Asymmetric synthesis of 1-deoxynojirimycin and its congeners from a common chiral building block

Article abstract of DOI:10.1016/j.tet.2004.06.112

A new, promising chiral building block 9 for the synthesis of 1-deoxy-4,5-trans-oriented azasugars such as 1-deoxynojirimycin (1) was prepared in only four steps from the Garner aldehyde 10 using catalytic ring-closing metathesis (RCM) for the construction of the piperidine ring. In practical test, the first synthesis of all four isomers (1 and 6-8) of trans-4,5-orientated 1-deoxyiminosugars using 9 as a common chiral building block was demonstrated. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.06.112

Tetrahedron 60 (2004) 8199–8205
Asymmetric synthesis of 1-deoxynojirimycin and its congeners
from a common chiral building block
a,*
b
Hiroki Takahata, Yasunori Banba, Mayumi Sasatani, Hideo Nemoto, Atsushi Kato
b
b
c
c
and Isao Adachi
a
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
b
c
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
Received 19 May 2004; accepted 16 June 2004
Available online 21 July 2004
Abstract—A new, promising chiral building block 9 for the synthesis of 1-deoxy-4,5-trans-oriented azasugars such as 1-deoxynojirimycin
1) was prepared in only four steps from the Garner aldehyde 10 using catalytic ring-closing metathesis (RCM) for the construction of the
(
piperidine ring. In practical test, the first synthesis of all four isomers (1 and 6-8) of trans-4,5-orientated 1-deoxyiminosugars using 9 as a
common chiral building block was demonstrated.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
therapeutic importance of these compounds has increasing
interest in developing methods for their preparation.
Interest in polyhydroxylated piperidines has undergone a
1
remarkable expansion in recent years since the discovery of
In previous studies, we reported on the straightforward and
stereoselective synthesis of 2 and 3 using dioxanylpiperi-
nojirimycin, a glycosidase inhibitor that mimics glucose (by
analogy with the glycosyl oxocarbenium intermediate
9
dene 4, and hydroxymethylpiperidene 5, respectively, as
10
2
produced during the enzymatic cleavage of glycosides).
chiral building blocks (Scheme 1).
The biological properties of iminosugars can be attributed to
their structural resemblance to oxygenated analogues found
in natural substrates. Thus, because of these mimetic
properties, iminosugars could be of great value in treating
3
4
a variety of diseases such as diabetes, viral infections, and
5
tumor metastasis. Typical examples of natural products
that have shown potent glycosidase inhibition properties are
6
-deoxynojirimycin 1, 1-deoxygalactstatin 2, and fago-
7
Scheme 1.
1
mine 3, which have varying levels of oxygenation and a
stereochemical array on the piperidine ring (Fig. 1). The
8
However, 1 and its three stereoisomers, that is, 1-deoxy-
altronojirimycin (6), 1-deoxymannonojirimycin (7), and
1-deoxyallonojirimycin (8) of trans-4,5-substituted
1-deoxyazasugars (nojirimycin-type) have been not syn-
thesized from a common chiral building block (Fig. 2). In a
project focused on the asymmetric synthesis of glycosidase
inhibitors, we envisioned dioxanylpiperidene 9 as a new
common chiral building block, which represents an ideal
precursor for synthesis of 1-deoxynojirimycin (1) and its
congeners (Fig. 2). Herein we describe a straightforward
synthesis of 1-deoxynojirimycin (1) and its congeners 6-8
via 9 starting from the Garner aldehyde 10 using catalytic
Figure 1.
Keywords: Iminosugars; Garner aldehyde; Asymmetric synthesis.
1
1
ring-closing metathesis (RCM) to construct the piperidine
ring (Scheme 2).
*
Corresponding author. Tel.: C81-22-234-4181; fax: C81-22-275-2013.;
e-mail: takahata@tohoku-pharm.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.06.112

8200
H. Takahata et al. / Tetrahedron 60 (2004) 8199–8205
Figure 2. Structures of 1-deoxynojirimycin and its congeners.
Scheme 3. Reagents and conditions: (a) 0.15 N HCI gas in CHCI
overnight, 13 (1.8%), 14 (47%), 11 (32%); (b) allyl iodide, NaH, THF, 0 8C,
overnight, 95%; (c) cat. (Cl (Cy )RuZCHPh, CH Cl , rt, 2 h, 97%; (d)
i) H , cat. 10% Pd–C, MeOH, rt, overnight; (ii) 5 N HCI, MeOH, 60 8C,
h, 91%.
3
, rt,
2
3
P
2
2
2
(
2
2
transition state in each reaction. According to the well-
known Felkin-Anh model, the nucleophile preferentially
attacks the si-face of aldehyde 10 thereby leading to the
anti-configuration. The chromatographic separation of a
diastereomeric mixture of alcohols 11 was not successful.
Scheme 2. Retrosynthesis of 1, 6, 7, and 8.
2
. Results and discussion
Accordingly, treatment of 11 (anti:synZ5.2:1) prepared
from entry 5 with HCl in chloroform afforded the readily
separable 1,3-acetonides 13 (1.8%), 14 (47%), and 11
Our retorosynthetic analysis of 1-deoxyazasugars 1, 6-8 is
outlined in Scheme 2. The proposed preparation of the
common intermediate 9 involves the RCM of diolefin 12,
produced by the stereoselctive coupling of 10 with vinyl
metals.
1
4
(32%). The relative configuration at the C-4 and C-5 of 14
was confirmed from the H–H-coupling constant (J4,5),
1
5
which is 9.5 Hz for the trans configuration. The N-allyla-
tion of 14 with allyl iodide using NaH as a base gave the
diolefin product 12 in 95% yield. Finally, 12 was subjected
to RCM in the presence of Grubbs’ catalyst [(Cl (Cy P)
2-
The D-serine-derived Garner aldehyde 10 provided an
attractive starting point for the synthesis since it reacts
with organometalic reagents with a high degree of
diastereoselectivity and racemization is minimal. The
diastereoselective addition of vinyl metals to 10 could
furnish the anti-vinyl alcohol anti-11, depending on the
2
3
RuZCHPh)] in dichloromethane. Under these conditions,
the desired piperidene 9 was obtained in 97% yield. In
addition, the stereochemistry of 9 was unambiguously
confirmed by its transformation to the known trans-3-
1
2
1
6,17
hydroxy-2-hydroxymethyl piperidine (15) (Scheme 3).
