Unusual ring contraction by substitution of 4-O-activated-pentono-1,5-lactams with cyanide. Stereospecific synthesis of 6-amino-1,4,5,6-tetradeoxy-1,4-imino-hexitols

Article abstract of DOI:10.1016/S0957-4166(99)00536-4

Reaction of 4-O-sulfonylated 2,3-O-isopropylidene-D-ribo- or -D-lyxo-1,5-lactams with tetrabutylammonium cyanide gave 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxo-5 or -L-ribo-15-1,4-lactams, respectively. A stereospecific ring contraction with inversion at C-4 had taken place in each case. Reduction of the cyano-lactams with LiAlH₄ gave 6-amino-1,4,5,6-tetradeoxy-1,4-imino-L-lyxo-6 or -L-ribo-16-hexitol, respectively. The 6-amino-1,4,5,6-tetradeoxy-1,4-imino-L-ribo-hexitol 16 was found to be a moderate inhibitor of α-L-fucosidase with a K(i) of 110 μM. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(99)00536-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 567–579
Unusual ring contraction by substitution of 4-O-activated-
pentono-1,5-lactams with cyanide. Stereospecific synthesis of
6-amino-1,4,5,6- tetradeoxy-1,4-imino-hexitols
Michael Godskesen,a Inge Lundt a,∗ and Inger Søtofte b
aDepartment of Organic Chemistry, Technical University of Denmark, Building 201, DK-2800 Lyngby, Denmark
bDepartment of Chemistry, Technical University of Denmark, Building 207, DK-2800 Lyngby, Denmark
Received 31 October 1999; accepted 23 November 1999
Abstract
Reaction of 4-O-sulfonylated 2,3-O-isopropylidene-D-ribo- or -D-lyxo-1,5-lactams with tetrabutylammonium
cyanide gave 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxo-5 or -L-ribo-15-1,4-lactams, respec-
tively. A stereospecific ring contraction with inversion at C-4 had taken place in each case. Reduction of the cyano-
lactams with LiAlH4 gave 6-amino-1,4,5,6-tetradeoxy-1,4-imino-L-lyxo-6 or -L-ribo-16-hexitol, respectively. The
6-amino-1,4,5,6-tetradeoxy-1,4-imino-L-ribo-hexitol 16 was found to be a moderate inhibitor of α-L-fucosidase
with a Ki of 110 µM. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The success of iminosugars as glycosidase inhibitors has stimulated the interest in design and
development of synthetic procedures by which new sugar analogues with nitrogen in the ring instead of
oxygen can be obtained.1 We became interested in studying the branching of an iminosugar at the 2- or
3-position to the nitrogen, partly because new carbon frameworks might thus be available, partly because
introduction of a one-carbon unit would provide a simple method for carbon labelling in a glycosidase
inhibitor. Having access to specific labelled glycosidase inhibitors is of importance, since in the process
of selecting an inhibitor as a drug candidate, a metabolic study is necessary. The isotope of choice is
dependent on the methods used in the study. Labelling of a compound with a carbon isotope (14C or
13C) from the available labelled precursor potassium cyanide requires a procedure whereby the one-
carbon unit is introduced late in the synthesis. We have previously developed a method to introduce the
branching at the 2-position with respect to the nitrogen, by addition of trimethylsilyl cyanide (TMSCN)
∗
Corresponding author. Tel: +45 4525 2133; fax: +45 4593 3968; e-mail: okil@pop.dtu.dk
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00536-4
tetasy 3171

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M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
to (3R,4R)-dibenzoyloxy-1-pyrroline.2 By this procedure 14C-5 1,4-dideoxy-1,4-imino-D-arabinitol was
prepared using 14C labelled TMSCN. The TMS14CN was prepared in situ from K14CN.2
In this paper we present results related to the branching at the 3-position with respect to the nitrogen.
2. Results and discussion
A suitable precursor for the study was 5-amino-5-deoxy-2,3-O-isopropylidene-D-ribono-1,5-lactam 1
which is easily available from D-ribonolactone.3 Activation of the OH-4 group, followed by substitution
with cyanide and reduction of the lactam function, should result in a 3-cyano piperidine derivative. Thus,
the free hydroxy group was activated by mesylation, tosylation or triflation to give the O-sulfonylated
lactams 2, 3 or 4, respectively (Scheme 1), ready for nucleophilic substitution by a carbon nucleophile.
To our surprise, however, reaction of each of the three lactams with tetrabutylammonium cyanide in DMF
afforded in all cases the 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxono-1,4-lactam 5
as a crystalline compound. The reaction proceeded in 65% yield when the mesylate 2 was used as the
starting material, while the tosylate 3 only yielded 36% of 5. Nevertheless, since the tosylated lactam 3
was more easily prepared (87%) this was chosen as the substrate for the practical preparation of 5.
Scheme 1. (a) MsCl, pyridine, 0°C, 1 h (50% 2). (b) TsCl, pyridine, 0°C, 1 h (87% 3). (c) Tf2O, pyridine, 0°C, 1 h (80% 4).
(d) Bu4NCN, DMF, 100°C, 8 h (65% from 2, 36% from 3). (e) LiAlH4, THF, 60°C, 4 h. (f) TsOH, H2O, 50°C, 20 h. (g) NaN3,
DMF, rt, 3 h (from 4). (h) LiAlH4, THF, rt, 22 h. (i) TsOH, MeOH, 50°C, 10 h
The structure of 5 was deduced from 1H and 13C NMR spectra. Thus, the 13C NMR spectrum showed
the acetal carbon at 116.9 ppm compared to 109.7 ppm in 3, indicating that the five-membered acetal is
now fused to a five-membered ring.4 This furthermore results in a downfield shift of C-2 to 80.2 ppm and
C-3 to 78.5 ppm, both from ca. 73 ppm in the six-membered starting material 3. The chemical shift of
C-4, 53.7 ppm, suggested that the substituent was a nitrogen function, and the chemical shift of C-5, 20.8
ppm, indicated that the cyano group had been introduced at this carbon. The structure of 5 was confirmed
by X-ray crystallography which furthermore shows that the ring contraction had occurred with inversion
of configuration at C-4 (Fig. 1).
