Synthesis of 1-Deoxynojirimycin Derivatives from L-Sorbose via Wittig Reactions

Article abstract of DOI:10.1080/07328303.2011.619287

A strategy for the synthesis of 1-deoxynojirimycin (DNJ) derivatives from L-sorbose is described. The sequence involved eight steps and afforded DNJ derivatives in 13% to 44% overall yield.

Full text of DOI:10.1080/07328303.2011.619287

This article was downloaded by: [University of Saskatchewan Library]
On: 04 October 2012, At: 05:28
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Carbohydrate Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lcar20
Synthesis of 1-Deoxynojirimycin
Derivatives from L-Sorbose via Wittig
Reactions
Colin O’ Brien a & Paul V. Murphy b
a Centre for Synthesis and Chemical Biology, School of Chemistry and
Chemical Biology, Conway Institute of Biomolecular and Biomedical
Research, University College Dublin, Belfield, Dublin 4, Ireland
b School of Chemistry, National University of Ireland Galway,
University Road, Galway, Ireland
Version of record first published: 14 Dec 2011.
To cite this article: Colin O’ Brien & Paul V. Murphy (2011): Synthesis of 1-Deoxynojirimycin
Derivatives from L-Sorbose via Wittig Reactions, Journal of Carbohydrate Chemistry, 30:7-9, 626-640
To link to this article: http://dx.doi.org/10.1080/07328303.2011.619287
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Journal of Carbohydrate Chemistry, 30:626–640, 2011
ꢀ
C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.619287
Synthesis of 1-Deoxynojirimycin
Derivatives from L-Sorbose via
Wittig Reactions
Colin O’Brien1 and Paul V. Murphy2
1Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical
Biology, Conway Institute of Biomolecular and Biomedical Research, University
College Dublin, Belfield, Dublin 4, Ireland
2School of Chemistry, National University of Ireland Galway, University Road,
Galway, Ireland
A strategy for the synthesis of 1-deoxynojirimycin (DNJ) derivatives from L-sorbose is
described. The sequence involved eight steps and afforded DNJ derivatives in 13% to
44% overall yield.
Keywords 1-Deoxynojirimycin; Wittig reactions; Lactol
INTRODUCTION
1-Deoxynojirimycin (DNJ) 1 (Fig. 1) is a naturally occurring iminosugar[1] and
its derivatives have found clinical application[2] due to their inhibition of gly-
coprocessing enzymes. These compounds have been investigated for their po-
tential in treating HIV and hepatitis C virus infection, diabetes, and other
metabolic disorders.[3] Besides these applications, there have been efforts to
generate peptidomimetics based on DNJ also (Fig. 1).[4] Such research benefits
from development of synthetic approaches to DNJ derivatives, and there have
been a number of syntheses of polyhydroxylated N-heterocycles published.[5]
Herein an approach to 6-modified analogs of DNJ is described from L-sorbose.
RESULTS AND DISCUSSION
Synthesis of 1 has been carried out from L-sorbose previously, including a
synthesis[6] wherein peptidomimetics based on DNJ have been prepared. The
Received July 25, 2011; accepted August 29, 2011.
Address correspondence to Paul V. Murphy, School of Chemistry, National Univer-
sity of Ireland Galway, University Road, Galway, Ireland. E-mail: Paul.V.Murphy@
nuigalway.ie
626

Synthesis of 1-Deoxynojirimycin Derivatives
627
Figure 1: Structures of DNJ and a DNJ-based peptidomimetic.
preparation of peptidomimetics based on 1 requires the establishment of syn-
thetic routes where pharmacophoric groups can be grafted strategically to the
core scaffold, in this case the chiral piperidine. We wished to obtain DNJ
derivatives 2, which are functionalized at C-5. The retrosynthesis is shown
in Scheme 1. This use of the Wittig reaction with the aldehyde 4[7] would allow
the modification at the sorbose C-1, and this would subsequently lead to the
desired DNJ analogs 2 via 3.
Scheme 1: Retrosynthetic analysis.
The synthesis of 2 was commenced as outlined in Scheme 2. The generation
of the ylide in dry THF at –78◦C and subsequent addition of the aldehyde,
also at –78◦C, afforded the desired alkene intermediates after 15 h (75% to
91%). The subsequent reduction of the alkenes was carried out using catalytic
hydrogenation (1 atm) to give 5a–d with yields in each case over 95%. The
regioselective hydrolysis of the 6-membered acetonide of 5a–d gave diols 6a–d
(89% to 97%) and the subsequent regioselective introduction of the azide via a
cyclic sulfite gave azides 7a–d (75% to 92%). Next the acid-promoted hydrolysis
of the 5-membered acetonide led to the formation and observation of the acyclic
compounds 8a,c,d and a 1:1 mixture of interconverting isomers 8b and its
cyclic isomer 9. The assignment of acyclic structures was supported by 13C
NMR data. The absence of a signal in the region of δ 110 to 120 ppm indicated
the absence of any expected quaternary carbons, while the presence of signals
at δ 208 to 209 ppm, suggested the presence of ketone group in each case. In the
case of compounds 8b and 9 (Sch. 3), the 1:1 isomeric ratio was determined by
integration of the signals for the methoxy groups of the two different isomers
observed in the 1H NMR spectrum.

C. O’Brien and P. V. Murphy
628
Scheme 2: Synthesis of 8a–d.
Scheme 3: Synthesis of 2a–d.
Catalytic hydrogenation of compounds 8b–d and 9 using 10% Pd(OH)2-C
in dry methanol led to the formation of the DNJ derivatives 2b–d; in the case
of the reaction of 8a, the benzylated derivative 10 was obtained (Sch. 3). The
removal of the benzyl group from 10 was effected by catalytic hydrogenolysis
in dry methanol in the presence 10% Pd(OH)2-C and HCl (1 equiv) for 1 h. All
of the final compounds 2a–d were purified by chromatography using an acid
ion-exchange resin (DOWEX 50-X8) as the stationary phase to give the free
amines.

