%. Higher yields were obtained
when beginning with protected glycosyl azides, which
were first deacetylated using sodium methoxide in
MeOH and subsequently subjected to hydrogenolysis.
The resulting crude glycosyl amines were further reacted
to give 3, 7, and 11 in 67%, 63%, and 52% purified
yields, respectively, for the three-step reaction sequence.
The next task was to selectively oxidize the C-6 hydroxyl
of the Fmoc-protected glycosyl amine intermediates,
and this was accomplished by TEMPO-catalyzed so-
dium hypochlorite oxidation with careful pH control.12
tural studies of amide-linked homooligomeric neurami-
nic acids have revealed important factors governing
conformational stability, we are currently not able to
rationally design compounds with desirable biological
activity. To address this important issue, we have initi-
ated combinatorial studies to complement our rational
design investigations. The advent of combinatorial
chemistry and the ability to make libraries of com-
pounds, which are only limited in size by building block
variation, have prompted us to develop routes to more
diverse sugar amino acid building blocks. Reported
herein are facile and efficient methods for the synthe-
sis of N-(fluoren-9-ylmethoxycarbonyl)glycopyranosyl-
amine uronic acids.
2. Results and discussion
Our investigations began with the conversion of
copyranose (1), -galactopyranose (5) and -manno-
pyranose (9) to the corresponding N-fluoren-9-
D-glu-
D
D
Scheme 1. (A) Aq NH4HCO3; Fmoc-OSu, pyridine. (B) NaOMe, MeOH; 10% Pd/C, H2MeOH; Fmoc-OSu, pyridine. (C) TEMPO, NaOCl, KBr,
NaHCO3, THF, H2O. (D) NaOMe, H2MeOH; Raney nickel, MeOH; Fmoc-OSu, pyridine.

L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
369
The oxidation went smoothly for the gluco- and gal-
actopyranosyl sugars (3 and 7); however, conversion of
b-D-N-(fluoren-9-ylmethoxycarbonyl)mannopyranosyl-
The synthesis of b-D-glucopyranosyl-N-(fluoren-9-yl-
methoxycarbonyl)methane was previously reported by
von Roedern and Kessler,14 and simple extension of this
protocol enabled the preparation of the galactosyl ana-
amine (11) was much less efficient. Poor yields in
mannosyl oxidations have been reported by others as
well, and are presumably due to stereoelectronic factors
imposed by the C-2 axial hydroxyl group.13 In related
studies, N-acetylglucosamine analog (15) was added to
our library of monosaccarides by subjecting 13 to ami-
nolysis and subsequent protection to provide 14, which
was efficiently oxidized to the corresponding glucuronic
acid in 76% yield.
As shown in Scheme 2, disaccharide-derived com-
pounds were accessed using the same methods as those
described for the monosaccharides; however, the yields
when using method B showed no improvement relative
to method A. And since this route accommodates mul-
tigram reaction scales beginning with commercially
available disaccharides, it is clearly the method of choice
for preparing 18, 22, and 26. Subsequent oxidation of
the N-fluoren-9-ylmethoxycarbonyl disaccharides pro-
ceeded smoothly yielding 19, 23, and 27 in 71%, 68%,
and 64% purified yields, respectively.
log 29 (Scheme 3). In the event, b-D-galactopyranosyl
nitromethane (28) was prepared via aldol condensation,
followed by acid-catalyzed intramolecular ring closure.15
Reduction of the nitro compound with hydrogen using
10% Pd/C, protection of the resulting amine with Fmoc-
Cl, and TEMPO oxidation afforded 29 in 74% yield for
the three-step sequence.
In the 1950s Fodor, and Paulsen and co-workers,
independently reported the synthesis 2-N-benzyloxy-
carbonyl-2-amido-2-deoxyglycuronic acids as interme-
diates en route to naturally occurring sugar amino acid
conjugates.16 We found that similar strategies could be
employed in the synthesis of Fmoc-protected analogs
(Scheme 4). Accordingly, the HCl salt of
was reacted with AcBr to yield 3,4,6-tri-O-acetyl-2-
amino-2-deoxy-a-
-glucopyranosyl bromide,17 which
was treated with MeOH in pyridine to obtain a mixture
of methyl a,b- -glucosides (1:9). The mixture was pro-
tected with Fmoc-OSu, after which the a,b-anomers
D-glucosamine
D
D
Scheme 2. (A) Aq NH4HCO3; Fmoc-OSu, pyridine. (B) NaOMe, MeOH; 10% Pd/C, H2MeOH; Fmoc-OSu, pyridine. (C) TEMPO, NaOCl, KBr,
NaHCO3, THF, H2O.

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L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
Scheme 3.
Scheme 4.
were separated to provide 31a,b in 86% combined yield.
The b-anomer 31b was deacetylated with NaOMe to
give 32 in 85% yield, and selective oxidation of the pri-
mary hydroxyl group with TEMPO gave 33 in 81%
yield. The a-anomer (36) was most efficiently prepared
thesis of diverse libraries of amide-linked oligomers in
an effort to create unique structural motifs with impor-
tant biological activities.
from
treatment of 30 with Ac2O. Acid-catalyzed methanolysis
-glucopyranoside,
which was protected to provide 3518 in 65% yield and
finally oxidized to provide 36 (Scheme 4).
