An expedient asymmetric synthesis of a calystegine B4 analogue

Article abstract of DOI:10.1055/s-2002-33706

A convenient high-yielding synthetic route to polyhydroxylated 6-oxa-nor-tropanes that mimic the structural framework of calystegine B₄ is reported.

Full text of DOI:10.1055/s-2002-33706

PAPER
1707
An Expedient Asymmetric Synthesis of a Calystegine B4 Analogue
An
Expedient
o
A
symmetric
fSynthesis of
a
C
aalystegine 4
B
AnD
alogue . Koulocheri,a Emmanuel N. Pitsinos,b Serkos A. Haroutounian*a
a
Chemistry Laboratory, Agricultural University of Athens, Iera odos 75, 11855 Athens, Greece
Fax +30(1)5294265; E-mail: sehar@aua.gr
b
Laboratory of Organic and Bioorganic Chemistry, Institute of Physical Chemistry, NCSR ‘Demokritos’, P.O. Box 60228, 15310 Athens,
Greece
Received 11 April 2002; revised 5 June 2002
OH
OH
OH
NH
NH
NH
Abstract: A convenient, high-yielding synthetic route to polyhy-
droxylated 6-oxa-nor-tropanes that mimic the structural framework
of calystegine B4 is reported.
HO
HO
HO
HO
HO
HO
Key words: alkaloids, glycosidase inhibitors, piperidines, asym-
metric synthesis, calystegines
1
2
OH
NH
HO
HO
HO
HO
The design and synthesis of compounds that selectively
inhibit glycosidases have attracted considerable research
interest during the last years.1,2 Such inhibitors are not
only useful for probing the biological functions of oligo-
saccharides but are also significant as potential drugs for
the treatment of carbohydrate mediated diseases, such as
diabetes,3 cancer,4 and viral infections (including AIDS).5
For this purpose, numerous natural and synthetic polyhy-
droxy alkaloids have been extensively investigated, in-
cluding compounds with the piperidine, pyrrolidine,
indolizidine and pyrrolizidine azasugar skeletons.6
O
O
3
4
Figure 1
bridged 1,3-O,N-heterobicyclic system, was found to pos-
sess strong and highly specific inhibitory activity against
bovine liver -glucosidases. Accordingly, we were inter-
ested to develop a convenient route for the preparation of
the corresponding glucomimetic analogue of calystegine
B4 4 (Figure 1). As precursor (Scheme 1) we envisioned
the structural framework of chiral 2S-hydroxymethyl-di-
hydropyridone 5, which is easily accessible from D-glu-
cal, according to our recently reported method.14
Protection of substrate 6 followed by reduction, according
to previously reported modified Luche conditions, result-
ed in the formation of alcohol 7 as a single diastereomer.
Benzylation of the hydroxyl group and subsequent dihy-
droxylation of the double bond with OsO4 in the presence
of 4-methylmorpholine N-oxide afforded the dihydroxy-
piperidine derivative 9 as a single diastereomer. The dias-
tereoselectivity of this reaction may be rationalized
considering the effective steric shielding of the re-face of
the double bond by the pseudo axially oriented 2,6-bulky
substituents (Figure 2).