Having access to this interesting functionalised five-membered lactam 5 we investigated if the cyano
function could be selectively reduced to an amine. However, hydrogenation in the presence of Pd
on carbon was not successful, either under neutral or under acidic conditions. Besides the 6-amino-
substituted 1,4-lactam, approximately 10% of, presumably, the corresponding seven-membered lactam

M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
569
Fig. 1. View of 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxono-1,4-lactam 5. Thermal ellipsoids are drawn at
the 50% probability level
was formed. Instead, compound 5 was treated with lithium aluminium hydride whereby both the
cyano group as well as the lactam function were reduced. The resulting 6-amino-1,4,5,6-tetradeoxy-
2,3-O-isopropylidene-1,4-imino-L-lyxo-hexitol was deprotected using 2.05 equivalents of p-TsOH in
methanol, and the crystalline 6-amino-1,4,5,6-tetradeoxy-1,4-imino-L-lyxo-hexitol, ditosylate 6 was
isolated (Scheme 1).
The unexpected ring contraction led us to investigate the substitution of the OH-4 activated pentonolac-
tams with another nucleophile. When the triflate 4 was treated with sodium azide or tetrabutylammonium
azide5 in DMF, the isolated product was the expected 4-azido-1,5-lactam 7 (Scheme 1). The structure of
7 was confirmed by reduction of both the azide- and the lactam-functionality using lithium aluminium
hydride. Deprotection by treatment with a slight excess of p-toluene sulfonic acid gave crystalline 4-
amino-1,4,5-trideoxy-1,5-imino-L-lyxitol ditosylate 8, having NMR spectra and the numerical value of
the specific rotation identical to those of the enantiomeric compound.6
In order to test whether this ring contraction was specific for a five-membered lactam with ribo con-
figuration the lactam having lyxo configuration was synthesised. Thus, potassium D-lyxonate 97 was lac-
tonised by treatment with conc. aq. HCl–methanol (ca. 1:9). After concentration the residue was treated
with dimethoxypropane, acetone and methanesulfonic acid to give methyl 2,3:4,5-di-O-isopropylidene-
D-lyxonate 10. Selective cleavage of the 4,5-O-isopropylidene group with acetic acid:water (9:1) gave
the 2,3-O-isopropylidene-D-lyxono-1,4-lactone 11. Previous attempts to prepare this compound by
treatment of D-lyxono-1,4-lactone with acetone under acidic conditions, gave a mixture of 11 and the
3,5-O-isopropylidene-1,4-lactone.8 Mesylation of the OH-5 gave 12, which by reaction with aqueous
ammonia yielded the lactam 13, according to our procedure for the L-enantiomer.3 Tosylation of the
OH-4 of lactam 13 proved unsastifactory and thus the mesylate 14 was synthesised. Reaction of 14 with
tetrabutylammonium cyanide in DMF gave a 5-C-cyano-substituted 1,4-lactam, 15, as indicated by 13
C

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M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
NMR spectra. Thus, also in this case a ring contraction had occurred as discussed above for substitution
reactions of the lactams 2–4 with ribo configuration. The structure of lactam 15 was established by X-ray
crystallography, showing an inversion at C-4 compared to the starting material (Fig. 2).
Fig. 2. View of 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-ribono-1,4-lactam 15. Thermal ellipsoids are drawn at
the 50% probability level
Reduction of 15 with lithium aluminium hydride gave the corresponding 6-amino-1,4,5,6-tetradeoxy-
2,3-O-isopropylidene-1,4-imino-L-ribo-hexitol, which could be deprotected by treatment with excess
p-TsOH to give 6-amino-1,4,5,6-tetradeoxy-1,4-imino-L-ribo-hexitol ditosylate 16 (Scheme 2).
Scheme 2. (a) Aq. HCl. (b) Dimethoxypropane, MsOH, rt, 20 h. (c) AcOH:H2O 90:10, 30°C, 16 h (45% from 9). (d) MsCl,
pyridine, 0°C 1 h (79%). (e) Aq. NH3, rt, 5.5 h (85%). (f) MsCl, pyridine, 0°C, 2 h (59%). (g) Bu4NCN, DMF, 100°C, 5 h
(62%). (h) LiAlH4, THF, rt, 18 h. (i) TsOH, MeOH, 50°C, 4 h (43% from 15)

M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
571
Attempts to substitute a leaving group at C-4 in aldonolactams, having either ribo or lyxo configuration,
with cyanide ion, resulted in products where the nucleophile was introduced at C-5 with simultaneous
ring contraction and inversion of the configuration at C-4. A most likely explanation would be formation
of an intermediate aziridine I by deprotonation of the NH group, followed by nucleophilic displacement
of the mesyl group at C-4 (Scheme 3). Subsequent opening by cyanide ions at the less hindered
primary position gave the 1,4-lactam. The reaction was very fast as the reaction of the triflate 4 with
tetrabutylammonium cyanide was completed in less that 5 min at room temperature. Attempts to follow
the substitution reaction of either the mesylated or tosylated lactam, 2 or 3, by 13C NMR spectroscopy
gave no results. This might be due to low concentration of the possible aziridine intermediate I.
If the mechanism proceeds via deprotonation of the nitrogen atom in the lactam function, the ring
contraction should be blocked if an N-alkylated lactam is used as the substrate. In order to validate this
hypothesis, synthesis of N-ethyl-5-amino-5-deoxy-2,3-O-isopropylidene-D-ribono-1,5-lactam 18 was
initiated. Treatment of the lactone 178 with aqueous ethylamine gave the lactam 18. The reaction is
analogous to the reaction of the mesylated lactone 11 with ammonia to give the lactam 13, as discussed
above. Conversion to the very reactive triflate 19 followed by reaction with tetrabutylammonium cyanide
led to two unsaturated lactams, probably compounds 20 and 21, in a ratio of 1:4 (Scheme 3). This result
supports the mechanism suggested, as the deprotonation of the nitrogen should be a prerequisite for the
ring contraction.
Scheme 3. (a) Bu4NCN, DMF, 100°C, 8 h. (b) 70% aq. EtNH2, rt, 6 days (100%). (c) Tf2O, pyridine, 0°C, 30 min. (d) Bu4NCN,
DMF, rt, 28 h
Ring contractions9 or enlargements10 have been observed in similar substitution reactions of cyclic
amines, where aziridine intermediates have been suggested as intermediates. Ring contractions in systems
involving the less basic amide nitrogen have, to our knowledge, not been reported so far. Recently,
however, a ring contraction of an N,N-dialkylated seven-membered cyclic urea, having two hydroxy
groups, was reported. During its reaction with the fluorinating reagent (diethylamino)sulfur trifluoride
(DAST) a ring contraction to a fluorinated six-membered piperidine derivative was observed.11 The
lactams investigated in the present study underwent ring contraction only, when treated with cyanide

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M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
and not with azide ions. The ring contraction must therefore be dependent on the basic and nucleophilic
character of the nucleophile.