D-glucosamine pentaacetate, obtained upon
4. Experimental
afforded methyl 2-amino-2-deoxy-a-
D
4.1. General methods
All chemicals were used as supplied without further
purification. Solvents (MeOH 99.8%, CH2Cl2 99.8%,
benzene 99.8%) were purchased in anhydrous Sure/
SealTM bottles from Aldrich, used without further
purification, and stored under argon. Dowex 50W-X8
(200 mesh) acidic resin was purchased from Aldrich,
washed copiously with MeOH, and used without fur-
ther purification. NaOMe/MeOH (0.5 M) was pur-
chased from Aldrich. Glass-backed EM Science TLC
plates (Silica Gel 60 with a 254-nm fluorescent indi-
cator) were purchased from VWR International, cut
into 2 cm · 5 cm portions, used without further manip-
ulation, and stored over desiccant. Developed TLC
plates were visualized under a short-wave UV lamp,
then stained with a cerium–molybdate solution and
charred. Column chromatography was conducted using
flash silica gel (32–63 lm) available from Scientific
Adsorbents and solvents purchased from EM Science.
NMR experiments (1D and 2D) were conducted on
Bruker DRX500 MHz spectrometers at 298 K. Optical
data were taken on a JASCO DIP-370 Digital Polari-
meter. RP-HPLC preparative separations were carried
3. Conclusions
We have developed facile and efficient protocols for
10 N-(fluoren-9-ylmethoxycarbonyl)glycuronic amino
acids that can be carried out on multigram scale.
Beginning with readily available starting materials,
amine functionalities can be introduced either through
aminolysis or azide reduction. Subsequent protection of
the amines occurs without incident, providing substrates
for TEMPO oxidation in order to introduce the acid
functionality. For the most part, the oxidation proceeds
smoothly giving selective oxidation of the C-6 hydroxyl
or bis-oxidation in the case of disaccharides possessing
C-6 and C-60 hydroxyl groups. The only problem
encountered was in the oxidation of mannopyranosyl
analogs, which are somewhat resistant to oxidation,
apparently due to stereoelectronic effects posed by the
C-2 axial hydroxyl group. Preparation of the com-
pounds described herein is a prerequisite for the syn-

L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
371
out on a Vydac C18 column. Solvents: (A) H2O+0.1%
TFA and (B) CH3OH with UV detection at 220 and
254 nm.
were added. After TLC indicated the reaction was
complete, the solution was extracted with Et2O
(2 · 10 mL). The aqueous layer was acidified with 2 N
HCl to pH 1–2 and extracted with EtOAc (3 · 30 mL).
The combined organic layers were washed with brine,
dried (Na2SO4), and concentrated to yield a residue that
was purified by preparative HPLC.
4.2. General procedure for the synthesis of N-(fluoren-
9-ylmethoxycarbonyl)-b-D-glycopyranosylamines:
method A
4.5. N-(Fluoren-9-ylmethoxycarbonyl)-b-D-gluco-
pyranylamine (3)
The saccharide (5 g) was dissolved in aq NH4HCO3
(200 mL) and stirred for 7 days at 30 ꢁC. The reaction
mixture was diluted with equal volumes of water, and
NH4HCO3 was removed by concentration in vacuo
(bath temperature 30 ꢁC) to the original volume. This
procedure was repeated five times. After lyophilization
of the solution, the product was used directly in the next
step. The glycopyranosylamine (ꢀ10 mmol) was sus-
pended in pyridine (50 mL), Fmoc-OSu (10 mmol) was
added, and the mixture was stirred overnight at room
temperature. The solution was concentrated in vacuo.
The residue was washed with water, CH2Cl2, and was
purified by crystallization from MeOH or by column
chromatography (silica gel, 8:1–4:1 CH2Cl2–CH3OH).
A white powder was obtained in 27% yield from 1 and
1
67% from 2. H NMR (CD3OD, 500 MHz): d 3.17 (t, J
9.0 Hz, 1H, H-2), 3.25 (m, 2H, H-4, H-5), 3.31 (t, J
9.0 Hz, 1H, H-3), 3.59 (dd, J 3.5, 11.5 Hz, 1H, H-6), 3.76
(d, J 11.5 Hz, 1H, H-60), 4.16 (t, J 6.5 Hz, 1H, Fmoc-
CH), 4.34 (m, 2H, Fmoc-CH2), 4.63 (d, J 8.5Hz, 1H,
H-1), 7.25 (app-t, 2H, Fmoc-Ar), 7.33 (app-t, 2H,
Fmoc-Ar), 7.61 (d, J 7.5 Hz, 2H, Fmoc-Ar), 7.73 (d, J
7.5 Hz, 2H, Fmoc-Ar). 13C NMR (DMSO, 125 MHz): d
46.9 (Fmoc-CH), 61.1 (C-6), 66.2 (Fmoc-CH2), 70.1,
72.2 (C-2), 77.6 (C-3), 78.5, 82.7 (C-1), 120.5, 125.7,
127.6, 128.2, 141.1, 144.0, 144.2, 156.6. ESIMS: calcd
for C12H23NO7Na [M+Na]þ 424.2, found 424.2.
4.3. Method B
azide9
4.6. N-(Fluoren-9-ylmethoxycarbonyl)-b-D-gluco-
pyranosylamine uronic acid (4)
2,3,4,6-Tetra-O-acetyl-a,b-
D
-glycopyranosyl
(5.0 mmol) was suspended in dry MeOH (20 mL). Na-
OMe (0.2 mL, 0.5 M) was added, and the mixture was
stirred for approximately 30 min. Upon completion of
the reaction as indicated by TLC, the solution was
neutralized with Dowex-50 (Hþ) resin, filtered, and
concentrated to dryness. The glycosyl azide (500 mg)
was dissolved in dry MeOH (20 mL), 10% Pd/C (wet,
40 mg) was added (Caution. Extreme fire hazard!). For
mannose, Raney nickel (50 mg) was added, and the
solution was bubbled with H2 for 3–4 h. After comple-
tion, as indicated by TLC, the Pd/C was removed by
filtration and the solution was concentrated to dryness.