Synthesis of 1-Deoxynojirimycin Derivatives
629
A strategy for the synthesis of 1-deoxynojirimycin derivatives 2 has been
demonstrated. This sequence involved eight steps and afforded 2a–d in 13%
to 44% yield from L-sorbose. The use of the Wittig reaction with aldehyde 4
has therefore been useful for generating DNJ derivatives, which are varied at
the C-6 position. Testing of compounds 2a–d for inhibition of α-glucosidase ac-
tivity at the enzyme level did not indicate that these compounds were potent
inhibitors. In addition, compounds 2a–d did not alter cell surface oligosaccha-
ride expression when evaluated for their ability to inhibit glycosidases in a
cellular context as has been observed for DNJ 1; this indicates they did not
inhibit glycosidase activity at the cellular level.[8] However, the approach may
have the potential for the synthesis of DNJ-based peptidomimetics and work
is under way in this regard.
EXPERIMENTAL
General Experimental Conditions
Optical rotations were determined with a Perkin-Elmer 343 model po-
larimeter at the sodium D line at 20◦C. NMR spectra were recorded with
JEOL JNM-GX270, Varian Inova 300 and 500, and VNMRS 500 and VNMRS
600 spectrometers. Chemical shifts are reported relative to internal Me4Si
1
in CDCl3 (δ 0.0), HOD for D2O (δ 4.80) and CD2HOD (δ 3.31) for H, and
CDCl3 (δ 77.0) and CD3OD (δ 49.0) for 13C. Coupling constants are reported
in Hertz. FTIR spectra were recorded with a Mattson Galaxy Series FTIR
3000 using either thin film between NaCl plates or Ge discs, as specified.
Melting points were measured on a Barnstead Electrothermal 9300 melting
point apparatus. High-resolution mass spectra were measured on either a mi-
cromass VG 70/70H, VG ZAB-E, or autospec spectrometers and were mea-
sured in positive and/or negative mode as indicated in each case. TLC was
performed on aluminium sheets precoated with silica gel 60 (HF254, E. Merck)
and spots visualized by UV and charring with H2SO4-EtOH (1:20), KMnO4,
ninhydrin, or cerium (IV) molybdate solutions. Flash column chromatography
was carried out with silica gel 60 (0.040–0.630 mm, E. Merck) using a step-
wise solvent polarity gradient correlated with TLC mobility. Chromatography
solvents used were EtOAc (Riedel-de Hae¨n), CH2Cl2 (Riedel-de Hae¨n), cyclo-
hexane (Sigma-Aldrich), MeOH (Sigma-Aldrich), CH3CN (Sigma-Aldrich), and
petroleum ether (b.p. 40–60◦C, BDH laboratory supplies). Reaction solvents
were freshly dried and distilled where stated: CH3CN, toluene, and CH2Cl2
from calcium hydride; MeOH from magnesium turnings; and THF from sodium
wires. Alternatively, CH2Cl2, THF, and MeOH were also used from a Pure-
Solvent drying system. Anhydrous DMF and pyridine were used as purchased
from Sigma-Aldrich.

C. O’Brien and P. V. Murphy
630
2,3:4,6-Di-O-isopropylidene-α-L-xylo-hexos-2-ulo-2,5-furanose (4)
Anhyd DMSO was added dropwise to a stirred solution of oxalyl chloride
(2.3 mL, 26.3 mmol) in anhyd CH2Cl2 (100 mL) at –78◦C under N2. After 15
min a solution of 2,3:4,6-di-O-isopropylidene-α-L-sorbofuranose[9] (5.7 g, 21.9
mmol) in anhyd CH2Cl2 (50 mL) was added dropwise, keeping the tempera-
ture at –78◦C. After 3 h the temperature was increased to –50◦C and anhyd
triethylamine (15.3 mL, 110 mmol) was added. After 30 min the temperature
was allowed to attain rt and water (60 mL) was added. The layers were sep-
arated and the aq layer was extracted with CH2Cl2 (3 × 30 mL). The com-
bined organic extracts were washed with brine, dried (MgSO4), and filtered
and the excess solvent was removed under diminished pressure. Chromatog-
raphy (EtOAc-cyclohexane 1:1, Rf 0.2) of the residue gave the title compound
as an off-white solid (4.50 g, 80%); 1H NMR (500 MHz, CDCl3): δ 9.67 ((s, 1H),
4.55 (m, 1H), 4.36 (m, 1H), 4.23 (br s, 1H), 4.12 (m, 2H), 1.54, 1.44, 1.39, 1.34
(each s, each 3H); 13C NMR (125 MHz, CDCl3): δ 194.5, 114.5, 112.1, 97.8,
90.7, 86.7, 74.0, 60.1, 29.0, 27.0, 26.1, 18.9; FTIR (film from CH2Cl2 on NaCl):
2991, 2939, 1744, 1455, 1377, 1198, 1119, 1091, 1040 cm−1; ESI-HRMS: calcd
259.1182; found 259.1170 [M+H]+.
2,3:4,6-Di-O-isopropylidene-(2R,3S,4S,5S)-2-(4-benzyloxybutyl)-
5-(hydroxymethyl)-tetrahydrofuran-2,3,4-triol 5a
To (4-benzyloxybutyl)-triphenylphosphonium bromide (3.31 g, 6.7 mmol) in
anhyd THF (22 mL) at –78◦C was added NaHMDS (6.7 mmol, 6.7 mL of an 0.1
M soln) dropwise. The reaction was stirred at –78◦C for 10 min, then at 0◦C
for 10 min and at rt for 20 min. The mixture was then cooled again to –78◦C
and 4 in anhyd THF (22 mL) was added dropwise. The reaction was stirred at
–78◦C and then stirring was continued at rt for 15 h. Satd NH4Cl was then
added and the layers were separated. The aq layer was extracted with EtOAc
(×3) and the combined organic layers were washed with water and brine,
dried (MgSO4), and filtered. The excess solvent was removed under dimin-
ished pressure. Chromatography (EtOAc-cyclohexane, 1:8) of the residue gave
the alkene intermediate (1.6 g, 91%). To this intermediate (590 mg, 1.5 mmol)
in anhyd MeOH (25 mL) was added 10% Pd-C (85 mg) and the reaction was
degassed. The reaction was stirred under H2 (1 atm) at rt for 30 min. The reac-
tion was then filtered through celite washing with MeOH (×3). The excess
solvent was removed under diminished pressure. Chromatography (EtOAc-
cyclohexane, 1:8) of the residue gave the title compound (573 mg, 97%); Rf
1
0.62 (EtOAc-cyclohexane, 1:1); [α]D +5.1 (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): δ 7.33–7.30 (m, 5H), 4.49 (m, 2H), 4.24 (overlapping signals, 2H), 4.03
(overlapping signals, 3H), 3.50–3.48 (overlapping signals, 2H), 1.91 (overlap-
ping signals, 2H), 1.6–1.8 (overlapping signals, 4H), 1.47, 1.41, 1.35, 1.33 (each

