Enantiomerically pure 3-hydroxypropyl diisopropylidene mannose derivatives

Article abstract of DOI:10.1016/j.carres.2011.03.035

Enantiomerically pure 3-hydroxypropyl diisopropylidene mannose derivatives were prepared and fully characterized. The procedure is generally applicable to monosaccharides and thus facilitates access to differently substituted glycosidic precursors.

Full text of DOI:10.1016/j.carres.2011.03.035

Carbohydrate Research 346 (2011) 1154–1160
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Enantiomerically pure 3-hydroxypropyl diisopropylidene mannose derivatives
⇑
Johannes Kunig, Peter Lönnecke, Evamarie Hey-Hawkins
Universität Leipzig, Fakultät für Chemie und Mineralogie, Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Enantiomerically pure 3-hydroxypropyl diisopropylidene mannose derivatives were prepared and fully
characterized. The procedure is generally applicable to monosaccharides and thus facilitates access to dif-
ferently substituted glycosidic precursors.
Received 15 January 2011
Received in revised form 17 March 2011
Accepted 24 March 2011
Available online 2 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Dedicated to Professor Peter Klüfers on the
occasion of his 60th birthday
Keywords:
Mannose
Isopropylidene
Propylene spacer
Glycosidic precursors
Since the introduction of boron neutron capture therapy (BNCT)
by Locher in 1936, numerous investigations toward new
boron-containing agents were performed, but until now only
-dihydroxyboryl phenylalanine (BPA), sodium mercaptounde-
acids and are responsible for miscellaneous biological and
biochemical processes, such as cell-to-cell recognition. They serve
as structural components, as well as being of central relevance as a
physiological energy source. They are highly interesting synthetic
targets due to the broad range of possible applications in treatment
of diabetes mellitus, cardiac diseases, Alzheimer’s disease, and can-
1
L
cahydrododecaborane (BSH) and Na 10 (GB-10) have made it
2 10
B H
into clinical trials on human patients. A suitable BNCT agent should
be water soluble, stable in blood buffer medium, and sufficiently
5
cer. Especially glucose is known as a good substituent for antitu-
10
nontoxic to deliver at least 30
lg
B per gram tumor with a tu-
mor compounds, because cancer cells have an extremely high
energy demand, since anaerobic glycolysis produces only two mol-
ecules of ATP per molecule of glucose (Warburg effect).6 Existing
glucose transportation systems guarantee its high biological avail-
ability and thus can support a sufficiently high T/B and T/N selec-
tivity of the chosen antitumor agent. Other hexoses, like mannose
or galactose, are expected to show similar behavior.
mor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratio of at
least 5:1. Most studies involve boron clusters, including carbabor-
1
0
anes, as B-containing moieties linked to different kinds of organic
or biomolecules to achieve the necessary water solubility and
2
selectivity.
Bechtold and Kaczmarczyk3 presented the first dodecaborane-
containing phosphates, some of which exhibited surprisingly high
tumor uptake in in vivo studies on rats, but were generally too
toxic. Using glycosyl moieties should not only reduce the toxicity
of the target compounds but also allow sufficiently high uptake ra-
Several groups have designed differently substituted carbabora-
nyl glycosides. Tietze et al. described mono- and diglycosylated
o-carbaboranes using glucose and galactose connected via the
7
C6-OH group and a bridging methylene group. Kononov and co-
4
10
tios to be achieved, due to selective binding to lectin receptors, as
workers focused on variation in spacer lengths and the B-deliver-
8
well as increasing the water solubility of compounds containing
hydrophobic carbaborane cages and biological availability by uti-
lizing existing transportation systems.
Carbohydrates are widespread in nature and play an important
role in various cellular processes. Thus, mono-, oligo-, and polysac-
charides are constituents of glycoproteins, glycolipids, and nucleic
ing moiety. Panza and co-workers prepared glucofuranose
9
attached via a peptide bond. Wiessler and co-workers described
a tetrakis-carbaboranyl precursor that can be easily connected to
1
0
different glycosidic moieties. Previously, we reported that galact-
1
1
ose-substituted carbaboranyl bis-phosphonates connected via
the C6-OH group feature most of the above-mentioned properties,
1
2
but show a lack of tumor selectivity. As the 6-position might be
crucial for lectin interaction, we have expanded our approach to
glycosyl derivatives which are connected via the 1-position9 to
the phosphonate. 2,3:4,6-Di-isopropylidene-protected mannose is
⇑
Corresponding author. Tel.: +49 341 9736151; fax: +49 341 9739319.
E-mail address: hey@rz.uni-leipzig.de (E. Hey-Hawkins).
0
008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.03.035

J. Kunig et al. / Carbohydrate Research 346 (2011) 1154–1160
1155
easily accessible and should allow to study which substitution pat-
tern is more suitable for our potential BNCT agents.13
20% yield. Allylation of acylated glycoside 3 with boron trifluoride
etherate also gave allyl glycoside 7, but was abandoned due to
21
Diisopropylidene-protected derivatives of
D
-mannose (3 and 4,
the extra step needed, compared to direct allylation.
Scheme 1) were prepared according to a method described by Ge-
Thus, no further attempts were made to prepare allyl glycoside
1
4
las and Horton. However, the reaction of a mixture of glycosides
and 4 with carbaboranylbis-phosphonite 5 promoted by benz-
a
-7 exclusively. Due to their very similar retention times, it was
difficult, albeit possible (at least for very small amounts), to isolate
the -isomers -7 and -8 by column chromatography. However,
3
15
imidazoliumtriflate (BIT) followed by oxidation or sulfurization
a
a
a
did not yield the corresponding bis-mannosylphosphonate 6
separation was much more facile following the next step. A
subsequent hydroboration of the allyl glycosides with 9-
borabicyclo[3.3.1]nonane (9-BBN) in THF forms the anti-Markovni-
(
R = (prot)Gly, Scheme 1). In all cases, 3 and 4 were recovered
and only the bis-phosphonic acid derivative of 6 (R = H) was
1
1
1
formed during acidic workup and identified by
B{ H} and
kov adducts, and oxidative cleavage gave glycosides
a-1 (83%), b-1
3
1
1
P{ H} NMR spectroscopy. Reasons could be the intermediate
(92%), -2 (92%), and b-2 (76%) in good yields with the respective
a
open-chain conformation or the fact that the secondary hydroxyl
group is too sterically hindered to react with the cationic BIT-
activated intermediate of 5.11
alcohol 10 (83%) as byproduct (Scheme 2). They were separated by
column chromatography and fully characterized. NMR correlations
were supported by COSY and HMQC studies.