The recent discovery of calystegines has introduced an en-
tirely new class of alkaloids to this group of biologically
active compounds.1 Calystegines constitute a novel class
of plant secondary metabolites, which have been implicat-
ed in the establishment and maintenance of specific plant-
bacterium relationships.7 Their structure consists of a nor-
tropane skeleton bearing two to four hydroxyl groups
varying in position and stereochemistry.8 Evaluation of
their biological activities has indicated that nor-tropanes
possess significant inhibitory activities against various
glycosidase enzymes,1,9 presumably because of their
structural similarities with known powerful enzyme in-
hibitors. Thus, calystegine B2 1 is an efficient inhibitor of
both -glucosidase and -galactosidase,10 while calyste-
gine B4 2 is a potent specific inhibitor of mammalian tre-
halases (Figure 1).11 It is also noteworthy that both
molecules have no inhibitory activity against other en-
zymes. Since there is a lack of convenient methods for
their asymmetric preparation, no SAR studies have been
reported to date.12
The diastereomeric purity of the product was revealed by
HPLC and 1H NMR spectroscopic analysis, since no trace
of the other diastereomer was detected. The relative stere-
ochemistry of compound 9 was deduced by 2D COSY and
NOESY studies. Thus, the NOE correlation between H-
5
ax and the hydroxyl proton on carbon atom C-3 and the
Recently, the synthesis of a polyhydroxylated 6-oxa-nor-
tropane analogue of calystegine B2 (Figure 1, 3) from L-
idofuranose derivatives was reported.13 This novel com-
pound, which contains the structural framework of a
small coupling constant between the H-2 and H-3 are in-
dicative of a 4C1 conformation and the axial orientation of
the hydroxy-group proton on carbon atom C-3. Further-
more, the interaction between the methylene-protons of
the hydroxymethyl moiety and H-4ax, is consistent with
the equatorial orientation of the hydroxyl-group at carbon
atom C-4 (Figure 2).
Synthesis 2002, No. 12, Print: 06 09 2002.
Art Id.1437-210X,E;2002,0,12,1707,1710,ftx,en;Z06402SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1708
S. D. Koulocheri et al.
PAPER
tilled from sodium-benzophenone, and CH2Cl2 over CaH2 immedi-
ately prior to use. Starting materials and reagents were purchased
from Aldrich (analytical reagent grades) and used without further
purification. Chiral 2S-hydroxymethyl-dihydropyridone (5)
O
OR1
b
89%
d
RO
N
O
N
96%
Ts
Ts
OTBDMS
OTBDMS
{[ ]22
= 26.7 (c 0.84, EtOAc), mp 101 103 °C} was prepared
D
5 R=H
6 R=Me
7 R1=H
according to literature procedure.14 Melting points were determined
on a Büchi apparatus and are uncorrected. IR spectra were recorded
a
c
(94%)
(91%)
8 R1=Bn
1
on a Nicolet Magna 750, series II spectrometer. H NMR spectra
were recorded in CDCl3 on Bruker AM-250 or DRX-400 spectro-
meters (250 MHz and 400 MHz, respectively) using TMS as inter-
nal standard. Optical rotations were measured with a Perkin-Elmer
241 polarimeter at ambient temperature. Elemental analyses were
provided by the University of Illinois microanalytical service labor-
atory. HPLC separations were performed using a Hewlett Packard
1100 series instrument with a variable wavelength UV detector and
coupled to HP Chem-Station utilizing the manufacturer’s 5.01 soft-
ware package. TLC was conducted on Merck glass plates coated
with silica gel 60 F254. Flash column chromatography was per-
formed using Merck silica gel 60 (230-400 mesh ASTM).
OR2
R2O
O
OBn
OBn
NTs
BnO
BnO
f
e
90%
89%
N
Ts
O
OTBDMS
11
9 R2=H
c
(91%)
10 R2=Bn
2
OH
OH
NTs
NH
HO
HO
HO
HO
g
1
4
7
5
68%
3
O
O
(2S,6R)-2-(tert-Butyl-dimethyl-silyloxymethyl)-6-methoxy-1-
(toluene-4-sulfonyl)-1,6-dihydro-2H-pyridin-3-one (6)
4
12
To an ice-cold soln of azapyranone 5 (1.53 g, 3.72 mmol), trimethyl
orthoformate (0.8 mL, 7.44 mmol) and 4Å molecular sieves (0.35
g) in anhyd THF (25 mL), BF3 Et2O (0.7 mL) was added. The reac-
tion mixture was stirred for 3 h at 0 °C, quenched with H2O and ex-
tracted with Et2O (2 30 mL). The combined organic layers were
washed with brine, dried over MgSO4 and concentrated under re-
duced pressure to give a yellowish solid which was chromato-
graphed (EtOAc hexane, 1:4, Rf 0.35) to furnish the desired
product 6 as colorless fine needles; yield: 1.49 g (94%).