Synthesis of 1-Deoxynojirimycin Derivatives
631
s, each 3H); 13C NMR (100 MHz, CDCl3): δ 138.5, 128.2, 127.5, 127.3, 115.6,
110.7, 97.1, 86.0, 73.6, 72.9, 71.6, 70.3, 60.3, 37.5, 29.9, 28.7, 27.4, 26.6, 20.4,
18.6; FTIR (film from CH2Cl2 on NaCl): 2989, 2934, 2864, 1454, 1381, 1284,
1239, 1197, 1123, 1082, 994, 924, 736, 698 cm−1; ESI-HRMS: calcd 393.2277;
found 393.2292 [M+H]+.
2,3:4,6-Di-O-isopropylidene-(2R,3S,4S,5S)-2-(2-methoxyethyl)-
5-(hydroxymethyl)-tetrahydrofuran-2,3,4-triol (5b)
To (methoxymethyl)triphenyl-phosphonium chloride (2.00 g, 5.9 mmol) in
anhyd THF (20 mL) at –78◦C was added NaHMDS (5.85 mL of a 0.1 M soln,
5.9 mmol) dropwise. The reaction was stirred at –78◦C for 10 min, then at
0◦C for 10 min and at rt for 20 min. The reaction was then recooled to –78◦C
and 4 (1.0 g, 3.9 mmol) in anhyd THF (20 mL) was added dropwise. The reac-
tion was stirred at –78◦C and the stirring was continued at rt for 15 h. Satd
NH4Cl was then added and the layers were separated. The aq layer was ex-
tracted with EtOAc (×3) and the combined organic layers were washed with
water and brine, dried (MgSO4), and filtered. The excess solvent was removed
and NMR analysis indicated the presence of a 1:1 mixture of isomers. Chro-
matography (EtOAc-cyclohexane, 1:5) gave the intermediates (880 mg, 79%).
To the intermediates (70 mg, 0.3 mmol) in anhyd MeOH (4 mL) was added 10%
Pd-C (16 mg) and the reaction was degassed (×3). The reaction was stirred
under H2 (1 atm) at rt for 1 h. The reaction was then filtered through celite
washing with MeOH (×3). The excess solvent was removed under diminished
pressure and chromatography of the residue (EtOAc-cyclohexane, 1:4) gave the
title compound (68 mg, 97%); Rf 0.48 (EtOAc-cyclohexane, 1:1); [α]D +6.3 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): δ 4.43 (m, 1H), 4.23 (d, 1H, J = 2.2 Hz),
4.06–3.97 (overlapping signals, 3H), 3.53 (m, 2H), 3.25 (s, 3H), 2.31 (dt, 1H J =
7.3, 14.5 Hz), 2.12 (ddd, 1H, J = 5.5, 7.0 Hz, J = 14.6 Hz), 1.39, 1.35, 1.30, 1.27
(each s, each 3H); 13C NMR (100 MHz, CDCl3): δ 114.1, 110.7, 97.0, 86.0, 73.5,
71.3, 68.1, 60.1, 58.1, 36.9, 28.7, 27.2, 26.2, 18.4; FTIR (film from CH2Cl2 on
NaCl): 2989, 2935, 2893, 2811, 1454, 1382, 1335, 1284, 1239, 1199, 1122, 1080,
1018 990, 952, 911, 874, 842, 812, 764 cm−1; ESI-HRMS: calcd 289.1651; found
289.1664 [M+H]+.
2,3:4,6-Di-O-isopropylidene-(2R,3S,4S,5S)-2-octyl-
(5-hydroxymethyl)-tetrahydrofuran-2,3,4-triol (5c)
To heptyltriphenylphosphonium bromide (2.85 g, 6.5 mmol) in anhyd THF
(22 mL) at –78◦C was added NaHMDS (6.45 mL of a 0.1 M soln, 6.5 mmol)
dropwise. The reaction was stirred at –78◦C for 10 min, then 0◦C for 10 min and
at rt for 20 min. The reaction was then recooled to –78◦C and 4 (1.1 g, 4.3 mmol)
in anhyd THF (22 mL) was added dropwise. The reaction was stirred at –78◦C

C. O’Brien and P. V. Murphy
632
and the stirring was continued at rt for 15 h. Satd NH4Cl was then added
and the layers were separated. The aq layer was extracted with EtOAc (×3)
and the combined organic layers were washed with water and brine, dried
(MgSO4), and filtered. The excess solvent was removed under diminished pres-
sure. Chromatography (EtOAc-cyclohexane, 1:10) of the residue gave the inter-
mediate alkene (1.279 g, 88%); Rf 0.4 (EtOAc-cyclohexane, 1:10). The reaction
of this intermediate (1.26 g, 3.7 mmol) in anhyd MeOH (40 mL) with 10% Pd-C
(250 mg) under H2 (1 atm) as described for 5a gave the title compound (1.22
1
g, 96%); Rf 0.63 (EtOAc-cyclohexane, 1:1); [α]D +23.3 (c 1.0, CHCl3); H NMR
(500 MHz, CDCl3): 4.22 (s, 1H), 4.19 (d, 1H, J = 1.7), 4.01 (overlapping sig-
nals, 3H), 1.92 (dd, 1H, J = 2.2, 6.9 Hz), 1.90 (dd, 1H, J = 1.6, 6.9 Hz), 1.45,
1.40, 1.34, 1.32 (each s, each 3H), 1.31–1.20 (overlapping signals, 12H), 0.86 (t,
J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 115.8, 110.6, 97.1, 86.1, 73.7,
71.7, 60.4, 37.7, 31.8, 29.8, 29.4, 29.2, 28.7, 27.5, 26.7, 24.1, 22.6, 18.7, 14.0;
FTIR (film from CH2Cl2 on NaCl): 2990, 2926, 2855, 1456, 1381, 1340, 1285,
1239, 1198, 1173, 1125, 1082, 993, 910, 858, 833, 765 cm−1; ESI-HRMS: calcd
343.2484; found 343.2488 [M+H]+.
2,3:4,6-Di-O-isopropylidene-(2R,3S,4S,5S)-2-ethyl-
(5-hydroxymethyl)-tetrahydrofuran-2,3,4-triol (5d)
To methytriphenylphosphonium iodide (1.38 g, 3.4 mmol) in anhyd THF
(10 mL) at –78◦C was added NaHMDS (3.41 mL of a 0.1 M soln, 3.4 mmol)
dropwise. The reaction was stirred at –78◦C for 10 min, then at 0◦C for 10
min and at rt for 20 min. The reaction was then recooled to –78◦C and 4 (580
mg, 2.3 mmol) in anhyd THF (10 mL) was added dropwise. The reaction was
stirred at –78◦C and then stirring was continued at rt for 15 h. Satd NH4Cl
was then added and the layers were separated. The aq layer was extracted
with EtOAc (×3) and the combined organic layers were washed with water
and brine, dried (MgSO4), and filtered. The excess solvent was removed under
diminished pressure. Chromatography (EtOAc-cyclohexane, 1:8) of the residue
gave the intermediate alkene (430 mg, 75%). The reaction of this intermediate
(87 mg, 0.3 mmol) in anhyd MeOH (4 mL) with 10% Pd-C (18 mg) under H2
(1 atm) at rt for 1 h as described for 5a gave the title compound (84 mg, 97%);
1
Rf 0.6 (EtOAc-cyclohexane, 1:1); [α]D +5.3 (c 1.0, CHCl3); H NMR (500 MHz,
CDCl3): δ 4.25 (overlapping signals, 2H), 3.97–4.06 (overlapping signals, 3H),
1.98 (2H, J = 7.5 Hz), 1.48, 1.42, 1.36, 1.34 (each s, each 3H), 1.08 (t, 3H, J =
7.5 Hz); 13C NMR (125 MHz, CDCl3): δ 116.1, 110.6, 97.1, 85.7, 73.7, 71.7, 60.4,
30.5, 28.7, 27.5, 26.7, 18.7, 8.6; FTIR (film from CH2Cl2 on NaCl): 2988, 2938,
2884, 1456, 1382, 1284, 1240, 1198, 1124, 1082, 993, 952, 907, 874, 842 cm−1
;
ESI-HRMS: calcd 259.1545; found 259.1536 [M+H]+.

