An expeditious synthesis of iminosugars

Article abstract of DOI:10.1071/CH10211

A short and expedient synthesis of the potent glycosidase inhibitors, 1-deoxynojirimycin, miglitol, miglustat, 1-deoxymannojirimycin, and 1-deoxygalactonojirimycin is presented.

Full text of DOI:10.1071/CH10211

Communication
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2010, 63, 1409–1412
An Expeditious Synthesis of Iminosugars
A
A
A B
,
Michael N. Gandy, Matthew J. Piggott, and Keith A. Stubbs
A
Chemistry M313, School of Biomedical, Biomolecular and Chemical Sciences,
The University of Western Australia, 35 Stirling Highway,
Crawley, WA 6009, Australia.
B
Corresponding author. Email: keith.stubbs@uwa.edu.au
A short and expedient synthesis of the potent glycosidase inhibitors, 1-deoxynojirimycin, miglitol, miglustat,
1-deoxymannojirimycin, and 1-deoxygalactonojirimycin is presented.
Manuscript received: 25 May 2010.
Manuscript accepted: 27 July 2010.
The iminosugars are a family of polyhydroxylated heterocycles
containing an endocyclic nitrogen atom, which are well known,
competitive glycosidase inhibitors.[1] The carbohydrate mimi-
cry displayed by iminosugars has resulted in their use as tools in
the investigation of enzymatic processes as well as in the study
of various disease states. The best known member of this family,
1-deoxynojirimycin 1 is an example of a naturally occurring
iminosugar that potently inhibits a-glucosidases,[2] and along
with some of its N-alkylated derivatives, namely N-butyl-1-
Samuelsson,[18] then elimination of hydroiodic acid with DBU
afforded the desired alkene 9 (Scheme 1).[19] Oxidation with
3-chloroperbenzoic acid, in the presence of benzyl alcohol,
providedthe presumedulososide 10 as a mixtureof stereoisomers.
Deacetylation gave the tetrol 11 in good yield with this compound
being shelf-stable for at least 2 weeks. Attention was then directed
at the reductive amination in an attempt to prepare 1. Treatment
of 11 with ammonium acetate in the presence of palladium(II)
hydroxide and hydrogen gratifyingly gave 1-deoxynojirimycin
in 76% yield. The overall yield for the preparation of 1 from 7
is 42% over four steps, which compares very favourably with
literature syntheses, including a chemoenzymatic method.[20]
With this result, we turned our attention to the preparation of
some N-alkylated derivatives. Debenzylation/reductive amination
of 11 with n-butylamine or 2-aminoethanol under the established
conditions gave N-butyl-1-deoxynojirimycin 2 and N-(2-hydroxy-
ethyl)-1-deoxynojirimycin 3, respectively, in high yields.
These excellent results encouraged further investigations
into the synthesis of other iminosugars; the analogous route
for methyl b-D-galactopyranoside 12 was explored. The results
were similarly satisfying; the iodide 13 was converted to the
alkene 14, followed by the ulososides 15, and thence tetrol 16.
Reductive amination of 16 then provided the desired imino-
sugar, 1-deoxygalactonojirimycin 4 exclusively and in high yield
(64%) not only for this reaction but for the overall synthesis
(33%). Similarly, starting from methyl a-D-mannopyranoside
17 the preparation of 1-deoxymannojirimycin 5, proceeded
smoothly (through the iodide 18, alkene 19, ulososides 20, and
tetrols 21) with an overall yield of 32%.
deoxynojirimycin
2 and N-(2-hydroxyethyl)-1-deoxynojir-
imycin 3, has clinical applications.[3–6] Other members of this
family, 1-deoxygalactonojirimycin 4, and 1-deoxymannojir-
imycin 5, have also been prepared and have been found to
exhibit potent a-mannosidase[7] and a-galactosidase[8] inhibi-
tory activity, respectively (Fig. 1).
