Direct chemical glycosylation with pentenyl- and thioglycoside donors of N-acetylglucosamine

Article abstract of DOI:10.1016/j.carres.2010.02.013

The use of pentenyl and thiophenyl glycosides of N-acetylglucosamine (GlcNAc) as glycosyl donors for the direct preparation of O-glycosides of GlcNAc promoted by N-iodosuccinimide (NIS) and metal triflates in dichloromethane has been investigated. Both glycosyl acceptors 1-octanol and (-)-menthol resulted in good glycosylation yields for both types of donors with pentenyl glycosides being somewhat superior in terms of yield. Carbohydrate-based acceptors were reacted with a benzylated GlcNAc-pentenyl donor but only provided disaccharides in poor to moderate yields. The results show that a variety of metal triflates are capable of acting as an activator for both NIS and the intermediate oxazoline.

Full text of DOI:10.1016/j.carres.2010.02.013

Carbohydrate Research 345 (2010) 872–879
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Direct chemical glycosylation with pentenyl- and thioglycoside donors
of N-acetylglucosamine
*
Jonas Krag, Mira S. Christiansen, Jette G. Petersen, Henrik H. Jensen
Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 January 2010
Received in revised form 10 February 2010
Accepted 16 February 2010
Available online 19 February 2010
The use of pentenyl and thiophenyl glycosides of N-acetylglucosamine (GlcNAc) as glycosyl donors for
the direct preparation of O-glycosides of GlcNAc promoted by N-iodosuccinimide (NIS) and metal triflates
in dichloromethane has been investigated. Both glycosyl acceptors 1-octanol and (ꢀ)-menthol resulted in
good glycosylation yields for both types of donors with pentenyl glycosides being somewhat superior in
terms of yield. Carbohydrate-based acceptors were reacted with a benzylated GlcNAc-pentenyl donor but
only provided disaccharides in poor to moderate yields. The results show that a variety of metal triflates
are capable of acting as an activator for both NIS and the intermediate oxazoline.
Keywords:
NIS activation
Metal triflate
Ó 2010 Elsevier Ltd. All rights reserved.
Transient oxazoline intermediate
1. Introduction
2. Results and discussion
A recent statistical analysis has revealed that the most frequently
encountered monosaccharide in mammalian oligosaccharide
frameworks is the b-D-N-acetylglucosamine unit (b-D-GlcNAc)
Thioglycosides have become one of the preferred donor types8
in modern glycosylation chemistry9 owing to their stability under
protecting group manipulations and many modes of activation.
Traditional ‘van Boom-activation’ employing N-iodosuccinimide
(NIS) in combination with catalytic amounts of triflic acid (TfOH)10
or other harsh catalysts like TMSOTf is still widely used with suc-
cess. Silver triflate (AgOTf)11 seems to be the only Lewis acid salt
used for thioglycoside activation under ‘van Boom’-type condi-
tions,12 albeit Li, Na, K, Mg13 and Bi14 salts have been used in com-
bination with N-bromosuccinimide (NBS). Pentenyl glycoside
donors can too be activated by NIS/TfOH15 and recently Fraser-Reid
and co-workers have reported that Sc(OTf)3 and In(OTf)3 but not,
for example, Yb(OTf)3 act well as catalysts.7
GlcNAc thioglycoside donors have been used as precursors to
mask the reducing sugar for later glycosyl amine synthesis16,17
and recently with some success in glycosylation reactions.18–20
GlcNAc-pentenyl glycoside donors have only been used to a very
limited extent for the synthesis of oxazoline for enzymatic glyco-
sylation21 and for the chemical introduction of a 1-azido function22
and never in combination with metal triflates. To the best of our
knowledge there are no reports investigating GlcNAc-pentenyl gly-
coside donors as reactants in O-glycosylation reactions.
where it by far exceeds the occurrence of glucose.1 This fact makes
further development of glycosylation reactions with GlcNAc (Glc-
NAc-ylation), an important task in carbohydrate chemistry. It is well
known that GlcNAc-ylation is hampered by the formation of an
intermediate oxazoline which typically reacts only sluggishly as a
glycosyl donor to form the glycoside product. For this reason other
masking groups than the biologically relevant N-acetyl has been
used extensively resulting in the lengthening of the synthetic
sequence.2,3
We have recently shown that b-GlcNAc tetraacetate (1) is a useful
donor in combination with rare earth metal triflates as catalytic pro-
moters for the direct synthesis of b-glycosides of GlcNAc.4 In this
reaction, the catalyst acts as an activator for both oxazoline forma-
tion and oxazoline breakdown (Scheme 1A).4,5 The present work de-
scribes our attempts to expand the previous results obtained with
acetate donors to thiophenyl and pentenyl GlcNAc-donors using
N-iodosuccinimide (NIS) promotion relying on a catalytic amount
of metal triflates to act as an activator of both NIS6,7 and the interme-
diate oxazoline. As hydroxyl-protecting groups, the use of both
O-acetyl and O-benzyl has been investigated (Scheme 1B).
Acetyl-protected thioglycoside donor 2 was synthesised accord-
ing to the literature procedures,23,24 whereas acetylated pentenyl
donor 4 was prepared by our published method4 using 4-penten-
1-ol/Yb(OTf)3 from the b-acetate under microwave irradiation in
excellent yield (Scheme 2). Zemplén deacetylation of both 2 and
* Corresponding author. Tel.: +45 89423963; fax: +45 86196199.
E-mail address: hhj@chem.au.dk (H.H. Jensen).
4
followed by careful NaH/BnBr/DMF benzylation of the
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.02.013

J. Krag et al. / Carbohydrate Research 345 (2010) 872–879
873
(A)
OAc
O
OAc
O
OAc
O
Mx+
O
M(OTf)x (cat)
CH2Cl2
R'-OH
AcO
AcO
AcO
AcO
AcO
AcO
O
OR'
OR'
CH2Cl2
Mx+
AcHN
N
AcHN
O
1
oxazoline
(B)
OR
O
OR
OR
O
NIS, M(OTf)x (cat)
CH2Cl2
O
N
R'-OH
RO
RO
RO
RO
RO
RO
X
CH2Cl2
Mx+
AcHN
AcHN
O
R = Ac, X = SPh
R = Bn, X = SPh
2
3
4
5
oxazoline
R = Ac, X = OPent
R = Bn, X = OPent
Scheme 1. Direct chemical GlcNAc-ylation; (A) acetate donor, see Ref. 4; (B) thiophenyl and pentenyl donors, present study.