The glycopyranosylamine (2.5 mmol) was suspended in
pyridine (20 mL), Fmoc-OSu (2.6 mmol) was added,
and the mixture was stirred overnight at room temper-
ature. The solution was concentrated in vacuo. The
residue was washed with CH2Cl2, and the precipitate
was purified by recrystallization from MeOH or by
column chromatography (Silica gel, 8:1–4:1) CH2Cl2–
CH3OH).
25
D
A white powder was obtained in 81% yield from 3. ½aꢁ
1
)5.0ꢁ (c 0.5, CH3OH). H NMR (DMSO, 500 MHz): d
3.17 (t, J 8.5 Hz, 1H, H-2), 3.22 (t, J 8.5 Hz, 1H, H-3),
3.29 (t, J 8.5 Hz, 1H, H-4), 3.61 (d, J 8.5 Hz, 1H, H-5),
4.22–4.32 (m, 3H, Fmoc-CH, Fmoc-CH2), 4.55 (d, J
8.5 Hz, 1H, H-1), 7.32 (app-t, 2H, Fmoc-Ar), 7.41 (app-
t, 2H, Fmoc-Ar), 7.71 (m, 2H, Fmoc-Ar), 7.87 (d, J
7.5 Hz, 2H, Fmoc-Ar). 13C NMR (DMSO, 125 MHz): d
46.7 (Fmoc-CH), 66.0 (Fmoc-CH2), 71.6 (C-2, C-4),
76.8 (C-3), 77.2 (C-5), 82.9 (C-1), 120.3, 125.4, 125.5,
127.4, 127.9, 140.9, 143.8, 144.0, 156.24, 170.5 (C-6).
HRFABMS: calcd for C12H12NO8Na [M+Na]þ
438.1159, found 438.1176.
4.7. N-(Fluoren-9-ylmethoxycarbonyl)-b-D-galacto-
pyranosylamine (7)
A white powder was obtained in 26% yield from 5 and
63% from 6. 1H NMR (CD3OD, 500 MHz): d 3.42–3.50
(m, 3H, H-2, H-3, H-5), 3.62 (m, 2H, H-6, H-60), 3.80 (br
s, 1H, H-4), 4.15 (t, J 6.5 Hz, 1H, Fmoc-CH), 4.32 (m,
2H, Fmoc-CH2), 4.59 (d, J 8.0 Hz, 1H, H-1), 7.23 (app-
t, 2H, Fmoc-Ar), 7.31 (app-t, 2H, Fmoc-Ar), 7.60 (d, J
7.5 Hz, 2H, Fmoc-Ar), 7.71 (d, J 7.5 Hz, 2H, Fmoc-Ar).
13C NMR (DMSO, 125 MHz): d 46.2 (Fmoc-CH), 62.4
(C-6), 68.0 (Fmoc-CH2), 70.3 (C-4), 71.1 (C-3), 75.7
(C-2), 78.0 (C-5), 84.2 (C-1), 121.0, 126.2, 128.2, 128.8,
4.4. General procedure for TEMPO oxidation
N-(Fluoren-9-ylmethoxycarbonyl)-b-D-glycopyranosyl-
amine (0.5 mmol) was suspended in 1:1 THF–aq
NaHCO3 (12 mL), and TEMPO (0.1 mmol) and potas-
sium bromide (0.15 mmol) were added. NaOCl (1.1 mL,
1.3 M) was added dropwise at 0 ꢁC. After 1 h, additional
amounts of NaOCl (0.6 mL) and TEMPO (0.05 mmol)

372
L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
142.6, 145.2, 158.8. ESIMS: calcd for C21H23NO7Na
[M+Na]þ 424.2, found 424.2.
(dd, J 3.5 Hz, 11.5 Hz, 1H, H-6), 3.53 (t, J 8.0 Hz, 1H,
H-2), 3.76 (d, J 11.5 Hz, 1H, H-60), 4.10–4.30 (m, 3H,
Fmoc-CH, Fmoc-CH2), 4.62 (d, J 8.0 Hz, 1H, H-1), 7.30
(app-t, 2H, Fmoc-Ar), 7.39 (app-t, 2H, Fmoc-Ar), 7.61
4.8. N-(Fluoren-9-ylmethoxycarbonyl)-b-D-galacto-
pyranosylamine uronic acid (8)
(m, 2H, Fmoc-Ar), 7.84 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13
C
NMR (DMSO, 125 MHz): d 23.3, 46.9 (Fmoc-CH), 54.9
(C-2), 61.3 (C-6), 66.8 (Fmoc-CH2), 70.6 (C-4), 74.7 (C-
3), 78.6 (C-5), 81.8 (C-1), 120.8, 125.8, 125.9, 127.9,
128.5, 141.3, 144.1, 144.2, 156.6, 171.9. ESIMS: calcd
for C23H26N2O7Na [M+Na]þ 465.2, found 465.2.
25
D
A white powder was obtained in 78% yield from 7. ½aꢁ
1
)2.7ꢁ (c 0.6, CH3OH). H NMR (DMSO, 500 MHz): d
3.41–3.43 (m, 2H, H-2, H-3), 3.94 (1H, H-4), 4.09 (br s,
1H, H-5), 4.20–4.28 (m, 3H, Fmoc-CH, Fmoc-CH2),
4.49 (d, J 8.0 Hz, 1H, H-1), 7.32 (app-t, 2H, Fmoc-Ar),
7.40 (app-t, 2H, Fmoc-Ar), 7.69 (m, 2H, Fmoc-Ar), 7.84
(d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR (DMSO,
125 MHz): d 47.0 (Fmoc-CH), 66.6 (Fmoc-CH2), 69.0,
70.4 (C-4), 73.9, 75.4 (C-5), 82.7 (C-1), 120.8, 125.9,
125.9, 127.9, 128.5, 141.3, 144.2, 144.3, 157.0, 170.7
(C-6). HRFABMS: calcd for C12H12NO8Na [M+Na]þ
438.1159, found [M+Na]þ 438.1178.