As a result of their biological importance, there have been
several syntheses of these and other iminosugars published to
date.[1,9–13] The route that was of interest to us, due to its
simplicity and efficiency, is the one employed by Stutz and
coworkers in their synthesis of 2-acetamido-1,2-dideoxynojir-
imycin-lysine hybrids.[14] An intermediate ulososide 6, which is
prepared by the 3-chloroperbenzoic acid oxidation of the corre-
sponding 5,6-alkene, in the presence of benzyl alcohol (followed
by a subsequent Zemplen O-deacetylation), was employed. This
method appealed to us as the ulososide 6 is not only quite stable
but can be readily used to generate, under reducing conditions,
the 1,5-dicarbonyl compound needed for the preparation of the
desired iminosugar in situ. Furthermore, the subsequent reduc-
tive amination and intramolecular cyclization, results in the
exclusive formation of the D-gluco configured iminosugar in
excellent isolated yields (Fig. 2).
To date, this synthetic methodology presented by Stutz and
coworkers has not been formally investigated for the preparation
of 1–5. It seemed to us, given the importance of access to
significant amounts of these compounds for biological studies,
coupled with what would be a short and inexpensive synthetic
route for the preparation of them, as well as the literature
precedent for the preparation of iminosugars using 1,5-dicarbo-
nyl precursors,[15–17] that such an exploration was warranted.
Methyl b-D-glucopyranoside 7, was converted into the
corresponding iodide 8, using the procedure of Garegg and
In conclusion, we have demonstrated a new synthesis for
commonly used iminosugars that is robust, efficient, and high
yielding. The stability and ease of preparation of the tetrol
precursors makes this route particularly attractive. Notably
one gram of 1-deoxynojirimycin 1 can now be prepared from
methyl b-D-glucopyranoside, in an overall yield of 42%, in
approximately 4 days, with similar yields and time periods for
analogous compounds.
Experimental
Standard workup refers to dilution with water, repeated
extraction into an organic solvent, sequential washing of the
Ó CSIRO 2010
10.1071/CH10211
0004-9425/10/101409

1410
M. N. Gandy, M. J. Piggott, and K. A. Stubbs
combined extracts with 1 M hydrochloric acid (where appro-
priate), saturated aqueous sodium bicarbonate and brine, fol-
lowed by drying over anhydrous magnesium sulfate, filtration,
and evaporation of the solvent by means of a rotary evaporator at
reduced pressure. 1H and 13C NMR spectra were recorded on a
Bruker AV600 (600 MHz for 1H and 150 MHz for 13C) in CDCl3
unless otherwise noted.
General Procedure for the Preparation of Iodides
Triphenylphosphine (30 mmol), imidazole (60 mmol), and I2
(29 mmol) were added to a suspension of the methyl glycoside
(20 mmol) in PhMe (200 mL) with vigorous stirring at 708C
(2 h). The mixture was cooled, quenched with H2O, and con-
centrated to give a yellow residue; pyridine (50 mL) and Ac2O
(50 mL) were added and the solution stirred (rt, 3 h). Con-
centration of the mixture, followed by a standard workup
(EtOAc) and flash chromatography (EtOAc/petrol 1:4), furn-
ished the desired iodides.
OH
HO
HO
HO
HO
HO
HO
HO
HO
NR
HO
NH
HO
NH
HO
Methyl Tri-O-acetyl-6-deoxy-6-iodo-b-D-
glucopyranoside 8
1 R ϭ H
4
5
2 R ϭ (CH2)3CH3
3 R ϭ (CH2)2OH
Obtained as a colourless oil (7.4 g, 86%). [a]D þ1.38 (in
CHCl3; lit.[19] þ2.08 in CHCl3). Gave 1H and 13C NMR spectra
consistent with those found in the literature.[19]
Fig. 1. Compounds synthesized in the present study.