In conclusion, we have prepared C-5 cyano substituted aldono-1,4-lactams by stereospecific ring con-
traction of C-4 activated aldono-1,5-lactams. These compounds, 5 and 15, are interesting chiral synthons
for further chemical transformations. In this work 6-amino-1,4,5,6-tetradeoxy-1,4-imino-hexitols with
L-lyxo- 6 and L-ribo-configuration 16 have been prepared.
The two amino-imines were tested as glycosidase inhibitors towards commercially available enzymes.6
While the L-lyxo-derivative, 6, did not show any activities the L-ribo-analogue, 16, was a moderate
inhibitor of α-L-fucosidase with a Ki of 110 µM.
3. Experimental
NMR spectra were recorded on a Bruker AC-250 or a Bruker AM-500 instrument. Chemical shifts
1
were measured in ppm and coupling constants (J) in hertz. For 13C spectra and H spectra recorded in
D2O, dioxane (δ=67.4) and acetone (δ=2.17) were used as internal references, respectively. In CDCl3
(δ=76.9), DMSO-d6 (δ=39.5), methanol-d4 (δ=49.0) and acetone-d6 (δ=29.8) the solvent signals were
1
used as internal reference for 13C spectra. For H spectra in CDCl3 (δ=7.26) and acetone-d6 (δ=2.05)
the solvent signals were used as internal reference unless otherwise stated. Assignments of signals
were obtained from COSY or CH correlated spectra, if necessary. Optical rotations were measured
on a Perkin–Elmer 241 polarimeter. Melting points are uncorrected. Evaporation was performed in
vacuo on a rotary evaporator below 40°C. Column chromatography was performed on silica gel 60,
Merck (mesh 230–400) using the flash technique. TLC was performed on aluminium sheets silica gel 60
F254. Microanalyses were performed by Leo Microanalytical Laboratory, University of Copenhagen and
Research Institute of Pharmacy and Biotechnology, Prague.
3.1. 5-Amino-5-deoxy-2,3-O-isopropylidene-4-O-methanesulfonyl-D-ribono-1,5-lactam 2
5-Amino-5-deoxy-2,3-O-isopropylidene-D-ribono-1,5-lactam 13 (9.51 g, 50.8 mmol) was dissolved
in pyridine (28.5 ml) and cooled to 0°C. Methanesulfonyl chloride (5.53 ml, 71.1 mmol) was added
during 40 min. The solution was stirred for another 30 min and then left at room temperature for 30
min. The reaction mixture was quenched with ice/H2O (100 g), concentrated to a syrup and extracted
with boiling acetone (3×100 ml). The acetone extracts were concentrated, redissolved in CH2Cl2,
filtered, and concentrated. The residue was purified by column (5×20 cm) chromatography eluting
with EtOAc→EtOAc:EtOH 9:1. This gave the title compound as a crystalline residue (5.35 g, 40%);
mp 166–167°C. Slightly impure fractions were concentrated to give an additional amount of 2 (1.40 g,
10%); mp 164–165.5°C. Recrystallisation from EtOAc furnished an analytical sample; mp 166–167°C;
20
[α] +35.8 (c 1.1, acetone); 1H NMR (CDCl3): δ 6.77 (bs, NH), 5.02 (ddd, H-4, J3,4=3.2 Hz, J4,5=8.3
D
0
0
0
Hz, J4,5 =3.9 Hz), 4.66 (ddd, H-3, J2,3=6.8 Hz, J3,5 =0.8 Hz), 4.54 (d, H-2), 3.76 (ddd, H-5, J5,5 =12.5
Hz, J5,NH=2.4 Hz), 3.45 (dddd, H-50, J5 ,NH=4.2 Hz), 3.12 (s, CH3SO2-), 1.53 (s, CH3) and 1.43 (s,
0
CH3); 13C NMR (CDCl3): δ 168.5 (C-1), 111.7 (acetal) 76.6, 76.6 (C-2, C-3), 71.5 (C-4), 40.5 (C-5),
38.8 (CH3SO2-), 26.3 (CH3) and 24.9 (CH3). Anal. calcd for C9H15NO6S (229.25): C, 40.75; H, 5.70;
N, 5.28. Found: C, 40.63; H, 5.70; N, 5.09.

M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
573
3.2. 5-Amino-5-deoxy-2,3-O-isopropylidene-4-O-p-toluenesulfonyl-D-ribono-1,5-lactam 3
The 2,3-O-isopropylidene-D-ribono-1,5-lactam 1 (7.07 g, 37.8 mmol) was dissolved in pyridine
(25 ml) and treated with p-toluenesulfonyl chloride (10.8 g, 56.7 mmol) as described above for the
mesylation. By addition of ice/H2O (100 g) a colourless crystalline precipitate was formed, filtered off
and washed with cold H2O. Drying in vacuo gave 3 (11.18 g, 87%); mp. 166–170 °C; [α]20 +35.7 (c 1.1,
D
20
D
acetone). Recrystallisation from MeOH furnished an analytical sample; mp 171.5–173°C; [α] +39.0
(c 1.0, acetone); 1H NMR (acetone-d6): δ 7.87 (d, 2H, Ph), 7.50 (d, 2H, Ph), 6.92 (bs, NH), 4.98 (ddd,
0
0
H-4, J3.4=3.0 Hz, J4,5=7.1 Hz, J4,5 =4.0 Hz), 4.55 (ddd, H-3, J2,3=6.8 Hz, J3,5 =1.1 Hz), 4.43 (d, H-2),
3.57 (ddd, H-5, J5,5 =12.1 Hz), 3.27 (ddd, H-5 ), 2.47 (s, Ph-CH3), 1.38 (s, CH3) and 1.29 (s, CH3); 13C
NMR (DMSO-d6): δ 166.9 (C-1), 145.2, 132.8, 130.2, 127.6 (aromatic), 109.7 (acetal), 73.5, 73.2, 72.9
(C-2, C-3 and C-4), 39.3 (C-5), 26.0 (CH3), 24.7 (CH3) and 21.1 (Ph-CH3). Anal. calcd for C15H19NO6S
(341.38): C, 52.78; H, 5.61; N, 4.10. Found: C, 52.82; H, 5.60; N, 4.17.