Therefore, a short alkylene spacer was introduced between the
OH group and the glycoside, as long alkylene spacers would
increase the lipophilicity, leading to lower water solubility and
higher cytotoxicity. In the case of mannose the alkylation of
the anomeric oxygen of a mixture of 3 and 4 would also prevent
the formation of the open-chain conformer and should thus
allow separation of all four isomers in enantiomerically pure
form.
The anomeric configuration in2a-1, b-1, 9, and 10 and was sup-
2
ported by X-ray crystallography (Fig. 1). Alcohol
a
-1 exhibits an
0
intermolecular hydrogen bond between O(7)–H(7) and O(5 ) and
1
6
0
alcohol b-1 between O(7)-H(7) and O(3 ), while alcohol 10 forms
an intramolecular hydrogen bond between O(7)–H(7) and O(6). Se-
lected data are given in Table 1.
In summary, a convenient synthesis of the 3-hydroxypropyl-
substituted derivatives mannopyranose 1 and mannofuranose 2
We focused on the corresponding derivatives with a C
namely and (Scheme 1), which were prepared by an
allylation–hydroboration sequence, as was reported by Wang and
3
spacer,
was developed. The four isomers
characterized, including X-ray crystallography for a
liminary results indicate that the subsequent reaction with 5 is
successful, supporting the assumption that a secondary hydroxyl
group is sterically too hindered to react with the BIT-activated
intermediate of 5.
a
-1, b-1,
a
-2, and b-2 were fully
-1 and b-1. Pre-
1
2
1
7
Ni for galactose. Isopropylidene-protected D-mannose was pre-
14
pared according to Gelas and Horton. Deprotonation of the
resulting mixture of 3 and 4 with sodium hydride and allylation
with allyl bromide gave a mixture of the allyl glycosides
8%), b-7 (17%), -8 (17%), and b-8 (17%) as pale yellow oils and
the byproduct 9 (2%) as a white solid. Only the alpha isomers of
a-7
(
a
1. Experimental section
1.1. General methods
1
8
19
allyl glycosides 7 and 8 have been reported. In our hands,
Fisher allylation of
-mannose with 3% hydrochloric acid18b or with
Cl as Lewis acid and subsequent isopropylidene protection
D
2
0
SiMe
3
All reactions were carried out under inert conditions using
standard Schlenk techniques. Dry THF was taken from a solvent
purification system, and dry DMF was prepared by azeotropic
did not furnish
a-7, while treatment with allyl alcohol saturated
1
8a
23
with HCl
and isopropylidenation provided
a-7 in approximately
1
2
) BIT
MeO
O
O
O
∗
P
OH
O
OH
O
NMe2
O
O
O
O
O
X
P
∗
P
RO
OMe
NMe2
∗
OMe
5
t
) BuOOH/H O or
2
Beaucage Reagent
O
O
O
O
O
O
O
or
O
OH
O
O
X
P
OMe
OH
∗
3
4
OR
R-OH = (prot)Gly-OH
6
O
H
N
X = O, S
= BH
= C
Beaucage Reagent
S
BIT = Benzimidazolium triflate
CF -SO
3
3
S
N
H
O
O
Scheme 1. Attempted condensation reaction with bis-phosphonite 5.

1
156
J. Kunig et al. / Carbohydrate Research 346 (2011) 1154–1160
HO
HO
OH
O
HO
OH
) 2-Methoxypropene, cat. pTsOH
1
2
3
) NaH
) allyl bromide
O
O
O
O
O
O
O
O
O
O
O
O
O
+
+
O
O
O
O
O
α-7, 8.4 %
β-7, 16.7 %
α-8, 16.7 %
β-8, 17.0 %
9, 2.0 %
1) 9-BBN
2
) NaOH,H O
2
2
O
O
O
O
O
O
O
O
O
O
OH
O
+
O
O
+
O
O
HO
O
O
O
OH
α-1
β-1
α-2
β-2
10
Scheme 2. Preparation of mannosyl alcohols 1, 2, and 10.
Figure 1. ORTEP views including atom labeling of alcohols a-1, b-1, allyl derivative 9, and alcohol 10 (left to right) with ellipsoids of 50% probability level. Hydrogen atoms
have been omitted for clarity.
Table 1
distillation with benzene (predried with CaH
2
), further drying with
Bond lengths (pm) and angles (°) at the anomeric center, as well as hydrogen-bonding
data (O–Hꢀ ꢀ ꢀO ) of
MgSO and distillation at 15 mbar using a 1-foot column filled with
4
0
a-1, b-1, and 10 (see Fig. 1)
Raschig rings. All solvents were stored under dry nitrogen and over
activated 3 Å molecular sieves. NMR spectra were recorded on a
a-1
b-1
9
10
O(1)–C(1)
O(6)–C(1)
C(1)–O(1)–C(5)
O(1)–C(1)–O(6)
d(O–H)
141.1(2)
139.8(2)
112.0(1)
111.7(2)
84
143.1(2)
137.8(2)
110.4(1)
109.5(1)
84(3)
195(3)
279.6(2)
175(2)
142.1(2)
139.1(2)
142.7(2)
138.9(2)b
110.01(9)
108.2(1)b
80(2)
208(2)
275.5(1)
142(2)
3
400 MHz NMR spectrometer using CDCl as solvent and TMS as
b
1
13
standard. Chemical shifts of H and C NMR spectra are given in
parts per million at 400.13 and 100.61 MHz, respectively. Mass
spectra were recorded on an FT-ICR-MS spectrometer, IR spectra
on an FT-IR spectrometer. Elemental analyses were obtained with
a VARIO EL. Optical rotation values were determined on an auto-
matic digital polarimeter and are given as mean values of five mea-
surements. Thin layer chromatography was performed on TLC
110.58(11)
b
107.6(1)
—
—
—
—
d(Hꢀ ꢀ ꢀO)
232a
0
d(Oꢀ ꢀ ꢀO )
288.7(3)
125(2)
0
<(O–Hꢀ ꢀ ꢀO )
a
C–OH is disordered in
a-1; therefore, position of H was calculated only.
b
O(6) replaced by O(4) (see Fig. 1).