OH
O
OAc
O
OBn
O
OAc
O
AcCl (neat)
ref. 23
1) NaOCH3, CH3OH
2) NaH, BnBr, DMF
PhSH, Et3N
ref. 24
HO
HO
AcO
AcO
BnO
BnO
AcO
AcO
SPh
SPh
OH
AcHN
AcHN
AcHN
AcHN
Cl
74%
80% (two steps)
80%
GlcNAc, 6
2
3
7
OBn
O
OAc
O
OAc
O
1) NaOCH3, CH3OH
2) NaH, BnBr, DMF
60% (two steps)
4-Penten-1-ol, Yb(OTf)3 (15%)
CH2Cl2, 80 oC, 91%
BnO
BnO
AcO
AcO
AcO
AcO
OPent
OAc
OPent
AcHN
AcHN
AcHN
microwave irradiation
5
1
4
Scheme 2. Preparation of thiophenyl and pentenyl donors 2–5.
corresponding crude triols gave the semi-armed donors 3 and 5,
respectively. Considering the possibility of NHAc-alkylation using
this benzylation procedure the overall yield for protecting group
interchange was acceptable and in our hands superior to the
Ba(OH)2/BaO/BnBr-protocol.25
As a more challenging acceptor, the secondary alcohol (ꢀ)-men-
thol was chosen for direct GlcNAc-ylation with acetylated thiogly-
coside 2 promoted by NIS in combination with Sc(OTf)3, Cu(OTf)2,
or Yb(OTf)3 resulting in a noteworthy drop in both yield and reac-
tion time. The reaction conditions, however, still successfully pro-
duced the expected glycoside product in acceptable yields around
50% (Table 1, entries 7–9).
To investigate the effect of O-protecting groups on reactivity
and glycosylation yield a similar series of reactions was carried
out with the benzylated thioglycoside donor 3 (Scheme 1B). Full
activation was found to proceed smoothly at ambient temperature
indicating an increased reactivity of ether protected over ester-
protected glycosyl donors in accordance with the armed/disarmed
principle27 and relative reactivity values.28
As the expected intermediate oxazoline (Scheme 1B) did not ap-
pear to be stable to TLC analysis hampering reaction monitoring, the
acceptor (1-octanol) was chosen to be the limiting reagent (Table 2,
entries 1–5). Only moderate yields (39–54%) being largely indepen-
dent of the catalyst could be isolated under these conditions. Upon
Cu(OTf)2-promoted reaction with secondary acceptor (ꢀ)-menthol,
a further drop in yield to 28% was observed (Table 2, entry 8).
However, changing the reaction stoichiometry by making the
thioglycoside (3) donor the limiting reagent a significant yield
improvement in both reactions with 1-octanol (Table 2, entry 6)
and (ꢀ)-menthol (Table 2, entry 9) was observed. Conducting the
reaction at reflux in CH2Cl2 had an insignificant effect on octyl gly-
coside formation (Table 2, entry 7).
Glycosylation was first explored with disarmed thioglycoside do-
nor 2 and 1-octanol as the acceptor at reflux in CH2Cl2 (Table 1, en-
tries 1–6). All metal triflates tested resulted in immediate colour
change of the reaction mixture and full conversion of the starting
material to the expected oxazoline intermediate as indicated by thin
layer chromatography (TLC) analysis. The yield of the product glyco-
side (8) was found largely to be independent of the catalyst used,
with Cu(OTf)2 giving slightly higher yield (76%) than the other metal
triflates (Sc(III), Yb(III), Zn(II) and Mg(II)) investigated, with Zn(OTf)2
giving the lowest isolated yield (52%). As previously found for the
activation of the acetylated acetate donor 1, the more Lewis acidic
26
Sc(OTf)3 proved to be the most active catalyst investigated with
Yb(OTf)3, Cu(OTf)2 and Zn(OTf)2 being less active. Mg(OTf)2 was
found to be the least active catalyst tested in the reaction with
NIS/2 only fully consuming the oxazoline intermediate by TLC anal-
ysis after 9.5 h. Interestingly, Yb(OTf)3 has previously been found to
be significantly less active than both Sc(OTf)3 and Cu(OTf)2 in the
activation of 1.4 This order of reactivity may indicate that Yb(OTf)3
is a more reactive catalyst for the activation of the intermediate
oxazoline5 than Cu(OTf)2, while the opposite holds true for the acti-
vation of acetate donor 1.4 As indicated by TLC analysis of the two
types of reactions (Scheme 1 A vs B) this originates from the resting
state of the thioglycoside activation being the oxazoline, while for
the acetate activation it is the acetate itself.
We next undertook a study of GlcNAc pentenyl donors 4 and 5
in combination with NIS/metal triflate promoters under similar

874
J. Krag et al. / Carbohydrate Research 345 (2010) 872–879
Table 1
Glycosylation results obtained in CH2Cl2, M(OTf)x 15 mol % with respect to thioglycoside donor 2
Entry
Donor
Acceptor
Product
D/Aa
Activation
Temp
Time (h)
Yieldb (%)
OAc
O
AcO
AcO
Sc(OTf)3
NIS
O
1
2
1-Octanol
1:3
Reflux
2
67
AcHN
7
8
2
3
4
5
6
2
2
2
2
2
1-Octanol
1-Octanol
1-Octanol
1-Octanol
1-Octanol
8
8
8
8
8
1:3
1:3
1:3
1:3
1:3
Yb(OTf)3
NIS
Cu(OTf)2
NIS
Zn(OTf)2
NIS
Mg(OTf)2
NIS
Reflux
Reflux
Reflux
Reflux
Reflux
3
65
76
52
67
69
4.5
4.5
9.5
16
Sc(OTf)3
NIS
OAc
O
Yb(OTf)3
NIS
AcO
AcO
7
2
(ꢀ)-Menthol
1:2
Reflux
23
54
O
AcHN
9
8
9
2
2
(ꢀ)-Menthol
(ꢀ)-Menthol
9
9
1:2
1:2
Sc(OTf)3
NIS
Cu(OTf)2
NIS
Reflux
Reflux
23
23
46
50
a
Donor/acceptor ratio.