1
3
reaction conditions used. The results are summarized in
Table 1. While the use of HMPA as a cosolvent accounts for
the high anti-selectivity (entry 5). The diastereoselectivity is
convincingly accounted for by considering the preferred
With the promising chiral building block 9 in hand, our
interest was directed to synthesis of 1-deoxynojirimycin
compounds 1 and 6-8. We first converted the double bond to
Table 1. Reaction of the Garner aldehyde with vinyl metals
a
Entry
M
Additive
Solvent
anti:syn
Yield %
1
2
3
4
5
6
MgBr
Li
Li
Li
Li
None
None
HMPA
HMPA
HMPA
Toluene/THF (1:1)
Et O
2
4.0:1
2.0:1
3.6:1
3.7:1
5.2:1
1.3:1
68
94
92
86
91
85
2
Toluene/Et O (1:1)
THF
Et
Et
2
2
O
O
Li
3 2
BF –Et O
a
1
Ratios were determined by H NMR (300 MHz) of acetates of 11.

H. Takahata et al. / Tetrahedron 60 (2004) 8199–8205
8201
an epoxy-functionality to give both 1 and 6 containing a
trans diol in the 3 and 4 positions. The dioxirane, generated
w
in situ from Oxone with 1,1,1-trifuluoroacetone was
reacted with 9 to give the anti epoxide 16 and syn epoxide
17 in 45 and 44% yields, respectively. The use of m-CPBA
also resulted in low stereoselectivity to provide 16 and 17 in
a ratio of 47:27 in 74% yield.
The stereochemistry of the epoxy products was determined
by stereoselective cleavage of the epoxy ring using Super-
w
w
Hydride . Treatment of 16 with Super-Hydride in THF
led to the hydroxylated product which, upon deprotection
using hydrochloric acid in methanol followed by treatment
of the resulting salts with an ion-exchange resin afforded the
1
0,17
known fagomine 3
cation of an analogous procedure to 17 provided 3-epi-
fagomine 18
in 65% overall yield. The appli-
1
0,17
in 52% overall yield (Scheme 4).
Scheme 6. Reagents and conditions; (a) cat. K
acetone, rt, overnight, 95% or AD-mix-b, CH SO
8C, 2 overnights; (b) 6 N HCI, 60 8C, 1 h; (c) pTsOH$H
4%; (d) cat. K OsO $2H O, NMO, acetone, rt, overnight, 87%; (e) Ac
2
OsO
NH
O, MeOH, rt, 2 h,
O,
4
$2H
2
O, NMO,
3
2
2 2
, t-BuOH–H O,
0
9
2
2
4
2
2
pyridine, rt, overnight, 22 (45%), 23 (49%); (f) 6 N HCI, MeOH, reflux, 8 h;
DOWEX-50wX8, 7 (94%) from 22, 8 (91%) from 23.
Scheme 4. Reagents and conditions (a) Na
Oxone, CH CN, 0 8C, 1 h, 16 (45%), 17 (44%); (b) (i) Super-Hydride, THF,
8H, 3 h, 78%; (ii) 6 N HCI, MeOH, 60 8C, 2 h; (iii) DOWEX-50wX8, 3
65%), 18 (52%).
2 3 3 3
EDTA, CF COCH NaHCO ,
16, however, a steric repulsion between a nucleophile and
substituent at 4 position would exist. Hence, the nucleophile
may attack at remote site (2 position) of 16 (Scheme 5).
3
0
(
The stereoselective dihydroxylation of the double bond was
next examined. Under modified Upjohn conditions, treat-
ment of 9 with a catalytic amount of K OsO $2H O
Acid hydrolysis of the epoxy ring of 16 was examined with
a 0.2/3/2 mixture of H SO /dioxane/H O, followed by
1
8
2
4
2
2
4
2
treatment with the ion-exchange resin to give 1-deoxyno-
1
7,19
17,20
(5 mol%) and 4-methylmorphorine N-oxide (NMO) as a
cooxidant gave diol 19 as a diastereomeric mixture, which
was deprotected with HCl in methanol to afford an
inseparable mixture of the hydrochloride salts of 1-deoxy-
mannojirimycin (7) and 1-deoxyallonojirimycin (8) in a
ratio of 1:4.2 (7 to 8) in 95% combined yield. Analogously,
AD-mix-b mediated dihydoxylation of 9 provided a mixture
of the hydrochlorides of 7 and 8 in a ratio (1:8.2) (7 to 8) in
jirimycin (1)
ratio of 1:1 in 89% yield. Basic cleavage of the epoxide 16
and 1-deoxyaltronojirimycin (6)
in a
using a mixture of KOH/dioxane/H O gave 6, preferentially
2
in a ratio of 1:1.5 (1 to 6) in 99% yield. In contrast, both
acidic hydrolysis and basic cleavage of the syn epoxide 17
afforded only 1-deoxyaltronojirimycin (6) in 63 and 68%
yields, respectively, after treatment with ion-exchange
resin. Although a rationale of these stereoselectivity remains
unclear, we consider the following explanation. It is known
that opening of cyclohexene oxides generally proceeds in
93% overall yield. Unfortunatly, their separation with ion-
exchange resin resulted in insufficiency. Deprotection of the
acetonide with p-TsOH in methanol gave diol 20 (94%),
which was treated under above modified Upjohn conditions
to give an inseparable mixture of tetraols 21 in 87% yield.
Fortunately, acetylation of the tetraols gave a mixture of
separable tetraacetates 22 and 23, which were isolated in 45
and 49% yields. Finally, exposure of 22 and 23 to 5 N HCl
in methanol followed by treatment with the ion-exchange
2
1
the diaxial reaction. The epoxy substituents at 2 position
of 16 and at 3 position of 17 are in quasi-equiatrial
orientation, because anti-dioxanyl ring is diequatrial
orientation. Accordingly, it is expected that axial attacks
occur at 2 position of 16 and 3 position of 17. In the case of
1
7,22
resin provided 1-deoxymannojirimycin (7)
1-deoxyallonojirimycin (8)
respectively (Scheme 6).
and
in 94 and 91% yields,
1
7,23
Scheme 5. Reagents and conditions: (a) (i) cH
reflux, 3 h, (ii), dowex-50wX8 1 and 6 (1:1, 89%) from 16, 6 (63%) from
7; (b) (i) 3 M KOH, 1,4-dioxane, reflux, overnight, (ii) DOWEX-1X2, 1
33%), 6 (51%) from 16, 6 (63%) from 17.