J. Kunig et al. / Carbohydrate Research 346 (2011) 1154–1160
1157
plates (Silica Gel 60 F254). Column chromatography was performed
on 0.035–0.070 mm silica gel 60 A using mixtures of petroleum
ether (80–110 °C) and ethyl acetate (EtOAc) as eluents. For detec-
tion of glycosidic compounds, a 1:10 v/v mixture of concentrated
derivative 11 as white crystals (n-hexane, ꢁ20 °C) and its structure
was confirmed by X-ray crystallography.
1.2.1. Allyl 2,3:4,6-di-O-isopropylidene-1-O-
a-D-
phosphoric acid and ethanol was used.
-methoxypropene, pTsOH, and 9-BBN are commercially available.
Crystallographic data were collected with an Oxford Diffraction
Gemini CCD diffractometer using Cu-K radiation (k = 154.184
pm) and -scan rotation. Data reduction was performed with Cry-
D
-Mannose, allyl bromide,
mannopyranoside ( -7)
a
2
D
5
2
The following data belong to pure
a
3
-7: ½
a
ꢃ
+12.0 (c 1.0,
1
8a
24
D
2
CH Cl
2
), lit.
½
a
ꢃ
+13.0 (c 1.0, CHCl
); R = 0.28 (petroleum
f
a
ether–EtOAc 5:1); IR (KBr) 3462 (m), 3082 (m), 2991 (s), 2936
(s), 2874 (m), 2735 (w), 2079 (w); 1870 (w), 1736 (m), 1648 (m),
1459 (s), 1425 (w), 1404 (w), 1382 (s), 1371 (s), 1312 (w), 1265
(m), 1243 (s), 1220 (s), 1199 (s), 1168 (s), 1138 (s), 1116 (s),
1087 (s), 1044 (s), 947 (m), 925 (s), 908 (m), 862 (s), 810 (s), 786
x
2
4
sAlis Pro including an analytical numeric absorption correction
25
using a multifaceted crystal model. The structures were solved
by direct methods and the refinement of all non-hydrogen atoms
was performed with SHELXL-97.26 With the exception of disordered
(s), 760 (s), 732 (m), 680 (m), 658 (w), 621 (w), 557 (w), 521 (s),
1
areas and methyl groups in
a
-1 and 9, all H atoms were located
496 (w), 473 (w), 420 (w); H NMR: d = 1.36 (s, 3H, CH
3
), 1.43 (s,
), 3.61 (td, 1H,
HH = 5.6 Hz, H-5), 3.73–3.79 (m, 2H, H-6, H-3),
on difference Fourier maps calculated at the final stage of the
structure refinement. Structure figures were generated with OR-
3 3 3
3H, CH ), 1.52 (s, 3H, CH ), 1.55 (s, 3H, CH
3
3
J
HH = 10.4 Hz,
J
2
7
2
3
0
TEP. Crystallographic data for compounds
are given in Table 2.
a-1, b-1, 9, and 10
3.88 (dd, 1H,
JHH = 10.8 Hz,
JHH = 5.6 Hz, H-6 ), 4.00 (dd, 1H,
2
HH = 12.4 Hz, 3JHH = 6.0 Hz, OCHH), 4.15–4.21 (m, 3H, H-2, H-4,
J
3
OCHH), 5.08 (s, 1H, H-1), 5.23 (d, 1H,
JHH = 10.4 Hz, CH@CHH),
3
2
1
.2. Mixture of allyl 2,3:4,6-di-O-isopropylidene-
D-
5.30 (dd, 1H,
1H, CH@CH );
(CH ), 29.1 (CH
4.9, 76.1 (C-2, C-4), 97.0 (C-1), 99.7 (dioxane–CMe
(dioxolane–CMe ), 117.0 (CH@CH ), 133.5 (CH@CH ); ESI (pos. in
: C, 59.98; H,
J
HH = 17.2,
J
HH = 1.2 Hz, CH@CHH), 5.85–5.95 (m,
C{ H} NMR: d = 18.8 (CH ), 26.2 (CH ), 28.2
), 61.4 (C-5), 62.1 (C-6), 68.2 (OCH ), 72.8 (C-3),
), 109.5
1
3
1
mannopyranoside (7) and allyl 2,3:5,6-di-O-isopropylidene-
D
-
2
3
3
mannofuranoside (8)
3
3
2
7
2
3
.6 g (20 mmol)
D
-mannose was protected according to Gelas
2
2
2
1
4
+
and Horton. The resulting mixture (white solid) of 3 and 4 was
dried for 3 h at 40 °C and 10 mbar and was then dissolved in
0 mL DMF and added at 0 °C to a suspension of 2.4 g (60 mmol)
MeOH): 323.0 [M+Na] . Anal. Calcd for C15
8.05. Found: C, 59.98; H, 7.92.
24 6
H O
ꢁ
3
4
sodium hydride (60% dispersion in oil) in 50 mL DMF. Stirring
was continued at 0 °C for an additional hour; then 5.1 mL
1.2.2. Allyl 2,3:4,6-di-O-isopropylidene-b-
(b-7)
D-mannopyranoside
2
5
(
60 mmol) allyl bromide was added. The mixture was stirred at
½
a
ꢃ
ꢁ56.3 (c 0.8, CH
2 2 f
Cl ); R = 0.20 (petroleum ether–EtOAc
D
rt overnight, cooled to 0 °C and quenched with 10 mL of methanol.
The solvent was evaporated and 100 mL EtOAc was added. The res-
idue was filtered off and washed with ethyl acetate (2 ꢂ 20 mL).
