Koenigs-Knorr reaction of fusel alcohols with methyl (1-bromo-2,3,4-tri-O- acetyl-α-d-glucopyranosid)uronate leading to the protected alkyl glucuronides - Crystal structures and high resolution 1H and 13C NMR data

Article abstract of DOI:10.1016/j.carres.2012.01.002

Crystal structures and high resolution ¹H and ¹³C NMR spectral data for methyl (alkyl 2,3,4-tri-O-acetyl-β-d-glucopyranosid) uronates (alkyl = methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, n-pentyl, 2-methyl-1-butyl and 3-methyl-1-butyl) are presented.

Full text of DOI:10.1016/j.carres.2012.01.002

Carbohydrate Research 352 (2012) 186–190
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Koenigs–Knorr reaction of fusel alcohols with methyl (1-bromo-2,3,4-tri-O
-acetyl-a-D-glucopyranosid)uronate leading to the protected alkyl
1
glucuronides—crystal structures and high resolution H and 13C NMR data
⇑
Bettina Mönch, Antje Gebert, Franziska Emmerling, Roland Becker , Irene Nehls
BAM Federal Institute for Materials Research and Testing, Berlin, Germany
a r t i c l e i n f o
a b s t r a c t
Crystal structures and high resolution 1H and 13C NMR spectral data for methyl (alkyl 2,3,4-tri-O-acetyl-
Article history:
Received 2 December 2011
Received in revised form 5 January 2012
Accepted 6 January 2012
b-
D-glucopyranosid)uronates (alkyl = methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, n-pen-
tyl, 2-methyl-1-butyl and 3-methyl-1-butyl) are presented.
Ó 2012 Elsevier Ltd. All rights reserved.
Available online 13 January 2012
Keywords:
D-Glucuronic acid derivates
X-ray analysis
High resolution NMR
Anomeric configuration
Synthesis
Glucuronidation is one of the main metabolic pathways to re-
move toxic substances from the human organism. By this means
the elimination of lipophilic drugs or pollutants for example, mor-
phine, paracetamol or some hydroxylated polychlorinated biphe-
nyls (PCBs),1 from the body after phase I oxidation is advanced
by urine or faeces, as the water solubility of these substances is in-
creased. To a lesser extent hydrophilic molecules are also metabo-
lized through glucuronidation. For example, 0.02–0.06% of ingested
ethanol is metabolised in this way,2 and the conversion rates for
longer chain alkyl alcohols are suspected to be higher than those
of ethanol.3 Because alcohol metabolites play a significant role in
alcohol-abuse related analytical research.2,4 the analysis of these
glucuronic metabolites, including their synthesis and full charac-
terisation is mandatory.
Several short-chain alkyl alcohols such as methanol, n-propa-
nol, n-butanol, i-butanol, sec-butanol and 2- and 3-methylbutanol
are found in alcoholic beverages as a result of fermentation pro-
cesses.5 These alcohols have significant importance as so-called fu-
sel alcohols, and their glucuronides are interesting markers for the
consumption of alcohol.3 We herein report the synthesis, high-res-
olution NMR and X-ray analysis of several protected short-chain
alkyl glucopyranuronates according to the reaction scheme given
in Figure 1.
Treatment of
oxide in methanol gave a mixture of
nuronates, which were then combined with acetic acid anhydride
and catalytic perchloric acid to yield the anomeric acetates (2,
Fig. 1). The crystalline product was subsequently reacted with
D
-glucurono-6,3-lactone (1) with sodium meth-
- and b-methyl-glucopyra-
a
hydrobromic acid to give the corresponding acetobromo-a-D-glu-
curonic acid methyl ester (3) as a crystalline product as reported
earlier.6
The yields of the following Koenigs–Knorr reaction with the
corresponding short chain alcohols to the fully protected glucopyr-
anuronates could be increased compared to earlier procedures7 by
thorough exclusion of any traces of water. Full NMR- and single
crystal structure characterisation were carried out for all products.
To complete the synthesis of the protected glucuronides of fusel
alcohols, the glucuronides of i-propanol and n-pentanol were also
prepared.
Table 1 shows the 1H NMR and 13C NMR data of the anomeric
centre of the synthesised glucuronides. It can be seen that the
NMR shifts and coupling constants differ only slightly in all of
the glucopyranuronates. The influence of the alkyl moiety on the
shift and coupling constants of the anomeric centre is negligible.
From the coupling constant of the anomeric proton with the
adjacent ring-proton a b-configuration can be deduced, which
was confirmed by the X-ray structures. From this reaction, b-gluco-
pyranuronates were obtained as anomerically pure products.8
Noticeable in the proton NMR is an ABX-pattern of the diastereo-
topic protons of the CH2-group at C-10, which leads to a complex
⇑
Corresponding author. Tel.: +49 30 8104 1121; fax: +49 30 8104 1127.