0
0
3.3. 5-Amino-5-deoxy-2,3-O-isopropylidene-4-O-trifluoromethanesulfonyl-D-ribono-1,5-lactam 4
The 2,3-O-isopropylidene-D-ribono-1,5-lactam 1 (0.866 g, 4.63 mmol) was dissolved in pyridine (2.5
ml) and cooled to 0°C. Trifluoromethanesulfonic anhydride (1.00 ml, 6.02 mmol) was added slowly in
a nitrogen atmosphere during 30 min. The mixture was stirred for an additional 30 min and left at room
temperature for 20 min. Addition of CH2Cl2 (10 ml) and ice/H2O (10 g), followed by washing of the
organic phase with 10% HCl (until acidic), water, aqueous NaHCO3, drying (Na2SO4) and filtration,
gave, after concentration, 4 as a pale yellow syrup (1.18 g, 80%). The syrup was pure according to a 13
C
NMR spectrum and was used directly for the synthesis of 7. 13C NMR (CDCl3): δ 168.8 (C-1), 117.3
(quartet, Tf), 111.4 (acetal) 78.4, 72.4, 72.3 (C-2, C-3, C-4), 40.2 (C-5), 25.3 (CH3) and 24.1 (CH3).
3.4. 4-Amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxono-1,4-lactam 5
From 3: The tosylated-D-ribono-1,5-lactam 3 (6.18 g, 18.1 mmol) was added to a solution of Bu4NCN
in DMF (1.12 M, 24.3 ml, 27.2 mmol) and the mixture was kept at 100°C for 8 h. The solution was
loaded on a column of mixed ion-exchange resin (Amberlite IR-120, H+, 71.4 ml and Amberlite IRA-
400, HCO3−, 123.4 ml) and eluted with H2O (400 ml). The eluate was concentrated, redissolved in
CH2Cl2 (15 ml), placed on a column of silica (4×15 cm) and eluted with EtOAc to give the lactam 5
20
(1.28 g, 36%); mp 162–163°C; [α] −14.1 (c 1.0, MeOH); 1H NMR (D2O): δ 4.93 (dd, H-3, J2,3=5.8
D
0
0
Hz, J3.4=4.9 Hz), 4.84 (d, H-2), 4.15 (ddd, H-4, J4,.5=6.9 Hz, J4,5 =5.0 Hz), 2.92 (dd, H-5, J5,5 =17.3
Hz), 2.88 (dd, H-50), 1.44 (s, CH3) and 1.38 (s, CH3); 13C NMR (D2O, acetone δ=33.01): δ 178.6 (C-1),
121.0 (CN), 116.9 (acetal), 80.5 (C-2), 78.5(C-3), 53.7 (C-4), 28.4 (CH3), 27.7 (CH3) and 20.8 (C-5).
Anal. calcd for C9H12N2O3 (196.21): C, 55.09; H, 6.16; N, 14.28. Found: C, 54.91; H, 6.12; N, 14.05.
From 2: The 4-O-mesylated-D-ribono-1,5-lactam 2 (2.87 g, 10.8 mmol) was added to a solution of
Bu4NCN in DMF (1.31 M, 11.5 ml, 15.1 mmol) and the mixture was kept at 100°C for 8 h. The solution
was poured on a column of mixed ion-exchange resin (Amberlite IR-120, H+, 40 ml and Amberlite IRA-
400, HCO3−, 70 ml) and eluted with H2O (400 ml). The eluate was concentrated, redissolved in boiling
EtOAc (15 ml), placed on a column of silica (4×15 cm) and eluted with EtOAc to give the lactam 5 (1.43
g, 68%); mp 159–162°C.

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M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
3.5. 6-Amino-1,4,5,6-tetradeoxy-1,4-imino-L-lyxo-hexitol, ditosylate 6
The 5-C-cyano-L-lyxono-1,4-lactam 5 (1.43 g, 7.29 mmol) was dissolved in dry tetrahydrofuran (40
ml) and slowly added to lithium aluminium hydride (2.75 g, 72.3 mmol) suspended in dry tetrahydrofuran
(10 ml). The mixture was kept for 4 h at 60°C and then for 16 h at room temperature. H2O (5.68 ml, 310
mmol) was slowly added over 1 h followed by tetrahydrofuran (20 ml). The precipitate was filtered off,
washed with tetrahydrofuran (50 ml) and the combined filtrates were concentrated to a residue, which
was purified on a column of silica (3×15 cm) by elution with 2.5% NH3 in MeOH. Concentration of
the appropriate fractions gave the aminohexitol (0.801 g) as a colourless syrup. The syrup was dissolved
in H2O (8 ml), p-toluenesulfonic acid monohydrate (1.73 g) was added and the mixture was kept at
50°C for 20 h. Concentration gave a crystalline residue. Recrystallisation from MeOH/Et2O gave 6 as
20
colourless crystals (1.53 g, 43%); mp. 179–181°C; [α] +6.7 (c 1.0, H2O). Further recrystallisation
D
20
from MeOH/EtOH furnished an analytical sample; mp. 182–183°C; [α] +5.8 (c 1.1, H2O); 1H NMR
D
(D2O, AcOH δ=2.07): δ 7.68 (d, 2H, aromatic, J=8.1 Hz), 7.34 (d, 2H, aromatic, J=8.1 Hz), 4.48 (dt,
0
H-2, J1,2=7.8 Hz, J1 ,2=7.6 Hz, J2,3=4.0 Hz), 4.26 (t, H-30 , J3,4=3.8 Hz), 3.66 (ddd, H-4, J4,5=8.1 Hz,
0
0
0
J4,5 =6.8 Hz), 3.53 (dd, H-1, J1,1 =12.2 Hz), 3.19 (dd, H-1 ), 3.12 (m, H-6, H-6 ), 2.36 (s, Ph-CH3), 2.29
(m, H-5) and 2.15 (m, H-50). 13C NMR (D2O, AcOH δ=23.37): δ 145.4, 142.5, 132.4, 128.3 (aromatic
carbon), 73.0 (C-2), 72.7 (C-3), 62.0 (C-4), 50.2 (C-1), 39.2 (C-6), 27.3 (C-5) and 23.4 (Ph-CH3). Anal.
calcd for C20H30N2O8S2 (490.60): C, 49.07; H, 6.16; N, 5.73. Found: C, 48.96; H, 6.16; N, 5.71.