The combined organic phases were washed with 20 mL of brine
and dried over magnesium sulfate. The solution was filtered, con-
centrated, and column chromatography was performed with a gra-
dient of petroleum ether (80–110 °C) and EtOAc of 5:1–2:1. The
5:1); IR (KBr) 3082 (s), 2992 (s), 2940 (s), 2727 (w), 2366 (w),
2091 (w), 1847 (w), 1736 (w), 1647 (s), 1463 (s), 1456 (s), 1373
(s), 1320 (m), 1303 (m), 1247 (s), 1219 (s), 1159 (s), 1082 (s),
973 (s), 947 (s), 890 (s), 864 (s), 805 (s), 774 (m) 754 (s), 732
(m), 713 (w), 673 (m) 647 (m), 600 (w), 559 (m), 537 (s), 521 (s),
1
500 (s), 477 (m), 440 (w); H NMR: d = 1.39 (s, 3H, CH
3
), 1.43 (s,
3H, CH
3
), 1.52 (s, 3H, CH
3
), 1.59 (s, 3H, CH
3
), 3.24 (td, 1H,
HH = 10.4 Hz, H-6),
3
3
2
allyl glycosides were eluted in the order
a
-7 and
.0 mmol, 25.1%, ratio 1:2 according to 1H NMR), b-7 (1.00 g,
.3 mmol, 16.7%), 9 (0.12 g, 0.4 mmol, 2.0%) and b-8 (1.02 g,
.4 mmol, 17.0%). The -isomers -7 and -8 could be separated
a
-8 (1.51 g,
J
HH = 10.0 Hz,
J
J
HH = 5.6 Hz, H-5), 3.79 (t, 1H,
HH = 10.8 Hz,
J
2
3
0
5
3
3
3.93 (dd, 1H,
J
HH = 5.6 Hz, H-6 ), 4.04 (dd, 1H,
3
HH = 10.4 Hz, 3JHH = 7.0 Hz, H-4), 4.14–4.19 (m, 2H, H-3, OCHH),
J
3
3
a
a
a
4.29 (dd, 1H,
J
HH = 6.0 Hz,
JHH = 2.4 Hz, H-2), 4.40 (ddt, 1H,
2
J
HH = 13.2 Hz, 3JHH = 4.8 Hz, 4JHH = 1.2 Hz, OCHH), 4.85 (d, 1H,
in analytical amounts by column chromatography (length
50 cm, band width <3 mm). The mixture of compounds -7 and
-8, as well as b-7 and b-8 were obtained as yellow oils, the 3-allyl
3JHH = 2.4 Hz, H-1), 5.23 (d, 1H,
3
JHH = 10.4 Hz, CH@CHH), 5.33
>
a
3
2
a
(dd, 1H, JHH = 17.2 Hz, JHH = 1.2 Hz, CH@CHH), 5.89–5.99 (m, 1H,
Table 2
Crystallographic data for compounds
a
-1, b-1, 9, and 10
-1
Compound
Empirical formula
Formula weight
T [K]
a
b-1
9
10
C
15
H
26
O
7
C
15
H
26
O
7
C
15
H
24
O
6
15 26 7
C H O
318.36
200(2)
318.36
130(2)
300.34
130(2)
318.36
130(2)
Crystal system
Space group
a [pm]
b [pm]
c [pm]
Monoclinic
P2
544.81(1)
1436.28(3)
1089.39(2)
90
100.800(2)
90
0.83735(3)
2
Monoclinic
P2
530.92(1)
1771.22(4)
868.95(2)
90
93.020(2)
90
0.81600(3)
2
Monoclinic
P2
568.50(2)
1539.21(5)
945.61(3)
90
102.440(3)
90
0.80802(5)
2
Orthorhombic
P2
562.24(1)
1532.43(2)
1917.32(2)
90
1
1
1
1 1 1
2 2
a
[deg]
b [deg]
[deg]
90
90
c
3
V [nm ]
1.65195(4)
4
1.280
0.846
688
Z
q
calcd [Mg/m3]
1.263
0.834
344
1.296
0.856
344
1.234
0.789
324
Absorption coefficient [mmꢁ1]
F(0 0 0)
Reflections collected
Absolute structure parameter
11,751
4173
14,183
27,855
0.05(12)
0.0269/0.0707
0.0274/0.0712
0.01(16)
0.0358/0.0987
0.0373/0.0997
0.12(14)
0.0255/0.0638
0.0272/0.0643
ꢁ0.08(14)
0.0305/0.0742
0.0351/0.0757
R
R
1
/wR
/wR
2
(I > 2
(all data)
r(I))
1
2

1
158
J. Kunig et al. / Carbohydrate Research 346 (2011) 1154–1160
1
CH@CH
CH ), 62.5 (C-6), 65.9 (C-5), 70.1 (OCH
6.5 (C-3), 97.3 (C-1), 99.7 (dioxane–CMe
CMe ), 118.3 (CH@CH ), 133.6 (CH@CH ); ESI (pos. in MeCN):
2
); 13C{ H} NMR: d = 18.9 (CH
3
), 26.1 (CH
), 72.2 (C-4), 74.6, (C-2),
), 111.1 (dioxolane–
3
), 27.8 (CH
3
), 29.0
2H, H-2, OCHH), 5.21–5.23 (m, 2H, H-1, CH@CHH), 5.30 (dd, 1H,
3
2
(
7
3
2
J
HH = 17.2 Hz,
J
HH = 1.2 Hz, CH@CHH), 5.91–6.00 (m, 1H,
); C{ H} NMR: d = 19.1 (CH ), 25.9 (CH ), 28.1 (CH ),
29.2 (CH ), 62.2 (C-6), 66.3 (C-5), 71.1 (C-4), 72.2 (OCH ), 75.2,
(C-3), 77.6 (C-2), 97.7 (C-1), 99.5 (dioxane–CMe ), 112.4 (dioxo-
lane–CMe ), 117.8 (CH@CH ), 135.0 (CH@CH ); ESI (pos. in MeOH):
23.1 [M+Na] . Anal. Calcd for C15 : C, 59.98; H, 8.05. Found:
C, 60.23; H, 8.05.
1
3
1
2
CH@CH
2
3
3
3
2
2
2
3
2
+
+
3
23.1 [M+Na] , 623.2 [2 M+Na] . Anal. Calcd for C15
9.98; H, 8.05. Found: C, 59.73; H, 8.10.
H
24
O
6
: C,
2
5
2
2
2
+
3
24 6
H O
1
.2.3. Allyl 2,3:5,6-Di-O-isopropylidene-
a-D-mannofuranoside
(
a
-8)
2
D
5
The following data belong to pure
a
-8: ½
a
ꢃ
+14.0 (c 0.6,
1.3. General hydroboration procedure
1
9b
20
D
CH
2
Cl
2
); lit.