2 4 2
SO , 1,4-dioxane, H 0,
3
. Conclusion
1
(
In summary, the new promising chiral building block 9 for

8202
H. Takahata et al. / Tetrahedron 60 (2004) 8199–8205
K1
135.7, 155.0; IR (neat) 3350.5, 1689.4, 1521.4 cm . Anal.
the synthesis of 1-deoxy-4,5-trans-oriented azasugars was
prepared in only four steps from the Garner aldehyde 10. In
practice, the first synthesis of all four isomers 1 and 6-8 of
trans-4,5-orientated 1-deoxyiminosugars using 9 as a
common chiral building block was achieved. In addition,
Calcd for C H NO : C, 60.68; H, 9.01; N, 5.44. Found: C,
1
3
23
4
60.70; H, 8.94; N, 5.49.
4.1.2. (4S,5R)-Allyl-(2,2-dimethyl-4-vinyl-[1,3]-dioxan-5-
yl)-carbamic acid tert-butyl ester (12). A mixture of 60%
NaH in oil (324 mg, 8.1 mmol) was added to a solution of
1,2,3-trideoxy and 1,2-dideoxy-trans-4,5-oriented aza-
sugars 15, 3, and 18 were also prepared.
1
4 (1.39 g, 5.4 mmol) in THF (32.2 mL) with ice cooling
and the mixture was stirred for 1 h. Allyl iodide (0.74 mL,
8.1 mmol) was added to the mixture and the mixture was
stirred overnight with ice cooling. The mixture was
4. Experimental
4
.1. General
quenched with saturated NH
was extracted with ethyl acetate three times. The extracts
were washed with brine, dried over Na SO , and evapo-
4
Cl and the whole mixture
Melting points are uncorrected. IR spectra were measured
with a JASCO A102 and a Perkin–Elmer 1600 spectro-
2
4
rated. The residue was purified by chromatography
(n-hexane/ethyl acetateZ15:1) to give 12 (1.53 g, 95%) as
1
13
photometers. H NMR and C spectra were recorded on a
JEOL FX 270, Varian Gemini-300, and Varian Unity-500.
MS and HRMS were taken on a JEOL-JMS D-200
spectrometer using the electron ionization. Elemental
analyses were performed by a Perkin–Elmer 2400
Elemental Analyzer. Optical rotations were measured with
a JASCO-DIP-1000 digital polarimeter.
2
D
0
1
); H NMR
d 1.38–1.58 (m, 15H), 3.32 (br s,
an oil. 12; [a]
(270 MHz, CDCl
K38.78 (c 1.78, CHCl
3
4
2
)
3
1H), 3.58–3.73 (m, 2H), 3.82–3.89 (m, 1H), 4.10 (m, 0.5H),
4.25–4.28 (m, 0.5H), 4.65 (m, 0.5H), 4.90 (m, 0.5H), 5.08–
5.30 (m, 4H), 5.70–5.79 (m, 2H); C NMR (67.5 MHz,
1
3
2
4
CDCl
0.7, 71.7, 79.8, 80.5, 98.6, 116.6, 117.0, 117.8, 118.1,
)
d 20.1, 28.3, 28.4, 51.5, 56.6, 57.3, 60.5, 61.2,
3
7
134.8, 136.0, 154.6; IR (neat) 3081, 1851, 1694 cm
HRMS Calcd for C16
297.1925.
K1
4
.1.1. (4R,5R)-(2,2-Dimethyl-4-vinyl-[1,3]-dioxan-5-yl)-
.
C
carbamic acid tert-butyl ester (13) and (4S,5R)-(2,2-
dimethyl-4-vinyl-[1,3]-dioxan-5-yl)-carbamic acid tert-
butyl ester (14). A solution of 1.18 M MeLi (6.79 mL,
H27NO (M ) 297.1940, found
4
8
mmol) in Et O was added to a solution of tetravinyltin
2
4.1.3. (4aR,8aS)-2,2-Dimethyl-4,4a,6,8a-terahydro-[1,3]-
dioxino[5,4-b]pyridine-5-carboxylic acid tert-butyl ester
(9). Grubbs’ catalyst 63.1 mg (5 mol%) was added to a
(
0.36 mL, 2 mmol) in Et O (15 mL) at 0 8C and the mixture
2
was stirred for 15 min at the same temperature. Then HMPA
1.4 mL, 8 mmol) was added to the mixture at K78 8C. A
solution of 10 (458.5 mg, 2 mmol) in Et O (5 mL) was
(
solution of 12 (492.3 mg, 1.65 mmol) in CH Cl (73 mL)
2 2
and the mixture was stirred for 2 h at room temperature.
After evaporation, the residue was purified by chromatog-
raphy (n-hexane/ethyl acetateZ15:1) to give 9 (432.3 mg,
2
slowly added to the mixture at K78 8C. The reaction was
stirred at the same tremperature for 2 h. Saturated NH Cl
was added to the mixture with ice cooling. Organic layer
was separated and the aqueous layer was extracted with
Et O twice. The combined organic phases were washed with
brine, dried over Na SO and evaporated. The residue was
2
purified by chromatography (n-hexane/ethyl acetate 5:1) to
give a mixture of anti and syn 11 (anti:synZ5.2:1) (466 mg,
4
2
0
1
97%) as an oil; [a]
(300 MHz, CDCl ) d 1.42 (s, 3H), 1.45 (s, 9H), 1.55 (s, 3H),
K3.208 (c 1.56, CHCl ); H NMR
D 3
3
1.60 (s, 1H), 3.06 (td, JZ9.5, 4.4 Hz, 1H), 3.65 (dd, JZ
18.4, 1.1 Hz, 1H), 4.19–4.37 (m, 3H), 4.55 (t, JZ11.2 Hz,
2
4
1
1H), 5.66–5.76 (m, 2H); C NMR (125 MHz, CDCl ) d
3
3
19.2, 28.6, 29.6, 46.3, 56.2, 63.2, 68.2, 80.7, 99.0, 126.0,
128.0, 184.0; IR (neat) 1702 cm . HRMS Calcd for
K1
9
1%) as pale yellow solids. 0.15 N HCl in CHCl (11 mL)
3
C
was added to a solution of 11 (anti:synZ5.2:1) (14.18 g,
5.1 mmol) in CHCl (633 mL). The mixture was stirred
C H23NO (M ): 269.1627, found 269.1494.