E-mail address: roland.becker@bam.de (R. Becker).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2012.01.002

B. Mönch et al. / Carbohydrate Research 352 (2012) 186–190
187
O
OMe
O
OMe
O
HO
O
1) NaOMe, MeOH
O
O
HBr in AcOH
AcO
AcO
OH
OAc
AcO
AcO
O
2) Ac2O, cat. HClO4
AcO
OAc
OH
Br
1
2
3
Ag2CO3,
ROH
4a
4f
R = sec-Bu
i-Bu
R = Me
4b
4c
4d
4e
4g
4h
4i
Et
n-Pro
i-Pro
n-Bu
n-Pent
2-Methyl-1-bu
OMe
4j
3-Methyl-1-bu
O
AcO
O
AcO
OR
AcO
4
Figure 1. Reaction scheme for short chain alkyl alcohols.
Table 1
crystal. The crystals were measured at room temperature. Data
reduction was performed by using Bruker AXS SAINT and SADABS
packages. The structures were solved by direct methods and
refined by full-matrix least-squares calculation using SHELX.9 Aniso-
tropic thermal parameters were employed for non-hydrogen
atoms. The hydrogen atoms were treated isotropically with
Uiso = 1.2 times the Ueq value of the parent atom. In the case of
methyl groups Uiso = 1.5 times the Ueq value was chosen. Crystal
data and selected refinement details for 4a–4j are summarised in
Table 2. CCDC-853961–853972 contain the supplementary crystal-
lographic data for 2–4j described in this paper. The data can be
obtained free of charge from the Cambridge Crystallographic Data
Centre via www.cdc.cam.ac.uk/data_request/cif.
NMR data of the anomeric centre at C-1
Anomeric centre C-1
1H NMR
13C NMR
dH-1
J1,2 (Hz)
dC-1
4a
4b
4c
4d
4e
4f
4.47
4.56
4.52
4.54
4.53
4.57
4.58
4.51
4.54
4.49
4.51
7.7
7.7
7.7
7.7
7.7
7.7
7.5
7.8
7.8
7.7
7.7
101.7
100.5
100.7
99.5
100.8
100.7
99.1
101.1
100.8
101.2
100.8
4g
4h
4i
4j
1.2. General procedure for the synthesis of protected short-
chain alkyl glucopyranuronates
spectrum if the alkyl alcohol itself carries an enantiomeric centre,
like the sec-butyl rest in 4f and the 2-methyl-1-butyl group in 4i.
The crystal structures of the glucuronides 4a–j are nearly in
congruence with each other. As deduced from the NMR data, the
alcohol attached to the sugar moiety has very little influence on
the ring itself. Comparing the shortest alkyl chain (Me, 4a) with
the longest (Pent, 4h) introduced, the plane of the sugar ring re-
mains untwisted and the alkyl chains changes the cell volume by
only 25%. Single crystal X-ray showed only one aberration of the
unit cell, which is that the unit cell of 4i (2-Me-1-Bu) contains
two molecules. Figure 2 shows two examples of the measured
crystal structures.
To a stirred solution of methyl (2,3,4-tri-O-acetyl-a-D-glucopyr-
anosyl)uronate bromide (3) in dry toluene under Argon atmo-
sphere the corresponding dried alcohol was added and the
solution was warmed to 75 °C. Subsequently, silver carbonate
was added in three portions over a period of 3 h. Then the reaction
was stirred at room temperature for 18 h. Afterwards, the suspen-
sion was filtered and the filtrate was evaporated to dryness.
Purification by flash chromatography (silica gel, cyclohexane–
ethyl acetate 1:1) or recrystallisation from i-propanol gave the
product 4.
1.2.1. Methyl (methyl 2,3,4-tri-O-acetyl-b-D-glucopyranosid)-
uronate (4a)
According to the general procedure, 0.75 g (1.89 mmol,
1.0 equiv) 3, 1.5 mL methanol (37.0 mmol, 19.6 equiv) and 0.75 g
silver carbonate (2.72 mmol, 1.4 equiv) were reacted to yield 4a
after recrystallisation from i-propanol as colourless crystals
1. Experimental
1.1. General procedures
(0.56 g, 1.61 mmol, 85.4%). Mp 154.1–154.4 °C; ½a D20
ꢁ30.3 (c
ꢀ
Melting points were determined on a Krüss melting point meter
KSP I N and are uncorrected. The NMR spectra were recorded on a
Bruker Avance II 500 instrument at 500 MHz with the CHCl3 peak
as internal standard. 13C assignments were done on the basis of
2D-NMR spectra (C–H COSY) and chemical shifts. Optical rotations
were measured with a Jasco Digital Polarimeter DIP-370 at room
temperature. Mass spectra were recorded with an Exactive Bench-
top Orbitrap™ from Thermo Fisher Scientific.