OH
O
O
O
O
AcO
AcO
AcO
AcO
AcO
AcO
OMe
OMe
OMe
NHAc
NHAc
NHAc
BnO
OH
O
HO
HO
HO
HO
HO
HO
O
NR
HO
HO
O
OMe
NHAc
R ϭ lysine derivatives
NHAc
NHAc
BnO
6
Fig. 2. Method used by Stutz and coworkers in the preparation of 2-acetamido-1,2-dideoxynojirimycin-lysine
hybrids.[14]
OH
R4
I
R6
R6
R6
R4
O
R4
O
(a)
(b)
(c)
O
R5
HO
R5
AcO
R5
AcO
R1
R1
R1
R3
R3
R2
R3
R2
R2
R1 R2 R3 R4 R5 R6
R1 R2 R3 R4 R5 R6
R1 R2 R3 R4 R5 R6
7
OMe
12 OMe
17
H
H
OH
OH
H
H
H
OH
H
H
OH
H
8
OMe
H
H
OAc
OAc
H
H
H
OAc
H
H
OAc
H
9
OMe
14 OMe
19
H
H
OAc
OAc
H
H
H
OAc
H
H
OAc
H
13 OMe
H
OMe
OH OH
18
H
OMe
OAc OAc
H
OMe
OAc OAc
OH
OH
R4
OH
R4
R6
R6
R2
NR5
R4
(d)
(e)
O
R5
AcO
R3
HO
O
R5
HO
R1
R1
R3
R1
R3
BnO
BnO
R2
R2
R1 R2 R3 R4 R5 R6
R1 R2 R3 R4 R5 R6
R1 R2 R3 R4
R5
H
10 OMe
15 OMe
20
H
H
OAc
OAc
H
H
H
OAc
H
H
11 OMe
16 OMe
21
H
H
OH
OH
H
H
H
OH
H
H
OH
H
1
2
3
4
5
OH
OH
H
H
H
OH
OH
H
H
OAc
H
(CH2)2CH3
H
OMe
OAc OAc
H
OMe
OH OH
OH OH
H
(CH2)2OH
OH
H
H
H
OH
H
H
H
OH OH
Scheme 1. (a) i. I2, Ph3P, imidazole, PhMe, ii. Ac2O, pyridine. (b) DBU, THF. (c) 3-Chloroperbenzoic acid, CH2Cl2, BnOH. (d) NaOMe, MeOH. (e)
NH4OAc (for 1, 4, 5) or n-BuNH2 (for 2) or 2-aminoethanol (for 3), Pd(OH)2/C, H2, MeOH:H2O (15:1).

Synthesis of Iminosugars
1411
Methyl Tri-O-acetyl-6-deoxy-6-iodo-b-D-
galactopyranoside 13
þ14.68 in CHCl3). dH 2.00 (s, 3H, CH3), 2.12 (s, 3H, CH3), 2.15
(s, 3H, CH3), 3.44 (s, 3H, OCH3), 4.55 (dd, J4,6EJ6,6 1.8, 1H,
H6), 4.76 (d, J1,2 2.4, 1H, H1), 4.78 (dd, J4,6 ¼ J6,6 1.8, 1H, H6),
5.30–5.34 (m, 2H, H2,3), 5.70 (ddd, J3,4 10.2, J4,6 1.8, J4,6 1.8,
1H, H4). dC 20.6 (CH3), 20.7 (CH3), 20.8 (CH3), 55.5 (OCH3),
67.2, 68.6, 69.4 (C2,3,4), 97.1, 99.3 (C1,6), 151.0 (C5), 169.6
(C¼O), 169.7 (C¼O), 169.9 (C¼O). m/z 300.1099; [MþH]þ
requires 300.1080. Anal. Calc. for C13H18O8: C 51.65, H 6.00.
Found: C 51.78, H 6.05%.