14 4
5
3
overnight at room temperature and concentrated. The
residue was purified by chromatography (n-hexane/ethyl
acetateZ15:1–2:1) to give 13 (0.21 g, 1.8%), 14 (6.7 g,
4.1.4. (2R,3S)-2-Hydroxymethylpiperidin-3-ol (15). A
suspension of 9 (214.3 mg, 0.797 mmol) and 10%Pd–C
(50%wet 10 mg) in methanol (3.5 mL) was stirred at
hydrogene atmosphere overnight. The mixture was filtered
off and the filtrate was evaporated. 5 N-HCl (22.9 mL) was
added to a solution of the residue in methanol (6.8 mL). The
mixture was heated at 60 8C for 2 h and evaporated. Two
drops of 30% NaOH were added to the residue with ice
2
3
4
7%), and 11 (4.54 g, 32%). 13: oil; [a] C10.08 (c 1.14,
D
1
CHCl ); H NMR (500 MHz, CDCl ) d 1.43 (s, 9H), 1.45 (s,
3
3
3
H), 1.49 (s, 3H), 3.59 (dd, JZ9.6, 1.6 Hz, 1H), 3.78 (dd,
JZ12.0, 1.3 Hz, 1H), 4.10 (dd, JZ11.9, 1.5 Hz,1H), 4.46–
.52 (m, 1H), 5.21 (d, JZ10.7 Hz, 1H), 5.27 (br s, 1H), 5.33
d, JZ17.3 Hz, 1H), 5.77 (ddd, JZ17.1, 10.7, 4.8 Hz, 1H);
4
(
cooling. A mixture of CHCl : isopropyl ether (4:1) (34 mL)
3
1
3
C NMR (125 MHz, CDCl ) d 18.5, 28.2, 29.5, 47.2, 64.6,
was added to the mixture and dried over K CO . After
2
3
3
7
1
2
1.5, 79.2, 98.9, 116.5, 134.5, 155.4; IR (neat) 3350.0,
700.2, 1498.6 cm ; HRMS Calcd for C H NO (M )
57.1670, found 257.1613. 14: mp 74–75 8C; [a] K10.68
evaporation, the residue was purified by chromatography
(CHCl /methanolZ10:1–5:1) to afford 15 (95.1 mg, 91%)
K1
C
1
3
23
4
3
1
D
9
16
as a solid; mp 154–155 8C, lit. mp 154–155 8C for
1
19
enantiomer of 15; [a]D C58.38 (c 1.06, MeOH), [lit.
16
(
c 1.19, CHCl ); H NMR (300 MHz, CDCl ) d 1.41 (s,
3
3
1
[a]D K59.88 (MeOH) for enantiomer of 15]; H NMR
1
1
1
1
1
2
2H), 1.47 (s, 3H), 3.44–3.58 (m, 1H), 3.63 (br t, JZ
0.0 Hz, 1H), 3.95 (dd, JZ11.0, 5.0 Hz, 1H), 4.00–4.11 (m,
H), 4.39 (br d, JZ8.2 Hz, 1H), 5.24 (dd, JZ9.6, 0.8 Hz,
H), 5.32 (dd, JZ15.6, 0.8 Hz, 1H), 5.83 (ddd, JZ17.2,
0.4, 6.8 Hz, 1H); C NMR (67.5 MHz, CDCl3) d 19.6,
8.0, 2821, 28.28, 28.3, 28.4, 48.9, 63.0, 74.5, 98.7, 135.4,
(500 MHz, D O): d 1.27 (br d, JZ10.2 Hz, 1H), 1.40 (br d,
2
JZ10.2 Hz, 1H), 1.65 (m, 1H), 1.93 (br s, 1H), 2.46 (br s,
2H), 2.91 (br d, JZ9.4 Hz, 1H), 3.34 (br s, 1H), 3.51 (m,
1
3
13
1H), 3.74 (br s, 1H); C NMR (125 MHz, D O) d 24.1,
2
1
32.9, 45.0, 61.9, 63.1, 68.1 (free); C NMR (125 MHz,
3

H. Takahata et al. / Tetrahedron 60 (2004) 8199–8205
8203
2
2
7
D O) d 21.0, 31.1, 44.1, 58.6, 62.2, 65.2 (HCl). Anal. Calcd
2
[a] C22.18 (c 0.60, H O), [lit. [a] C19.58 (c 1.0,
D 2 D
1
for C H NO : C, 54.94; H, 9.99; N, 10.68. Found C, 54.66;
13
H O)]; H NMR (300 MHz, D O) d 1.32 (qd, JZ12.3,
2 2
6
2
H, 9.71; N, 10.55.
4.4Hz, 1H), 1.86 (br d, JZ12.9 Hz, 1H), 2.37–2.52 (m, 2H),
2
.88 (br d, JZ11.2 Hz, 1H), 3.04 (1H, t, JZ9.3 Hz, 1H),
13
4
.1.5. (1R,3aR,7aR,8R)-6,6-Dimethylhexahydro-1,5,7-
3.37–3.53 (m, 2H), 3.72 (dd, JZ11.5, 2.2 Hz, 1H);
C
trioxa-3-azacyclopropa[a]naphthalene-3-carboxylic
acid tert-butyl ester (16) and (1S,3aR,7aR,8S)-6,6-
dimethylhexahydro-1,5,7-trioxa-3-azacyclopropa[a]-
naphthalene-3-carboxylic acid tert-butyl ester (17). To a
NMR (75 MHz, D
2
O/ HCl salt) d 29.30, 42.57, 58.41, 60.77,
70.25, 71.12; C NMR (75 MHz, D O) d 33.40, 43.42,
61.68, 62.33, 73.88, 73.95; Anal. Calcd for C : C,
1
3
2
H13NO
6 3
48.97; H, 8.90; N, 9.52. Found: C, 48.93; H, 8.90; N, 9.47.