þ
10.4, CHCl3); calcd for C14H20O10 349.1135; found 349.1108
[M+H]+; 1H NMR (500 MHz, CDCl3) d = 1.95 (s, 3H, OAc), 1.96 (s,
3H, OAc), 1.98 (s, 3H, OAc), 3.45 (s, 3H, H-10), 3.70 (s, 3H, OMe),
4.03 (d, J5,4 = 9.5 Hz, 1H, H-5), 4.47 (d, J1,2 = 7.7 Hz, 1H, H-1), 4.99
(dd, J2,3 = 9.3, J2,1 = 7.7 Hz, 1H, H-2), 5.23 (dd, J = 9.4, J = 9.3 Hz,
1H, H-4), 5.24 (dd, J = 9.3, J = 9.0 Hz, 1H, H-3); 13C NMR
(125 MHz, CDCl3) d = 20.5 ((C@O)CH3), 20.6 ((C@O)CH3), 20.7
((C@O)CH3), 52.9 (OMe), 57.3 (C-10), 69.5 (C-4), 71.2 (C-3), 72.1
(C-2), 72.6 (C-5), 101.7 (C-1), 167.3 (C-6), 169.3 ((C@O)CH3),
169.4 ((C@O)CH3), 170.1 ((C@O)CH3).
The single crystal X-ray data collection was carried out on a
Bruker AXS SMART diffractometer at room temperature using
Mo Ka radiation (l = 0.71073 Å), monochromatised by a graphite

188
B. Mönch et al. / Carbohydrate Research 352 (2012) 186–190
5.23 (dd, J = 9.5, J = 9.4 Hz, 1H, H-3), 5.24 (dd, J = 9.4, J = 9.1 Hz, 1H,
(a)
13
H-4); C NMR (125 MHz, CDCl3) d = 14.9 (C-20), 20.5 ((C@O)CH3),
C6
20.6 ((C@O)CH3), 20.6 ((C@O)CH3), 52.8 (OMe), 65.8 (C-10), 69.5
(C-4), 71.3 (C-3), 72.1 (C-2), 72.6 (C-5), 100.5 (C-1), 167.3 (C-6),
169.2 ((C@O)CH3), 169.3 ((C@O)CH3), 170.1 ((C@O)CH3).
C9
C5
O4
1.2.3. Methyl (n-propyl 2,3,4-tri-O-acetyl-b-D-glucopyranosid)-
uronate (4c)
O3
C8
O2
According to the general procedure, 0.75 g (1.89 mmol,
1.0 equiv) 3, 1.5 mL n-propanol (20.0 mmol, 10.6 equiv) and
0.75 g silver carbonate (2.72 mmol, 1.4 equiv) were reacted to yield
4c after recrystallisation from i-propanol as colourless crystals
C7
O6
C4
O5
C2
C1
(0.50 g, 1.33 mmol, 71%). Mp 113.5–113.8 °C; ½a D20
ꢀ
ꢁ35.7 (c 10.5,
O1
O9
C3
C14
CHCl3); calcd for C16H24Om10 377.1448; found 377.1417 [M+H]+;
¼
1H NMR (500 MHz, CDCl3) d = 0.87 (t, J3 ,2 = 7.5 Hz, 3H, H-30),
C10
C11
0
0
C15
1.52–1.61 (m, 2H, H-20), 2.00 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.04
O7
O8
(s, 3H, OAc), 3.41 (dt, J1 A,1 B = 9.4, J1 A,2 = 6.8 Hz, 1H, H-10A), 3.73
0
0
0
0
0
O8
(s, 3H, OMe), 3.84 (dt, J1 B, 1 A = 9.5, J1 B,2 = 6.4 Hz, 1H, H-0B), 4.01
(d, J5,4 = 9.3 Hz, 1H, H-5), 4.52 (d, J1,2 = 7.7 Hz, 1H, H-1), 4.98 (dd,
J2,3 = 8.6, J2,1 = 7.7 Hz, 1H, H-2), 5.20 (dd, J = 9.6, J = 8.7 Hz, 1H, H-
3), 5.24 (dd, J = 9.6, J = 9.3 Hz, 1H, H-4); 13C NMR (125 MHz, CDCl3)
d = 10.2 (C-30), 20.5 ((C@O)CH3), 20.5 ((C@O)CH3), 20.6 ((C@O)CH3),
22.5 (C-20), 52.8 (OMe), 69.5 (C-4), 71.2 (C-3), 71.9 (C-10), 72.1 (C-
2), 72.6 (C-5), 100.7 (C-1), 167.3 (C-6), 169.2 ((C@O)CH3), 169.4
((C@O)CH3), 170.2 ((C@O)CH3).