4.12. 2-Acetamido-2-deoxy-N1-(fluoren-9-ylmethoxy-
carbonyl)-b-D-glucopyranosylamine uronic acid (15)
25
D
A white powder was obtained in 76% yield from 14. ½aꢁ
+41.4ꢁ (c 0.2, CH3OH). 1H NMR (DMSO, 500 MHz): d
1.82 (s, 3H, NAc), 3.33 (t, J 9.0 Hz, 1H, H-4), 3.39 (t, J
9.0 Hz, 1H, H-3), 3.57 (t, J 9.0 Hz, 1H, H-2), 3.62 (d, J
9.0 Hz, 1H, H-5), 4.15–4.27 (m, 3H, Fmoc-CH, Fmoc-
CH2), 4.71 (d, J 9.0 Hz, 1H, H-1), 7.30 (app-t, 2H,
Fmoc-Ar), 7.40 (app-t, 2H, Fmoc-Ar), 7.61 (m, 2H,
Fmoc-Ar), 7.84 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR
(DMSO, 125 MHz): d 22.9, 46.7 (Fmoc-CH), 54.4 (C-2),
66.3 (Fmoc-CH2), 72.1 (C-4), 74.0 (C-3), 77.4 (C-5), 82.0
(C-1), 120.3, 125.4, 125.6, 127.3, 127.9, 141.0, 143.9,
156.1, 170.3, 170.7. HRFABMS: calcd for
C23H24N2O8Na [M+Na]þ 479.1424, found 479.1417.
4.9. N-(Fluoren-9-ylmethoxycarbonyl)-b-D-manno-
pyranosylamine (11)
A white powder was obtained in 24% yield from 9 and
1
52% from 10. H NMR (DMSO, 500 MHz): d 3.07 (m,
1H, H-5), 3.28–3.35 (m, 2H, H-3, H-4), 3.41 (m, 1H,
H-6), 3.60–3.63 (m, 2H, H-2, H-60), 4.20–4.33 (m, 3H,
Fmoc-CH, Fmoc-CH2), 4.76 (s, 1H, H-1), 7.31 (app-t,
2H, Fmoc-Ar), 7.39 (app-t, 2H, Fmoc-Ar), 7.66 (m, 2H,
Fmoc-Ar), 7.83 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR
(DMSO, 125 MHz): d 47.0 (Fmoc-CH), 61.5 (C-6), 66.7,
66.9, 71.0 (C-2), 74.1, 78.9 (C-5), 80.2 (C-1), 120.7,
125.7, 127.9, 128.4, 141.3, 144.2, 144.2, 156.2. ESIMS:
calcd for C12H23NO7Na [M+Na]þ 424.2, found 424.2.
4.13. b-
oxy carbonyl)-b-
D
-Glucopyranosyl-(1 ! 4)-N-(fluoren-9-ylmeth-
-glucopyranosylamine (18)
D
A white powder was obtained in 11% yield from 16 and
23% from 17. 1H NMR (DMSO, 500 MHz): d 2.98 (t, J
8.5 Hz, 1H, H-20), 3.04 (t, J 8.5 Hz, 1H, H-30), 3.13–3.21
(m, 4H, H-40, H-2, H-3, H-5), 3.24–3.40 (m, 4H, H-4, H-
50, H-600 , H-60), 3.56–3.70 (m, 3H, H-5, H-6, H-60), 4.21–
4.36 (m, 3H, H-10, Fmoc-CH, Fmoc-CH2), 4.52 (d, J
9.0 Hz, 1H, H-1), 7.33 (app-t, 2H, Fmoc-Ar), 7.42 (app-
t, 2H, Fmoc-Ar), 7.72 (m, 2H, Fmoc-Ar), 7.88 (d, J
7.5 Hz, 2H, Fmoc-Ar). 13C NMR (DMSO, 125 MHz): d
46.7 (Fmoc-CH), 60.2 (C-6), 61.1 (C-60), 65.9 (Fmoc-
CH2), 70.1 (C-30), 71.67, 73.4 (C-20), 75.8, 76.4, 76.4,
76.9, 80.3 (C-4), 82.4 (C-1), 103.2 (C-10), 120.4, 125.4,
125.5, 127.4, 128.0, 140.9, 143.9, 144.1, 156.4. ESIMS:
calcd for C27H33NO12Na [M+Na]þ 586.2, found 586.3.
4.10. N-(Fluoren-9-ylmethoxycarbonyl)-b-D-manno-
pyranosylamine uronic acid (12)
A white powder was obtained with yield 32% from 11.
25
D
½aꢁ
)3.8ꢁ (c 0.6, CH3OH). 1H NMR (DMSO,
500 MHz): d 3.40 (m, 1H, H-2), 3.56–3.65 (m, 3H, H-3,
H-4, H-5), 4.20–4.31 (m, 3H, Fmoc-CH, Fmoc-CH2),
4.85 (s, 1H, H-1), 7.31 (app-t, 2H, Fmoc-Ar), 7.39 (app-t,
2H, Fmoc-Ar), 7.67 (m, 2H, Fmoc-Ar), 7.84 (d, J
7.5 Hz, 2H, Fmoc-Ar). 13C NMR (DMSO, 125 MHz): d
46.9 (Fmoc-CH), 66.67 (Fmoc-CH2), 68.1, 70.5, 73.5
(C-2), 77.7 (C-5), 80.7 (C-1), 120.6, 125.7, 125.8, 127.8,
128.4, 141.2, 144.1, 144.2, 156.0, 170.9 (C-6).