solution of 9 (97.5 mg, 0.36 mmol) in CH CN (2.7 mL) was
3
K4
successively added 4!10 M Na EDTA (1.8 mL) and
w
4.1.7. 3-epi-Fagomine (18). Super-Hydride (0.79 mL,
2
CF COCH (0.36 mL) at 0 8C. A mixture of NaHCO3
3
(235 mg) and Oxone (1.10 g) was added to the reaction
mixture over 1 h at 0 8C and the whole mixture was stirred at
0.79 mmol) was added to a solution of 17 (113 mg,
0.39 mmol) in THF (2.2 mL) and the mixture was stirred
at 0 8C for 3 h. Several pieces of ice were added to the
3
the same temperature for 30 min. H O (2 mL) was added to
2
mixture. After the mixture was stirred for 15 min, H O
2
the reaction mixture and the mixture was extracted with
CH Cl three times. The extracts were washed with brine,
dried and evaporated. The residue was purified by
(1.29 mL) was added to the mixture. The mixture was
extracted with CH Cl (10 mL) four times. The extracts
2
2
2
2
were dried and evaporated. The residue was purified with
chromatography as eluent (n-hexane/ethyl acetateZ7: 1) to
yield (4aR,8S,8aR)-tert-butyl hexahydro-8-hydroxy-2,2-
dimethyl-[1,3]dioxino[5,4-b]pyridine-5-carboxylate (80 mg,
chromatography (n-hexane/ethyl acetateZ15:1–7:1) to yield
1
6 (46.2 mg, 45%) and 17 (44.9 mg, 44%) as oils. 16: oil;
2
4
1
[a] C42.48 (c 1.65, CHCl ); H NMR (300 MHz,CDCl )
D 3 3
d 1.42 (s, 3H), 1.44 (s, 9H), 1.55 (s, 2H), 1.63 (s, 1H), 2.79
2
3
1
70%) as an oil; [a] D K47.98 (c 0.67, CHCl ); H NMR
3
(
td, JZ10.5, 4.5 Hz, 1H), 3.15 (s, 2H), 3.26 (d, JZ15 Hz,
(300 MHz, CDCl ) d 1.40 (s, 3H), 1.43 (s, 9H), 1.52 (s, 3H),
3
1
1
H), 3.93 (dd, JZ11.2, 4.3 Hz, 1H), 4.00 (d, JZ10.5 Hz,
H), 4.41 (d, JZ15 Hz, 1H), 4.70 (br t, JZ10.2 Hz, 1H);
1.64–1.76 (m, 1H),1.85 (dd, JZ14.4, 2.6 Hz, 1H), 2.46 (s,
1H), 3.11 (td, JZ13.2, 2.4 Hz, 1H), 3.46 (td, JZ10.5,
4.9 Hz, 1H), 3.74 (dd, JZ10.4, 2.4 Hz,1H), 3.84 (br d, JZ
13.1 Hz, 1H), 3.95 (d, JZ2.4 Hz, 1H) 4.24 (dd, JZ11.8,
1
3
C NMR (75 MHz, CDCl ) d 19.4, 28.6, 29.5, 46.6, 50.3,
5.1, 56.4, 62.9, 65.5, 81.0, 100.0, 155.3; IR (neat) 1698.1,
3
5
1
K1
380.7, 1251.6, 1085.4 cm . HRMS Calcd for C H NO
5
13
4.9 Hz, 1H), 4.53 (t, JZ11.2 Hz, 1H); C NMR(75 MHz,
1
4
23
C
23
D
(
M ) 285.1576. found 285.1554. 17: oil; [a] K1.158 (c
D O) d 19.8, 28.7, 29.5, 30.5, 41.6, 51.9, 62.3, 66.1, 72.1,
.
2
1
.00, CHCl ); H NMR (300 MHz, CDCl ) d 1.44 (s,9H),
K
80.4, 99.0, 154.6; IR (neat) 3486.2, 1698.0, 1167.8 cm
K1
2
1
3
3
3
3
C
.46 (s, 3H), 1.51 (s, 1H), 1.52 (s, 2H), 3.21–3.39 (m, 3H),
.62 (d, JZ15.3 Hz, 1H) 3.95 (dd, JZ15.3, 3.3 Hz, 1H),
.79–4.06 (m, 1H), 4.18–4.06 (m, 1H), 4.18–4.31 (m, 2H);
HRMS Calcd for C H NO (M ) 287.1737. found
14 25 5
287.1732.
A solution of the above oil (80 mg,
0.278 mmol) and 6 N HCl (7.6 mL) in methanol (2.5 mL)
was heated at 60 8C for 2 h. The mixture was evaporated, the
residue was treated with cation-exchange resin (DOWEX-
50wX8) to 18 (30.2 mg, 74%) as a solid; mp 218–219 8C,
10a
1
3
C NMR (75 MHz, CDCl ) d 19.5, 27.9, 28.6, 29.3, 43.7,
3
5
1
0.7, 52.0, 52.5, 62.6, 69.8, 81.1, 99.4, 154.6; IR (neat)
770.8, 1698.2, 1381.8, 1198.0, 1103.6 cm . HRMS
K1
C
10a
24
Calcd for C H NO (M ) 285.1576. found 285.1511.
1
lit. mp 220–222 8C; [a]D C77.158 (c 0.68, H O), [lit.
2
26 1
4
23
5
[
a] C74.48 (c 0.68, H O)]; H NMR (300 MHz, D O) d
D 2 2
w
4
0
0
.1.6. Fagomine (3). Super-Hydride (0.91 mL,
.91 mmol) was added to a solution of 16 (130 mg,
.456 mmol) in THF (2.8 mL) and the mixture was stirred
1.57–1.72 (m, 2H), 2.62–2.74 (m, 3H), 3.32 (br d, JZ
9.9 Hz, 1H), 3.47 (dd, JZ11.5, 6.6 Hz, 1H), 3.67 (dd, JZ
1
3
11.4, 2.3 Hz, 1H), 3.94 (br s, 1H); C NMR (75 MHz, D
d 31.89, 39.17, 56.50, 62.89, 68.66, 70.35. Anal. Calcd for
C H13NO : C, 48.97; H, 8.90; N, 9.52. Found: C, 48.94; H,
6 3
O)
2
at 0 8C for 3 h. Several pieces of ice were added to the
mixture. After the mixture was stirred for 15 min, H O
2
(
1.29 mL) was added to the mixture. The mixture was
extracted with CH Cl (10 mL) four times. The extracts
8.98; N, 9.49.