Synthesis of 1-Deoxynojirimycin Derivatives
633
2,3-O-Isopropylidene-(2R,3S,4S,5S)-2-(3-benzyloxybutyl)-
5-(hydroxymethyl)-tetrahydrofuran-2,3,4-triol (6a)
To 5a (500 mg, 1.1 mmol) was added acetic acid in water (60% v/v,
35 mL) and the reaction was heated at 60◦C for 1 h. The excess solvent
was removed under diminished pressure. Chromatography of the residue
(EtOAc-cyclohexane, 1:1) gave the title compound (395 mg, 97%); Rf 0.18
(EtOAc-cyclohexane, 1:1); [α]D +5.6 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
δ 7.32–7.27 (m, 5H), 4.49 (s, 2H), 4.25 (s, 1H), 4.23 (s, 1H), 4.17 (d, 1H, J = 2.7
Hz), 4.05 (dd, 1H, J = 3.1, 12.3 Hz), 3.96 (dd, 1H, J = 4.2, 12.3 Hz), 3.49 (t, 2H,
J = 5.3 Hz), 3.04 (br s, 1H), 1.94 (m, 2H), 1.63 (overlapping signals, 4H), 1.46,
1.32 (each s, each 3H); 13C NMR (100 MHz, CDCl3): δ 138.2, 128.3, 127.6, 127.5,
115.1, 110.7, 87.2, 78.7, 77.5, 72.8, 70.1, 61.3, 37.6, 29.7, 27.4, 26.5, 20.7; FTIR
(film from CH2Cl2 on NaCl): 3414 (broad), 2986, 2934, 2868, 1454, 1372, 1216,
1178, 1101, 1075, 988, 906, 868, 737, 698 cm−1; ESI-HRMS: calcd 353.1964;
found 353.1972 [M+H]+.
2,3-O-Isopropylidene(2R,3S,4S,5S)-2-(2-methoxyethyl)-
5-(hydroxymethyl)-tetrahydrofuran-2,3,4-triol (6b)
The reaction of 5b (110 mg, 0.4 mmol) with acetic acid and water (60%
v/v, 5 mL) as described above for 5a gave the title compound (83 mg, 89%); Rf
1
0.19 (EtOAc-cyclohexane, 1:1); [α]D +0.3 (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): δ 4.53 (br s, 1H), 4.40 (s, 1H), 4.20 (dd, 1H, J = 4.2, 7.1 Hz), 4.17 (s,
1H), 3.97 (dd, 1H, J = 4.7, 12.9 Hz), 3.93 (dd, 1H, J = 4.2, 12.9 Hz), 3.76 (ddd,
1H, J = 4.7, 8.4, 9.9 Hz), 3.50 (dt, 1H, J = 4.9, 9.9 Hz), 3.32 (s, 3H), 3.14 (br
s, 1H), 2.27–2.22 (m 1H), 1.44, 1.30 (each s, each 3H); 13C NMR (100 MHz,
CDCl3): δ 113.5, 110.3, 87.5, 80.2, 77.4, 68.8, 61.1, 58.4, 37.1, 27.1, 26.3; FTIR
(film from CH2Cl2 on NaCl): 3401 (broad), 2986, 2935, 2895, 1457, 1383, 1247,
1210, 1181, 1099, 986, 870 cm−1; ESI-HRMS: calcd 271.1158; found 271.1164
[M+Na]+.
2,3-O-Isopropylidene-(2R,3S,4S,5S)-2-octyl-5-
(hydroxymethyl)-tetrahydrofuran-2,3,4-triol (6c)
The reaction of 5c (90 mg, 0.3 mmol) with 60% acetic acid in water (5 mL)
as described for 5a gave the title compound (81 mg, quant); Rf 0.15 (EtOAc-
1
cyclohexane, 1:1); [α]D +7.0 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3): 4.29
(d, 1H, J = 1.9 Hz), 4.26 (s, 1H), 4.21 (dd, 1H, J 3.2, 5.6 Hz), 4.10 (dd, 1H,
=
J = 3.5, 12.4 Hz), 4.02 (dd, 1H, J = 1.9, 12.4 Hz), 3.93 (br s, 1H), 2.57 (br s,
1H), 1.91 (m, 1H), 1.90 (m, 1H), 1.20–1.50 (overlapping signals, 12H), 1.47 and
1.34 (each s, each 3H), 0.88 (t, 3H, J = 6.5 Hz); 13C NMR (100 MHz, CDCl3): δ
115.3, 110.8, 87.1, 78.6, 77.7, 61.4, 37.9, 31.8, 29.8, 29.4, 29.2, 27.4, 26.6, 24.1,
22.6, 14.0; FTIR (film from CH2Cl2 on NaCl): 3383 (broad), 2988, 2921, 2850,