3.6. 5-Amino-4-azido-4,5-dideoxy-2,3-O-isopropylidene-L-lyxono-1,5-lactam 7
5-Amino-5-deoxy-2,3-O-isopropylidene-4-O-trifluoromethanesulfonyl-D-ribono-1,5-lactam 4 (1.18
g, 3.7 mmol) was dissolved in DMF (5.0 ml) and sodium azide (2.4 g, 37.0 mmol) was added.
The mixture was stirred for 3 h at room temperature under N2, followed by addition of EtOAc
(20 ml). Filtration and concentration gave a residue which was dissolved in EtOAc and purified by
chromatography on a column of silica (3×15 cm) by elution with EtOAc:hexane 1:1→EtOAc:hexane
3:1. Pure fractions were concentrated to give 7 (0.37 g, 47%); 1H NMR (CDCl3): δ 7.72 (bs, NH) 4.50
0
0
(d, H-2, J2,3=7.0 Hz), 4.35 (dt, H-3, J3,4=5.5 Hz, J3,5 =0.5 Hz), 3.81 (ddd, H-4, J4,5=3.4 Hz, J4,5 =6.6
Hz), 3.53 (dt, H-5, J5,5 =13.3 Hz, J5,NH=3.2 Hz), 3.19 (dddd, H-50, J5 ,NH=0.5 Hz), 1.49 (s, CH3) and
1.38 (s, CH3). 13C NMR (CDCl3): δ 168.9 (C-1), 110.8 (acetal), 75.7, 72.9 (C-2, C-3), 58.3 (C-4), 40.4
(C-5), 26.6 (CH3) and 24.6 (CH3). (C8H12N4O3) m/z 197 (M−CH3), 213 (M+H+).
0
0
3.7. 4-Amino-1,4,5-trideoxy-1,5-imino-L-lyxitol, ditosylate 8
The lactam 7 (0.32 g, 1.51 mmol) was dissolved in THF (10 ml) under N2. LiAlH4 was added slowly
and stirring was continued for 22 h, then quenched by addition of H2O (0.5 ml), filtered and concentrated.
Purification of the residue by column chromatography using MeOH as eluent gave a residue (75 mg)
which was dissolved in H2O, followed by addition of p-TsOH (170 mg) and kept at 50°C for 10 h.
Concentration gave a crystalline residue which was recrystallised from MeOH twice to give 8 (248 mg,
20
5%) as colourless crystals; [α]20 +25.4 (c 1.0, H2O) [enantiomer: [α] −24.4 (c 1.0, H2O)6]; 1H NMR
D
D
(D2O): δ 7.62 (d, 2H, aromatic, J=8.0 Hz), 7.32 (d, 2H, aromatic, J=8.0 Hz), 4.24 (ddd, H-2, J2,3=3.0
0
0
Hz, J1,2=3.0 Hz, J1 ,2=1.4 Hz), 3.87 (dd, H-3, J3,4=10.2 Hz), 3.73 (ddd, H-4, J4,5=4.7 Hz,0J4,5 =12.2 Hz0),
0
0
3.69 (ddd, H-5, J5,5 =12.2 Hz, J1,5=2.0 Hz), 3.46 (ddd, H-1, J1,1 =13.7 Hz), 3.22 (dd, H-1 ) 3.13 (t, H-5 )
and 2.34 (s, CH3); 13C NMR (D2O, acetone δ=29.8): δ 141.8, 139.2, 129.0, 124.9 (aromatic), 68.3 (C-3),
64.8 (C-2), 47.8 (C-1), 46.0 (C-4), 42.9 (C-5) and 20.0 (CH3).

M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
575
3.8. 2,3-O-Isopropylidene-D-lyxono-1,4-lactone 11
Potassium-D-lyxonate 9 (20.00 g, 97.9 mmol) was dissolved in MeOH (140 ml) and conc. aq. HCl
(15 ml) and concentrated. Successive concentration with MeOH, toluene and MeOH gave a residue to
which acetone (300 ml), 2,2-dimethoxypropane (50 ml, 408 mmol) and methanesulfonic acid (0.5 ml)
were added, and the mixture was stirred for 20 h at room temperature. Neutralisation with NaHCO3,
filtration and concentration gave a syrupy residue (22.8 g), which was dissolved in H2O (150 ml) and
extracted with Et2O (1×100 ml and 4×50 ml), dried (Na2SO4) and concentrated to give 10 (13.97 g) as
a semi-crystalline residue. A mixture of acetic acid:H2O (9:1, 69.8 ml) was then added and the solution
was stirred for 16.5 h at 28–29°C. Concentration gave a residue to which toluene was added with stirring
to give a crystalline precipitate. The crystals were collected by filtration and dried in vacuo over KOH
to give the lactone 11 (8.33 g, 45%); mp. 81–85°C. Further purification by dissolving the compound
in acetone, filtration through activated carbon and recrystallisation from EtOAc furnished an analytical
20
sample of 11; mp 99–100°C; [α] +90.3 (c 1.0, acetone); 1H NMR (D2O): δ 5.10 (d, H-2, J2,3=5.6 Hz),
D
0
0
5.03 (dd, H-3, J3,4=3.7 Hz), 4.76 (ddd, H-4, J4,5=4.2 Hz, J4,5 =8.0 Hz), 3.91 (dd, H-5, J5,5 =12.5 Hz),
3.87 (dd, H-50), 1.40 (s, CH3) and 1.36 (s, CH3); 13C NMR (D2O): δ 177.9 (C-1), 115.5 (acetal), 81.8
(C-4), 77.2 (C-2), 77.0 (C-3), 60.5 (C-5), 26.6 and 25.6 (2×CH3). Anal. calcd for C8H12O5 (188.18): C,
51.06; H, 6.43. Found: C, 50.75; H, 6.43.