Obtained as a colourless oil (7.0 g, 81%). [a]D ꢀ3.68 (in
CHCl3; lit.[21] ꢀ4.38 in CHCl3). dH (500 MHz, CDCl3) 1.96 (s,
3H, CH3), 2.05 (s, 3H, CH3), 2.15 (s, 3H, CH3), 3.15 (dd, J5,6 6.1,
J6,6 10.4, 1H, H6), 3.24 (dd, J5,6 7.8, J6,6 10.4, 1H, H6), 3.55 (s,
3H, OCH3), 3.82 (ddd, J4,5 1.0, J5,6 6.1, J5,6 7.8, 1H, H5), 4.39 (d,
J1,2 7.7, 1H, H1), 5.02 (dd, J2,3 10.4, J3,4 3.3, 1H, H3), 5.16 (dd,
J1,2 7.7, J2,3 10.4, 1H, H2), 5.54 (dd, J3,4 3.3, J4,5 1.0, 1H, H4). dC
(125.8 MHz, CDCl3) 0.1 (C6), 20.5 (CH3), 20.6 (CH3), 20.8
(CH3), 57.2 (OCH3), 68.4, 68.6, 71.0, 73.4 (C2,3,4,5), 101.9
(C1), 169.5 (C¼O), 170.1 (C¼O), 170.2 (C¼O). m/z 431.0219;
[MþH]þ requires 431.0203. Anal. Calc. for C13H19IO8: C
36.30, H 4.45. Found: C 36.29, H 4.40%.
General Procedure for the Preparation of the Ulososides
To a 1% solution of the alkene (10 mmol) in a mixure of
dichloromethane/benzyl alcohol (1:1 v/v), 3-chloroperbenzoic
acid (20 mmol) was added, and the mixture was stirred at
ambient temperature overnight. The mixture was partitioned
between dichloromethane (120 mL) and aqueous sodium
bicarbonate (5%), the organic layer was dried (Na2SO4), the
solvent removed under reduced pressure, and the resulting
residue was chromatographed (EtOAc/hexane 2:3) on silica gel
providing a presumed diastereomeric mixture of ulososides. The
residue was then dissolved in MeOH and treated with sodium
methoxide and then stirred at ambient temperature (30 min). The
mixture was quenched with resin (Amberlite IR-120, Hþ), fil-
tered, and concentrated. The residue obtained was sufficiently
pure for the next step of the synthesis. Purification of the major
epimer by flash chromatography (MeOH/EtOAc 1:9) gave the
desired tetrols.
Methyl Tri-O-acetyl-6-deoxy-6-iodo-a-D-
mannopyranoside 18
Obtained as a colourless oil (7.0 g, 82%). [a]D þ35.98 (in
CHCl3; lit.[21] þ37.08 in CHCl3). dH 1.97 (s, 3H, CH3), 2.05 (s,
3H, CH3), 2.13 (s, 3H, CH3), 3.17 (dd, J5,6 9.6, J6,6 10.8, 1H,
H6), 3.29 (dd, J5,6 2.4, J6,6 10.8, 1H, H6), 3.46 (s, 3H, OCH3),
3.78 (ddd, J4,5 9.6, J5,6 2.4, J5,6 9.6, 1H, H5), 4.71 (d, J1,2 1.8, 1H,
H1), 5.09 (dd, J3,4 9.6, J4,5 9.6, 1H, H4), 5.20 (dd, J1,2 1.8, J2,3
3.6, 1H, H2), 5.29 (dd, J2,3 3.6, J3,4 9.6, 1H, H3). dC 3.8 (C6),
20.6 (CH3), 20.7 (CH3), 20.8 (CH3), 55.4 (OCH3), 68.6, 69.5,
70.0, 70.1 (C2,3,4,5), 98.5 (C1), 169.7 (C¼O), 169.8 (C¼O),
170.0 (C¼O). m/z 431.0214; [MþH]þ requires 431.0203. Anal.
Calc. for C13H19IO8: C 36.30, H 4.45. Found: C 36.22, H 4.43%.