0
0
0
0
C12
C13
(b)
C6
1.2.4. Methyl (i-propyl 2,3,4-tri-O-acetyl-b-
uronate (4d)
D
-glucopyranosid)-
C9
O4
According to the general procedure, 0.9 g
3
(2.27 mmol,
C5
C8
1.0 equiv), 1.8 mL i-propanol (23.4 mmol, 10.3 equiv) and 0.81 g
silver carbonate (2.95 mmol, 1.3 equiv) were reacted to yield 4d
after purification by flash chromatography (silica gel, cyclohex-
ane/ethyl acetate 1:1) as colourless crystals (0.49 g, 1.31 mmol,
O6
O3
O5
C7
58%). Mp 129.2–129.4 °C; ½a D20
ꢀ
ꢁ31.4 (c 9.7, CHCl3); calcd for
C4
O1
375.1291; found 375.1301 [M+H]+; 1H NMR
þ
C3
C18H28O10
O10
C1
C2
C16
(500 MHz, CDCl3) d = 1.12 (d, J3 ,1 = 6.3 Hz, 3H, H-30), 1.20 (d,
0
0
J2 ,1 = 6.2 Hz, 3H, H-20), 2.00 (s, 6H, OAc), 2.02 (s, 3H, OAc), 3.73
(s, 3H, OMe), 3.93 (sept, J = 6.2 Hz, 1H, H-10), 4.01 (d, J5,4 = 9.5 Hz,
1H, H-5), 4.54 (d, J1,2 = 7.7 Hz, 1H, H-1), 4.94 (dd, J2,3 = 8.8,
J2,1 = 7.7 Hz, 1H, H-2), 5.20 (dd, J = 9.6, J = 9.5 Hz, 1H, H-3), 5.23
(dd, J = 9.5, J = 9.3 Hz, 1H, H-4); 13C NMR (125 MHz, CDCl3)
d = 20.5 ((C@O)CH3), 20.6 ((C@O)CH3), 20.6 ((C@O)CH3), 21.7 (C-
20), 23.2 (C-20Me), 52.8 (OMe), 69.5 (C-4), 71.5 (C-3), 72.2 (C-2),
72.6 (C-5), 72.9 (C-10), 99.5 (C-1), 167.3 (C-6), 169.2 ((C@O)CH3),
169.4 ((C@O)CH3), 170.2 ((C@O)CH3).
0
0
C10
C17
C11
O2
O9
O7
O8
C12
C13
C15
1.2.5. Methyl (n-butyl 2,3,4-tri-O-acetyl-b-D-glucopyranosid)-
uronate (4e)
C14
According to the general procedure 0.47 g (1.18 mmol,
1.0 equiv) 3, 9.5 mL n-butanol (103.8 mmol, 87.7 equiv) and
0.42 g silver carbonate (1.54 mmol, 1.3 equiv) were reacted to yield
4e after purification with flash chromatography (silica gel, cycloh-
exan/ethyl acetate 1:1) as colourless crystals (0.28 g, 0.72 mmol,
Figure 2. Molecular structure of 4b (a) and 4g (b), with displacement ellipsoids
drawn at the 50% probability level.
61%). Mp 88.8–90.7 °C; ½a D20
ꢀ
ꢁ25.8 (c 9.58, CHCl3); calcd for
1.2.2. Methyl (ethyl 2,3,4-tri-O-acetyl-b-D-glucopyranosid) urona
C17H26O10
391.1604; found 391.1572 [M+H]+; 1H NMR
þ
te (4b)
(500 MHz, CDCl3) d = 0.87 (t, J4 ,3 = 7.2 Hz, 3H, H-40), 1.29–1.38
According to the general procedure, 0.9 g
3
(2.27 mmol,
0
0
(m, 2H, H-30), 1.48–1.60 (m, 2H, H-20), 2.01 (s, 6H, OAc), 2.03 (s,
1.0 equiv), 0.8 mL ethanol (13.7 mmol, 6.1 equiv) and 0.81 g silver
carbonate (2.95 mmol, 1.3 equiv) were reacted to yield 4b after
recrystallisation from i-propanol as colourless crystals (0.68 g,
3H, OAc),3.47 (dt, J1 A,1 B = 9.6, J1 A,2 = 6.4 Hz, 1H, H-10A), 3.75 (s,
0
0
0
0
3H, OMe), 3.89 (dt, J1 B,1 A = 9.6, J1 B,2 = 6.5 Hz, 1H, H-0B), 4.02 (d,
J5,4 = 9.5 Hz, 1H, H-5), 4.53 (d, J1,2 = 7.7 Hz, 1H, H-1), 4.99 (dd,
J2,3 = 9.2, J2,1 = 8.0 Hz, 1H, H-2), 5.21 (dd, J = 9.3, J = 9.2 Hz, 1H, H-
3), 5.24 (dd, J = 9.4, J = 9.3 Hz, 1H, H-4); 13C NMR (125 MHz, CDCl3)
d = 13.3 (C-40), 18.9 (C-30), 20.5 ((C@O)CH3), 20.5 ((C@O)CH3), 20.6
((C@O)CH3), 31.3 (C-20), 52.8 (OMe), 69.5 (C-4), 70.1 (C-10), 71.2 (C-
3), 72.1 (C-2), 72.6 (C-5), 101.1 (C-1), 167.3 (C-6), 169.1
((C@O)CH3), 169.3 ((C@O)CH3), 170.1 ((C@O)CH3).