HRFABMS: calcd for C12H12NO8Na [M+Na]þ
438.1159, found [M+Na]þ 438.1180.
4.14. b-
carbonyl)-b-
D
-Glucuronyl-(1 ! 4)-N-(fluoren-9-ylmethoxy-
-glucopyranosylamine uronic acid (19)
D
25
D
A white powder was obtained in 71% yield from 18. ½aꢁ
4.11. 2-Acetamido-2-deoxy-N1-(fluoren-9-ylmethoxy-
carbonyl)-b-D-glucopyranosylamine (14)
)7.9ꢁ (c 0.3, CH3OH). 1H NMR (CD3OD, 500 MHz): d
2.97 (t, J 8.5 Hz, 1H, H-20), 3.24 (t, J 8.5 Hz, 1H, H-2),
3.28 (t, J 8.5 Hz, 1H, H-30), 3.40 (t, J 8.5 Hz, 1H, H-40),
3.48 (t, J 8.5 Hz, 1H, H-3), 3.63 (t, J 8.5 Hz, 1H, H-4),
3.78 (d, J 8.5 Hz, 1H, H-50), 3.93 (d, J 8.5 Hz, 1H, H-5),
4.13 (t, J 7.0 Hz, 1H, Fmoc-CH), 4.29 (m, 2H, Fmoc-
1
A white powder was obtained in 23% yield from 13. H
NMR (DMSO, 500 MHz): d 1.82 (s, 3H, NAc), 3.09–
3.12 (m, 2H, H-4, H-5), 3.34 (t, J 8.0 Hz, 1H, H-3), 3.44

L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
373
CH2), 4.38 (d, J 8.5 Hz, 1H, H-10), 4.68 (d, J 8.5 Hz, 1H,
H-1), 7.20 (app-t, 2H, Fmoc-Ar), 7.28 (app-t, 2H,
Fmoc-Ar), 7.57 (d, J 7.5 Hz, 2H, Fmoc-Ar), 7.68 (d, J
7.5 Hz, 2H, Fmoc-Ar). 13C NMR (CD3OD, 125 MHz):
d 48.3 (Fmoc-CH), 68.2 (Fmoc-CH2), 72.9, 73.0, 74.6
(C-20), 76.1, 76.3, 76.8, 77.1, 81.9 (C-4), 84.0 (C-1), 104.4
(C-10), 120.9, 126.3, 128.2, 128.8, 142.6, 145.2, 158.8,
171.8, 172.3. HRFABMS: calcd for C27H29NO14Na
[M+Na]þ 614.1477, found 614.1457.
H-5), 3.60–3.69 (m, 5H, H-20, H-30, H-6, H-600 , H-60),
3.80–3.87 (m, 3H, H-40, H-50, H-60), 4.14–4.36 (m, 3H,
Fmoc-CH, Fmoc-CH2), 4.63 (d, J 9.0 Hz, 1H, H-1), 4.80
(1H, H-10), 7.25 (app-t, 2H, Fmoc-Ar), 7.32 (app-t, 2H,
Fmoc-Ar), 7.60 (d, J 7.5 Hz, 2H, Fmoc-Ar), 7.72 (d, J
7.5 Hz, 2H, Fmoc-Ar). 13C NMR (CD3OD, 125 MHz): d
48.2 (Fmoc-CH), 62.8 (C-60), 67.6 (C-6), 68.0 (Fmoc-
CH2), 70.5, 71.2, 71.4, 71.6, 72.3, 73.6, 78.0, 79.0, 83.9
(C-1), 100.3 (C-10), 120.9, 126.1, 128.2, 128.8, 142.6,
145.2, 158.7. ESIMS: calcd for C27H33NO12Na
[M+Na]þ 586.2, found 586.2.
4.15. b-
D
-Galactopyranosyl-(1 fi 4)-N-(fluoren-9-yl-
-glucopyranosylamine (22)
methoxycarbonyl)-b-
D
4.18. a-
ren-9-ylmethoxycarbonyl)-b-
D
-Galactopyranosyluronic acid-(1 fi 6)-N-(fluo-
-glucopyranosylamine (27)
A white powder was obtained in 18% yield from 20 and
34% from 21. 1H NMR (DMSO, 500 MHz): d 3.11 (t, J
9.0 Hz, 1H, H-2), 3.20–3.28 (m, 5H, H-20, H-30, H-3,
H-4, H-5), 3.39–3.63 (m, 6H, H-40, H-50, H-6, H-60,
H-600 , H-60), 4.14–4.28 (m, 4H, H-10, Fmoc-CH, Fmoc-
CH2), 4.46 (d, J 9.0 Hz, 1H, H-1), 7.27 (app-t, 2H,
Fmoc-Ar), 7.35 (app-t, 2H, Fmoc-Ar), 7.65 (m, 2H,
Fmoc-Ar), 7.81 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR
(DMSO, 125 MHz): d 47.0 (Fmoc-CH), 60.5 (C-6), 60.9
(C-60), 66.3 (Fmoc-CH2), 68.6 (C-40), 71.0 (C-20), 71.9
(C-2), 73.4, 75.9 (2C), 76.6, 80.5, 82.5 (C-1), 104.1 (C-10),
120.7, 125.7, 125.8, 127.8, 128.3, 141.2, 144.1, 144.3,
156.8. ESIMS: calcd for C27H33NO12Na [M+Na]þ
586.2, found 586.2.
D
A white powder was obtained with yield 64% from 26.