3.9. 2,3-O-Isopropylidene-5-O-methanesulfonyl-D-lyxono-1,4-lactone 12
To the protected lyxono-1,4-lactone 11 (8.33 g, 44.3 mmol) in pyridine (25 ml) methanesulfonyl
chloride (4.47 ml, 57.6 mmol) was added at 0°C in the course of 40 min. After stirring for 20 min at
0°C and 30 min at room temperature, ice/water (100 g) was added to give a crystalline precipitate. The
product was collected by filtration, carefully washed with H2O (0°C) and dried in vacuo over KOH to
give colourless crystals of 12 (9.34 g, 79%); mp 125–127°C. Recrystallisation from EtOAc furnished
20
1
an analytical sample; mp 127.5–128.5°C; [α] −76.6 (c 1.0, MeOH); H NMR (acetone-d6): δ 5.11
D
0
(d, H-2, J2,3=6.3 Hz), 5.05 (dd, H-3, J3,4=3.8 Hz), 4.95 (ddd, H-4, J4,5=3.5 Hz, J4,5 =8.2 Hz), 4.65 (dd,
H-5, J5,5 =11.5 Hz), 4.45 (H-5 ), 3.19 (Ms), 1.42 (s, CH3) and 1.36 (s, CH3); 13C NMR (acetone-d6): δ
173.9 (C-1), 114.6 (acetal C), 77.4 (C-4), 77.0 (C-2), 77.0 (C-3), 68.9 (C-5), 37.4 (Ms), 26.9 and 25.9
(2×CH3). Anal. calcd for C9H14O7S (266.27): C, 40.60; H, 5.30. Found: C, 40.63; H, 5.28.
0
0
3.10. 5-Amino-5-deoxy-2,3-O-isopropylidene-D-lyxono-1,5-lactam 13
The mesylated lyxono-1,4-lactone 12 (9.34 g, 35.1 mmol) was dissolved in aq. NH3 (25%, 50 ml) and
left for 5.5 h at room temperature in a sealed flask. Concentration and successive co-concentrations with
MeOH, MeOH/toluene and EtOAc gave a residue which was extracted with boiling EtOAc (150 ml).
The extract was cooled to 30°C, filtered and concentrated to give 13 (5.58 g, 85%) as colourless crystals;
mp 95–122°C. According to a 13C NMR spectrum the lactam was sufficiently pure for further reactions.
Purification by flash chromatography (EtOH:EtOAc 1:4), furnished an analytical sample, mp 125–126°C;
20
[α] −6.7 (c 1.0, MeOH); 1H NMR (D2O): δ 4.61 (d, H-2, J2,3=6.8 Hz), 4.46 (ddd, H-3, J3,4=5.3 Hz,
D
0
0
0
0
J3,5 =0.7 Hz), 4.02 (ddd, H-4, J4,5=3.2 Hz, J4,5 =6.0 Hz), 3.47 (dd, H-5, J5,5 =13.5 Hz), 3.22 (dd, H-5 ),
1.41 (s, CH3) and 1.38 (s, CH3); 13C NMR (D2O, acetone δ=29.8): δ 170.9 (C-1), 110.8 (acetal), 77.3
(C-3), 72.0 (C-2), 65.6 (C-4), 42.0 (C-5), 25.4 and 23.7 (2×CH3). Anal. calcd for C8H13NO4 (187.20):
C, 51.33; H, 7.00; N, 7.48. Found: C, 51.16; H, 6.97; N, 7.48.

576
M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
3.11. 5-Amino-5-deoxy-2,3-O-isopropylidene-4-O-methanesulfonyl-D-lyxono-1,5-lactam 14
The protected D-lyxono-1,5-lactam 13 (4.55 g) was mesylated in pyridine (13.7 ml) with methane-
sulfonyl chloride (2.65 ml, 34.1 mmol) at 0°C as described above for the preparation of 2. Ice/water
(20 ml) was added and the solution was concentrated and co-concentrated with toluene to a residue.
This was dissolved in H2O (20 ml) and extracted with EtOAc (4×20 ml). The organic phase was dried
(Na2SO4), filtrated and concentrated to a syrup (5.49 g) which could be crystallised from EtOAc to give
the mesylated lactam 14 as colourless crystals (3.77 g, 59%); mp 130.5–132.5°C. Recrystallisation from
20
EtOAc furnished an analytical sample; mp 133–134°C; [α] −47.7 (c 1.0, acetone); 1H NMR (acetone-
D
0
d6 δ=2.05): δ 7.07 (d, NH), 4.80 (m, H-4, J2,4=1.2 Hz, J3,4=4.0 Hz, J4,5=2.7 Hz, J4,5 =4.5 Hz), 4.63
0
0
(ddd, H-3, J2,3=7.0 Hz, J3,5 =1.4 Hz), 4.56 (dd, H-2), 3.67 (ddd, H-5, J5,5 =13.7 Hz, J5,NH=0.8 Hz), 3.50
(ddt, H-50), 3.25 (s, Ms), 1.46 (s, CH3) and 1.37 (s, CH3); 13C NMR (acetone-d6): δ 167.8 (C-1), 111.0
(acetal), 76.5, 76.2 and 74.3 (C-2, C-3 and C-4), 41.6 (C-5), 38.4 (Ms), 26.6 (CH3) and 24.5 (CH3). Anal.
calcd for C9H15NO6S (265.29): C, 40.97; H, 5.72 N, 5.28. Found: C, 40.75; H, 5.70; N, 5.28.
3.12. 4-Amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-ribono-1,4-lactam 15
The mesylated D-lyxono-1,5-lactam 14 (6.78 g, 25.5 mmol) was added to a solution of Bu4NCN in
DMF (1.31 M, 27.3 ml, 35.8 mmol) and the mixture was kept at 100°C for 5 h. The solution was poured
on a column of mixed ion-exchange resin (Amberlite IR-120, H+, 94.0 ml and Amberlite IRA-400,
HCO3−, 162.5 ml) and eluted with H2O (400 ml). The eluate was concentrated and acetone (20 ml)
was added to the residue which crystallised by cooling in dry ice/2-propanol. Filtration gave the title
20
compound 15 (2.48 g, 50%); mp 199–201°C; [α] +47.6 (c 0.5 acetone); 1H NMR (acetone-d6): δ 4.69
D
0
0
(s, H-2), 4.69 (d, H-3, J3.4=1.6 Hz), 3.95 (ddd, H-4, J4,5=5.0 Hz, J4,5 =6.1 Hz), 3.94 (dd, H-5, J5,5 =17.0
Hz), 3.89 (dd, H-50), 1.39 (s, CH3) and 1.35 (s, CH3); 13C NMR (acetone-d6): δ 172.5 (C-1), 117.1 (CN),
111.9 (acetal), 78.8 (C-2), 76.2 (C-3), 54.3 (C-4), 26.3 (CH3), 24.9 (CH3) and 22.8 (C-5). Anal. calcd for
C9H12N2O3 (196.21): C, 55.09; H, 6.16; N, 14.28. Found C, 54.90; H, 6.12; N, 14.02.