0
0
0
0
1.88 mmol, 83%). Mp 150.3–151.0 °C; ½a D20
ꢁ35.4 (c 10.3, CHCl3);
ꢀ
calcd for C15H22O10 363.1291; found 363.1264 [M+H]+; 1H NMR
þ
(500 MHz, CDCl3) d = 1.19 (t, J2 ,1 = 7.0 Hz, 3H, H-20), 2.01 (s, 3H,
0
0
0
0
OAc), 2.02 (s, 3H, OAc), 2.04 (s, 3H, OAc), 3.58 (dq, J1 A,1 B = 9.9,
J1 A,2 = 7.1 Hz, 1H, H-10 ), 3.75 (s, 3H, OMe), 3.93 (dq, J1 B,1 A = 9.9,
0
0
0
0
A
J1 B,2 7.1 Hz, 1H, H-0B), 4.04 (d, J5,4 = 9.6 Hz, 1H, H-5), 4.56 (d,
J1,2 = 7.7 Hz, 1H, H-1), 4.88 (dd, J2,3 = 9.2, J2,1 = 7.8 Hz, 1H, H-2),
0
0

B. Mönch et al. / Carbohydrate Research 352 (2012) 186–190
189
Table 2
Crystal data and structure refinement of protected glucuronides 4a–j
Alkyl moiety
Compound
4a
Me
4b
Mt
4c
nPro
4d
iPro
4e
nBu
4f
sBu
4g
iBu
4h
nPent
4i
4j
2-Me-1-bu
3-Me-1-bu
Molecular formula
Crystal system
C
14H20O10
C15H22O10
Ortho-
rhombic
P212121
7.4822(6)
14.2337(13) 14.533(4)
17.7818(16) 17.244(4)
1893.8(3)
4
C16H24O10
Ortho-
rhombic
P212121
C16H24O10
Ortho-
C17H26O10
Ortho-
C17H26O10
Ortho-
C17H26O10
Ortho-
rhombic
P212121
9.0667(7)
14.0702(9)
16.3679(10) 17.349(2)
2088.1(2)
4
0.0474
0.1036
C18H28O10
Ortho-
rhombic
P212121
C18H28O10
Ortho-
rhombic
P212121
C18H28O10
Ortho-
rhombic
P212121
Ortho-
rhombic
P212121
7.260(4)
13.605(7)
18.070(9)
1784.8(16)
4
rhombic
P212121
6.0479(13)
16.774(3)
19.097(5)
1937.3(7)
4
rhombic
P212121
5.7486(14)
16.217(5)
22.957(6)
2140.2(10)
4
rhombic
P212121
6.947(3)
14.829(6)
20.445(8)
2106.2(15)
4
Space group
a (Å)
b (Å)
7.6044(17)
9.5511(12)
13.5932(16) 14.9085(16) 13.2024(15)
14.4629(17) 9.4748(11)
c (Å)
21.127(2)
4555.4(8)
8
0.0455
0.2126
17.841(3)
2231.7(5)
4
0.0471
0.1483
Cell volume (Å3)
Unit cell Z
Final R indices
Final R indices (all
data)
1905.7(8)
4
0.0472
0.1637
2252.4(5)
4
0.0573
0.1108
0.0389
0.0499
0.0626
0.1104
0.0441
0.1737
0.0508
0.2308
0.0620
0.0964
Goodness of fit on F2 0.961
0.894
0.579
0.640
0.696
0.985
0.818
0.898
0.701
0.748
1.2.6. Methyl (sec-butyl 2,3,4-tri-O-acetyl-b-
uronate (4f)
D
-glucopyranosid)-
28.2 (C-20), 52.8 (OMe), 69.5 (C-4), 71.2 (C-3), 72.1 (C-2), 72.6 (C-5),
76.9 (C-10), 101.1 (C-1), 167.3 (C-6), 169.1 ((C@O)CH3), 169.3
((C@O)CH3), 170.1 ((C@O)CH3).