25
D
½aꢁ )40.1ꢁ (c 0.7, CH3OH). 1H NMR (DMSO,
500 MHz): d 3.11 (m, 2H, H-2, H-4), 3.19 (t, J 9.0 Hz,
1H, H-3), 3.29 (m, 1H, H-5), 3.51–3.63 (m, 4H, H-20, H-
30, H-6, H-60), 3.99 (s, 1H, H-50), 4.21–4.34 (m, 4H, H-40,
Fmoc-CH, Fmoc-CH2), 4.46 (d, J 9.0 Hz, 1H, H-1), 4.72
(d, J 2.5 Hz, 1H, H-10), 7.32 (app-t, 2H, Fmoc-Ar), 7.40
(app-t, 2H, Fmoc-Ar), 7.68 (m, 2H, Fmoc-Ar), 7.85 (d,
J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR (DMSO, 125 MHz):
d 47.0 (Fmoc-CH), 66.5 (Fmoc-CH2), 66.6 (C-6), 68.1,
69.2, 70.1, 70.6, 70.7, 72.2, 76.6 (C-5), 77.7 (C-3), 82.9
(C-1), 98.8 (C-10), 120.7, 125.8, 125.9, 127.8, 128.4,
141.2, 141.2, 144.2, 144.4, 156.7, 171.1. HRFABMS:
calcd for C27H31NO13Na [M+Na]þ 600.1684, found
600.1711.
4.16. b- -Galactopyranosyl-(1 fi 4)-N-(fluoren-9-yl-
D
methoxycarbonyl)-b-D-glucopyranosylamine uronic
acid (23)
4.19. N-(Fluoren-9-ylmethoxycarbonyl)-C-(b-D-galacto-
pyranosyluronic acid)methylamine
25
D
A white powder was obtained in 68% yield from 22. ½aꢁ
1
)12.0ꢁ (c 1.0, CH3OH). H NMR (CD3OD, 500 MHz):
d 3.31 (t, J 9.0 Hz, 1H, H-2), 3.49 (m, 2H, H-20, H-30),
3.55 (t, J 9.0 Hz, 1H, H-3), 3.65 (t, J 9.0 Hz, 1H, H-4),
3.94 (d, J 9.0 Hz, 1H, H-5), 4.09 (s, 1H, H-40), 4.15 (t, J
7.0 Hz, 1H, Fmoc-CH), 4.21 (s, 1H, H-50), 4.29 (m, 2H,
Fmoc-CH2), 3.39–3.63 (m, 6H, H-40, H-50, H-6, H-60, H-
600 , H-60), 4.30–4.33 (m, 3H, H-10, Fmoc-CH2), 4.72 (d, J
9.0 Hz, 1H, H-1), 7.22 (app-t, 2H, Fmoc-Ar), 7.30 (app-
t, 2H, Fmoc-Ar), 7.59 (d, J 7.5 Hz, 2H, Fmoc-Ar), 7.70
(d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR (CD3 OD,
125 MHz): d 48.3 (Fmoc-CH), 68.2 (Fmoc-CH2), 71.1
(C-40), 71.8 (C-20), 73.0 (C-2), 74.1 (C-50), 76.7 (C-5),
77.0 (C-30), 82.3 (C-4), 83.8 (C-1), 104.6 (C-10), 120.9,
126.2, 128.2, 128.8, 142.6, 145.2, 158.7, 171.6, 172.4.
HRFABMS: calcd for C27H29NO14Na [M+Na]þ
614.1477, found 614.1476.
A white powder was obtained in 30% over yield from 5.
1H NMR (CD3OD, 500 MHz): d 3.17 (m, 1H, H-1), 3.22
(m, 1H, CH2), 3.41 (t, J 9.0 Hz, 1H, H-2), 3.46 (dd, J
3.5, 9.0 Hz, 1H, H-3), 3.63 (m, 1H, CH2), 4.11–4.16 (m,
3H, H-4, H-5, Fmoc-CH), 4.31 (m, 2H, Fmoc-CH2),
7.16 (app-t, 2H, Fmoc-Ar), 7.24 (app-t, 2H, Fmoc-Ar),
7.51 (d, J 7.5 Hz, 2H, Fmoc-Ar), 7.64 (d, J 7.5 Hz, 2H,
Fmoc-Ar). 13C NMR (CD3OD, 125 MHz): d 43.0
(CH2), 48.4 (Fmoc-CH), 67.7 (Fmoc-CH2), 69.3 (C-2),
71.7 (C-4), 75.5 (C-3), 78.6 (C-5), 80.3 (C-1), 120.9,
126.2, 128.1, 128.7, 142.6, 145.3, 145.3, 159.1, 173.0
(C-6). HRFABMS: calcd for C22H22NO8Na2
[M+2Na)H]þ 474.1135, found 474.1184.
4.20. Methyl 3,4,6-tri-O-acetyl-2-deoxy-2-(fluoren-9-yl-
-glucopyranoside (31a,b)
methoxycarbonylamino)-a,b-
D
4.17. a-
ylmethoxycarbonyl)-b-
D
-Galactopyranosyl-(1 fi 6)-N-(fluoren-9-
-glucopyranosylamine (26)
D
AcBr (20 mL) was slowly added to
D
-glucosamine
hydrochloride (3 g, 13.9 mmol) under argon. The flask
was tightly sealed and stirred overnight at room tem-
perature. The a-glucosyl bromide crystallized out of
solution, the excess AcBr was removed by filtration, and
A white powder was obtained in 14% yield from 24 and
30% from 25. 1H NMR (CD3OD, 500 MHz): d 3.20 (t, J
9.0 Hz, 1H, H-2), 3.33 (m, 2H, H-3, H-4), 3.43 (m, 1H,

374
L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
the residue was washed with anhyd benzene. MeOH
(50 mL) and pyridine (10 mL) were added to the a-glu-
cosyl bromide with stirring for 1 h at room temperature.