Isolated yield.
b
Table 2
Glycosylation results obtained in CH2Cl2, M(OTf)x 15 mol % with respect to thioglycoside donor 3
Entry
Donor
Acceptor
Product
D/Aa
Activation
Temp
rt
Time (h)
16
Yieldb (%)
OBn
O
BnO
BnO
Sc(OTf)3
NIS
O
1
3
1-Octanol
2:1
39
AcHN
7
10
2
3
4
5
6
7
3
3
3
3
3
3
1-Octanol
1-Octanol
1-Octanol
1-Octanol
1-Octanol
1-Octanol
10
10
10
10
10
10
2:1
2:1
2:1
2:1
1:3
1:3
Yb(OTf)3
NIS
Cu(OTf)2
NIS
Zn(OTf)2
NIS
Mg(OTf)2
NIS
Cu(OTf)2
NIS
Cu(OTf)2
NIS
rt
16
16
16
16
16
16
49
50
43
54
71
70
rt
rt
rt
rt
Reflux
OBn
O
Cu(OTf)2
NIS
BnO
BnO
8
9
3
3
(ꢀ)-Menthol
(ꢀ)-Menthol
2:1
1:2
rt
rt
16
16
28
67
O
AcHN
11
11
Cu(OTf)2
NIS
a
Donor/acceptor ratio.
Isolated yield.
b
conditions as described for the corresponding thioglycoside donors
(vide supra). Jayaprakash and Fraser-Reid have described the suc-
cessful use of Sc(OTf)3 in the activation of armed and disarmed
n-pentenyl glucoside and mannoside donors, but have also noted
that milder metal triflates like Yb(OTf)3 do not promote glycosyla-
tion in combination with NIS.7
We first investigated the activation of disarmed pentenyl do-
nor 4 with NIS/Sc(OTf)3 in the presence of 1-octanol (Table 3, en-
try 1). This successfully produced the octyl glycoside product
although in a disappointing yield of 50%. We next turned to the
more reactive, semi-armed donor 5 where GlcNAc-ylation was
carried out according to the standard modus operandi for pentenyl

J. Krag et al. / Carbohydrate Research 345 (2010) 872–879
875
Table 3
Glycosylation results obtained in CH2Cl2, M(OTf)x 15 mol % with respect to pentenyl donors 4 and 5
Entry
1
Donor
Acceptor
Product
D/Aa
1:3
Activation
Temp
Time
3 h
Yieldb
4
1-Octanol
8
Sc(OTf)3
NIS
Sc(OTf)3
NIS
Yb(OTf)3
NIS
Cu(OTf)2
NIS
Zn(OTf)2
NIS
Mg(OTf)2
NIS
Yb(OTf)3
NIS
Sc(OTf)3
NIS
Cu(OTf)2
NIS
Mg(OTf)2
NIS
Zn(OTf)2
NIS
TfOH
Reflux
50
88
81
84
88
85
53
65
76
42
73
67
2
3
5
5
5
5
5
5
5
5
5
5
5
1-Octanol
10
10
10
10
10
11
11
11
11
11
11
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
16 h
16 h
16 h
16 h
16 h
24 h
25 h
25 h
24 h
26 h
26 h
1-Octanol
4
1-Octanol
5
1-Octanol
6
1-Octanol
7
(ꢀ)-Menthol
(ꢀ)-Menthol
(ꢀ)-Menthol
(ꢀ)-Menthol
(ꢀ)-Menthol
(ꢀ)-Menthol
8
9
10
11
12
NIS
OH
OBn
O
O
O
O
BnO
BnO
O
O
O
NHAc
O
Cu(OTf)2
NIS
O
13
5
3:1
rt
5 days
37
O
O
12
O
O
15
OH
OBn
O
O
BnO
BnO
BnO
BnO
Cu(OTf)2
NIS
14
15
5
5
3:1
3:1
rt
rt
2 days
50
BnO
OMe
NHAc
O
BnO
BnO
13
BnO
OMe
16
OH
OBn
O
O
BzO
BzO
BnO
BnO
O
Cu(OTf)2
NIS
2 days
17
BzO
OMe
NHAc
O
BzO
14
BzO
BzO
OMe
17
a
Donor/acceptor ratio.
Isolated yield.
b
donor glycosylation with excess donor and NIS.7,29 As in the case
of the analogous thioglycoside donor (3) all metal triflates were
found to catalyse donor activation, which is in contrast to other
pentenyl donors not being activated by Yb(OTf)3 (vide supra).7
Although the reactions were carried out at room temperature,
full activation was found to occur within minutes even at 0 °C.
In GlcNAc-ylation of 1-octanol, the yields were significantly high-
er (81–88%) compared to those of the thioglycoside examples
(39-54%) but also largely independent of the metal triflate used
(Table 3, entries 2–6). The pentenyl glycoside donor (5) was also
superior in terms of yield to the analogous thioglycoside (3) in
GlcNAc-ylation of secondary alcohol (ꢀ)-menthol where yields
ranged between 42% and 76% (Table 3, entries 7–11), with
Cu(OTf)2 giving the best result. Traditional NIS-activation with tri-
fluoromethanesulfonic acid (TfOH)15 (entry 12) was also found to
efficiently give the (ꢀ)-menthyl glycoside (11) in acceptable yield
(67%).
NIS/Cu(OTf)2-mediated direct GlcNAc-ylation of carbohydrate-
based acceptors (12–14)30 was next investigated with the superior
pentenyl donor system (Table 3, entries 13–15) and indeed found
to be possible. However, a significant drop in the yield and exten-
sion of the reaction time was observed for all three acceptors (12–
14) despite them being primary alcohols. Diacetone galactose (12)
could be GlcNAc-ylated in only 37% yield, whereas benzylated glu-
coside 13 gave a moderate glycosylation yield of 50%. The more
electron poor primary alcohol of benzoylated glucoside 14 gave a
disappointing yield of 17%.
Pentenyl glycosides and especially thioglycosides are widely
used efficient donors in glycosylation reactions but this study has
shown a noteworthy difference between the two types with re-
spect to direct GlcNAc-ylation in terms of reaction yield with the
former being superior. This could be a result of the pentenyl donor
by-products being more benign than those arising from thioglyco-
side activation.