According to the general procedure 1.00 g (2.52 mmol,
1.0 equiv) 3, 3.7 mL sec-butanol (40.43 mmol, 16.05 equiv) and
0.90 g silver carbonate (3.28 mmol, 1.3 equiv) were reacted to yield
4f after purification with flash chromatography (silica gel, cycloh-
exan/ethyl acetate 1:1) as colourless crystals (0.39 g, 1.00 mmol,
1.2.8. Methyl (n-pentyl 2,3,4-tri-O-acetyl-b-
uronate (4h)
D
-glucopyranosid)-
(2.27 mmol,
According to the general procedure 0.9 g
3
40%). Mp 111.1–111.9 °C; ½a D20
ꢀ
ꢁ34.7 (c 10.69, CHCl3); calcd for
1.0 equiv), 1.4 mL n-pentanol (12.9 mmol, 5.7 equiv) and 0.81 g sil-
ver carbonate (2.95 mmol, 1.3 equiv) were reacted to yield 4h as
colourless crystals after recrystallisation from i-propanol (0.62 g,
þ
C
17H26O10
391.1604; found 391.1567 [M+H]+; 1H NMR
0
0
(500 MHz, CDCl3) diastereomer A: d = 0.86 (t, J3 ,2 = 7.4 Hz, 3H, H-
30), 1.19 (d, J4 ,1 = 6.5 Hz, 3H, H-40), 1.53–1.60 (m, 2H, H-20), 1.99
(s, 3H, OAc), 2.01 (s, 6H, OAc), 3.64 (dq, J = 6.5, J = 5.5 Hz, 1H, H-
10), 3.73 (s, 3H, OMe), 4.00 (d, J5,4 = 9.4 Hz, 1H, H-5), 4.58 (d,
J1,2 = 7.5 Hz, 1H, H-1), 4.97 (dd, J = 9.0, J = 8.3 Hz, 1H, H-2), 5.18
(dd, J = 9.7, J = 9.7 Hz, 1H, H-3), 5.23 (dd, J = 9.6, J = 9.6 Hz, 1H, H-
1.55 mmol, 68%). Mp 99.5–100.2 °C; ½a D20
ꢀ
ꢁ33.0 (c 10.5, CHCl3);
0
0
calcd for C18H28O10 405.1761; found 405.1731 [M+H]+; 1H NMR
þ
(500 MHz, CDCl3) d = 0.87 (t, J5 ,4 = 7.2 Hz, 3H, H-50), 1.25–1.34
(m, 4H, H-30 and H-40), 1.52–1.61 (m, 2H, H-20), 2.01 (s, 6H, OAc),
2.03 (s, 3H, OAc), 3.56 (dt, J = 6.8, J = 6.4 Hz, 1H, H-10A), 3.74 (s,
3H, OMe), 3.89 (dt, J = 6.8, J = 6.4 Hz, 1H, H-0B), 4.01 (d,
J5,4 = 9.4 Hz, 1H, H-5), 4.54 (d, J1,2 = 7.8 Hz, 1H, H-1), 4.99 (dd, J
2,3 = 9.0, J2,1 = 7.9 Hz, 1H, H-2), 5.21 (dd, J = 9.9, J = 9.4 Hz, 1H, H-
3), 5.25 (dd, J = 9.9, J = 9.4 Hz, 1H, H-4); 13C NMR (125 MHz, CDCl3)
d = 13.9 (C-50), 20.5 ((C@O)CH3), 20.6 ((C@O)CH3), 20.6 ((C@O)CH3),
22.3 (C-40), 27.9 (C-30), 28.9 (C-20), 52.8 (OMe), 69.5 (C-4), 70.4 (C-
10), 71.3 (C-3), 72.1 (C-2), 72.6 (C-5), 100.8 (C-1), 167.3 (C-6), 169.1
((C@O)CH3), 169.3 ((C@O)CH3), 170.2 ((C@O)CH3).