½
aꢃ
+62.3 (c 1.2, acetone); R = 0.26 (petroleum
f
ether–EtOAc 5:1); IR (KBr) 3449 (m), 3082 (m), 2989 (s), 2937
s), 2347 (w), 2164 (w), 2067 (w), 2018 (w), 1859 (w), 1741 (s),
648 (m), 1458 (s), 1427 (m), 1372 (s), 1262 (s), 1211 (s), 1163
s), 1117 (s), 1085 (s), 1022 (s), 976 (s), 891 (s), 850 (s), 820 (m),
The allyl glycosides b-7 (1.00 g, 3.3 mmol), b-8 (1.02 g,
3.4 mmol), 9 (0.12 g, 0.4 mmol), and the mixture of -7 and -8
(
1
(
a
a
(1.51 g, 5.0 mmol, ratio 1:2) obtained according to 1.2 were dis-
solved in THF, cooled to 0 °C (ice bath), and 1.5 equiv of a 0.5 M
9-BBN solution in THF was added. The ice bath was removed and
the reaction mixture was stirred overnight at rt. The mixture was
cooled to 0 °C and unreacted 9-BBN was destroyed by addition of
water. 10 mL of a 3 M sodium hydroxide solution and 10 mL of
35% hydrogen peroxide were added to oxidize the intermediate
hydroboration product. The mixture was stirred overnight, satu-
rated with sodium carbonate, filtered, and the phases were sepa-
rated. The aqueous phase was washed with 20 mL of ethyl
acetate and the combined organic phases were washed with
7
4
CH
30 (w), 691 (m), 653 (w), 632 (w), 600 (w), 567 (w), 515 (s),
1
60 (w), 418 (w); H NMR: d = 1.33 (s, 3H, CH
), 1.46 (s, 3H, CH ), 1.47 (s, 3H, CH ), 3.93–3.98 (m, 2H, H-4,
HH = 4.4 Hz, H-6), 4.10–4.15
3
), 1.38 (s, 3H,
3
3
3
2
J J
HH = 8.8 Hz, 3
OCHH), 4.04 (dd, 1H,
0
(
m, 2H, H-6 , OCHH), 4.39–4.43 (m, 1H, H-5), 4.62 (d, 1H,
J
3
HH = 6.0 Hz, H-2), 4.80 (dd, 1H, 3
HH = 6.0 Hz, 3
J
J
HH = 3.6 Hz, H-3),
3
2
5
.03 (s, 1H, H-1), 5.20 (dd, 1H,
J
HH = 10.4 Hz,
J
HH = 0.8 Hz,
HH = 1.6 Hz, CH@CHH),
); 13C{ H} NMR: d = 24.6 (CH
), 25.2
), 67.0 (C-6), 68.0 (OCH ), 73.2 (C-5),
9.6 (C-3), 80.4 (C-4), 85.1 (C-2), 105.7 (C-1), 109.2 (CMe ), 112.6
), 117.6 (CH@CH ), 133.8 (CH@CH ); ESI (pos. in MeCN):
23.0 [M+Na] . Anal. Calcd for C15 : C, 59.98; H, 8.05. Found:
3
2
CH@CHH), 5.28 (dd, 1H,
.83–5.93 (m, 1H, CH@CH
CH ), 25.9 (CH ), 26.9 (CH
JHH = 17.2 Hz, J
1
5
(
7
2
3
3
3
3
2
20 mL of brine and dried (MgSO
1.4 mmol, 83%), b-1 (0.97 g, 3.0 mmol, 92%),
92%), b-2 (0.82 g, 2.5 mmol, 76%), and 10 (0.07 g, 0.2 mmol, 83%)
were obtained by column chromatography. Pyranoses -1, b-1,
4
). Pure compounds
a-1 (0.44 g,
2
a
-2 (0.98 g, 3.1 mmol,
(CMe
2
2
2
+
3
H
24
O
6
a
C, 59.96; H, 7.98.
and 10 were obtained as white crystals (n-hexane, ꢁ20 °C) suitable
for X-ray crystallography, furanoses
oils.
a-2, and b-2 as pale yellow
1
.2.4. Allyl 2,3:5,6-di-O-isopropylidene-b-
D-mannofuranoside
(
b-8)
2
D
5
0
½
a
ꢃ
ꢁ95.3 (c 1.5, CH
2
Cl
2
); R
f
= 0.13 (petroleum ether–EtOAc
1.3.1. 3 -Hydroxypropyl 2,3:4,6-di-O-isopropylidene-
a
-
D
-
5
2
1
7
:1); IR (KBr) 3531 (m), 3082 (m), 2987 (s), 2938 (s), 2874 (s),
287 (w), 2015 (w), 1858 (w), 1647 (m), 1459 (m), 1375 (s),
215 (s), 1156 (s), 1119 (s), 1069 (s), 928 (m), 847 (s), 792 (m),
54 (m), 675 (w), 514 (m), 442 (w); 1H NMR: d = 1.36 (s, 3H,
mannopyranoside (
a
-1)
2
D
5
Mp 111 °C; ½
aꢃ
+4.8 (c 5.0, CH Cl ); R = 0.32 (petroleum ether–
2 2 f
EtOAc 1:2); IR (KBr) 3505 (s), 2986 (s), 2917 (s), 2879 (m), 2803
(w), 1631 (w), 1458 (m), 1381 (s), 1319 (m), 1267 (s), 1250 (s),
1221 (s), 1198 (s), 1169 (s), 1135 (s), 1088 (s), 1045 (s), 1020 (s),
985 (m), 950 (m), 924 (m), 852 (s), 806 (m), 788 (m), 760 (m),
733 (m), 679 (m), 643 (w), 521 (s), 495 (m), 475 (m); 1H NMR:
CH
3 3 3 3
), 1.38 (s, 3H, CH ), 1.45 (s, 3H, CH ), 1.56 (s, 3H, CH ), 3.60
3
3
3
(
dd, 1H, JHH = 7.6 Hz, JHH = 4.0 Hz, H-4), 4.09 (d, 2H, JHH = 4.8 Hz,
0
2
3
4
H-6, H-6 ), 4.15 (ddt, 1H, JHH = 12.8 Hz, JHH = 6.4 Hz, JHH = 1.2 Hz,
2
3
HH = 5.2 Hz, 4
OCHH), 4.35 (ddt, 1H,
JHH = 13.2 Hz,
J
J
HH = 1.6 Hz,
d = 1.36 (s, 3H, CH
3H, CH ), 1.65 (br, 1H, OH) 1.87 (pent, 2H,
CH CH CH
6, H-4, CH
3
), 1.43 (s, 3H, CH
3
), 1.52 (s, 3H, CH
3
), 1.55 (s,
OCHH), 4.46 (dt, 1H, 3JHH = 7.6 Hz, 3
J
HH = 5.2 Hz, H-5), 4.62 (dd,
3
JHH = 6.0 Hz,
3
3
3
3
1
H,
JHH = 6.4 Hz,
JHH = 3.6 Hz, H-2), 4.73 (dd, 1H,
J
HH = 6.4 Hz,
2
2
2
), 3.55–3.60 (m, 2H, H-5, OCHH), 3.73–3.79 (m, 4H, H-
3
3
0
J
HH = 4.0 Hz, H-3), 4.77 (d, 1H,
J
HH = 3.6 Hz, H-1), 5.21 (dd, 1H,
2
OH), 3.84–3.91 (m, 2H, H-6 , OCHH), 4.12–4.18 (m,
3
3
2
3
13
J
J
HH = 10.4 Hz, JHH = 1.2 Hz, CH@CHH), 5.31 (dd, 1H, JHH = 17.2 Hz,
2H, H-2, H-3), 5.03 (s, 1H, H-1);
C NMR: d = 18.8 (qq,
13
1
1
CH = 126.4 Hz, 3JCH = 3.2 Hz, CH
), 26.2 (qq, 1JCH = 126.6 Hz,
HH = 1.6 Hz, CH@CHH), 5.90–6.00 (m, 1H, CH@CH
), 25.3 (CH ), 25.7 (CH ), 27.0 (CH
), 73.3 (C-5), 77.1 (C-4), 79.1, (C-3), 79.8 (C-2),
01.7 (C-1), 109.2 (CMe ), 113.7 (CMe ), 117.9 (CH@CH ), 133.9
); ESI (pos. in MeOH): 323.1 [M+Na] . Anal. Calcd for
: C, 59.98; H, 8.05. Found: C, 60.10; H, 8.05.