C. O’Brien and P. V. Murphy
634
1468, 1371, 1337, 1247, 1217, 1171, 1070, 1028, 983, 930, 874, 833, 786 cm−1
;
ESI-HRMS: calcd 303.2171; found 303.2182 M+H]+.
2,3-O-Isopropylidene-(2R,3S,4S,5S)-2-ethyl-5-
(hydroxymethyl)-tetrahydrofuran-2,3,4-triol (6d)
The reaction of 5d (70 mg, 0.3 mmol) with 60% acetic acid in water (5 mL)
as described for 5a gave the title compound (57 mg, 96%); Rf 0.17 (EtOAc-
cyclohexane, 1:1); [α]D +10.2 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3): δ 4.28
(d, 1H, J = 1.8 Hz), 4.25 (s, 1H), 4.20 (br s, 1H), 4.10 (dd, 1H, J = 3.0, 12.4 Hz),
4.00 (dd, 1H, J = 2.2, 12.4 Hz), 1.96 (q, 2H, J = 7.5 Hz), 1.48, 1.34 (each s, each
3H), 1.06 (t, 3H, J = 7.5 Hz); 13C NMR (100 MHz, CDCl3): δ 115.7, 110.8, 86.7,
78.7, 77.6, 61.3, 30.0, 27.4, 26.6, 8.6; FTIR (film from CH2Cl2 on NaCl) 3442,
3352 (broad), 2990, 2937, 1454, 1367, 1245, 1191, 1120, 1070, 1031, 980, 910,
867, 838, 791 cm−1; ESI-HRMS: calcd 219.1232; found 219.1240 [M+H]+.
2,3-O-Isopropylidene(2R,3S,4S,5S)-2-(4-benzyloxybutyl)-
5-(azidomethyl)-tetrahydrofuran-2,3,4-triol (7a)
To 6a (230 mg, 0.7 mmol) in anhyd CH2Cl2 (25 mL) under N2 was added
anhyd pyr. (127 µL, 1.6 mmol). The reaction was stirred at 0◦C and SOCl2 (57
µL, 0.8 mmol) in anhyd CH2Cl2 (12.5 mL) was added dropwise. The reaction
was then stirred at 0◦C for 2 h. The reaction was then washed with water (3
× 20 mL), dried (MgSO4), and filtered and the excess solvent was removed
under diminished pressure keeping the temperature of the water bath below
30◦C. The residue was dissolved in anhyd DMF (25 mL) and NaN3 (128 mg, 2.0
mmol) was added and the mixture stirred at 110◦C for 15 h. Water (25 mL) was
added and the mixture was extracted with Et2O (3 × 20 mL). The combined
organic layers were then washed with water (3 × 20 mL), dried (MgSO4), and
filtered. The excess solvent was removed under diminished pressure and chro-
matography of the residue (EtOAc-cyclohexane, 1:4) gave the title compound
(185 mg, 75%); Rf 0.51 (EtOAc-cyclohexane, 1:1); [α]D +13.2 (c 1.0, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 7.33–7.25 (m, 5H), 4.50 (s, 2H), 4.31 (dd, 1H, J =
5.7, 8.1 Hz), 4.23 (s, 1H), 4.18 (br s, 1H), 3.60 (dd, 1H, J = 6.3, 12.7 Hz), 3.52
(dd, 1H, J = 4.6, 12.7 Hz), 3.48 (t, 2H, J = 5.8 Hz), 2.43 (d, 1H, J = 4.4 Hz), 1.91
(m, 2H), 1.65 (overlapping signals, 4H), 1.48, 1.32 (each s, each 3H); 13C NMR
(100 MHz, CDCl3): δ 138.4, 128.3, 127.6, 127.5, 115.2, 111.0, 87.0, 78.4, 75.9,
72.9, 70.1, 49.3, 37.7, 29.7, 27.4, 26.6, 20.7; FTIR (film from CH2Cl2 on NaCl):
3440 (broad), 2987, 2934, 2867, 2102, 1454, 1372, 1260, 1216, 1176, 1078, 989,
910, 801, 738, 698 cm−1; ESI-HRMS: calcd 378.2029; found 378.2028 [M+H]+.

Synthesis of 1-Deoxynojirimycin Derivatives
635
2,3-O-Isopropylidene(2R,3S,4S,5S)-2-(2-methoxyethyl)-
5-(azidomethyl)-tetrahydrofuran-2,3,4-triol (7b)
The azidation of 6b (290 mg, 1.2 mmol) as described for 6a gave the title
compound (265 mg, 83%); Rf 0.46 (EtOAc-cyclohexane, 1:1); [α]D –6.4 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): δ 4.44 (s, 1H), 4.26 (dt, 1H, J = 2.6, 6.6
Hz), 4.19 (d, 1H, J = 9.1), 4.02 (dd, 1H, J = 2.6, 9.0 Hz), 3.81 (dt, 1H, J =
6.9, 9.9 Hz), 3.55 (dd, 1H, J = 5.8, 12.6 Hz), 3.51 (dd, 1H, J = 5.8, 12.6 Hz),
3.44 (dt, 1H, J = 4.4, 9.9 Hz), 3.33 (s, 3H), 2.25 (dd, 2H, J = 4.4, 6.5 Hz), 1.46,
1.30 (each s, each 3H); 13C NMR (100 MHz, CDCl3): δ 113.3, 110.1, 87.1, 79.8,
76.0, 69.1, 58.3, 49.4, 36.9, 26.9, 26.2; FTIR (film from CH2Cl2 on NaCl): 3338
(broad), 2987, 2935, 2899, 2103, 1455, 1383, 1260, 1209, 1182, 1097, 1024, 871,
803 cm−1; ESI-HRMS: calcd 274.1403; found 274.1416 [M+H]+.
2,3-O-Isopropylidene(2R,3S,4S,5S)-2-octyl-5-
(azidomethyl)-tetrahydrofuran-2,3,4-triol (7c)
The azidation of 6c (80 mg, 0.3 mmol) as described for 6a gave the title
compound (73 mg, 85%); Rf 0.6 (EtOAc-cyclohexane, 1:1); [α]D +14.0 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): 4.32 (ddd, 1H, J = 2.9, 5.3, 6.2 Hz), 4.25
(s, 1H), 4.20 (dd, 1H, J = 2.8, 4.6 Hz), 3.64 (dd, 1H, J = 6.3, 12.7 Hz), 3.52 (dd,
1H, J = 5.2, 12.7 Hz), 2.42 (d, 1H, J = 4.8 Hz), 1.90 (dd, 1H, J = 3.4, 6.4 Hz),
1.86 (dd, 1H, J = 2.6, 6.5 Hz), 1.20–1.56 (overlapping signals, 12H), 1.47, 1.32
(each s, each 3H), 0.86 (t, 3H, J = 6.5 Hz); 13C NMR (100 MHz, CDCl3): δ 115.4,
111.0, 87.0, 78.3, 76.0, 49.4, 38.0, 31.8, 29.7, 29.4, 29.1, 27.4, 26.6, 23.8, 22.6,
14.0; FTIR (film from CH2Cl2 on NaCl): 3403 (broad), 2946, 2920, 2847, 2106,
1465, 1387, 1337, 1283, 1261, 1224, 1171, 1078, 1003, 933, 857, 800, 741 cm−1
;
ESI-HRMS: calcd 328.2236; found 328.2236 M+H]+.
2,3-O-Isopropylidene(2R,3S,4S,5S)-2-ethyl-5-
(azidomethyl)-tetrahydrofuran-2,3,4-triol (7d)
The azidation of 6d (205 mg, 0.9 mmol) as described for 6a gave the title
compound (210 mg, 92%); Rf 0.52 (EtOAc-cyclohexane, 1:1); [α]D +22.6 (c 1.0,
1
CHCl3); H NMR (500 MHz, CDCl3): δ 4.33 (ddd, 1H, J = 3.0, 5.3, 6.2 Hz),
4.24 (s, 1H), 4.20 (dd, 1H, J = 3.0, 4.7 Hz), 3.63 (dd, 1H, J = 6.3, 12.8 Hz),
3.53 (dd, 1H, J = 5.2, 12.8), 2.41 (d, 1H, J = 4.9 Hz), 1.93 (dq, 2H, J 1.8, 7.4
Hz), 1.48, 1.32 (each s, each 3H), 1.06 (t, 3H, J = 7.4 Hz); 13C NMR (125 MHz,
CDCl3): δ 115.7, 111.0, 86.6, 78.3, 76.0, 49.4, 30.7, 27.4, 26.6, 8.4; FTIR (film
from CH2Cl2 on NaCl): 3391 (broad), 2985, 2939, 2887, 2222, 2101, 1454, 1376,
1276, 1173, 1117, 1071, 1032, 1001, 953, 928, 860, 830, 742 cm−1; ESI-HRMS:
calcd 242.1141; found 242.1133 [M+H]−.