0
0
4), diastereomer B: d = 0.84 (t, J3 ,2 = 7.1 Hz, 3H, H-30), 1.08 (d,
0
0
J4 ,1 = 6.2 Hz, 3H, H-40), 1.54–1.53 (m, 2H, H-20), 1.99 (s, 3H, OAc),
2.01 (s, 6H, OAc), 3.70 (dq, J = 6.2, J = 6.2 Hz, 1H, H-10), 3.72 (s,
3H, OMe), 3.99 (d, J5,4 = 9.3 Hz, 1H, H-5), 4.57 (d, J1,2 = 7.7 Hz, 1H,
H-1), 4.97 (dd, J = 9.1, J = 8.4 Hz, 1H, H-2), 5.17 (dd, J = 9.6,
J = 9.3 Hz, 1H, H-3), 5.23 (dd, J = 9.6, J = 9.6 Hz, 1H, H-4); 13C NMR
(125 MHz, CDCl3) diastereomer A: d = 9.4 (C-30), 20.9 (C-10Me),
20.4 ((C@O)CH3), 20.5 ((C@O)CH3), 20.9 ((C@O)CH3), 29.6 (C-20),
52.7 (OMe), 69.5 (C-4), 71.4 (C-3), 72.2 (C-2), 72.4 (C-5), 79.2 (C-
10), 100.7 (C-1), 167.3 (C-6), 169.1 ((C@O)CH3), 169.3 ((C@O)CH3),
170.2 ((C@O)CH3), diastereomer B: d = 9.4 (C-30), 18.9 (C-10Me),
20.4 ((C@O)CH3), 20.5 ((C@O)CH3), 20.9 ((C@O)CH3), 29.0 (C-20),
52.7 (OMe), 69.4 (C-4), 71.3 (C-3), 72.2 (C-2), 72.4 (C-5), 79.2 (C-
10), 99.1 (C-1), 167.2 (C-6), 169.1 ((C@O)CH3), 169.3 ((C@O)CH3),
170.3 ((C@O)CH3).
0
0
1.2.9. Methyl (2-methyl-1-butyl 2,3,4-tri-O-acetyl-b-D-glucopyrano-
sid)uronate (4i)
According to the general procedure 2.00 g
3 (5.04 mmol,
1.0 equiv), 8.7 mL 2-methyl-1-butanol (79.9 mmol, 15.9 equiv)
and 2.2 g silver carbonate (7.98 mmol, 1.6 equiv) were reacted to
yield 4i as purple crystals after recrystallisation from i-propanol
(0.61 g, 1.51 mmol, 30%). Mp 111.3–112.4 °C; ½a D20
ꢁ32.7 (c 10.2,
ꢀ
CHCl3); calcd for C18H28O10 405.1761; found 405.1734 [M+H]+;
þ
1.2.7. Methyl (i-butyl 2,3,4-tri-O-acetyl-b-
uronate (4g)
D
-glucopyranosid)-
(1.79 mmol,
Distinguishable diastereomers given in brackets; 1H NMR (500 MHz,
CDCl3) d = 0.82 (d, J4 ,3 = 8.6 Hz, 3H, H-40), 0.85 (d, J5 ,2 = 7.5 Hz,
3H, H-50), 1.08–1.14 (m, 1H, H-20), 1.33–1.43 (m,2H, H-30), [1.59–
1.67 (m, 2H, H-30)], 1.98 (s, 6H, OAc), 2.00 (s, 3H, OAc), 3.18 (dd,
J = 9.3, J = 7.1 Hz, 1H, H-10A), [3.26 (dd, J = 9.3, J = 6.8 Hz, 1H,
H-10A)], 3.70 (dd, J = 9.6, J = 6.2 Hz, 1H, H-0B), [3.79 (dd, J = 9.3,
J = 5.6 Hz, 1H, H-0B)], 3.74 (s, 3H, OMe), 4.00 (d, J5,4 = 9.5 Hz, 1H,
H-5), 4.49 (d, J1,2 = 7.7 Hz, 1H, H-1), 4.99 (dd, J2,3 = 8.6,
J2,1 = 7.7 Hz, 1H, H-2), 5.18 (dd, J = 9.6, J = 9.3 Hz, 1H, H-3), 5.23
(dd, J = 9.6, J = 9.3 Hz, 1H, H-4); 13C NMR (125 MHz, CDCl3)
d = 11.0 (C-40), [11.1 (C-40)], 16.0 (C-20Me), [16.3 (C-20Me)], 20.5
((C@O)CH3), 20.5 ((C@O)CH3), 20.6 ((C@O)CH3), 25.7 (C-30), [25.8
(C-30)], 34.7 (C-20), 52.8 (OMe), 69.5 (C-4), 71.2 (C-3), 72.1 (C-2),
72.6 (C-5), 75.2 (C-10), [75.4 (C-10)], 101.2 (C-1), 167.3 (C-6),
169.1 ((C@O)CH3), 169.3 ((C@O)CH3), 170.1 ((C@O)CH3).