2
);
C{ H}
J
3
3JCH = 2.7 Hz, CH
), 28.2 (qq, 1JCH = 127.0 Hz,,
3
J
CH = 2.8 Hz, CH
NMR: d = 25.1 (CH
6
1
3
3
3
3
), 66.9 (C-
3
3
),
1
3
1
), 71.1 (OCH
2
29.1 (qq, JCH = 127.6 Hz, JCH = 3.4 Hz, CH
3
), 32.1 (t, JCH = 126.0 Hz,
CH = 4.6 Hz, CH OH), 61.5
CH = 140.7 Hz, OCH ), 72.7, 74.9 (d,
CH = 1.6 Hz, C-2, C-3,
CH = 169.2 Hz, C-1), 99.8 (dioxane–CMe ), 109.5 (q,
); ESI (pos. in MeCN): 341.0
: C, 56.59; H, 8.23. Found: C,
1
2
2
2
2
CH
2
CH
2
CH
2
), 60.5 (tt,
J
CH = 142.2 Hz,
J
2
+
1
(CH@CH
2
(C-5), 62.1 (C-6), 65.5 (t,
J
2
1
CH = 152.5 Hz), 76.1 (dd, 1JCH = 151.7 Hz,
J
2
C
15
H
24
O
6
J
1
C-4), 97.9 (d,
J
2
2
1
.2.5. 3-O-Allyl-1,2:4,6-di-O-isopropylidene-b-
D-
J
CH = 4.7 Hz, dioxolane–CMe
2
+
mannopyranose (9)
[M+Na] . Anal. Calcd for C15
56.65; H, 8.43.
H O
26 7
25
½
a
ꢃ
ꢁ0.5 (c 0.1, CH
2
Cl
IR (KBr) 3449 (m), 3082 (m), 2994 (s), 2939 (m), 2910 (s), 2886 (s),
649 (m), 1478 (w), 1460 (m), 1426 (m), 1377 (s), 1349 (m), 1330
2 f
); R = 0.17 (petroleum ether–EtOAc 5:1);
D
0
1
1.3.2. 3 -Hydroxypropyl 2,3:4,6-di-O-isopropylidene-b-
D-
(
(
9
m), 1310 (m), 1266 (s), 1232 (m), 1218 (s), 1202 (s), 1173 (s), 1158
s), 1131 (s), 1091 (s), 1071 (s), 1002 (m), 944 (w), 929 (s), 912 (w),
mannopyranoside (b-1)
2
5
Mp 77 °C; ½
aꢃ
ꢁ90.3 (c 5.0, CH
2 2 f
Cl ); R = 0.20 (petroleum
D
01 (m), 861 (s), 820 (m), 768 (m), 739 (m), 682 (w), 644 (w), 572
ether–EtOAc 1:2); IR (KBr) 3482 (s), 2992 (m), 2963 (m), 2941
(m), 2894 (m), 2824 (w), 2727 (w), 1628 (w), 1484 (w), 1459
(w), 1423 (w), 1382 (s), 1324 (m), 1245 (s), 1219 (s), 1190 (s),
1139 (s), 1073 (s), 972 (m), 949 (m), 934 (m), 885 (m), 850 (s),
804 (s), 770 (w), 753 (m), 715 (w), 522 (m), 476 (w); 1H NMR:
1
(
w), 524 (m), 503 (w); H NMR: d = 1.41 (s, 3H, CH
3
), 1.42 (s, 3H,
CH
3
), 1.53 (s, 3H, CH
3
), 1.58 (s, 3H, CH
3
), 3.17 (td, 1H,
3
HH = 10.0 Hz, 3JHH = 5.6 Hz, H-5), 3.69 (dd, 1H,
3
J
J
J
JHH = 9.2 Hz,
3
2
3
HH = 4.0 Hz, H-3), 3.76 (t, 1H,
JHH = 10.4 Hz, H-6), 3.89 (dd, 1H,
3
0
3
HH = 10.8 Hz,
J
HH = 5.2 Hz, H-6 ), 4.09 (t, 1H,
J
HH = 9.6 Hz, H-4),
d = 1.38 (s, 3H, CH
3
), 1.43 (s, 3H, CH
3
3
), 1.53 (s, 3H, CH ), 1.57 (s,
.25 (dd, 1H, 2JHH = 13.2 Hz, 3
J
HH = 6.4 Hz, OCHH), 4.31–4.36 (m,
3H, CH ), 1.90 (pent, 2H,
3
J
HH = 5.6 Hz, CH CH CH ), 2.20 (br, 1H,
4
3
2
2
2

J. Kunig et al. / Carbohydrate Research 346 (2011) 1154–1160
1159
OH), 3.30 (td, 1H, 3JHH = 10.4 Hz, JHH = 5.6 Hz, H-5), 3.68–3.77 (m,
3
79.1 (d, 1JCH = 158.6 Hz, C-3), 79.4 (dd, 1JCH = 157.2 Hz,
3
2
1
2
J
H, H-6, OCHH), 3.80 (t, 2H,
J
HH = 5.6 Hz, CH
HH = 5.6 Hz, H-6 ), 4.05–4.12 (m, 2H, H-4, OCHH),
2
OH), 3.94 (dd, 1H,
J
CH = 6.1 Hz, C-2), 102.8 (d,
J
CH = 164.0 Hz, C-1), 109.2 (septet,
), 113.8 (CMe ); ESI (pos. in MeCN): 341.2
: C, 56.59; H, 8.23. Found: C,
2
3
0
2JCH = 2.3 Hz, CMe
HH = 10.4 Hz,
.18 (t, 1H,
J
J
2
2
3
3
+
4
HH = 6.4 Hz, H-3), 4.30 (dd, 1H,
J
HH = 6.4 Hz,
[M+Na] . Anal. Calcd for C15
56.42; H, 8.34.