C. O’Brien and P. V. Murphy
636
9-Azido-1-O-benzyl-2,3,4,9-tetradeoxy-α-L-xylo-non-5-ulose (8a)
Acetonide 7a (180 mg, 0.5 mmol) was dissolved in MeCN-water (1:4, 20 mL)
and DOWEX (50 × 8 × 100) (1.8 g) was added. The reaction was then stirred
at 110◦C for 3 h. The DOWEX was removed by filtration and washed with
water and CH3CN. The combined CH3CN-water layers were concentrated un-
der diminished pressure and the residue purified by column chromatography
(EtOAc-cyclohexane, 1:1) to give 8a (142 mg, 89%); Rf 0.23 (EtOAc-cyclohexane
1:1); [α]D +24.6 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.28–7.18 (m, 5H),
4.40 (s, 2H), 4.11 (s, 1H), 4.07 (s, 1H), 3.91 (overlapping signals, 2H), 3.51 (s,
1H), 3.41 (t, 2H, J = 6.3 Hz), 3.36 (dd, 1H, J = 6.1, 12.7 Hz), 3.31 (dd, 1H, J =
5.1, 12.7 Hz), 3.00 (s, 1H), 2.58 (dt, 1H, J = 7.2, 17.4 Hz), 2.46 (dt, 1H, J = 7.2,
17.4 Hz), 1.72–1.48 (overlapping signals, 4H); 13C NMR (125 MHz, CDCl3): δ
208.3, 138.2, 128.3, 127.6, 127.5, 79.0, 72.9, 71.8, 70.4, 69.9, 52.9, 37.4, 28.8,
20.3; FTIR (film from CH2Cl2 on NaCl): 3415 (broad), 2929, 2865, 2103, 1716,
1454, 1364, 1264, 1207, 1100, 937, 912, 804, 739, 699 cm−1; ESI-HRMS: calcd
336.1559; found 336.1571 [M+H]−.
7-Azido-2,7-dideoxy-1-O-methyl-α-L-xylo-hept-3-ulose (8b) and 9
Hydrolysis of the acetonide 7b (255 mg, 0.9 mmol) as described for 7a
gave an interconverting mixture of 8b and 9 (69 mg, 32%); Rf 0.1 (EtOAc-
1
cyclohexane, 1:1); NMR data for 8b; H NMR (500 MHz, CDCl3): δ 4.33 (m,
1H), 4.27 (s, 1H), 4.01 (dd, 1H, J = 5.3 Hz, J = 9.5 Hz), 3.70 (ddd, 2H, J = 2.3
Hz, J = 5.4 Hz, J = 6.5 Hz), 3.45 (d, 2H, J = 5.3 Hz), 3.32 (s, 3H), 2.87 (ddd,
1H, J = 5.3 Hz, J = 6.3 Hz, J = 16.3 Hz), 2.76 (ddd, 1H, J = 5.3 Hz, J = 6.3
Hz, J = 16.3 Hz); 13C NMR (125 MHz, CDCl3): δ 208.3, 79.3, 76.5, 71.6, 67.5,
58.8, 52.9, 38.3; selected NMR data for 9: 13C NMR (125 MHz, CDCl3): δ 108.2,
80.4, 76.6, 70.5, 68.9, 58.9, 51.1, 36.7; FTIR (film from CH2Cl2 on NaCl): 3396
(broad), 2931, 2837, 2104, 1720, 1643, 1457, 1391, 1276, 1197, 1108, 970, 821
cm−1; ESI-HRMS: calcd 232.0933; found 232.0928 [M+H]−.
13-Azido-1,2,3,4,5,6,7,8,13-nondeoxy-α-L-xylo-tridec-9-ulose
(8c)
Hydrolysis of the acetonide 7c (70 mg, 0.2 mmol) as described for 7a gave
the title compound (18 mg, 30%); Rf 0.27 (EtOAc-cyclohexane, 1:1); [α]D +39.0
1
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3): 4.25 (s, 1H), 4.14 (s, 1H), 4.07 (dt,
1H, J = 2.5, 5.8 Hz), 4.03 (s, 1H), 3.50 (dd, 1H, J = 6.1, 12.6 Hz), 3.43 (dd, 1H,
J = 5.6, 12.6 Hz), 2.76 (s, 1H), 2.63 (dt, 1H, J = 7.4, 16.0 Hz), 2.51 (td, 1H, J =
7.4, 16.0 Hz), 1.75–1.20 (overlapping signals, 12H), 0.87 (t, 3H, J = 6.5 Hz); 13
C
NMR (100 MHz, CDCl3): δ 208.6, 79.4, 72.0, 70.0, 52.8, 37.8, 31.7, 29.2, 29.1,
29.0, 23.3, 22.6, 14.0; FTIR (film from CH2Cl2 on NaCl): 3416 (broad), 2956,