Methyl (5R/S)-5-C-Benzyloxy-b-D-xylo-hexopyranoside 11
General Procedure for the Preparation of the 5,6-Alkenes
Obtained as a colourless oil (2.4 g, 81% over two steps). [a]D
ꢀ26.68 (in CH3OH). dH 5S epimer (600 MHz, CD3OD) 3.50 (s,
3H, OCH3), 3.58–3.64 (m, 2H, H2,3), 3.78 (d, J3,4 7.3, 1H, H4),
3.83–3.87 (m, 2H, H6,6), 4.59 (d, J1,2 6.8, 1H, H1), 4.66 (A part
of ABq, J 10.9, 1H, CH2Ph), 4.72 (B part of ABq, J 10.9, 1H,
CH2Ph), 7.21–7.41 (m, 5H, Ph). dC 5S epimer (125.8 MHz,
CD3OD) 56.9 (OCH3), 62.2, 64.5 (C6,CH2Ph), 74.5, 75.6, 76.0
(C2,3,4), 102.9, 103.6 (C1,5), 128.2, 128.9, 129.1, 140.0 (Ph).
m/z 301.1299; [MþH]þ requires 301.1287. Anal. Calc. for
C14H20O7: C 55.99, H 6.71. Found: C 55.82, H 6.79%.
1,8-Diazabicyclo[5.4.0]undec-7-ene (40 mmol) was added to
the iodide (10 mmol) in THF (60 mL) and the mixture refluxed
until no starting material was observed (t.l.c.). Concentration of
the mixture, followed by a standard workup (EtOAc) and flash
chromatography (EtOAc/petrol 2:3), gave the desired hex-5-
enopyranosides.
Methyl Tri-O-acetyl-6-deoxy-b-D-xylo-hex-
5-enopyranoside 9
The title compound was obtained as a colourless oil (2.7 g,
89%) after a reaction time of 2 h. [a]D ꢀ32.98 (in CHCl3; lit.[19]
Methyl (5R/S)-5-C-Benzyloxy-a-L-arabino-
hexopyranoside 16
1
ꢀ34.68 in CHCl3). Gave H and 13C NMR spectra consistent
with that found in the literature.[19]
Obtained as a colourless oil (2.3 g, 78% over two steps). [a]D
ꢀ37.98 (in CH3OH). dH 5S epimer (600 MHz, CD3OD) 3.46 (s,
3H, OCH3), 3.59 (dd, J1,2 7.9, J2,3 9.8, 1H, H2), 3.79 (d, J6,6 12.1,
1H, H6), 3.87 (d, J6,6 12.1, 1H, H6), 3.88 (dd, J2,3 9.8, J3,4 3.4,
1H, H3), 3.96 (d, J3,4 3.4, 1H, H4), 4.41 (d, J1,2 7.9, 1H, H1), 4.66
(A part of ABq, J 11.4, 1H, CH2Ph), 4.70 (B part of ABq, J 11.4,
1H, CH2Ph), 7.25–7.40 (m, 5H, Ph). dC 5S epimer (125.8 MHz,
CD3OD) 57.2 (OCH3), 59.7, 63.6 (C6, CH2Ph), 70.6, 71.7, 72.0
(C2,3,4), 102.3, 102.8 (C1,5), 127.9, 128.5, 129.3, 139.3 (Ph).
m/z 301.1276; [MþH]þ requires 301.1287. Anal. Calc. for
C14H20O7: C 55.99, H 6.71. Found: C 56.07, H 6.76%.