26 7
H O
3
HH = 2.8 Hz, H-2), 4.84 (d, 1H, 3JHH = 2.8 Hz, H-1); C NMR:
13
J
1
3
J ), 25.8 (qq,
CH = 126.6 Hz, 3JCH = 3.1 Hz, CH
d = 18.9 (qq,
1
CH = 126.5 Hz, 3JCH = 2.8 Hz, CH
1
0
J
J
3
), 27.4 (qq,
J
CH = 127.1 Hz,
CH = 3.3 Hz, CH ),
CH CH ), 61.1 (tt,
CH = 146.0 Hz, C-
CH = 141.4 Hz, OCH ), 71.8 (d,
CH = 146.8 Hz, C-4), 74.1 (dd, 1JCH = 150.2 Hz,
JCH = 3.4 Hz, C-2),
1.3.5. 3-O-(3 -Hydroxypropyl)-1,2:4,6-di-O-isopropylidene-b-
D
-
3
), 29.0 (qq, 1JCH = 127.5 Hz,
3
CH = 2.9 Hz, CH
3
J
3
mannopyranose (10)
1
2
25
D
3
1.9 (tt,
J
CH = 126.0 Hz,
J
CH = 2.1 Hz, CH
2
2
2
Mp 72 °C; ½
aꢃ
ꢁ0.9 (c 0.1, CH
2 2 f
Cl ); R = 0.22 (petroleum ether–
1
2
1
J
CH = 142.0 Hz,
J
CH = 4.4 Hz, CH OH), 62.8 (t,
2
J
EtOAc 1:2); IR (KBr) 3489 (s), 3442 (s), 2992 (m), 2927 (m), 2964
(m), 2361 (m), 2343 (m), 1735 (w), 1718 (w), 1701 (w), 1685
(w), 1654 (m), 1636 (m), 1577 (w), 1559 (w), 1541 (w), 1522
(w), 1507 (w), 1458 (w), 1420 (w), 1387 (m), 1374 (m), 1311
(w), 1266 (m), 1234 (m), 1207 (m), 1172 (m), 1129 (m), 1093 (s),
1063 (s), 994 (m), 945 (m), 902 (m), 862 (s), 806 (m), 769 (m),
1
6
), 66.0 (C-5), 68.0 (t,
J
2
1
2
J
1
1
2
7
6.2 (d, JCH = 154.0 Hz, C-3), 98.4 (dd, JCH = 162.6 Hz, JCH = 1.8 Hz,
C-1), 99.7 (dioxane–CMe ), 111.0 (dioxolane–CMe ); ESI (pos. in
MeCN): 341.0 [M+Na] . Anal. Calcd for C15 : C, 56.59; H,
2
2
+
26 7
H O
8
.23. Found: C, 56.61; H, 8.31.
740 (m), 669 (m), 651 (m), 580 (m), 542 (m), 523 (m), 498 (m),
1
4
70 (w), 452 (w); H NMR: d = 1.41 (s, 3H, CH
3
), 1.43 (s, 3H,
0
1
.3.3. 3 -Hydroxypropyl 2,3:5,6-di-O-isopropylidene-
a
-
D
-
CH
3
), 1.53 (s, 3H, CH
CH CH ), 2.74 (br, 1H, OH), 3.19 (td, 1H,
3
), 1.58 (s, 3H, CH ), 1.79–1.92 (m, 2H,
3
3
mannofuranoside (
a
-2)
CH
2
2
2
JHH = 9.6 Hz,
2
D
5
3
3
3
½
aꢃ
+46.9 (c 5.6, CH
2
Cl
2
); R
f
= 0.30 (petroleum ether–EtOAc
J
HH = 5.2 Hz, H-5), 3.64 (dd, 1H,
J
HH = 9.2 Hz,
J
HH = 4.0 Hz, H-3),
2
1
2
:2); IR (KBr) 3456 (s), 2987 (s), 2938 (s), 2885 (s), 2286 (w),
170 (w), 2064 (w), 1739 (m), 1641 (w), 1457 (s), 1375 (s), 1211
3.73–3.83 (m, 4H, H-6, CH
2
OH, OCHH), 3.90 (dd, 1H, JHH = 10.8 Hz,
3
0
2
3
3
J
HH = 5.2 Hz, H-6 ), 3.97 (dd, 1H,
J
HH = 10.4 Hz,
J
J
HH = 4.8 Hz,
3
(
6
3
s), 1162 (s), 1086 (s), 889 (s), 850 (s), 729 (m), 729 (w), 682 (m),
OCHH), 4.03 (t, 1H,
J
HH = 9.2 Hz, H-4), 4.39 (dd, 1H,
HH = 4.0 Hz,
30 (w), 516 (m), 425 (w); 1H NMR: d = 1.32 (s, 3H, CH
), 1.38 (s,
HH = 6.0 Hz,
3
J
HH = 2.0 Hz, H-2), 5.23 (d, 1H,
d = 19.1 (CH ), 25.9 (CH ), 28.2 (CH
(CH CH CH ), 61.1 (CH OH), 62.1 (C-6), 66.3 (C-5), 69.6 (OCH
70.4 (C-4), 76.8 (C-2), 77.5 (C-3), 97.7 (C-1), 99.8 (dioxane–
CMe ), 112.5 (dioxolane–CMe ); ESI (pos. in MeOH): 341.0
: C, 56.59; H, 8.23. Found: C,
3
J
HH = 2.0 Hz, H-1); C{ H} NMR:
13
1
3
3
H, CH
CH CH
HH = 6.0 Hz, OCHH), 3.73 (t, 2H,
3
), 1.47 (s, 6H, 2 ꢂ CH
3
), 1.82 (pent, 2H,
J
3
3
3
), 29.1 (CH
3
), 31.8
),
CH
2
2
2
), 1.99 (br, 1H, OH), 3.55 (dt, 1H, 2JHH = 10.0 Hz,
2
2
2
2
2
3
3
J
J
HH = 6.0 Hz, CH
2
OH), 3.81 (dt,
2
3
3
1
J
H, JHH = 10.0 Hz, JHH = 6.0 Hz, OCHH), 3.94 (dd, 1H, JHH = 7.6 Hz,
2
2
3
2
HH = 8.8 Hz, 3
+
HH = 3.6 Hz, H-4), 4.04 (dd, 1H,
J
J
HH = 4.8 Hz, H-6),
JHH = 6.4 Hz, H-6 ), 4.41 (dt, 1H,
[M+Na] . Anal. Calcd for C15
56.61; H, 8.34.