The mother liquor was concentrated and crystallised from EtOAc (15 ml) to give a product having
an mp 149–152°C. A 13C NMR spectrum showed that it was a mixture of the lactam 15 and the
corresponding unprotected compound, 4-amino-5-C-cyano-4,5-dideoxy-L-ribono-1,5-lactam. Separation
was performed by refluxing in acetone (10 ml) followed by filtration to give the 4-amino-5-C-cyano-4,5-
dideoxy-L-ribono-1,5-lactam as a crystalline compound (0.34 g); mp 155–162°C. Concentration of the
filtrate gave a residue which was recrystallised from H2O to give 15 as colourless crystals (0.19 g, 4%);
20
D
mp 201–202°C; [α] +49.2 (c 0.6 acetone). The EtOAc from the precipitation of the lactam mixture
was concentrated and purified on a column of silica (4×15 cm) by elution with EtOAc. This gave an
20
D
additional amount of 15 (0.41 g, 8%; mp 202–203°C; [α] +49.9 (c 0.6, acetone)), bringing the total
yield of 15 to 62%.
3.13. 6-Amino-1,4,5,6-tetradeoxy-1,4-imino-L-ribo-hexitol, ditosylate 16
A solution of 15 (2.50 g, 12.7 mmol) in dry tetrahydrofuran (80 ml) was slowly added to lithium
aluminium hydride (2.42 g, 55.9 mmol) suspended in dry tetrahydrofuran (10 ml). The mixture was
stirred for 18 h at room temperature. Then H2O (4.27 ml, 237 mmol) was added with stirring in the
course of 1 h, and stirring was continued for another 30 min. The precipitate was filtered off, washed with
tetrahydrofuran (50 ml) and the combined filtrate was concentrated to a syrup. This was dissolved in H2O
(20 ml) and p-toluenesulfonic acid monohydrate (4.00 g) was added and the mixture was kept at 50°C

M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
577
for 4 h. Concentration gave a crystalline residue, which by recrystallisation from EtOH/Et2O gave 16 as
20
colourless crystals (2.61 g, 42%); mp 151–155°C; [α] −21.6 (c 1.0, H2O). Further recrystallisation
D
20
from EtOH/Et2O furnished an analytical sample; mp. 163–164°C; [α] −22.4 (c 1.0, H2O); 1H NMR
D
(D2O, AcOH δ=2.07): δ 7.68 (d, 2H, aromatic, J=8.1 Hz), 7.33 (d, 2H, aromatic, J=8.1 Hz), 4.35 (dt,
0
H-2, J1,2=4.4 Hz, J1 ,2=1.5 Hz, J2,3=4.2 Hz), 4.12 (dd, H-3, J3,4=9.1 Hz), 3.58 (dd, H-4), 30.55 (dd, H-1,
J1,1 =13.2 Hz), 3.36 (dd, H-1 ), 3.21 (m, H-6, H-6 ), 2.36 (s, Ph-CH3), 2.22 (m, H-5, H-5 ); 13C NMR
(D2O, AcOH δ=23.37): δ 145.4, 142.6, 132.4, 128.4 (aromatic carbon), 78.0 (C-3), 72.0 (C-2), 62.5
(C-4), 52.7 (C-1), 39.4 (C-6), 30.7 (C-5) and 23.5 (Ph-CH3). Anal calcd for C20H30N2O8S2 (490.60): C,
48.93; H, 6.15; N, 5.70. Found: C, 48.96; H, 6.16; N, 5.71.
0
0
0
3.14. N-Ethyl-5-amino-5-deoxy-2,3-O-isopropylidene-D-ribono-1,5-lactam 18
2,3-O-Isopropylidene-5-O-methanesulfonyl-D-ribono-1,4-lactone 178 (4.0 g, 15.0 mmol) was dissol-
ved in 70% aq. ethylamine (20 ml) and left for 144 h at room temperature in a sealed flask. Concentration
and subsequent co-concentration with H2O and EtOAc gave a residue which was extracted with EtOAc
(100 ml), filtered and concentrated to give 18 (3.46 g, 107%) as a slightly coloured syrup. The syrup
was pure enough for further synthesis according to a 13C NMR spectrum. A small amount of 18 was
chromatographed on a column of silica (3×15 cm) and eluted with EtOAc→EtOAc:EtOH 9:1. All
fractions were analysed by HPLC (column: Hewlett–Packard Hypersil 5 µm 100×4.6 mm, eluent: 1%
i-PrOH in EtOAc), and fractions containing the lactam 18 were pooled and concentrated to give an
20
1
analytical sample; [α] +11.2 (c 1.5, acetone); H NMR (acetone-d6): δ 4.54 (ddd, H-3, J2,3=6.7
D
0
0
Hz, J3,4=3.0 Hz, J3,5 =1.1 Hz), 4.41 (d, H-2), 4.03 (m, H-4, J4,.5=9.3 Hz, J4,5 =4.3 Hz), 03.54 (dd, H-
0
0
5, J5,5 =11.8 Hz), 3.48 (dq, CH3-CH2, JCH2,CH3=7.2 Hz, JCH2,CH2 =13.3 Hz), 3.24 (dq, CH2 ), 3.20 (ddd,
H-50), 2.87 (bs, OH), 1.37 (s, CH3), 1.34 (s, CH3) and 1.07 (t, CH3-CH2); 13C NMR (acetone-d6): δ
166.6 (C-1), 110.5 (acetal), 76.8 (C-3), 75.6 (C-2), 66.0 (C-4), 47.7 (C-5), 42.4 (CH2-CH3), 26.8 (CH3),
25.2 (CH3) and 12.3 (CH3-CH2). C10H17NO4(215.25) m/z 200 (M−CH3), 215 (M).
3.15. N-Ethyl-5-amino-5-deoxy-2,3-O-isopropylidene-4-O-trifluoromethanesulfonyl-D-ribono-1,5-
lactam 19
Compound 18 (0.745g, 3.45 mmol) was dissolved in pyridine (5.0 ml), cooled to 0°C and treated with
trifluoromethane-sulfonic anhydride (0.63 ml, 4.50 mmol) as described above for the preparation of 4 to
give 19 as a pale yellow syrup (0.98 g, 81%). The syrup was pure according to a 13C NMR spectrum. 13
C
NMR (CDCl3): δ 165.0 (C-1), 118.1 (quartet, Tf), 111.7 (acetal) 78.4, 73.2, 72.5 (C-2, C-3, C-4), 45.2
(C-5), 42.1 (CH2-CH3), 25.6 (CH3), 24.3 (CH3) and 11.6 (CH2-CH3).