Scheme 1 a) HC(OMe)3, BF3 OEt2, 4Å molecular sieves, THF,
0 °C (b) NaBH4, CeCl3 7H2O, MeOH, -30 °C (c) NaH, BnBr, Bu4NI,
THF (d) OsO4, NMO, t-BuOH acetone, 1:1 (e) LiAlH4, AlCl3, THF
(f) H2, Pd/C, MeOH (g) Na, naphthalene, THF.
Mp 68–70 °C (Et2O hexane).
[ ]D22 +106 (c 0.51, EtOAc).
IR (neat): 1695 (C=O), 1637 (C=C) cm–1
.
1H NMR (400 MHz, CDCl3): = 0.05 (s, 6 H, CH3), 0.89 (s, 9 H,
C CH3), 2.40 (s, 3 H, ArCH3), 3.58 (s, 3 H, OCH3), 3.94 (dd,
J = 10.1, 7.3 Hz, 1 H, CHHOTBDMS), 4.00 (dd, J = 10.1, 7.5 Hz,
1 H, CHHOTBDMS), 4.39 (t, J = 7.3 Hz, 1 H, H-2), 5.55 (dd,
J = 4.4, 0.9 Hz, 1 H, H-6), 5.78 (d, J = 10.1 Hz, 1 H, H-4), 6.74 (dd,
J = 10.1, 4.4 Hz, 1 H, H-5), 7.25 (d, J = 8.3 Hz, 2 H, Ar-H), 7.59 (d,
J = 8.3 Hz, 2 H, ArH).
Figure 2
Anal. Calcd for C20H30NO5SSi (425.6): C, 56.44; H, 7.34; N, 3.29.
Found: C, 56.55; H, 7.11; N, 3.34.
Diol 9 was protected and then treated with aluminum
trichloride and lithium aluminum hydride in tetrahydrofu-
ran. The analytical and spectroscopic data of the reaction
product were consistent with the structure of bicyclic ox-
azolidone 11. Apparently, under the reaction conditions
cleavage of the TBDMS ether takes place, while the in-
tramolecular nucleophilic attack of the unmasked alcohol
to the corresponding imminium ion leads to the observed
product. These results are in accordance with previous ob-
servations made by Fleet on corresponding polyhydroxy-
lated -lactam derivatives.15 Use of alternative reaction
conditions such as sodium borohydride, formic acid or
BF3 Et2O, lithium aluminum hydride resulted in the for-
mation of the same product. Finally, hydrogenolysis of the
benzyl ethers and cleavage of the tosyl group provided the
target calystegine B4 glucomimetic 4 in 8 steps and 36%
overall yield (from 5).
(2S,6R)-2-(tert-Butyl-dimethyl-silyloxymethyl)-6-methoxy-1-
(toluene-4-sulfonyl)-1,2,3,6-tetrahydro-pyridin-3-ol (7)
To a stirred soln of compound 6 (0.76 g, 1.79 mmol) and
CeCl3 7H2O (0.33 g, 0.89 mmol) in MeOH (20 mL) at -30 °C,
NaBH4 (0.24 g, 6.23 mmol) was added in portions. After 40 min of
stirring at that temperature, the reaction was quenched with sat. aq
NH4Cl (15 mL) and extracted with EtOAc (3 20 mL). The com-
bined organic phases were washed with brine, dried (MgSO4) and
chromatographed (EtOAc–hexane, 1:4, Rf 0.3) to afford 7 as a col-
orless oil; yield: 0.681 g (89%).
[ ]D22 +60 (c 0.9, EtOAc).
1
IR (neat): 3445 (OH), 1650 (C=C) cm .