2
2
were dried and evaporated. The residue was purified with
chromatography as eluent (hexane/ethyl acetateZ7: 1) to
yield (4aR,8R,8aR)-tert-butyl hexahydro-8-hydroxy-2,2-
dimethyl-[1,3]dioxino[5,4-b]pyridine-5-carboxylate (102 mg,
4.1.8. D-1-Deoxynojirimycin (1) and D-1-deoxyaltrojiri-
mycin (6). Acidic hydrolysis. A mixture of 16 (84.8 mg,
0.29 mmol), 1,4-dioxane (1.8 mL), H O (1.2 mL), and c
2
H SO (210 mg) was refluxed for 3 h. After evaporation of
4
2
2
4
1
7
8%) as an oil; [a] C4.528 (c 1.43, CHCl ); H NMR
3
the reaction mixture, the residue was treated with ion-
exchange resin DOWEX-50wX8 using water as eluent to
yield a mixture of 1 and 6 (43.3 mg, 89%) as a ratio (1:1).
By similar procedure described the above, 17 (62.1 mg,
0.217 mmol) provided 6 (22.4 mg, 63%) as oil. Basic
hydrolysis. A mixture of 16 (160 mg, 0.56 mmol), 1,4-
dioxane (13.8 mL), (.3 M KOH (28 mL) was refluxed
overnight. After evaporation, methanol (5.1 mL) and 6 N
HCl (15.4 mL) were added to the residue. The mixture was
heated at 60 8C for 1 h and evaporated. The residue was
D
(
300 MHz, CDCl ) d 1.43 (s, 3H), 1.43 (s, 9H), 1.51 (s, 3H),
3
1
1
2
1
1
9
.74 (s, 1H), 1.93–1.98 (m, 1H), 2.62 (br s, 1H), 2.75 (t, JZ
3.5 Hz, 1H), 2.96 (td, JZ10.5, 4.9 Hz, 1H), 3.50–3.61 (m,
H), 4.10 (br d, JZ3.0 Hz, 1H), 4.31 (dd, JZ11.6, 5.0Hz,
1
3
H), 4.43 (t, JZ11.2Hz, 1H); C NMR (75 MHz, D O) d
2
9.6, 28.6, 29.6, 31.4, 44.4, 55.6, 62.3, 71.9, 75.7, 80.7,
9.0, 154.4; IR (neat) 3471.8, 2977.9, 1694.1, 1165.6 cm
K1
.
C
HRMS Calcd for C H NO (M ) 287.1732. found
5
1
4
25
2
0
87.1722. A solution of the above oil (85 mg,
.296 mmol) and 6 N HCl (6 mL) in methanol (2.7 mL)
K
treated with ion-exchange resin DOWEX-1X2 (OH form)
was heated at 60 8C for 2 h. The mixture was evaporated, the
residue was treated with cation-exchange resin (DOWEX-
using water as eluent to yield 1 (29.7 mg, 33%) and 6
(46.9 mg, 51%)/. By similar procedure described the above,
17 (120 mg, 0.42 mmol) provided 6 (43 mg, 63%) as oil. 1:
5
0wX8) to 3 (36.3 mg, 83%) as a solid; mp 185–186 8C;

8204
H. Takahata et al. / Tetrahedron 60 (2004) 8199–8205
2
D
3
25
mp 199–199.5 8C; [a] C40.38 (c 1.47, H O); [lit. mp
1
4.1.11. 2,3,4,6-Tetra-O-acetyl-N-tert-butyloxycarbonyl-
1,5-imino-D-mannitol (22) and 2,3,4,6-tetra-O-acetyl-N-
tert-butyloxycarbonyl-1,5-imino-D-allitol (23). A solution
of 50% NMO (180 mL) in water and a solution of
K OsO $2H O (1.33 mg, 0.5 mol%) in water (0.5 mL)
2
2
5
1
99–201 8C, [a] C42.18 (c 1, H O)]; H NMR (500 MHz,
D 2
D O) d 2.35 (td, JZ8.4, 1.2 Hz,1H), 2.41–2.45 (m, 1H),
.00 (dd, JZ7.5, 3.0 Hz, 1H), 3.12 (td, JZ10.6, 1.7 Hz,
H), 3.20 (td, JZ8.9, 2.1 Hz, 1H), 3.35–3.40 (m, 1H), 3.52
2
3
1
2
4
2
(
1
7
ddd, JZ12.0, 6.2, 1.9 Hz, 1H) 3.72 (1dd, JZ11.5, 2.5 Hz,
were successively added to a solution of 9 (165 mg,
0.72 mmol) in acetone (5.5 mL) and the mixture was stirred
at room temperature three overnights. Na SO (170 mg)
was added to the mixture and the mixture was stirred for
30 min. The insoluble materials were filtered off and the
filtrate was evaporated. The residue was purified by
1
H); C NMR(125 MHz, D O) d 49.46, 61.28, 62.13,
3
2
2
4
1.66, 72.27, 79.16. 6: oil; [a] C19.58 (c 2.15, H O);
2
D
2
3
2
3b
1
[a]D C17.98 (c 1.3, H O)]; H NMR (500 MHz,
[
lit.
2
D O) d 2.61–2.70 (m, 2H), 2.82 (dd, JZ14.5, 2.5 Hz, 1H),
2
3
(
.58–3.65 (m, 2H), 3.68 (dd, JZ9.6, 3.2 Hz, 1H), 3.74–3.76
13
m, 1H), 3.80–3.81 (m, 1H); C NMR (125 MHz, D O) d
chromatography (CHCl /methanolZ12:1) to yield 21
2
3
4
C H NO (M ) 163.0788, found 163.0856. Anal. Calcd
5.30, 56.36, 61.62, 66.96, 70.17, 71.44. HRMS Calcd for
(165 mg, 87%) as a solid of a diasteromeric mixture.
Ac O (1.74 mL) was added to a mixture of 21 (107 mg,
C
6
13
4
2
for C H NO : C, 44.16;; H, 8.03; N, 8.58. Found: C, 44.23;
6
H, 7.81; N, 8.54.
0.41 mmol) in pyridine (4.1 mL) with ice cooling. The
mixture was stirred at room temperature overnight, diluted
with H O, and extracted with ethyl acetate three times.
13
4
2
The extracts were successively washed with 1 N HCl, sat.