876
J. Krag et al. / Carbohydrate Research 345 (2010) 872–879
The present method of pentenyl glycoside-mediated GlcNAc-
dry MeCN (60 mL). The reaction mixture was stirred at room tem-
perature under an atmosphere of nitrogen. After 2 h, TLC analysis
showed full conversion of the starting material. The mixture was
diluted with CH2Cl2, washed with aq HCl (0.5 M), water, brine,
dried (MgSO4), filtered and concentrated. Column chromatography
(CH2Cl2/EtOAc 1:1?1:2?1:4?EtOAc) gave the phenyl thioglyco-
side 3 as a white solid (5.197 g, 80%). Rf (EtOAc/CH2Cl2 1:3) 0.46.
Mp 205–206 °C. 1H NMR (CDCl3): d 7.51–7.48 (m, 2H, Ar), 7.30–
7.29 (m, 3H, Ar), 5.58 (d, 1H, JNH,2 9.6 Hz, NH), 5.22 (t, 1H, J
9.6 Hz, H-3), 5.05 (t, 1H, H-4), 4.85 (d, 1H, J1,2 9.6 Hz, H-1), 4.21
(dd, 1H, J5,6a 5.4 Hz, J6a,6b 12.2 Hz, H-6a), 4.16 (dd, 1H, J5,6b 2.6 Hz,
H-6b), 4.02 (q, 1H, J 9.6 Hz, H-2), 3.72 (ddd, 1H, J5,6b 2.6 Hz, J5,6a
5.4 Hz, J4,5 9.6 Hz, H-5), 2.07, 2.02, 2.01, 1.98 (s, 12H, COCH3). 13C
NMR (CDCl3): d 171.2, 170.8, 170.2, 169.5 (COCH3), 132.7, 129.1,
128.3, (Ar), 86.9 (C-1), 76.0 (C-5), 73.9 (C-3), 68.6 (C-4), 62.6
(C-6), 53.6 (C-2), 23.6, 21.0, 20.9, 20.8 (COCH3). LRMS(ES+):
calcd for C20H25O8NSNa: 462.1; found: 462.1. The spectral data
were in accordance with the previously published values, see
Ref. 24.
ylation appears to be equally efficient to our previously published
method involving acetate donors (Scheme 1A)4 in reaction with
simple primary and secondary alcohols. In the reaction with more
demanding carbohydrate-based acceptors, however, the yields
seem to be somewhat diminished. We believe this to be the result
of the unfavourable resting state of the pentenyl glycoside method,
which according to TLC analysis is the oxazoline intermediate. This,
contrary to the slowly converting acetate donor 1, produces a high
concentration of the oxazoline in solution, which in the presence of
less reactive alcohols is capable of reacting as an acceptor causing
unproductive dimerisation.
The results presented here clearly demonstrate that it is possi-
ble to perform direct GlcNAc-ylation with traditionally used
pentenyl and thioglycoside donors and exclusively obtain the bio-
logically important b-anomers. The glycosylation reaction was
found to be largely independent of the choice of the metal triflate
tested. The yields were found to be good in the case of simple
acceptors such as 1-octanol and (ꢀ)-menthol, but moderate to
poor in the case of carbohydrate-based acceptors. It, however,
has to be kept in mind that several protecting group manipulation
is avoided when performing direct GlcNAc-ylation, and we believe
that this in certain cases can be a viable alternative to known gly-
cosylation methods employing traditional N-protecting groups
such as phthalimido and trichloroethylcarbamate.
3.2. Phenyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-1-thio-b-D-
glucopyranoside (3)
Sodium methoxide (0.5 M in MeOH) (2.0 mL, 1.00 mmol) was
added to a suspension of acetyl-protected thiophenyl glycoside 2
(3.629 g, 8.26 mmol) in dry MeOH (50 mL). The reaction mixture
was stirred at room temperature under an atmosphere of nitrogen.
After 10 min, an aliquot of the precipitated product was analysed
by NMR, which showed the reaction completion. The mixture
was concentrated and co-evaporated several times with toluene
to give the deprotected thioglycoside as a white solid (2.816 g
crude). This was pure enough for further reaction. Rf (MeOH/EtOAc
1:2) 0.57. 1H NMR (D2O): d7.50–7.48 (m, 2H, Ar), 7.31–7.23 (m, 3H,
Ar), 4.78 (d, 1H, J1,2 10.4 Hz, H-1), 3.87 (dd, 1H, J5,6a 2.4 Hz, J6a,6b
12.4 Hz, H-6a), 3.76 (dd, 1H, J2,3 9.6 Hz, J1,2 10.4 Hz, H-2), 3.68
(dd, J5,6b 5.6 Hz, H-6b), 3.49–3.32 (m, 3H, H-3, H-4, H-5), 1.99 (s,
3H, COCH3). The deprotected thioglycoside (2.816 g crude) was dis-
solved in dry DMF (35 mL) and cooled to 0 °C before sodium hy-
dride (60% in mineral oil) (1.00 g, 25.0 mmol) and benzyl
bromide (3.90 mL, 32.8 mmol) were added. The reaction mixture
was stirred under an atmosphere of nitrogen and allowed to warm
to room temperature. TLC analysis after 22 h indicated incomplete
reaction. Additional sodium hydride (60% in mineral oil) (329 mg,
8.22 mmol) was added. After five days, the reaction mixture was
diluted with water and then EtOAc causing precipitation. The
aqueous phase was removed and the organic phase was filtered.
The precipitated product was washed repeatedly with water and
then co-evaporated several times with toluene. The organic filtrate
was washed alternately with water and brine, dried (MgSO4), fil-
tered and concentrated. The combined crude mixture was purified
by column chromatography (EtOAc/CH2Cl2 5:95?8:92) to give the
benzylated thioglycoside 3 as a white solid (3.854 g, 80% over two
3. Experimental section
All reagents except otherwise stated were used as purchased
from Sigma–Aldrich without further purification. Oven-dried
glassware (ca. 120 °C) was used for the reactions carried out under
nitrogen or argon atmosphere. The solvents were dried according
to the standard procedures prior to use.32 Dichloromethane was
dried by distillation over CaH2. THF was dried over sodium and dis-
tilled from benzophenone. Flash chromatography was performed
with Merck silica 60 (230–400 mesh) as stationary phase and TLC
was performed on silica-coated aluminium plates (Merck 60
F254). TLC plates were first observed in UV-light and then visualised
with ceric sulphate/ammonium molybdate in 10% H2SO4 stain or
KMnO4-stain. 1H NMR (400 MHz) and 13C NMR (100 MHz) were re-
corded at a Varian Mercury 400 spectrometer. CDCl3 (d 7.26 ppm
(CHCl3) for proton and d 77.16 ppm for carbon resonances) and
D2O (d 4.79 ppm for proton) were used as internal references.