1H NMR (400 MHz, CDCl3): = 0.05 (s, 6 H, CH3), 0.84 (s, 9 H,
C CH3), 2.40 (s, 3 H, ArCH3), 3.45 (s, 3 H, OCH3), 3.66 (dd,
J = 10.5, 3.9 Hz, CHHOTBDMS), 3.82 (m, 1 H, CHHOTBDMS),
4.04 (dt, J = 10.1, 5.3 Hz, 1 H, H-3), 4.3 (m, 2 H, OH, H-2), 5.24 (s,
1 H, H-6), 5.66 (dt, J = 10.3, 2.2 Hz, 1 H, H-4), 5.77 (d, J = 10.3 Hz,
1 H, H-5), 7.25 (d, J = 8.3 Hz, 2 H, ArH), 7.66 (d, J = 8.3 Hz, 2 H,
ArH).
All reactions were carried out under an argon atm unless otherwise
noted. Solvents were dried by distillation prior to use. THF was dis-
Synthesis 2002, No. 12, 1707–1710 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Expedient Asymmetric Synthesis of a Calystegine B4 Analogue
1709
Anal. Calcd for C20H33NO5SSi (427.6): C, 65.17; H, 7.78; N, 3.28.
Found: C, 56.35; H, 7.89; N, 3.11.
(5 mL) and extracted with EtOAc (3 20 mL). The combined or-
ganic extracts were washed with brine, dried (MgSO4) and evapo-
rated to a yellowish slurry which was purified by chromatography
(EtOAc–hexane, 1:4, Rf 0.67) yielding 10 as a colorless oil; 1.76 g
(91%).
(2S,3S,6R)-3-Benzyloxy-2-(tert-butyl-dimethyl-silyloxymethyl)-
6-methoxy-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydro-pyridine
(8)
[ ]D22 +21 (c 1.2, EtOAc).
To an ice-cold stirred soln of compound 7 (0.941 g, 2.2 mmol) in
anhyd THF (3.5 mL), NaH (63 mg, 2.64 mmol) was added in por-
tions. The reaction mixture was allowed to reach r.t. and stirred for
30 min. Then, a catalytic amount of Bu4NI (40 mg, 0.11 mmol) was
added followed by addition of BnBr (0.37 mL, 3.31 mmol). After 2
h of stirring, the reaction was quenched with sat. aq NH4Cl (8 mL)
and extracted with EtOAc (3 10 mL). The combined organic ex-
tracts were washed with brine, dried (MgSO4) and evaporated to a
yellowish slurry which was purified by chromatography (EtOAc–
hexane, 1:4, Rf 0.55) yielding 8 as a colorless oil; yield: 1.036 g
(91%).
1H NMR (400 MHz, CDCl3): = 0.03 (s, 6 H, CH3), 0.88 (s, 9 H,
C-CH3), 2.23 (s, 3 H, ArCH3), 3.37 (s, 3 H, OCH3), 3.69 (m, 1 H,
CHHOTBDMS), 3.82 (m, 3 H, CHHOTBDMS, H-5, H-4), 4.01 (m,
2 H, H-3, H-2), 4.36-4.60 (m, 5 H, CH2Ar), 4.69 (d, J = 11.8 Hz, 1
H, CH2Ar), 5.17 (d, J = 1.8 Hz, 1 H, H-6), 6.84 (d, J = 7.9 Hz, 2 H,
ArH), 7.21 (m, 15 H, ArH), 7.58 (d, J = 8.3 Hz, 2 H, ArH).
Anal. Calcd for C41H53NO7SSi (732.0): C, 67.27; H, 7.30; N, 1.91.
Found: C, 67.41; H, 7.49; N, 1.82.
(1S,2R,3S,4S,5R)-2,3,4-Tris-benzyloxy-8-(toluene-4-sulfonyl)-
6-oxa-8-aza-bicyclo[3.2.1]octane (11)
[ ]D22 +82 (c 0.4, EtOAc).