Synthesis of 1-Deoxynojirimycin Derivatives
637
2925, 2855, 2104, 1716, 1462, 1377, 1262, 1124, 1084, 910, 802, 724 cm−1; ESI-
HRMS: calcd 286.1767; found 286.1778 M+H]−.
7-Azido-1,2,7-trideoxy-α-L-xylo-hept-3-ulose (8d)
Hydrolysis of the acetonide of 7d (190 mg, 0.8 mmol) as described for 7a
gave the title compound (128 mg, 81%); Rf 0.15 (EtOAc-cyclohexane, 1:1); [α]D
+43.4 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3): δ 4.27 (br s, 1H), 4.12 (d, 1H,
J = 2.0 Hz), 4.01–4.07 (overlapping signals, 2H), 3.65 (s, 1H), 3.49 (dd, 1H, J =
6.1, 12.7 Hz), 3.45 (dd, 1H, J = 5.4, 12.7 Hz), 2.80 (d, 1H, J = 9.5 Hz), 2.69
(dq, 1H, J = 7.3, 17.9 Hz), 2.53 (dq, 1H, J = 7.3, 17.9 Hz), 1.16 (t, 3H, J = 7.3
Hz); 13C NMR (125 MHz, CDCl3): δ 209.4, 79.2, 72.0, 70.2, 52.9, 31.1, 7.3; FTIR
(film from CH2Cl2 on NaCl): 3401 (broad), 2940, 2927, 2360. 2105, 1716, 1646,
1458, 1406, 1352, 1261, 1107, 1032, 981, 799 cm−1; ESI-HRMS: calcd 202.0828;
found 202.0825 [M+H]−.
(2R,3R,4R,5S)-2-(4-Hydroxybutyl)piperidine-3,4,5-triol (2a)
To 8a (52 mg, 0.2 mmol) in anhyd MeOH (3 mL) was added 20% Pd(OH2)-C
(20 mg). The reaction was degassed and then stirred for 15 h under H2 (1 atm)
at rt. The reaction was then filtered and the excess solvent was removed to give
the benzylated piperidine intermediate 10. This intermediate was dissolved in
1.2 M methanolic HCl (3 mL) and 20% Pd(OH2)-C (20 mg) was again added.
The reaction mixture was stirred under H2 (1 atm) at rt for 1 h and filtered and
the solvent was removed under diminished pressure. The residual hydrochlo-
ride salt was purified on a DOWEX (50 × 8 × 100) column to give 2a as the
1
amine (30 mg, 95%); Rf 0.16 (CH2Cl2-MeOH, 4:1); [α]D +15.6 (c 1.0, H2O); H
NMR (600 MHz, D2O): δ 3.53 (t, 2H, J = 6.5 Hz), 3.40 (ddd, 1H, J = 5.2, 9.3,
10.8 Hz), 3.19 (t, 1H, J = 9.2 Hz), 2.99 (t, 1H, J = 9.1 Hz), 2.98 (dd, 1H, J = 4.3,
13.0 Hz), 2.33 (overlapping signals, 2H), 1.73 (ddd, 1H, J = 4.0, 8.0, 10.7 Hz),
1.53–1.36 (overlapping signals, 3H), 1.25 (overlapping signals, 2H); 13C NMR
(150 MHz, D2O): δ 78.5, 75.0, 71.1, 61.1, 59.3, 49.1, 31.6, 30.9, 21.3; FTIR (film
from water on Ge): 3324 (broad), 2927, 2864, 1458, 1368, 1072, 999, 843, 748,
646, 563, 525 cm−1; ESI-HRMS: calcd 206.1395; found 206.1392 [M+H]+.
(2R,3R,4R,5S)-2-(2-methoxyethyl)piperidine-3,4,5-triol (2b)
To the mixture of 8b and 9 (45 mg, 0.2 mmol) in anhyd MeOH (3 mL)
was added 20% Pd(OH2)-C (25 mg). The reaction was degassed (× 3) and then
stirred for 15 h under H2 (1 atm) at rt. The reaction was then filtered and
the excess solvent was removed to give a residue, which was stirred in 1.2M
methanolic HCl at rt for 1 h. The excess solvent was removed under diminished
pressure and the residual hydrochloride salt was purified on a DOWEX (50 ×
8 × 100) column to yield the title compound as the free amine (34 mg, 92%);

C. O’Brien and P. V. Murphy
638
1
Rf 0.15 (CH2Cl2-MeOH, 4:1); [α]D +31.2 (c 1.0, CH3OH); H NMR (500 MHz,
CD3OD): δ 3.61 (ddd, 1H, J = 5.7, 6.6 and 9.6 Hz), 3.55 (ddd, 1H, J = 5.8, 6.7
and 9.6 Hz), 3.44 (ddd, 1H, J = 5.2, 9.1, 10.6 Hz), 3.34 (s, 3H), 3.19 (t, 1H,
J = 9.0 Hz), 3.07 (dd, 1H, J = 5.1, 12.0 Hz), 3.03 (t, 1H, J = 9.2 Hz), 2.50
(ddd, 1H, J = 3.0, 8.8, 9.6 Hz), 2.45 (dd, 1H, J = 10.9, 11.9 Hz), 2.16 (m, 1H),
1.59 (m, 1H); 13C NMR (125MHz, CD3OD): δ 80.6, 76.4, 72.5, 72.0, 60.6, 58.9,
51.3, 32.7; FTIR (film from MeOH solution on Ge): 3375, 3330, 2918, 2895,
2834, 1457, 1100, 646, 561, 525, 423 cm−1; ESI-HRMS: calcd 190.1079; found
190.1083 [M+H]−.
(2R,3R,4R,5S)-2-Octylpiperidine-3,4,5-triol (2c)
To 8c (16 mg, 0.1 mmol) in anhyd MeOH (3 mL) was added 20% Pd(OH2)-C
(20 mg). The reaction was degassed (× 3) and then stirred for 15 h under H2
(1 atm) at rt. The reaction was then filtered and the excess solvent removed
to give a residue, which was stirred in 1.2 M methanolic HCl at rt for 1 h..
The excess solvent was removed under diminished pressure and the residual
hydrochloride salt was purified on a DOWEX (50 × 8 × 100) column to yield
2c as the free amine (13 mg, 95%); Rf 0.41 (CH2Cl2-MeOH, 4:1); [α]D +12.5 (c
1
1.0, CH3OH); H NMR (500 MHz, CD3OD): 3.40 (ddd, 1H, J = 5.1, 9.1, 10.7
Hz), 3.14 (t, 1H, J = 9.0 Hz), 3.05 (dd, 1H, J = 5.1, 12.1 Hz), 2.97 (t, 1H, J
= 9.2 Hz), 2.39 (dd, 1H, J = 10.9, 12.0 Hz), 2.33 (ddd, 1H, J = 3.1, 7.7, 9.2
Hz), 1.85–1.30 (overlapping signals, 14H), 0.89 (t, 3H, J = 6.9 Hz); 13C NMR
(125 MHz, CD3OD): δ 79.4, 75.4, 71.3, 60.4, 50.1, 31.8, 31.7, 29.8, 29.4, 29.2,
25.5, 22.5, 13.2; FTIR (film from MeOH solution on Ge): 3280, 2922, 2852,
1467, 1099, 1075, 1040, 1006, 889, 838, 753, 722, 645, 561, 527, 422 cm−1; ESI-
HRMS: calcd 244.1913; found 244.1918 M+H]−.
(2R,3R,4R,5S)-2-Ethylpiperidine-3,4,5-triol (2d)
To 8d (58 mg, 0.3 mmol) in anhyd MeOH (3 mL) was added 20% Pd(OH2)-
C (40 mg). The reaction was degassed (× 3) and then stirred for 15 h under
H2 (1 atm) at rt. The reaction was then filtered and the excess solvent was
removed to give a residue, which was stirred in 1.2M methanolic HCl at rt
for 1 h. The excess solvent was removed under diminished pressure and the
residual hydrochloride salt was purified on a DOWEX (50 × 8 × 100) column
to yield the title compound as the free amine (31 mg, 69%); Rf 0.15 (CH2Cl2-
1
MeOH, 4:1); [α]D +28.6 (c 1.0, CH3OH); H NMR (500 MHz, CD3OD): δ 3.44
(ddd, 1H, J = 5.2, 9.2, 10.6 Hz), 3.18 (t, 1H, J = 8.9 Hz), 3.09 (dd, 1H, J = 5.2,
12.1 Hz), 3.02 (t, 1H, J = 9.2 Hz), 2.44 (dd, 1H, J = 10.5, 12.2 Hz), 2.30 (dt,
1H, J = 2.9, 9.4 Hz), 1.93 (ddq, 1H, J = 3.0, 7.6, 15.3 Hz), 1.36 (dt, 1H, J =
7.6, 14.8 Hz), 1.00 (t, 3H, J = 5.5 Hz); 13C NMR (125 MHz, CD3OD): δ 80.7,
76.3, 72.7, 62.9, 51.5, 25.5, 10.3; FTIR (film from MeOH solution on Ge): 3397