Spectra were assigned based on gCOSY, gHMQC and DEPT-135
experiments. MS spectra were recorded at a Micromass LC-TOF
instrument by using electrospray ionisation (ESI). High resolution
spectra were recorded with either of the following compounds as
internal standard: (Boc-L-alanine: C8H15NO4Na: 212.0899; BzGly-
PheOMe: C19H20N2O4Na: 363.1321; BocSer(OBn)SerLeuOMe: C25
-
H39N3O8Na: 532.2635; erythromycin: C37H67NO13Na: 756.4510).
Masses of standards and analytes are calculated and reported in
Daltons for uncharged species. Melting points were measured on
a Büchi B-540 instrument and are uncorrected. Optical rotation
was measured on a PE-241 polarimeter and reported in units of
degꢁcm2/g. Concentrations are reported in g/100 mL. Microwave
experiments were carried out on a Biotage Initiator (Biotage, Swe-
steps). Rf (EtOAc/pentane 1:1.5) 0.31. Mp 177–181 °C. ½a D23
ꢂ
14.5 (c
1.0, CHCl3). 1H NMR (CDCl3): d 7.52–7.49 (m, 2H, Ar), 7.34–7.21 (m,
18H, Ar), 5.35 (d, 1H, JNH,2 8.4 Hz, NH), 5.05 (d, 1H, J1,2 10.0 Hz, H-
1), 4.83 (d, 1H, 2J 12.0 Hz, OCH2Ph), 4.80 (d, 1H, 2J 12.0 Hz, OCH2Ph),
4.64 (d, 1H, 2J 12.0 Hz, OCH2Ph), 4.61 (d, 1H, 2J 12.0 Hz, OCH2Ph),
4.60 (d, 1H, 2J 12.0 Hz, OCH2Ph), 4.53 (d, 1H, 2J 12.0 Hz, OCH2Ph),
3.99 (t, 1H, J 9.2 Hz, H-3), 3.79 (dd, 1H, J5,6a 2.0 Hz, J6a,6b 11.2 Hz,
H-6a), 3.74 (dd, 1H, J5,6b 4.4 Hz, H-6b), 3.66–3.58 (m, 3H, H-2, H-
4, H-5), 1.87 (s, 3H, COCH3). 13C NMR (CDCl3): d 170.5 (COCH3),
138.5, 138.3, 133.6, 132.2, 129.1–127.7 (Ar), 85.9 (C-1), 82.5 (C-
3), 79.4, 78.8 (C-3, C-4), 75.1, 75.0, 73.7 (OCH2Ph), 69.3 (C-6),
55.6 (C-2), 23.8 (COCH3). HRMS(ES+): calcd for C35H37O5NSNa:
606.2290; found: 606.2301.
´
´
den). Reaction times listed refer to hold time at the specified
temperature.
3.1. Phenyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-D-
glucopyranoside (2)
Thiophenol (1.80 mL, 17.6 mmol) and triethylamine (4.20 mL,
30.1 mmol) were added to 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-a-D
-glucopyranosyl chloride (7)23 (5.483 g, 15.0 mmol) in

J. Krag et al. / Carbohydrate Research 345 (2010) 872–879
877
3.3. 4-Pentenyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
glucopyranoside (4)
D-
was observed by TLC analysis, the mixture was diluted with
CH2Cl2, washed with aq Na2S2O3/NaHCO3, brine, dried (MgSO4), fil-
tered and concentrated. the products were purified by column
chromatography on silica.
Peracetylated b-GlcNAc 1 (3.00 g, 7.7 mmol), 4-penten-1-ol
(1.6 mL, 15.4 mmol) and Yb(OTf)3 (720 mg, 1.16 mmol) were dis-
solved in dry CH2Cl2 (7.5 mL) in a microwave vial under nitrogen
atmosphere and heated at 80 °C under microwave irradiation for
1 h. The reaction mixture was diluted with CH2Cl2 and washed
with saturated NaHCO3, dried over MgSO4 and filtered. The resi-
due was purified by column chromatography (pentane/EtOAc
2:1?EtOAc) to give the pentenyl glycoside (2.90 g, 91%) as a
white solid. Rf (EtOAc) 0.43. Mp 127–129 °C, 1H NMR (CDCl3): d
5.77 (m, 1H, CH@CH2), 5.60 (d, 1H, JNH,2 8.4 Hz, NH), 5.29 (t, 1H,
J 10.0 Hz, H-3), 5.00 (m, 3H, H-4, CH@CH2), 4.66 (d, 1H, J1,2
8.0 Hz, H-1), 4.25 (dd, 1H, J6a,5 4.4 Hz, J6a,6b 12.0 Hz, H-6a), 4.12
(dd, 1H, J6b,5 2.0 Hz, H-6b), 3.84 (m, 2H, OCHH, H-2) 3.69 (ddd,
1H, J5,6b 2.4 Hz, J4,5 10.0 Hz, H-5) 3.48 (m, 1H, OCHH), 2.02 (m,
14H, –CH2–, COCH3), 1.66 (m, 2H, –CH2–). 13C NMR (CDCl3): d
171.0, 171.0, 170.6, 169.6 (COCH3), 138.1 (CH2@CH2), 115.2
(CH2@CH2), 100.9 (C-1), 72.7, 71.8, 69.3, 69.1, 62.5, 54.9 (C-2, C-
3, C-4, C-5, C-6, OCH2), 30.1, 28.8 (CH2) 23.4, 21.0, 20.9, 20.8
(COCH3). LRMS(ES+) calcd for C19H29NO9Na: 438.2; found 438.1.
The spectral data were in accordance with the previously pub-
lished values, see Ref. 31.