To a soln of 10 (1.10 g, 1.5 mmol) in anhyd THF (30 mL), LiAlH4
(0.114 g, 3 mmol) and AlCl3 (0.4 g, 3 mmol) were added. The reac-
tion mixture was stirred for 3 h, then quenched with H2O (30 mL)
and extracted with EtOAc (3 20 mL). The combined organic ex-
tracts were washed with brine, dried (MgSO4) and evaporated under
reduced pressure to a yellowish slurry which was purified by chro-
matography (hexane–EtOAc, 4:1, Rf 0.65) to afford product 11 as
colorless oil; yield: 0.8 g (90%).
1H NMR (250 MHz, CDCl3): = 0.05 (s, 6 H, CH3), 1.04 (s, 9 H,
C CH3), 2.41 (s, 3 H, ArCH3), 3.48 (s, 3 H, ArCH3), 3.97 (dd,
J = 11.1, 3.2 Hz, 1 H, CHHOTBDMS), 4.01 (m, 1 H, CHHOTB-
DMS), 4.15 (m, 2 H, H-3, H-2), 4.53 (d, J = 11.5 Hz, 1 H, CH2Ar),
4.60 (d, J = 11.5 Hz, 1 H, CH2Ar), 5.24 (s, 1 H, H-6), 5.66 (dt,
J = 10.2, 2.4 Hz, 1 H, H-4), 5.75 (d, J = 10.2 Hz, 1 H, H-4), 7,21 (d,
J = 7.9 Hz, 2 H, ArH), 7.25 (d, J = 8.3 Hz, 2 H, ArH), 7,34 (m, 3 H,
ArH), 7,67 (d, J = 8.3 Hz, 2 H, ArH).
[ ]D22 +35 (c 1.02, EtOAc).
Anal. Calcd for C27H39NO5SSi (517.8): C, 62.63; H, 7.59; N, 2.71.
Found: C, 62.85; H, 7.77; N, 2.51.
1
IR (neat): 1700 (C=O) cm .
1H NMR (400 MHz, CDCl3): = 2.37 (s, 3 H, ArCH3), 3.10 (dd,
J = 7.5, 4.4 Hz, 1 H, H-7), 3.57 (dd, J = 8.8, 4.9 Hz, 1 H, H-3), 3.75
(t, J = 4.9 Hz, 1 H, H-2), 3.79 (d, J = 7.5 Hz, 1 H, H-7), 3.85 (dd,
J = 8.8, 3.5 Hz, 1 H, H-4), 4.14 (t, J = 4.9 Hz, 1 H, H-1), 4.51-4.61
(m, 5 H, CH2aAr), 4.66 (d, J = 11.4 Hz, 1 H, CH2aAr), 5.61 (d,
J = 3.5 Hz, 1 H, H-5), 7.15-7.32 (m, 17 H, ArH), 7.73 (d, J = 8.8 Hz,
2 H, ArH).
(2R,3S,4R,5R,6S)-5-Benzyloxy-6-(tert-butyl-dimethyl-silyl-
oxymethyl)-2-methoxy-1-(toluene-4-sulfonyl)-piperidin-3,4-
diol (9)
To a stirred soln of alkene 8 (0.46 g 1.08 mmol), in t-BuOH–ace-
tone, 1:1 (5 mL), NMO (0.234 g, 2 mmol) and catalytic amount of
soln OsO4 (1% w/v, 1 mL) were added. The mixture was stirred for
6 h, then quenched with Na2SO3 (0.284 g, 2 mmol) and stirred for
30 min. The mixture was extracted with EtOAc (2 30 mL), the
combined organic extracts were washed with brine, dried over
MgSO4 and evaporated to a yellowish slurry which was purified by
chromatography (EtOAc–hexane, 1:1, Rf 0.3) yielding 9 as a color-
less oil; yield: 0.530 g (96%).
Anal. Calcd for C34H35NO6S (585.7): C, 69.72; H, 6.02; N, 2.39.