Methyl Tri-O-acetyl-6-deoxy-a-L-arabino-hex-
5-enopyranoside 14
The title compound was obtained as a colourless oil (2.5 g,
83%) after a reaction time of 2 h. [a]D ꢀ48.18 (in CHCl3; lit.[22]
ꢀ46.28 in CHCl3). dH 2.03 (s, 3H, CH3), 2.08 (s, 3H, CH3), 2.11
(s, 3H, CH3), 3.53 (s, 3H, OCH3), 4.52 (d, J1,2 5.9, 1H, H1), 4.55
(s, 1H, H6), 4.78 (s, 1H, H6), 5.06 (dd, J2,3 8.7, J3,4 3.7, 1H, H3),
5.28 (dd, J1,2 5.9, J2,3 8.7, 1H, H2), 5.70 (d, J3,4 3.7, 1H, H4). dC
20.6 (CH3), 20.7 (CH3), 20.9 (CH3), 56.7 (OCH3), 67.9, 68.8,
69.3 (C2,3,4), 101.5, 102.2 (C1,6), 150.0 (C5), 169.4 (C¼O),
169.8 (C¼O), 170.0 (C¼O). m/z 300.1086; [MþH]þ requires
300.1080. Anal. Calc. for C13H18O8: C 51.65, H 6.00. Found:
C 51.61, H 6.12%.
Methyl (5R/S)-5-C-Benzyloxy-a-D-lyxo-hexopyranoside 21
Obtained as a colourless oil (2.2 g, 74% over two steps). [a]D
þ27.18 (in CH3OH). dH 5R epimer (600 MHz, CD3OD) 3.50 (s,
3H, OCH3), 3.70 (dd, J1,2 7.5, J2,3 3.6, 1H, H2), 3.77 (d, J6,6 12.1,
1H, H6), 3.86 (d, J6,6 12.1, 1H, H6), 3.94 (dd, J2,3 3.6, J3,4 3.9,
1H, H3), 4.02 (d, J3,4 3.9, 1H, H4), 4.73–4.75 (m, 3H, H1,
CH2Ph), 7.25–7.45 (m, 5H, Ph). dC 5S epimer (125.8 MHz,
Methyl Tri-O-acetyl-6-deoxy-a-D-lyxo-hex-
5-enopyranoside 19
The title compound was obtained as a colourless oil (2.7 g,
91%) after a reaction time of 6 h. [a]D þ15.88 (in CHCl3; lit.[23]

1412
M. N. Gandy, M. J. Piggott, and K. A. Stubbs
CD3OD) 57.1 (OCH3), 60.8, 64.2 (C6, CH2Ph), 69.2, 69.7, 73.7
(C2,3,4), 100.0, 104.6 (C1,5), 127.9, 128.8, 129.5, 139.1 (Ph).
m/z 301.1283; [MþH]þ requires 301.1287. Anal. Calc. for
C14H20O7: C 55.99, H 6.71. Found: C 56.10, H 6.79%.
[2] N. Asano, R. J. Molyneaux, G. W. J. Fleet, Tetrahedron Asymmetry
2000, 11, 1645. doi:10.1016/S0957-4166(00)00113-0
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General Procedure for the Intramolecular
Reductive Amination
[5] S. Franz, L. Calvillo, J. Tillmanns, I. Elbing, C. Dienesch, H. Bischop,
G. Ertl, FASEB J. 2005, 19, 591.
To a 0.03 M solution of the ulososide in MeOH/H2O (20 mL,
15:1v/v), one equivalent of the amine component as well as Pd
(OH)2/C (20%, 0.1 equiv.) was added, and the heterogeneous
reaction mixture was stirred under an atmosphere of hydrogen at
ambient pressure and room temperature for 24 h. After filtration
and evaporation of the solvent under reduced pressure, the
residue was purified by column chromatography on silica gel
(CHCl3/MeOH/concd NH3, 10:10:1 v/v/v), yielding the target
compounds. The formation of L-ido configured products was not
observed in any of the reported cases.
[6] H. E. Lebovitz, Diabetes Rev. 1998, 6, 132.
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[9] K. Tatsuta, in Carbohydrate Mimics 1998, pp. 283 (Ed. Y. Chapleur)
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[10] M. H. Fechter, A. E. Stutz, A. Tauss, Curr. Org. Chem. 1999, 3, 269.
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to Therapeutic Applications 2007, pp. 25 (Eds P. A. M. Compain,
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[12] M. S. M. Pearson, V. Mathe´-Allainmat, V. Fargeas, J. Lebreton, Eur. J.