3.6. n-Octyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-D-
glucopyranoside (8)
White solid. Rf (pentane/EtOAc 1:2) 0.27. Mp 124–126 °C. 1H
NMR (CDCl3): d 5.97 (d, 1H, JNH,2 8.8 Hz, NH), 5.27 (dd, 1H, J2,3
9.2 Hz, J3,4 10.2 Hz, H-3), 5.01 (t, 1H, J 10.2 Hz, H-4), 4.66 (d,
1H, J1,2 8.0 Hz, H-1), 4.22 (dd, 1H, J5,6a 4.8 Hz, J6a,6b 12.2 Hz, H-
6a), 4.08 (dd, 1H, J5,6b 2.4 Hz, H-6b), 3.82–3.76 (m, 2H, H-2,
OCH2), 3.68 (ddd, 1H, H-5), 3.43 (dt, 1H, 2J 9.6 Hz, 3J 6.8 Hz,
OCH2), 2.03, 1.98, 1.97, 1.89 (s, 12H, COCH3), 1.51 (br s, 2H,
OCH2CH2), 1.20 (br s, 10 H, OCH2CH2(CH2)5CH3), 0.82 (t, 3H, J
7.0 Hz, O(CH2)7CH3). 13C NMR (CDCl3): d 171.0, 170.9, 170.5,
169.6 (COCH3), 100.9 (C-1), 72.7 (C-3), 71.9 (C-5), 70.1 (OCH2),
69.1 (C-4), 62.5 (C-6), 54.9 (C-2), 32.0, 29.6, 29.5, 29.4, 26.0
(CH2), 23.4 (COCH3) 22.8 (CH2), 20.9, 20.9, 20.8 (COCH3), 14.3
(O(CH2)7CH3). LRMS (ES+): calcd for C22H37O9NNa: 482.2; found:
482.2. The spectral data were in accordance with the previously
published values, see Ref. 33.
3.7. (ꢀ)-Menthyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
D-
3.4. 4-Pentenyl 2-acetamido-3,4,6-O-tri-benzyl-2-deoxy-b-D-
glucopyranoside (5)
glucopyranoside (9)
White solid. Rf (pentane/EtOAc 1:2) 0.30. Mp 201–204 °C. 1H
NMR (CDCl3): d 5.53 (d, 1H, JNH,2 8.8 Hz, NH), 5.40 (dd, 1H, J3,4
9.6 Hz, J2,3 10.8 Hz, H-3), 5.01 (t, 1H, J 9.6 Hz, H-4), 4.79 (d, 1H,
J1,2 8.4 Hz, H-1), 4.17 (dd, 1H, J5,6a 5.6 Hz, J6a,6b 11.8 Hz, H-6a),
4.10 (dd, 1H, J5,6b 2.8 Hz, H-6b), 3.71–3.62 (m, 2H, H-2, H-5), 3.39
(dt, 1H, J 4.4 Hz, J 10.8 Hz, CHOGlcNAc), 2.22 (d septet, 1H, J
2.4 Hz, J 6.8 Hz, CH(CH3)2), 2.04, 2.01, 2.01, 1.93 (s, 12H, COCH3),
1.89 (m, 1H, H-60eq), 1.64–1.60 (m, 2H), 1.33 (m, 1H), 1.18 (m,
1H), 0.96–0.75 (m, 3H), 0.89 (d, 3H, J 6.8 Hz, CH3CHCH3), 0.85 (d,
3H, J 7.2 Hz, CH3CHCH3), 0.72 (d, 3H, J 7.2 Hz, CH3). 13C NMR
(CDCl3): d 170.9, 170.8, 170.3, 169.7 (COCH3), 98.3 (C-1), 78.7
(CHOGlcNAc), 72.5 (C-3), 71.5 (C-5), 69.4 (C-4), 62.8 (C-6), 55.6
(C-2), 47.7, 40.9, 34.4, 31.6, 25.1, 23.5 (COCH3), 23.1, 22.4, 21.1,
20.9, 20.8, 20.8 (COCH3), 15.5. HRMS(ES+): calcd for C24H39O9NNa:
508.2523; found: 508.2517. The spectral data were in accordance
with the previously published values, see Ref. 34.
A catalytic amount of a freshly prepared solution of NaOCH3 in
MeOH (1 M, 5 mL, 5 mmol) was added to acetylated pentenyl gly-
coside 4 (2.80 g, 7.17 mmol) in dry MeOH (20 mL) under nitrogen
atmosphere. After 45 min TLC analysis indicated full consumption
of the starting material and the reaction mixture was then concen-
trated under reduced pressure. The resulting solid was dissolved in
dry DMF (25 mL) and cooled to 0 °C before NaH (60% in mineral oil)
(1.13 g, 28.3 mmol) and BnBr (4.5 mL, 37.7 mmol) were added.