Found: C, 70.03; H, 6.17; N, 2.21.
(1S,2R,3S,4S,5R)-8-(Toluene-4-sulfonyl)-6-oxa-8-aza-bicyclo-
[3.2.1]octane-2,3,4-triol (12)
Tris-benzyloxy piperidine 11 (0.3 g, 0.49 mmol) was dissolved in
MeOH (2 mL) and hydrogenated over 10% Pd/C (30 mg) under 1
bar pressure for 20 h. The mixture was filtered through celite and
concentrated under reduced pressure to give a yellowish oil which
was purified by chromatography (CHCl3–MeOH, 9:1, Rf 0.41) fur-
nishing 12 as a white amorphous solid; yield: 137 mg (89%).
[ ]D22 +39 (c 0.65, EtOAc).
1
IR (neat): 3475 (OH) cm .
1H NMR (400 MHz, CDCl3): = 0.05 (s, 6 H, CH3), 0.90 (s, 9 H,
C-CH3), 2.30 (d, J = 2.2 Hz, 1 H, OH), 2.43 (s, 3 H, ArCH3), 2.48
(d, J = 2.2 Hz, 1 H, OH), 3.39 (s, 3 H, OCH3), 3.40 (m, 1 H, H-5),
3.82 (dd, J = 10.5, 5.7 Hz, 1 H, CHHOTBDMS), 3.95 (dt, J = 10.5,
5.7 Hz, 1 H, H-4), 4.01 (dd, J = 10.5, 6.1 Hz, 1 H, CHHOTBDMS),
4.08 (br s, 1 H, H-3), 4.16 (dt, J = 10.7, 5.7 Hz, 1 H, H-6), 4.23 (d,
J = 11.4 Hz, 1 H, CHHAr), 4.65 (d, J = 11.4 Hz, 1 H, CHHAr), 5.22
(d, J = 0.9 Hz, 1 H, H-2), 7.16 (dd, J = 5.7, 3.5 Hz, 2 H, ArH), 7.25
(d, J = 8.3 Hz, 2 H, ArH), 7.31 (m, 3 H, ArH), 7.82 (d, J = 8.3 Hz,
2 H, ArH).
Mp 80–82 °C; [ ]D22 +67 (c 0.3, MeOH).
1
IR (neat): 3400–3340 (OH) cm .
1H NMR (250 MHz, DMSO): = 2.42 (s, 3 H, ArCH3), 3.22 (dd,
J = 7.4, 4.2 Hz, 1 H, H-7), 3.70 (m, 1 H, H-3), 3.78-3.82 (m, 2 H,
H-7, H-4), 4.02 (m, 1 H, H-2), 4.55 (t, J = 4.9 Hz, 1 H, H-1), 5.73
(d, J = 3.2 Hz, 1 H, H-5), 7.25 (d, J = 8.3 Hz, 2 H, ArH), 7.70 (d,
J = 8.3 Hz, 2 H, ArH).
Anal. Calcd for C27H41NO7SSi (551.8): C, 58.77; H, 7.49; N, 2.54.
Found: C, 58.50; H, 7.61; N, 2.39.
Anal. Calcd for C13H17NO6S (315.3): C, 49.51; H, 5.43; N, 4.44.
Found: C, 49.77; H, 5.27; N, 4.36.
(2S,3R,4S,5S,6R)-3,4,5-Tris-benzyloxy-2-(tert-butyl-dimethyl-
silyloxy methyl)-6-methoxy-1-(toluene-4-sulfonyl)-6-piperidine
(10)
To an ice-cold stirred soln of compound 9 (1.46 g 2.64 mmol) in an-
hyd THF (7 mL), sodium hydride was added in portions (126 mg,
5.28 mmol). The reaction mixture was allowed to warm to 15 °C
and stirred for additional 30 min. Then a catalytic amount of Bu4NI
(80 mg, 0.22 mmol) and BnBr (0.74 mL, 6.61 mmol) were added.