3.16. Treatment of N-ethyl-5-amino-5-deoxy-2,3-O-isopropylidene-4-O-trifluoromethanesulfonyl-D-
ribono-1,5-lactam 19 with tetrabutylammonium cyanide
To the lactam 19 (0.868 g, 2.5 mmol) was added a solution of Bu4NCN in DMF (1.0 M, 3.75 ml,
3.75 mmol) and the mixture was allowed to stand for 28 h at room temperature. The solution was poured
through a column of mixed ion-exchange resin (Amberlite IR-120, H+, 10.0 ml and Amberlite IRA-400,
HCO3−, 16.0 ml) which was washed with H2O (40 ml). The eluate was concentrated and the isomers
were separated on a short column of silica (1.5–40 µm) using EtOAc as eluent. Fractions containing
the compound with the highest Rf-value were collected to give a syrup (15 mg), probably of N-ethyl-5-
amino-4,5-dideoxy-4-ene-2,3-O-isopropylidene-D-erythro-pentono-1,5-lactam 20; 1H NMR (CDCl3): δ

578
M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
6.17 (d, H-5, J4,5=8.1 Hz), 5.21 (dd, H-4, J3,4=4.6 Hz), 4.71 (dd, H-3, J2,3=6.9 Hz), 4.51 (d, H-2), 3.56
(m, CH2-CH3), 1.18 (t, CH2-CH3, J=7.2 Hz).
Fractions containing the slower moving compound were concentrated to give a syrup (60 mg), prob-
ably of N-ethyl-5-amino-4-deoxy-3-ene-2,3-O-isopropylidene-D-glycero-pentono-1,5-lacta0m 21; 1H
0
NMR (CDCl3): δ 4.86, 4.70 (m, H-2, m, H-4) 3.94 (ddd, H-5, J5,5 =16.2 Hz), 3.64 (ddd, H-5 ), 3.49 (m,
CH2-CH3), 1.09 (t, CH2-CH3, J=7.2 Hz). 13C NMR (CDCl3): δ 165.0 (C-1), 148.5 (C-3), 114.3 (acetal),
85.3 (C-4), 72.0 (C-2), 45.2 (C-5), 41.0 (CH2-CH3), 26.1 (CH3), 24.5 (CH3) and 12.3 (CH2-CH3).
3.17. Crystal structure determination for compound 512
Crystals were obtained by crystallisation from acetone. A colourless crystal of 5 with the dimensions
0.38×0.13×0.08 mm3 was measured on a CAD-4F diffractometer using CuKα radiation (λ=1.5418 Å).
Crystal data: C9H12N2O3, M=196.21, orthorhombic space group P212121, a=6.118(2) Å, b=9.714(4)
Å, c=16.172(5) Å, V=961.1(6) Å3, Z=4, Dc=1.36 g/cm3, F(000)=416, µ(CuKα)=0.86 mm−1. At 120 K
in the range of 5.31°<θ<73.93° 2248 reflections were measured of which 1954 were unique and 1693
(R)(int)= 0.039, observed with I>2σ(I). The structure was solved by direct methods and refined by least
squares procedure within the SHELXL program system. The final residuals were wR2(all)=0.1003 and
R1(obs)= 0.0406. The maximum and minimum peaks in the final electron density difference map were
−0.20 and −0.14 e/Å3, respectively. The absolute structure could not be determined reliably.
3.18. Crystal structure determination for compound 1512
Crystals were obtained by crystallisation from acetone. A colourless crystal of 15 with the dimensions
0.28×0.07×0.06 mm3 was measured on a CAD-4F diffractometer using MoKα radiation (λ=0.71073 Å).
Crystal data: C9H12N2O3, M=196.20, orthorhombic space group P212121, a=11.134(7) Å, b=11.544(5)
Å, c=15.595(8) Å, V=2004.4(18) Å3, Z=8, Dc=1.30 g/cm3, F(000)=832, µ(MoKα)=0.099 mm−1. At
120 K in the range of 2.19°<θ<24.93° 5583 reflections were measured of which 3479 were unique and
1625 (R)(int)= 0.126, observed with I>2σ(I). The structure was solved by direct methods and refined by
least squares procedure within the SHELXL program system. The final residuals were wR2(all)=0.1615
and R1(obs)=0.0855. The maximum and minimum peaks in the final electron density difference map were
−0.31 and 0.28 e/Å3, respectively. The absolute structure could not be determined reliably.
Acknowledgements
Financial support by the Danish Technical Research Council is gratefully acknowledged.
References
1. Lundt, I.; Madsen, R. In Iminosugars as Glycosidase Inhibitors — Nojirimycin and Beyond; Stütz, A. E., Ed.; Wiley-VCH:
Weinheim, 1999; pp. 93–111 and pp. 112–124.
2. Folkersen, B. M.; Lundt, I.; Foged, C.; Valsborg, J. S. J. Label. Comp. Radiopharm. 1999, 42, 1145.
3. Godskesen, M.; Lundt, I.; Madsen, R.; Winchester, B. Bioorg. Med. Chem. 1996, 4, 1857.
4. Buchanan, J. G.; Edgar, A. R.; Rawson, D. I.; Shahidi, P.; Wightman, R. H. Carbohydr. Res. 1982, 100, 75.
5. Brändström, A.; Lamm, B.; Palmertz, I. Acta Chem. Scand. 1974, B28, 699.
6. Godskesen, M.; Lundt, I. Submitted for publication.
7. Humphlett, W. J. Carbohydr. Res. 1967, 4, 157.

M. Godskesen et al. / Tetrahedron: Asymmetry 11 (2000) 567–579
579
8. Kold, H.; Lundt, I.; Pedersen, C. Acta Chem. Scand. 1994, 48, 675.
9. Le Merrer, Y.; Poitout, L.; Depezay, J.-C.; Dosbaa, I.; Geoffroy, S.; Foglietty, M.-J. Bioorg. Med. Chem. 1997, 5, 519.
10. Kim, D.-K.; Kim, G.; Kim, Y.-W. J. Chem. Soc., Perkin Trans. 1 1996, 803.
11. De Lucca, G. V. J. Org. Chem. 1998, 4755.
12. Crystallographic data for the structures reported in this paper have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication nos. CCDC-000000 (5), CCDC-000000 (15). Copies of the data can be obtained
free of charge on application to CCDD, 12 Union Road, Cambridge CB2 1EZ, UK. (Fax: 44-1223/336-033; e-mail:
deposit@chemcrys.cam.ac.uk).