Synthesis of 1-Deoxynojirimycin Derivatives
639
(broad), 2965, 2918, 2879, 1653, 1458, 1100, 1077, 1031, 989, 907, 874, 761,
648 cm−1; ESI-HRMS: calcd 160.0974; found 160.0973 [M+H]−.
ACKNOWLEDGEMENT
The authors thank Science Foundation Ireland (03/IBN/B352) and the Higher
Education Authority’s Programme for Research in Third Level Institutions for
funding. This work was presented (in part) at the European Young Investiga-
tors Workshop on “Carbohydrate Chemistry: From Synthesis to Applications”
in Lyon, April 11–15, 2011.
REFERENCES
1. Asano, N.; Nash R.J.; Molyneaux, R.J.; Fleet, G.W.J. Sugar-mimic glycosidase in-
hibitors: natural occurrence, biological activity and prospects for therapeutic applica-
tion. Tetrahedron Asymm. 2000, 11, 1645–1680.
2. Kingma, P.J.; Menheere, P.P.; Sels, J.A.; Nieuwenhuijzen Kruseman, A.C. α-
Glucosidase inhibition by miglitol in NIDDM patients. Diabetes Care 1992, 15, 478–483.
3. (a) Hughes, A.B.; Rudge, A.J. Deoxynojirimycin: synthesis and biological activity.
Nat. Prod. Rep. 1994, 135; (b) Winchester, B.; Fleet, G.W.J. Amino-sugar glycosidase
inhibitors: versatile tools for glycobiologists. Glycobiology 1992, 2, 199; (c) Alonzi, D.S.;
Butters, T.D. Therapeutic targets for inhibitors of glycosylation. Chimia, 2011, 65,
35–39; (d) Winchester, B.G. Iminosugars: From Botanical Curiosities to Licensed Drugs.
Tetrahedron Asymm. 2009, 20, 645–651.
4. (a) Gouin, S.; Murphy, P.V. Synthesis of Somatostatin Mimetics Based on the 1-
Deoxymannojirimycin Scaffold. J. Org. Chem. 2005, 70, 8527–8532; (b) Le Merrer,
Y.; Poitout, L.; Depezay, J.C.; Dosbaa, I.; Geoffroy, S.; Foglietti, M.J. Polyhydroxylated
piperidines and azepanes from D-mannitol synthesis of 1-deoxynojirimycin and ana-
logues. Bioorg. Med. Chem. 1997, 5, 519–533; (c) Chagnault, V.; Lalot, J.; Murphy, P.V.
Synthesis of Somatostatin Mimetics Based on 1-Deoxynojirimycin. ChemMedChem,
2008, 3, 1071–1076.
5. For selected reviews on the synthesis of iminosugars and other polyhydroxylated
nitrogen-containing heterocycles see (a) Tatsuta, K. Design and synthesis of glycosidase
inhibitors. In Carbohydrate mimics; Chapleur, Y. Ed.; Wiley-VCH; Weinheim, 1998;
283–305; (b) Fechter, M.H.; Stu¨tz, A.E.; Tauss, A. Chemical and Chemo-Enzymatic Ap-
proaches to Unnatural Ketoses and Glycosidase Inhibitors with Basic Nitrogen in the
Sugar Ring. Curr. Org. Chem. 1999, 3, 269–285; (c) Afarinkia, K.; Bahar, A. Recent ad-
vances in the chemistry of azapyranose sugars. Tetrahedron Asymm. 2005 16, 1239;
(d) Stocker, B.L.; Dangerfield, E.M.; Win-Mason, A.L.; Haslett, G.W.; Timmer, M.S.M.
Recent Developments in the Synthesis of Pyrrolidine-Containing Iminosugars. Eur. J.
Org. Chem. 2010, 1615–1637; (e) Nishimura, Y. Gem-Diamine 1-N-Iminosugars as Ver-
satile Glycomimetics: Synthesis, Biological Activity and Therapeutic Potential. J. An-
tibiotics 2009, 62, 407–423; (f) Compain, P.; Chagnault, V.; Martin, O.R. Tactics and
strategies for the synthesis of iminosugar C-glycosides: a review. Tetrahedron Asymm.
2009, 20, 672–711; (g) Davis, B.G. A silver-lined anniversary of Fleet iminosugars:
1984–2009, from DIM to DRAM to LABNAc. Tetrahedron Asymm. 2009, 20, 652–671;
(h) Wrodnigg, T.M.; Steiner, A.J.; Ueberbacher, B.J. Natural and synthetic iminosugars
as carbohydrate processing enzyme inhibitors for cancer therapy. Anti-Cancer Agents

C. O’Brien and P. V. Murphy
640
Med. Chem. 2008, 8, 77–85; (i) Murphy, P.V. Peptidomimetics, Glycomimetics and Scaf-
folds from Carbohydrate Building Blocks. Eur. J. Org. Chem. 2007, 4177–4187.
6. For previous syntheses of 1-deoxynojirimycin from L-sorbose see: (a) Tian, L.-
L.; Li, Z-J.; Li, H. Synthesis of deoxynojirimycin. Yingyong Huaxue 2004, 21, 12–15;
(b) Behling, J.; Farid, P.; Medich, J.R.; Scaros, M.G.; Prunier, M.; Weier, R.M.; Khanna,
I. A Short and Practical Synthesis of 1-Deoxynojirimycin. Synth. Commun. 1991, 21,
1383–1386; (c) Beaupere, D.; Stasik, B.; Uzan, R.; Demailly, G. Selective azidation of
L-sorbose. Application to the rapid synthesis of 1-deoxynojirimycin. Carbohydr. Res.
1989, 191, 163–166; (d) Danieli, E.; Lalot, J.; Murphy, P.V. Selective protecting group
manipulations on the 1-deoxynojirimycin scaffold. Tetrahedron 2007, 63, 6827–6834.
7. Izquierdo, I.; Plaza, M.-T.; Kari, N. Synthesis of optically active chalcogran from
L-sorbose. Carbohydr. Res. 1994, 261, 231–242.
8. Zhao, Y.; Zhou, Y.; O’ Boyle K.M.; Murphy, P.V. Hybrids of 1-deoxynojirimycin and
aryl-1,2,3-triazoles and biological studies related to angiogenesis. Bioorg. Med. Chem.
2008, 16, 6333–6337.
9. Kartha, K.P.R. Iodine, a novel catalyst in cabohydrate reactions. Part I. O-
isopropylidenation of carbohydrates. Tetrahedron Lett. 1986, 27, 3415–3416.