0
0
0
0
According to the general rocedure 0.71 g
3
1.0 equiv), 1.5 mL i-butanol (16.2 mmol, 9.1 equiv) and 0.71 g sil-
ver carbonate (2.57 mmol, 1.4 equiv) were reacted to yield 4g as
colourless crystals after recrystallisation from i-propanol (0.52 g,
1.3 mmol, 75%). Mp 144.2–144.4 °C; ½a D20
ꢁ27.1 (c 10.3, CHCl3);
ꢀ
calcd for C17H26O10 391.1604; found 391.1574 [M+H]+; 1H NMR
(500 MHz, CDCl3) d = 0.86 (t, J = 6.5 Hz, 6H, H-30 and H-40), 1.84
(sept, J = 6.6 Hz, 1H, H-20), 2.00 (s, 6H, OAc), 2.03 (s, 3H, OAc),
þ
3.18 (dd, J1 A,1 B = 9.3, J1 A,2 = 7.1 Hz, 1H, H-10 ), 3.71 (dd, J1 B,1 A = 9.3,
0
0
0
0
0
0
A
J1 B,2 = 6.2 Hz, 1H, H-0B), 3.74 (s, 3H, OMe), 4.01 (d, J5,4 = 9.5 Hz, 1H,
H-5), 4.51 (d, J1,2 = 7.8 Hz, 1H, H-1), 5.01 (dd, J2,3 = 9.6, J2,1 = 7.6 Hz,
1H, H-2), 5.21 (dd, J = 9.3, J = 9.2 Hz, 1H, H-3), 5.24 (dd, J = 9.6,
0
0
13
J = 9.3 Hz, 1H, H-4); C NMR (125 MHz, CDCl3) d = 18.8 (C-30),
18.9 (C-20Me), 20.5 ((C@O)CH3), 20.5 ((C@O)CH3), 20.6 ((C@O)CH3),

190
B. Mönch et al. / Carbohydrate Research 352 (2012) 186–190
1.2.10. Methyl (3-methyl-1-butyl 2,3,4-tri-O-acetyl-b-
glucopyranosid)uronate (4j)
D
-
((C@O)CH3), 20.6 ((C@O)CH3), 20.6 ((C@O)CH3), 22.2 (C-40), 22.6
(C-30Me), 24.7 (C-30), 38.0 (C-20), 52.8 (OMe), 68.8 (C-10), 69.5 (C-
4), 71.3 (C-3), 72.1 (C-2), 72.6 (C-5), 100.8 (C-1), 167.3 (C-6),
169.2 ((C@O)CH3), 169.3 ((C@O)CH3), 170.1 ((C@O)CH3).
According to the general procedure 2.00 g (5.04 mmol,
1.0 equiv) 3, 8.7 mL 3-methyl-1-butanol (79.9 mmol, 15.9 equiv)
and 2.2 g silver carbonate (7.98 mmol, 1.6 equiv) were reacted to
yield 4j after recrystallisation from i-propanol as yellow crystals
References
(0.76 g, 1.89 mmol, 37%). Mp 106.4–107.7 °C; ½a D20
ꢁ33.4 (c 10.6,
ꢀ
CHCl3); calcd for C18H28O10 405.1761; found 405.1737 [M+H]+;
þ
1. Tampal, N.; Lehmler, H. J.; Espandiari, P.; Malmberg, T.; Robertson, L. W. Chem.
Res. Toxicol. 2002, 15, 1259–1266.
1H NMR (500 MHz, CDCl3); d = 0.87 (d, J4 ,3 = 6.6 Hz, 3H, H-40),
0
0
2. Pragst, F.; Balikova, M. A. Clin. Chim. Acta 2006, 370, 17–49.
3. Sticht, G.; Käferstein, H. Rechtsmedizin 1999, 9, 184–189.
4. Peterson, K. Alcohol Res. Health 2004/2005, 28, 30–37.
5. Lachenmeier, D. W.; Musshoff, F. Rechtsmedizin 2004, 14, 454–462.
6. Bollenback, G. N.; Long, J. W.; Benjamin, D. G.; Lindquist, J. A. J. Am. Chem. Soc.
1954, 77, 3310–3315.
7. Schmitt, G.; Aderjan, R.; Keller, T.; Wu, M. J. Anal. Toxicol. 1995, 19, 91–94.
8. Koenigs, W.; Knorr, E. Chem. Ber. 1901, 34, 957–981.
9. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112–122.
0.88 (d, J5 ,3 = 6.6 Hz, 3H, H-50), 1.32–1.51 (m, 2H, H-20), 1.64 (tsept,
J = 6.9; 6.7 Hz, 3H, H-30), 2.01 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.03 (s,
3H, OAc), 3.51 (dt, J = 7.2, J = 6.9 Hz, 1H, H-10A), 3.76 (s, 3H, OMe),
3.93 (dt, J = 7.2, J = 6.9 Hz, 1H, H-0B), 4.01 (d, J5,4 = 9.3 Hz, 1H, H-5),
4.51 (d, J1,2 = 7.7 Hz, 1H, H-1), 4.97 (dd, J2,3 = 9.3, J2,1 = 7.8 Hz, 1H,
H-2), 5.19 (dd, J = 9.9, J = 9.2 Hz, 1H, H-3), 5.23 (dd, J = 9.3,
J = 9.2 Hz, 1H, H-4); 13C NMR (125 MHz, CDCl3) d = 20.5
0
0