Additional NaH (377 mg, 9.4 mmol) was added after 20 h and
92 h. The reaction mixture was then poured into water and the
formed precipitate was filtered off and recrystallised from cyclo-
hexane/EtOAc to give the benzylated glycoside (3.09 g, 60%) as a
white solid. Rf (pentane/EtOAc 1:1) 0.45. Mp 129–131 °C. ½a D23
ꢂ
ꢀ10.4 (c 1, CHCl3). 1H NMR (CDCl3) d 7.37–7.18 (m, 15 H, ArH),
5.80 (ddt, 1H, J 6.8 Hz J 10.2 Hz J 17.0 Hz –CH@CH2), 5.54 (d, 1H,
JNH,2 8.0 Hz, NH), 5.00 (dd, 1H, J 1.4 Hz, J 17.0 Hz, H-50), 4.95 (dd,
1H, J 1.4 Hz, J 10.2 Hz, H-50), 4.83–4.77 (m, 2H, PhCH, H-1), 4.67–
4.50 (m, 5H, PhCH), 4.10 (dd, 1H, J 1.6 Hz, J 8.0 Hz, H-3), 3.86 (dt,
1H, 3J 6.4 Hz, 2J 10.0 Hz, OCH2(CH2)2), 3.77 (dd, 1H, J5,6a 2.2 Hz,
J6a,6b 10.6 Hz, H-6a) 3.71 (dd, 1H, J5,6b 4.4 Hz, H-6b), 3.63 (t, 1H, J
9.0 Hz, H-4), 3.58 (ddd, 1H, J4,5 9.0 Hz, H-5), 3.47 (dt, 1H, 3J
6.4 Hz, 2J 13.6 Hz, OCH2(CH2)2), 3.42–3.35 (m, 1H, H-2), 2.09 (m,
2H, CH2), 1.85 (s, 3H, HNCOCH3), 1.65 (m, 2H, CH2). 13C NMR
3.8. n-Octyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-b-D-
glucopyranoside (10)
White solid. Rf (pentane/EtOAc 1:1) 0.55. Mp 115–118 °C. ½a D23
ꢂ
14.2 (c 1.0, CHCl3). 1H NMR (CDCl3): d 7.35–7.19 (m, 15H, Ar),
5.56 (d, 1H, JNH,2 8.0 Hz, NH), 4.82 (d, 1H, 2J 11.4 Hz, OCH2Ph),
4.82 (d, 1H, J1,2 8.0 Hz, H-1), 4.78 (d, 1H, 2J 11.4 Hz, OCH2Ph),
4.67 (d, 1H, 2J 11.4 Hz, OCH2Ph), 4.62 (d, 1H, 2J 12.2 Hz, OCH2Ph),
4.58 (d, 1H, 2J 11.4 Hz, OCH2Ph), 4.55 (d, 1H, 2J 12.2 Hz, OCH2Ph),
4.13 (dd, 1H, J2,3 8.0 Hz, J3,4 9.6 Hz, H-3), 3.85 (dt, 1H, 3J 6.8 Hz,
2J 9.6 Hz, OCH2(CH2)6CH3), 3.77 (dd, 1H, J5,6a 2.4 Hz, J6a,6b 11.0 Hz,
H-6a), 3.72 (dd, 1H, J5,6b 4.4 Hz, H-6b), 3.65-3.58 (m, 2H, H-4,
H-5), 3.45 (dt, 1H, 3J 6.8 Hz, 2J 9.6 Hz, OCH2(CH2)6CH3), 3.38 (q,
(CDCl3)
d 170.5 (COCH3), 138.7, 138.4, 138.3, 138.3 (ipso-C,
CH@CH2), 128.7, 128.6, 128.6, 128.2, 128.1, 128.0, 127.8 (Ar),
115.2 (CH@CH2), 100.1 (C-1), 80.5, 79.8, 75.0, 74.8, 73.7, 69.3,
69.1 (C-2, C-3, C-4, C-5, C-6, PhCH2), 57.1, 30.3, 29.0 (CH2), 23.8
(COCH3). HRMS(ES+) calcd for C34H41O6Na: 582.2828; found
582.2825.
1H,
J 8.0 Hz, H-2), 1.85 (s, 3H, COCH3), 1.56 (br s, 2H,
3.5. General procedure for the coupling of glycosyl donors to
various acceptors
OCH2CH2(CH2)5CH3), 1.26 (br s, 10H, OCH2CH2(CH2)5CH3), 0.88 (t,
3H, J 6.4 Hz, O(CH2)7CH3). 13C NMR (CDCl3): d 170.5, (COCH3),
138.8, 138.5, 138.3, 128.7–127.8, 100.0 (C-1), 80.6 (C-3), 79.0,
75.0 (C-4, C-5), 74.8, 74.8, 73.7 (OCH2Ph), 69.9 (OCH2(CH2)6CH3),
69.3 (C-6), 57.4 (C-2), 32.1, 29.8, 29.6, 29.5, 26.2 (CH2), 23.8
(COCH3) 22.9 (1 CH2), 14.3 (O(CH2)7CH3). HRMS(ES+): calcd for
C37H49O6NNa: 626.3458; found: 626.3453.
Donor 2, 3, 4 or 5 (100 or 200 mg, 1 equiv), N-iodosuccinimide32
(2.5 equiv), acceptor and M(OTf)x (0.15 equiv) were dissolved in
dry CH2Cl2 (2.0 mL) and heated to reflux (in the case of 2 and 4)
or stirred at ambient temperature (in the case of 3 and 5) under
an atmosphere of nitrogen. When no further reaction development

878
J. Krag et al. / Carbohydrate Research 345 (2010) 872–879
3.9. (ꢀ)-Menthyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-b-
D
-
80.4, 80.0, 79.0, 77.9, 76.0, 75.2, 75.0, 74.8, 74.8, 73.6, 69.8, 69.4,
67.7 (PhCH, C-3, C-30, C-4, C-40, C-5, C-50, C-6, C-60, OCH3) 57.0,
55.3 (C-2, C-20) 23.8 (COCH3). LRMS(ES+) calcd for C57H63NO11Na:
960.43; found 960.4. The spectral data were in accordance with
the previously published values, see Ref. 36.
glucopyranoside (11)
Colourless oil. Rf (pentane/EtOAc 1:2) 0.29. ½a D23
ꢀ5.6 (c 1.0,
ꢂ
CHCl3). 1H NMR (CDCl3): d 7.19–7.11 (m, 15H, Ar), 5.53 (d, 1H,
JNH,2 7.2 Hz, NH), 4.95 (d, 1H, J1,2 8.4 Hz, H-1), 4.85 (d, 1H, 2J
12.0 Hz, OCH2Ph), 4.81 (d, 1H, 2J 11.2 Hz, OCH2Ph), 4.67 (d, 1H, 2J
12.0 Hz, OCH2Ph), 4.64 (d, 1H, 2J 11.2 Hz, OCH2Ph), 4.62 (d, 1H, 2J
12.2 Hz, OCH2Ph), 4.54 (d, 1H, 2J 12.2 Hz, OCH2Ph), 4.33 (dd, 1H,
J2,3 8.8 Hz, J3,4 9.6 Hz, H-3), 3.75 (dd, 1H, J5,6a 4.2 Hz, J6a,6b
11.0 Hz, H-6a), 3.69 (dd, 1H, J5,6b 1.8 Hz, H-6b), 3.62 (t, 1H, J
9.6 Hz, H-4), 3.51 (ddd, 1H, H-5), 3.42 (dt, 1H, J 4.4 Hz, J 10.8 Hz,
CHOGlcNAc), 3.13 (m, 1H, H-2), 2.31 (d septet, 1H, J 2.8 Hz,
J 7.2 Hz, CH(CH3)2), 1.93 (m, 1H), 1.84 (s, 3H, COCH3), 1.64–1.61
(m, 2H), 1.32 (m, 1H), 1.18 (m, 1H), 0.97–0.74 (m, 3H), 0.89 (d,
3H, J 6.0 Hz, CH3CHCH3), 0.88 (d, 3H, J 7.2 Hz, CH3CHCH3), 0.79
(d, 3H, J 6.8 Hz, CH3). 13C NMR (CDCl3): d 170.6 (COCH3), 139.0,
138.6, 138.5, 128.6–127.7 (Ar), 97.5 (C-1), 80.7 (C-3), 79.4 (C-4),
78.3, 75.0 (C-5, OCH2Ph), 73.9 (OCH2Ph), 69.5 (C-6), 58.8 (C-2),
48.1, 41.1, 34.6, 31.6, 25.3, 23.8 (COCH3), 23.3, 22.5 (CH3), 21.3
(CH3), 16.0 (CH3). HRMS(ES+): calcd for C39H51O6NNa: 652.3614;
found: 652.3611.