The solution was concentrated in vacuo, and the residue
was dissolved in pyridine (50 mL) and Et3N (3.8 mL,
25.8 mmol). Fmoc-OSu (5.6 g, 16.6 mmol) was added to
the solution, and the mixture was stirred overnight. The
solution was concentrated in vacuo to afford a residue
that was dissolved in CH2Cl2 (200 mL). The solution
was washed with water, aq NaHCO3, brine, and dried
Fmoc-Ar), 7.33 (app-t, 2H, Fmoc-Ar), 7.62 (d, J 7.5 Hz,
2H, Fmoc-Ar), 7.75 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13C
NMR (CD3OD, 125 MHz): d 48.0 (Fmoc-CH), 56.2
(OCH3), 57.8 (C-2), 61.7 (C-6), 66.2 (Fmoc-CH2), 71.3
(C-4), 74.9 (C-3), 77.1 (C-5), 102.9 (C-1), 120.20, 125.6,
127.4, 128.0, 141.5, 144.5, 144.5, 157.4. HRFABMS:
calcd for C22H25NO7Na [M+Na]þ 438.1522, found
438.1547.
4.22. Methyl 2-deoxy-2-(fluoren-9-ylmethoxycarbonyl-
amino)-b-D-glucopyranosiduronic acid (33)
(Na2SO4). The resulting methyl a,b-
D
-glucosides were
separated by column chromatography to give 31a and
31b in 86% over all yield (a:b 1:9). 31a: 1H NMR
(CDCl3, 500 MHz): d 1.96, 2.02, 2.10 (3s, 9H, 3OAc),
3.42 (s, 3H, OCH3), 3.93 (m, 1H, H-5), 4.05–4.12 (m,
2H, H-2, H-6), 4.19 (t, J 7.0 Hz, 1H, Fmoc-CH), 4.24–
4.31 (m, 2H, H-60, Fmoc-CH2), 4.43 (m, 1H, Fmoc-
CH2), 4.75 (d, J 3.5 Hz, 1H, H-1), 5.05 (d, J 9.5 Hz, 1H,
NH), 5.10 (d, J 10.0 Hz, 1H, H-4), 5.24 (d, J 10.0 Hz,
1H, H-3), (4.55 (br s, 1H, H-1), 5.07 (br s, 1H, H-4), 5.22
(br s, 1H, NH), 7.31 (app-t, 2H, Fmoc-Ar), 7.40 (app-t,
2H, Fmoc-Ar), 7.56 (m, 2H, Fmoc-Ar), 7.76 (d, J
7.3 Hz, 2H, Fmoc-Ar). 13C NMR (CDCl3, 125 MHz): d
20.8, 20.9, 47.2 (Fmoc-CH), 53.9 (C-2), 55.7 (OCH3),
62.2 (C-6), 66.3 (Fmoc-CH2), 67.6 (C-5), 68.4 (C-4), 71.3
(C-3), 98.7 (C-1), 120.2, 120.19, 125.2, 125.2, 127.2,
127.9, 141.5, 143.8, 143.9, 155.9, 169.3, 169.6, 170.9.
HRFABMS: calcd for C28H31NO10Na [M+Na]þ
564.1837, found: 564.1856. 31b: 1H NMR (CDCl3,
500 MHz): d 1.98, 2.01, 2.08 (3s, 9H, 3OAc), 3.49 (s, 3H,
OCH3), 3.63 (br s, 1H, H-2), 3.70 (br s, 1H, H-5), 4.11–
4.35 (m, 5H, H-6, H-60, Fmoc-CH, Fmoc-CH2), 4.55 (br
s, 1H, H-1), 5.07 (br s, 1H, H-4), 5.22 (br s, 1H, NH),
5.32 (br s, 1H, H-3), 7.27 (m, 2H, Fmoc-Ar), 7.37 (app-t,
2H, Fmoc-Ar), 7.54 (m, 2H, Fmoc-Ar), 7.74 (d, J
7.3 Hz, 2H, Fmoc-Ar). 13C NMR (CDCl3, 125 MHz): d
20.6, 20.7, 46.9 (Fmoc-CH), 55.9 (C-2), 57.0 (OCH3),
62.0 (C-6), 66.8 (Fmoc-CH2), 68.6 (C-4), 71.6 (C-5), 72.0
(C-3), 101.7 (C-1), 119.9, 124.9, 126.9, 127.6, 141.2,
143.6, 143.8, 155.7, 169.4, 170.7. HRFABMS: calcd for
C28H31NO10Na [M+Na]þ 564.1837, found 564.1867.
1
A white powder was obtained in 81% yield from 32. H
NMR (CD3OD) d 3.28–3.37 (m, 5H, H-2, H-3, OCH3),
3.45 (t, J 8.5 Hz, 1H, H-4), 3.65 (d, J 8.5 Hz, 1H, H-5),
4.11 (t, J 7.0 Hz, 1H, Fmoc-CH), 4.17–4.27 (m, 3H, H-1,
Fmoc-CH2), 7.19 (app-t, 2H, Fmoc-Ar), 7.27 (app-t,
2H, Fmoc-Ar), 7.55 (d, J 7.5 Hz, 2H, Fmoc-Ar), 7.67 (d,
J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR (CD3OD, 125 MHz):
d 48.37 (Fmoc-CH), 57.46 (OCH3), 58.60 (C-2), 67.83
(Fmoc-CH2), 73.65 (C-4), 75.38 (C-3), 76.71 (C-5),
104.30 (C-1), 120.90, 126.24, 126.30, 128.14, 128.75,
142.58, 145.36, 158.99, 172.37 (C-6). HRFABMS:
calcd for C22H23NO8Na [M+Na]þ 452.1315, found
452.1332.