NaHCO , H O, and brine. The organic layer was dried
and evaporated. The residue was purified by chromato-
4
.1.9. Dihydroxylation of 9. A solution of 50% NMO
99.4 mL) in water and a solution of K OsO $2H O
3
2
(
(
2
4
2
0.74 mg, 0.5 mol%) in water (0.29 mL) were successively
graphy (n-hexane/ethyl acetateZ2:1–1:1) to yield 22
added to a solution of 9 (114 mg, 0.42 mmol) in acetone
2.9 mL) and the mixture was stirred at room temperature
overnight. Na SO (100 mg) was added to the mixture and
(
79.7 mg, 45%) and 23 (86.2 mg, 49%) as oils. 22: oil;
(
24 1
a]D K28.38 (c 2.13, CHCl ); H NMR (300 MHz, CDCl )
[
d 1.42 (s, 9H), 1.98 (s, 3H), 2.02 (s, 3H), 2.05 (s, 3H), 2.10
3
3
2
3
the mixture was stirred for 30 min. The insoluble materials
were filtered off and the filtrate was evaporated. The residue
was purified by chromatography (n-hexane/ethyl acetateZ
(s, 3H), 3.09 (m, 1H), 3.95–4.21 (m, 2H), 4.42 (t, JZ
1
1
2
1
1
0.0 Hz, 1H), 4.57 (br s, 1H), 4.91 (br s, 1H), 5.01–5.08 (m,
H), 5.25 (br s, 1H); C NMR (75 MHz, CDCl ) d 20.6,
13
3
2
:3) to yield the diols (122 mg, 95%) as a diasteromeric
0.7, 28.1, 59.8, 65.0, 67.0, 68.0, 80.7, 154.4, 168.7, 168.8,
69.2; IR (neat) 1747.6, 1698.7, 1369.5, 1226.3, 1155.6,
mixture. 6 N HCl (6 mL) was added to a solution of the
above diol. The mixture was heated at 60 8C for 1 h and
evaporated to yield a mixture of hydrochlorides of 7 and 8
K1
054.8, 1026.3 cm . HRMS Calcd for C H NO
10
1
9
23
29
C
(
M C1) 432.1862, found 432.1876. 23: oil; [a] K1.978
1
3
D
(
88 mg, 100%). Their ratio was estimated by C NMR to be
1
c 2.41, CHCl ); d H NMR (300 MHz, CDCl ) d 1.45 (s,
(
1
3
3
3
1
4
:4.2. The hydrochloride of 7: C NMR (125 MHz, D O) d
2
9
4
H), 2.01 (s, 6H), 2.08 (s, 3H), 3.17 (br d, JZ15.3 Hz, 1H),
1
8.3 (C-1), The hydrochloride of 8: C NMR (125 MHz,
3
.14 (dd, JZ11.5, 5.7 Hz, 1H), 4.28–4.41 (m, 2H), 4.75 (br
D O) d 42.4 (C-1). To a mixture of AD-mix-b (840 mg) in
2
H O (3 mL) was added a solution of 9 (162 mg, 0.6 mmol)
2
in t-BuOH (3 mL) and CH SO NH (57 mg) at 0 8C. The
3
mixture was stirred at the same temperature 2 overnights.
After addition of Na SO (50 mg), the mixture was stirred
for 0.5 h and extracted with ethyl acetate three times. The
organic solvent was washed with water, dried, and
evaporated added. The residue was purified by chromatog-
raphy (n-hexane/ethyl acetateZ2:3) to yield the diols
13
t, JZ6.1 Hz, 1H), 5.11 (br s,1H), 5.16 (br s, 1H); C NMR
(
75 MHz, CDCl ) d 20.7, 20.8, 20.9, 21.0, 28.3, 42.3, 54.1,
3
2
2
6
1
1.0, 66.7, 67.0, 80.5, 155.0; IR (neat) 1744.8, 1701.0,
369.0, 1230.4, 1145.7, 1068.6 cm . HRMS Calcd for
K1
2
3
C
C H NO (M C1) 432.1868, found 432.1872.
1
9
29
10
4
.1.12. D-1-Deoxymannojirimycin (7). A mixture of 22
65.8 mg, 0.15 mmol) and 6 N HCl (4.58 mL) in methanol
(
(
1.5 mL) was refluxed for 8 h and evaporated. The residue
(
(
169 mg, 93%) as a diasteromeric mixture. 6 N HCl
8 mL) was added to a solution of the above diol. The
C
was treated with ion-exchange resin DOWEX-50wX8 (H
form) using water as eluent to yield 7 (23.3 mg, 94%) as
mixture was heated at 60 8C for 1 h and evaporated to yield
a mixture of hydrochlorides of 7 and 8 (111 mg, 100%). The
ratio was 1:8.2.
26
white solid. mp (dec.) 179–180 8C; [lit. mp (dec.) 182–
25
27
1
84 8C]; [a]D K40.28 (c 0.33, H O); [lit. [a]D K41.48
2
1
(H O)]; H NMR (300 MHz, D O/ HCl salt) d 3.03–3.09
2 2
(m, 1H), 3.15 (br d, JZ13.5 Hz, 1H), 3.32 (dd, JZ13.5,
4.1.10. (2R,3S)-3-Hydroxy-2-hydroxymethyl-3,6-dihy-
dro-2H-pyridine-1-carboxylic acid tert-butyl ester
2.9 Hz, 1H), 3.60 (dd, JZ9.5, 2.9 Hz, 1H), 3.71–3.80 (m,
13
2H), 3.90 (dd, JZ12.6, 3.0 Hz, 1H), 4.15 (br s, 1H);
NMR (75 MHz, D O / HCl salt) d 48.2, 58.8, 61.0, 66.4,
66.6, 73.1; H NMR (300 MHz, D O) d 2.41–2.43 (m, 1H),
2.70 (d, JZ14.2 Hz, 1H), 2.95 (d, JZ14.2 Hz, 1H), 3.53–
C
.
20). pTsOH H O (53.7 mg) was added to a solution of 9
(
2
2
1
(540 mg, 2 mmol) in methanol (25 mL). The mixture was
stirred for 2 h at room temperature and evaporated. The
2
1
3
residue was purified by chromatography (CHCl /metha-
3
3.56 (m, 2H), 3.72 (d, JZ2.7 Hz, 2H), 3.94 (br s, 1H);
NMR (75 MHz, D O) d 48.9, 61.1, 61.4, 69.0, 69.8, 75.2.
HRMS Calcd for C
found 132.0853. Anal. Calcd for C
C
2
D
4
nolZ20:1) to yield 20 (430 mg, 94%) as an oil; [a]
C
6.28 (c 2.25, CHCl ); H NMR (300 MHz, CDCl ) d 1.45
2
1
C
8
6
H13NO
4
(M KCH
2
OH) 132.0537,
H13NO : C, 44.16; H,
6 4
3
3
(
s, 9H), 2.25–2.87 (br s, 1H), 2.87–3.41 (br s, 1H), 3.44–
3
2
6
1
.59 (m, 3H), 4.06–4.25 (t, JZ7.4 Hz, 2H), 5.83–5.94 (m,
8.03; N, 8.58. Found: C, 44.06; H, 7.98; N, 8.57.