3.12. Methyl O-(2-N-acetamido-2-deoxy-3,4,6-tri-O-benzyl-b-D-
glucopyranosyl)-(1?6)-2,3,4-tri-O-benzoyl-a-D-
glucopyranoside (17)
Colourless syrup. Purified by column chromatography (CH2Cl2/
EtOAc 8:1). Rf 0.23 (CH2Cl2/EtOAc 8:1). 1H NMR (CDCl3) d 7.89 (d,
2H, J 7.6 Hz, ArH), 7.85 (d, 2H, J 7.6 Hz, ArH), 7.75 (d, 2H, J 7.6 Hz,
ArH), 7.47–7.10 (m, 24H, ArH), 6.06 (t, 1H, J3,4 9.6 Hz, H-3 or
H-4), 5.89 (d, 1H, JNH,2 8.0 Hz, NH), 5.54 (t, 1H, J3,4 9.6 Hz, H-3 or
H-4), 5.18–5.14 (m, 2H, H1, H2) 4.72 (t, 2H, 2J 10.8 Hz, PhCH),
4.64 (d, 1H, 2J 11.6 Hz, PhCH), 4.48 (d, 1H, 2J 12.4 Hz, PhCH), 4.48
2
(d, 1H, J 12.4 Hz, PhCH), 4.40–4.41 (m, 2H, PhCH, H-10), 4.13–
4.05 (m, 2H, H-20, H-40), 3.83–3.78 (m, 1H, H-6a), 3.71 (q, 1H,
J 8.0 Hz, H-30), 3.63 (dd, 1H, J6a,5 2.4 Hz J6a,6b 10.8 Hz, H-60a),
3.60–3.53 (m, 2H, H60b, H6b), 3.48 (dd, J 4.0 Hz, J 11.2 Hz, H-5),
3.42 (ddd, 1H, J 5.2 Hz, J 10.8 Hz, H-50), 3.37 (s, 3H, OCH3), 1.87
(s, 3H, COCH3). 13C NMR (CDCl3) d 170.7 (COCH3), 165.9 (PhCO),
138.7, 138.4, 138.3, 133.9, 133.5, 133.3 (ipso-C), 130.1, 130.1,
129.8, 129.5, 129.4, 129.0, 128.8, 128.6, 128.6, 128.5, 128.3,
128.1, 128.0, 127.9, 127.8 (Ar), 101.5 (C-10), 97.2 (C-1), 81.9, 78.6,
75.4, 74.9, 73.6, 72.2, 71.0, 69.4, 69.2, 68.6, 68.0, 56.4 (C-3, C-30,
C-4, C-40, C-5, C-50, C-6, C-60, PhCH, OCH3), 55.8, 53.7 (C-2, C-20),
23.7 (COCH3). HRMS(ES+): calcd for C57H57NO14Na: 1002.3677;
found 1002.3655.
3.10. 6-O-(2-Acetamido-3,4,6-tri-O-benzyl-2-deoxy-b-D-
glucopyranosyl)-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranose (15)
Colourless syrup. Purified by column chromatography (pen-
tane/EtOAc 3:1?1:1). Rf 0.25 (pentane/EtOAc 2:1). 1H NMR (CDCl3)
d7.34–7.17 (m, 15H, ArH), 5.55 (d, 1H, JNH,2 8.0 Hz, NH), 5.50 (d, 1H,
J1,2 5.2 Hz, H-1), 4.80 (d, 1H, 2J 11.2 Hz, PhCH) 4.76 (d, 1H, 2J
11.2 Hz, PhCH), 4.70 (d, 1H, J 7.6 Hz, H-10), 4.68 (d, 1H, 2J 11.6 Hz,
PhCH), 4.62 (d, 1H, 2J 12.0 Hz, PhCH), 4.57–4.51 (m, 3H, PhCH,
H-3), 4.28 (dd, 1H, H-2), 4.16 (dd, 1H, J 1.6 Hz, J 6.4 Hz, H-60a),
4.00 (dd, 1H, J 3.6 Hz, J 7.2 Hz, H-6a), 3.96–3.88 (m, 2H, H-4,
H-20), 3.76–3.64 (m, 4H, H-30, H-40, H-5, H-60b), 3.57–3.53 (m, 1H,
H-5), 1.89 (s, 3H, COCH3), 1.50, 1.41, 1.30, 1.29 (s, 12H, CH3). 13C
NMR (CDCl3) d 170.8 (COCH3), 138.7, 138.5, 138.4 (ipso-C) 128.6,
128.6, 128.3, 128.1, 128.0, 128.0, 127.9, 127.8 (Ar), 109.6, 108.9
((CH3)2CO2), 101.4 (C-10), 96.5 (C-1), 81.5, 78.6, 75.2 (PhCH), 74.9,
74.7, 73.7, 71.4, 70.9, 70.7, 69.2, 69.0, 68.1 (C-2, C-3, C-30, C-4, C-
40, C-5, C-50, C-6, C-60), 56.4 (C-20), 26.3, 26.2, 25.3, 24.6, 23.8
((CH3)2CO2, COCH3). LRMS(ES+) calcd for C41H51NO11Na: 756.34;
found 756.3. The spectral data were in accordance with the previ-
ously published values, see Ref. 35.
Acknowledgements
We are grateful for the financial support from The Danish Na-
tional Science Research Foundation and for the Carlsberg Scholar-
ship to M.S.C. OChem Graduate School, Aarhus University is also
acknowledged for the support.
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