After 2 h of stirring, the reaction was quenched with sat. aq NH4Cl
(1S,2R,3S,4S,5R)-6-Oxa-8-aza-bicyclo[3.2.1]octane-2,3,4-triol
(4)
To a soln of naphthalene (300 mg, 2.34 mmol) in freshly distilled
THF (10 mL) sodium (54 mg, 2.28 mmol) was added. The mixture
was stirred at ambient temperature for 45 min (dark-green color),
then cooled to –78 °C and a soln of compound 12 (130 mg, 0.376
mmol) in THF (3 mL) was added. The reaction mixture was stirred
at that temperature for 30 min, quenched with brine (2 mL) and con-
Synthesis 2002, No. 12, 1707–1710 ISSN 0039-7881 © Thieme Stuttgart · New York

1710
S. D. Koulocheri et al.
PAPER
Svensson, B.; Pinto, B. M. J. Am. Chem. Soc. 2001, 123,
centrated under reduced pressure to give a slurry which was purified
by chromatography (CHCl3–MeOH, 4:1, Rf 0.33) to furnish the de-
sired product as an off white solid; yield: 41 mg (68%).
Mp 61–62 °C; [ ]D22 +81.4 (c 0.7, H2O).
6268. (c) Mao, H.; Joly, G. J.; Peeters, K.; Hoornaert, G. J.;
Compernolle, F. Tetrahedron 2001, 57, 6955. (d) Pandey,
G.; Kapur, M. Tetrahedron Lett. 2000, 41, 8821.
(e) Enders, D.; Kirchhoff, J. H. Synthesis 2000, 2099.
(f) Herdeis, C.; Telser, J. Eur. J. Org. Chem. 1999, 1407.
(g) Herdeis, C.; Schiffer, T. Tetrahedron 1999, 55, 1043.
(h) For a comprehensive recent review on stereoselective
synthesis of Prosopis and Cassia piperidine alkaloids see:
Laschat, S.; Dickner, T. Synthesis 2000, 1781.
1
IR (neat): 3440-3390 (OH), 3324 (NH) cm .
1H NMR (250 MHz, D2O): = 3.43 (t, J = 4.9 Hz, 1 H, H-2), 3.47
(m, 1 H, H-4), 3.50 (dd, J = 8.8, 4.9 Hz, 1 H, H-3), 3.65-3.71 (m, 2
H, H-1, H-7), 3.91 (d, J = 7.2 Hz, 1 H, H-7), 4.90 (d, J = 2.9 Hz, 1
H, H-5).
(7) Tepfer, D.; Goldman, A.; Pamboukdjian, N.; Maille, M.;
Lepingle, A.; Chevalier, D.; Denarie, J.; Rosenberg, C. J.
Bacteriol. 1988, 170, 1153.
Anal. Calcd for C6H11NO4 (161.2): C, 44.72; H, 6.88; N, 8.69.
Found: C, 44.56; H, 6.70; N, 8.48.
(8) Molyneux, R. J.; Nash, R. J.; Asano, N. The Chemistry and
Biological Activity of Calystegines and Related Nortropane
Alkaloids, In Alkaloids: Chemical and Biological
Perspectives, Vol. 11; Pelletier, S. W., Ed.; Pergamon:
Oxford, 1996, 303.
References
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Withers, S. G. Acc. Chem. Res. 2000, 33, 11. (b) Stütz, A.
E. In Iminosugars as Glycosidase Inhibitors: Nojirimycin
and Beyond; Wiley-VCH: Weinheim, 1999. (c)Heightman,
T. D.; Vasella, A. T. Angew. Chem., Int. Ed. 1999, 38, 750.
(3) (a) Holman, R. R.; Cull, C. A.; Turner, R. C. Diabetes Care
1999, 22, 960. (b) Platt, F. M.; Neises, G. R.; Reinkensmeir,
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