4.23. Methyl 2-deoxy-2-(fluoren-9-ylmethoxycarbonyl-
amino)-a-D-glucopyranoside (35)
2-Amino-2-deoxy-
ylated using Ac2O, Et3N, and pyridine to produce
2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-a,b- -gluco-
D-glucose (D-glucosamine) was acet-
D
pyranose (a,b-glucosamine pentaacetate, 34) in 90%
yield. Glucosamine pentaacetate 34 (1 g, 2.6 mmol) in
AcCl (6.0 mL, 84.1 mmol) and dry MeOH (60 mL) was
refluxed 14 h to afford methyl 2-amino-2-deoxy-a-
glucopyranoside (415 mg, 70%).18 Methyl 2-amino-2-
deoxy-a-glucopyranoside (300 mg, 1.3 mmol) in Et3N
(0.4 mL (2.6 mmol), Fmoc-OSu (525 mg (1.6 mmol), and
pyridine (30 mL) were stirred overnight. The solution
was concentrated in vacuo, and the residue was dis-
solved in CH2Cl2 (100 mL). The solution was washed
with water, aq NaHCO3, brine, and dried (Na2SO4).
The residue was purified by column chromatography to
provide 35 in 92% yield. 1H NMR (CD3OD, 500 MHz):
d 3.26 (m, 1H, H-5), 3.29 (s, 3H, OCH3), 3.45 (m, 1H,
H-4), 3.52 (m, 2H, H-2, H-3), 3.58–3.75 (m, 2H, H-6,
H-60), 4.14 (t, J 7.0 Hz, H-1, Fmoc-CH), 4.27 (m, 2H,
Fmoc-CH2), 4.58 (s, 1H, H-1), 7.22 (app-t, 2H, Fmoc-
Ar), 7.30 (app-t, 2H, Fmoc-Ar), 7.58 (m, 2H, Fmoc-Ar),
7.70 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR (CD3OD,
125 MHz): d 48.4 (Fmoc-CH), 55.6 (OCH3), 57.2 (C-2),
62.8 (C-6), 67.9 (Fmoc-CH2), 72.3 (C-5), 73.0 (C-3),
73.7 (C-4), 100.2 (C-1), 120.9, 126.2, 128.2, 128.8,
142.6, 145.2, 145.4, 158.9. HRFABMS: calcd for
C22H25NO7Na [M+Na]þ 438.1522, found: 438.1534.
4.21. Methyl 2-deoxy-2-(fluoren-9-ylmethoxycarbonyl-
amino)-b-D-glucopyranoside (32)
To a solution of 31b (400 mg, 0.74 mmol) in dry MeOH
(50 mL) was added 0.5 M NaOMe (0.1 mL, 0.05 mmol,
pH < 9), and the reaction was stirred for 20 min. The
methanolic solution was acidified with Dowex-50 (Hþ)
resin and evaporated to dryness. Purification of the
residue by column chromatography afforded 32 in 85%
1
yield. H NMR (CD3 OD, 500 MHz): d 3.13–3.23 (m,
3H, H-2, H-4, H-5), 3.30 (t, J 8.0 Hz, 1H, H-3), 3.35 (s,
3H, OCH3), 3.54 (dd, J 5.5, 12.0 Hz, 1H, H-6), 3.73 (d, J
12.0 Hz, 1H, H-60), 4.16–4.23 (m, 3H, H-1, Fmoc-CH,
Fmoc-CH2), 4.28 (m, 1H, Fmoc-CH2), 7.25 (app-t, 2H,

L. Ying, J. Gervay-Hague / Carbohydrate Research 339 (2004) 367–375
375
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4.24. Methyl 2-deoxy-2-(fluoren-9-ylmethoxycarbonyl-
amino)-a- -glucopyranosiduronic acid (36)
D
1
A white powder was obtained in 82% yield from 35. H
NMR (CD3OD, 500 MHz): d 3.28 (s, 3H, OCH3), 3.46
(t, J 8.0 Hz, 1H, H-4), 3.51 (t, J 8.0 Hz, 1H, H-3), 3.56
(dd, J 2.5, 8.0 Hz, 1H, H-2), 3.89 (d, J 8.0 Hz, 1H, H-5),
4.11 (t, J 7.0 Hz, 1H, Fmoc-CH), 4.24 (m, 2H, Fmoc-
CH2), 4.59 (d, J 2.5 Hz, 1H, H-1), 7.12 (app-t, 2H,
Fmoc-Ar), 7.27 (app-t, 2H, Fmoc-Ar), 7.55 (m, 2H,
Fmoc-Ar), 7.67 (d, J 7.5 Hz, 2H, Fmoc-Ar). 13C NMR
(CD3OD, 125 MHz): d 48.4 (Fmoc-CH), 56.01 (OCH3),
58.8 (C-2), 67.9 (Fmoc-CH2), 72.5 (C-3), 72.7 (C-5), 73.7
(C-4), 100.7 (C-1), 120.9, 126.24 126.3, 128.2, 128.8,
142.6, 145.2, 145.4, 158.9, 173.1 (C-6). HRFABMS:
calcd for C22H23NO8Na [M+Na]þ 452.1315, found
452.1338.
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8. Gregar, T. Q. Ph.D. Dissertation, The University of
Arizona, 2001.
This work was supported by National Science Foun-
dation CHE-0196482. NSF CRIF program (CHE-
9808183), NSF Grant OSTI 97-24412, and NIH Grant
RR11973 provided funding for the NMR spectrometers
used on this project.
€
ꢀ
ꢀ
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Chem. 1993, 12, 139–163; For more recent examples see:
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