26 7
H O
2
3
0
4
J
.11 (dd, 1H,
JHH = 8.8 Hz,
3
3
3
HH = 6.4 Hz,
J
J
HH = 4.8 Hz, H-5), 4.58 (d, 1H,
J
HH = 6.0 Hz, H-2),
3
3
4
.78 (dd, 1H,
HH = 6.0 Hz,
J
HH = 3.6 Hz, H-3), 4.99 (s, 1H, H-1);
Acknowledgments
1
3
1
3
C NMR: d = 24.5 (qq,
JCH = 126.5 Hz,
J
CH = 2.7 Hz, CH
3
), 25.2
CH = 127.2 Hz,
CH = 2.9 Hz, CH ),
CH CH ), 60.6 (tt,
CH = 143.0 Hz,
CH = 3.1 Hz, C-6),
CH = 1.4 Hz, C-5), 79.5
CH = 146.9 Hz, C-4), 85.1 (dd,
qq, 1
J
J
CH = 126.5 Hz,
3
JCH = 2.8 Hz, CH ), 25.9 (qq,
1
J
We thank Chemetall GmbH, Langelsheim, Germany, for a gener-
ous donation of sodium hydride and n-butyl lithium and we thank
Andreas Ott for synthetic support.\
(
3
3
1
3
CH = 2.9 Hz, CH ), 26.9 (qq,
3
J
CH = 126.8 Hz,
CH = 2.4 Hz, CH
CH = 4.5 Hz, CH OH), 65.3 (tt,
J
3
1
2
3
2.0 (tt,
J
CH = 126.0 Hz,
J
2
2
2
1
2
1
J
CH = 142.0 Hz,
J
2
J
2
1
2
J
2
CH = 4.0 Hz, OCH ), 66.9 (td, JCH = 149.3 Hz, J
Supplementary data
1
2
2
7
3.2 (ddd,
JCH = 152.4 Hz,
JCH = 4.1 Hz,
J
1
1
(
d,
J
J
CH = 159.2 Hz, C-2), 80.3 (d,
J
1H NMR, 13C NMR, COSY and HMQC spectra are given as
Supplementary Data. This material is available free of charge via
the internet at ScienceDirect: http://www.sciencedirect.com. CCDC
1
2
1
CH = 156.7 Hz,
J
CH = 3.6 Hz, C-3), 106.4 (d,
J
CH = 173.9 Hz, C-1),
CH = 4.7 Hz, CMe ); ESI
pos. in MeCN): 341.2 [M+Na] . Anal. Calcd for C15 : C,
2
2
1
(
09.2 (m,
J
CH = 2.3 Hz, CMe
2
), 112.7 (m,
J
2
+
26 7
H O
numbers 763710 (a-1), 763711 (b-1), 763712 (9) and 815049 (10)
5
6.59; H, 8.23. Found: C, 56.37; H, 8.38.
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/
data_request/cif. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/j.carres.2011.
0
1
.3.4. 3 -Hydroxypropyl 2,3:5,6-di-O-isopropylidene-b-
D
-
mannofuranoside (b-2)
2
D
5
½aꢃ
2 2 f
ꢁ25.4 (c 4.1, CH Cl ); R = 0.14 (petroleum ether–EtOAc
1
1
:2); IR (KBr) 3499 (s), 2985 (s), 2936 (s), 2879 (s), 1736 (w),
634 (w), 1457 (m), 1418 (m), 1374 (s), 1214 (s), 1155 (s), 1120
0
3.035.
(
(
1
s), 1068 (s), 930 (m), 889 (m), 845 (s), 795 (w), 749 (w), 513
References
1
m), 406 (w); H NMR: d = 1.36 (s, 3H, CH
3
), 1.38 (s, 3H, CH
3
),
3
.45 (s, 3H, CH ), 1.53 (s, 3H, CH ), 1.86 (pent, 2H,
3
3
J
HH = 5.6 Hz,
1. Locher, G. L. Am. J. Roentgenol. Radium Ther. 1936, 36, 1–13.
), 2.81 (br, 1H, OH), 3.65 (dd, 1H, 3JHH = 7.2 Hz,
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CH
CH CH
2 2 2
6
3
J
H,
HH = 4.0 Hz, H-4), 3.76–3.81 (m, 3H, CH
2
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2
3
0
1
J
HH = 9.6 Hz, J = 5.6 Hz, OCHH), 4.08–4.10 (m, 2H, H-6, H-6 ),
3
3
4
.44 (dt, 1H,
J
J
J
HH = 6.8 Hz,
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3
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HH = 4.0 Hz, H-3), 4.77 (d, 1H, 3JHH = 4.0 Hz, H-1); C NMR:
13
1
3
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4
3, 225–244.
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1
CH = 126.4 Hz, 3JCH = 2.8 Hz, CH
CH = 2.8 Hz, CH
1
J
J
3
), 25.6 (qq,
J
CH = 127.3 Hz,
CH = 2.9 Hz, CH ),
CH CH ), 60.7 (tt,
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1
3
), 26.9 (qq, 1JCH = 126.7 Hz,
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3
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1
2
3
2.0 (tt,
J
J
J
J
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OH), 66.7 (td,
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2
2
2
1
2
1
CH = 142.0 Hz,
CH = 3.2 Hz, C-6), 68.7 (t,
J
CH = 3.9 Hz, CH
2
J
2
1
1
J
2
), 73.3 (dd,
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1
CH = 152.3 Hz,
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