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1-Deoxynojirimycin 1
Obtained as a colourless oil (70 mg, 68%). [a]D þ34.08 (in
1
H2O; lit.[24] þ34.48 in H2O). Gave H and 13C NMR spectra
consistent with that found in the literature.[24]
[15] A. J. Steiner, G. Schitter, A. E. Stutz, T. M. Wrodnigg, C. A. Tarling,
S. G. Withers, K. Fantur, D. J. Mahuran, E. Paschke, M. Tropak, Bioorg.
Med. Chem. 2008, 16, 10216. doi:10.1016/J.BMC.2008.10.054
[16] A. J. Steiner, A. E. Stutz, C. A. Tarling, S. G. Withers, T. M. Wrodnigg,
Carbohydr. Res. 2007, 342, 1850. doi:10.1016/J.CARRES.2007.
03.024
N-Butyl-1-deoxynojirimycin 2
Obtained as a colourless oil (80 mg, 61%). [a]D ꢀ16.28 (in
H2O; lit.[24] ꢀ15.98 in H2O). Gave H and 13C NMR spectra
1
consistent with that found in the literature.[24]
[17] R. F. Frohlich, R. H. Furneaux, D. J. Mahuran, B. A. Rigat, A. E. Stutz,
M. B. Tropak, J. Wicki, S. G. Withers, T. M. Wrodnigg, Carbohydr.
Res. 2010, 345, 1371.
[18] P. J. Garegg, B. Samuelsson, J. Chem. Soc., Perkin Trans. 1 1980,
2866. doi:10.1039/P19800002866
N-(2-Hydroxyethyl)-1-deoxynojirimycin 3
Obtained as a colourless oil (72 mg, 58%). [a]D ꢀ7.28 (in
1
H2O; lit.[24] ꢀ7.78 in H2O). Gave H and 13C NMR spectra
consistent with that found in the literature.[24]
[19] B. W. Skelton, R. V. Stick, K. A. Stubbs, A. G. Watts, A. H. White,
Aust. J. Chem. 2004, 57, 345. doi:10.1071/CH03288
[20] R. W. Grabner, B. H. Landis, P. T. Wang, M. L. Prunier, M. G. Scaros,
European Patent EPO477160 Monsanto (US) Seattle (US) 1992.
[21] G. O. Aspinall, R. C. Carpenter, L. Khondo, Carbohydr. Res. 1987,
165, 281. doi:10.1016/0008-6215(87)80105-2
1-Deoxygalactonojirimycin 4
Obtained as a colourless oil (63 mg, 64%). [a]D þ50.58 (in
H2O; lit.[25] þ50.28 in H2O). Gave H and 13C NMR spectra
1
consistent with that found in the literature.[25]
[22] J. Lehmann, W. Weckerle, Carbohydr. Res. 1975, 42, 275. doi:10.1016/
S0008-6215(00)84270-6
[23] J. Lehmann, A. A. Benson, J. Am. Chem. Soc. 1964, 86, 4469.
doi:10.1021/JA01074A045
[24] A. L. Concia, C. Lozano, J. A. Castillo, T. Parella, J. Joglar, P. Clapes,
Chem. Eur. J. 2009, 15, 3808. doi:10.1002/CHEM.200802532
[25] H. Takahata, Y. Banba, H. Ouchi, H. Nemoto, Org. Lett. 2003, 5, 2527.
doi:10.1021/OL034886Y
1-Deoxymannojirimycin 5
Obtained as a colourless oil (62 mg, 61%). [a]D ꢀ35.58 (in
H2O; lit.[24] ꢀ36.18 in H2O). Gave H and 13C NMR spectra
1
consistent with that found in the literature.[24]
References
[1] B. La Ferla, F. Nicotra, in Iminosugars as Glycosidase Inhibitors:
Nojirimycin and Beyond 1999, pp. 68 (Ed. A. E. Stutz) (Wiley-VCH:
Weinheim).