1
H); C NMR (75 MHz, CDCl ) d 28.6, 41.2, 60.6, 61.1,
3
3
3.3, 80.7, 124.8, 127.4, 156.5; IR (neat) 3391.9, 1681.7,
417.2 cm . HRMS Calcd for C H NO (M K
4.1.13. D-1-Deoxyallonojirimycin (8). A mixture of 23
(59.9 mg, 0.14 mmol) and 6 N HCl (3.78 mL) in methanol
(1.2 mL) was refluxed for 8 h and evaporated. The residue
K1
C
1
1
19
4
CH OH) 198.1048, found 198.1150.
2

H. Takahata et al. / Tetrahedron 60 (2004) 8199–8205
8205
C
was treated with ion-exchange resin DOWEX-50wX8 (H
form) using water as eluent to yield 8 (20.6 mg, 91%) as
13. (a) Williams, L.; Zhang, Z.; Shao, F.; Carroll, P. J.; Joullie,
M. M. Tetrahedron 1996, 52, 11673–11694. (b) Coleman,
R. S.; Carpenter, A. J. Tetrahedron Lett. 1992, 33, 1697–1700.
14. The recovered 11 can be reused, but its diastereomeric ratio is
unknown
2
5
white solid. mp 165 8C; [a] C36.28 (c 0.83, methanol),
[
D
2
8
20
1
lit. [a]D C35.28 (methanol)]; H NMR (300 MHz, D O/
2
HCl salt) d 2.99 (t, JZ11.8 Hz,1H), 3.12–3.22 (m, 2H),
1
3
3
NMR (75 MHz, D O /HCl salt) d 44.0, 57.2, 60.1, 67.0,
.68–3.78 (m, 3H), 3.84–3.90 (m, 1H), 4.04 (br s, 1H);
C
15. The H–H coupling constant for C-4 and C-5 of 13 is 1.5 Hz,
indicating a cis configuration
2
1
7.8, 72.4; H NMR (300 MHz, D O) d 2.55–2.67 (m, 2H),
6
2
1
4
6
8
2
16. Moncerino, M.; Stick, R. V. Aust. J. Chem. 1990, 43, 1183–
.76 (dd, JZ12.0, 4.9 Hz, 1H), 3.38 (dd, JZ10.1, 2.5 Hz,
H), 3.52–3.63 (m, 2H), 3.71 (dd, JZ11.5, 2.5 Hz, 1H),
1
193.
1
7. The specific rotations and spectral data of these compounds
were in agreement with reported values; see Section 4
1
.00 (br s, 1H); C NMR (75 MHz, D O) d 44.5, 55.3, 62.2,
3
2
9.0, 69.5, 72.3. Anal. Calcd for C H NO : C, 44.16; H,
4
6
13
18. Severino, E. A.; Correia, C. R. D. Org. Lett. 2000, 2, 3039–
042.
.03; N, 8.58. Found: C, 44.21; H, 7.97; N, 8.44.
3
1
9. For previous synthesis of D-1-deoxynojirimycin, see: (a)
Somfai, P.; Marchand, P.; Torsell, S.; Lindstrom, U. M.
Tetrahedron 2003, 59, 1293–1299. (b) Comins, D. L.; Fulp, A. B.
Tetrahedron Lett. 2001, 42, 6839–6841. (c) Lindstrom,
U. M.; Somfai, P. Tetrahedron Lett. 1998, 39, 7173–7176. (d)
van den Broek, L. A. G. M. Tetrahedron 1996, 52, 4467–4478.
Acknowledgements
This research was supported by the Uehara Memorial
Foundation and a Grant-in-Aid for Scientific Research on
Priority Areas (A) ‘Exploitation of Multi-Element Cyclic
Molecules’ from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
(
e) Kiguchi, T.; Tajiri, K.; Ninomiya, I.; Naito, T.; Hiramatsu,
H. Tetrahedron Lett. 1995, 36, 253–256. (f) Rudge, A. J.;
Collins, I.; Holmes, A. B.; Baker, R. Angew. Chem. 1994, 106,
2
416–2418. (g) Ikota, N. Heterocycles 1989, 29, 1469–1472.
h) Iida, H.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 1987,
2, 3337–3342.
(
5
References and notes
2
0. For previous syntheses of D-1-deoxyaltronojirimycin, see: (a)
Singh, O. V.; Han, H. Tetrahedron Lett. 2003, 44, 2387–2391.
1
. (a) Asano, N. Glycobiology 2003, 13, 93R–104. (b) Asano, N.
Curr. Top. Med. Chem. 2003, 3, 471–484. (c) Compain, P.;
Martin, O. R. Curr. Top. Med. Chem. 2003, 3, 541–560.
. Inouye, S. E.; Tsuruoka, Y.; Ito, T.; Niida, T. Tetrahedron
(
b) Asano, K.; Hakogi, T.; Iwama, S.; Katsumura, S. Chem.
Commun. 1999, 41–42. (c) Xu, Y.-M.; Zhou, W.-S. J. Chem.
Soc., Perkin Trans. 1 1997, 741–746.
2
3
4
2
1. Eliel, E. L., Wilen, S. H., Eliel, E. L., Ed., Stereochemistry of
Organic Compounds. Wiley: New York; 1994. 730.
2. For previous syntheses of D-1-deoxymannonojirimycin, see:
1
968, 24, 2125–2129.
. Somsak, L.; Nagya, V.; Hadady, Z.; Docsa, T.; Gergely, P.
Curr. Pharm. Des. 2003, 9, 1177–1189.
2
(
a)Knight, J. G.; Tchabanenko, K. Tetrahedron 2003, 59, 281–
. Greimel, P.; Spreitz, J.; Stutz, A. E.; Wrodnigg, T. M. Curr.
Top. Med. Chem. 2003, 3, 513–523.
2
86. (b) O’Brien, J. L.; Tosin, M.; Murphy, P. V. Org. Lett.
001, 3, 3353–3356. (c) Haukaas, M. H.; O’Doherty, G. A. Org.
2
5. Nishimura, Y. Curr. Top. Med. Chem. 2003, 3, 575–591.
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