Syntheses of imido-substituted glycosans and their photocyclisation towards highly functionalised heterotricycles

Article abstract of DOI:10.1016/S0008-6215(01)00250-6

Reaction of O-protected amino-1,6-anhydro-β-D-hexopyranoses with succinic or glutaric anhydride and subsequent intramolecular acylation afforded the succinimido- and glutarimido-substituted glycosans. Irradiation with UV light of 254 nm wavelength led to γ-hydrogen abstraction at the pyranose ring by the excited carbonyl function. The stereoselective recombination of the resulting 1,4-diradicals gave annelated azetidinols, which fragmented by a retrotransannular ring opening reaction to give the glycosan-annelated azepanedione and azocanedione systems, respectively.

Full text of DOI:10.1016/S0008-6215(01)00250-6

Carbohydrate Research 336 (2001) 271–282
www.elsevier.com/locate/carres
Syntheses of imido-substituted glycosans and their
photocyclisation towards highly functionalised
heterotricycles
Swantje Thiering,a Christian Sund,a Joachim Thiem,a,* Anja Giesler,b Ju¨rgen Kopfb
aInstitut fu¨r Organische Chemie, Uni6ersita¨t Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
bInstitut fu¨r Anorganische Chemie, Uni6ersita¨t Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
Received 24 May 2001; accepted 14 September 2001
With great appreciation dedicated to Professor Ge´rard Descotes
Abstract
Reaction of O-protected amino-1,6-anhydro-b-D-hexopyranoses with succinic or glutaric anhydride and subse-
quent intramolecular acylation afforded the succinimido- and glutarimido-substituted glycosans. Irradiation with UV
light of 254 nm wavelength led to g-hydrogen abstraction at the pyranose ring by the excited carbonyl function. The
stereoselective recombination of the resulting 1,4-diradicals gave annelated azetidinols, which fragmented by a
retrotransannular ring opening reaction to give the glycosan-annelated azepanedione and azocanedione systems,
respectively. © 2001 Published by Elsevier Science Ltd.
Keywords: 1,6-Anhydrosugars; Imides; Photochemistry; Azepanediones; Azocanediones
1. Introduction
tronic aspects, such as polarisation of a CꢀH
bond by heteroatoms and the absence of a
hydrogen in g-position, can cause an abstrac-
tion of more remote hydrogen atoms, of
which principally the d-hydrogen abstraction
is quite common. Subsequent recombination
of the radical centres results in an intramolec-
ular alkylation (Yang cyclisation)1 and affords
the azacyclobutanol (azetidinol) or azacy-
clopentanol derivative, respectively (Scheme
1). Of these, the strained azetidinol system is
unstable and undergoes a fragmentation by an
aza-anologous retroaldol addition to give the
azepanedione system. In case of cyclic sub-
stituents, the Yang cyclisation of the diradi-
cals proceeds stereoselectively to give the
cis-annelated products, due to strain of the
resulting four or five membered rings.2–4
By irradiation of an N-substituted succin-
imide with ultraviolet light of 254 nm wave-
length, an excited state of the carbonyl group
is generated, the properties of which are com-
parable to those of a diradical. The approach
of the excited carbonyl function to a hydrogen
atom of a substituent in suitable distance re-
sults in the abstraction of this hydrogen gener-
ating a diradical. For steric reasons, formation
of a 1,4-diradical is preferred, because this
g-hydrogen abstraction proceeds via a six-
membered transition state. However, elec-
* Corresponding author. Tel.: +49-40-428384241; fax: +
49-40-428384325.
E-mail address: thiem@chemie.uni-hamburg.de (J. Thiem).
0008-6215/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0008-6215(01)00250-6

272
S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
which only the g-hydrogen abstraction should
Intensive studies on photoreactions of this
kind with N-glycopyranosyl-succinimides5 and
their 2-deoxy analogues6,7 have revealed that
the regiochemistry of the hydrogen abstrac-
tion and thus the cyclisation is distinctly con-
trolled by stereoelectronic as well as
conformational factors, caused by both the
nature of the individual monosaccharide
configuration and the applied protecting
groups. For example, with a cis-hydrogen
atom available both in the g- as well as in the
l-position, the results of the irradiation of
occur. This example clearly demonstrates the
influence displayed by the conformational
equilibrium on the course of these photocycli-
sations.
A fixation of conformation, as found in
bridged systems, should dispose stronger con-
trol and hence greater predictability of the
regiochemistry of the hydrogen abstraction.
For example, the conformationally fixed sys-
tems of 1,6-anhydro-b- -hexopyranoses con-
D
stitute promising objects for further studies on
such photochemical transformations and open
a gateway to interesting heterocyclic struc-
tures. We report here the syntheses and results
of irradiation of 2-imido-galactosan and 4-
imido-mannosan derivatives, whereas our
work with 3-imido-glucosan derivatives will be
discussed separately.8
persilylated N-[a- -mannopyranosyl]succini-
D
mide 1 are shown in Scheme 1.5 Proceeding
4
from the C1(
D
) conformation, hydrogen ab-
straction from both the g-position as well as
the electronically favoured d-position is possi-
ble, leading to the azepanedione derivative 2
and the tricyclic aminal 3, respectively. How-
ever, the inverse anomeric effect of the succin-
imide substituent partly forces the pyranose
1
chair to adopt the C4(
D
) conformation, from
2. Results and discussion
Syntheses of Imides.—The condensation of
primary amines with dicarbonic acid anhy-
drides has proven to be a versatile approach
to imido-substituted sugars of different kinds.5
The amino group of a saccharide readily re-
acted with anhydrides such as succinic and
glutaric anhydride. Under acylation condi-
tions, the resulting amidic acids underwent a
subsequent cyclisation reaction to afford the
saccharide imides.
The synthesis of the 2-azido galactosan and
the 4-azido mannosan started from galactosan
and mannosan, respectively, and followed the
pathway established by Cerny et al.9,10 leading
to 1,6;2,3-dianhydro-b-
D
-talopyranose 4 and
1,6;3,4-dianhydro-b- -talopyranose 10. Reac-
D
tion of the epoxides with sodium azide10,11
regioselectively gave the galacto-configurated
2-azido derivative 5 and the manno-configu-
rated 4-azido derivative 11, respectively. Due
to their extremely low nucleophilicity, a short
cut of the syntheses by nucleophilic epoxide
ring opening with the anions of aliphatic
imides such as succinimide or glutarimide was
not possible.
After protection of the hydroxyl functions
as photochemically inert isopropylidene ac-
etals 6 and 12, reduction of the azides by
Scheme 1. (i) 254 nm, CH3CN, 18 °C, 3 h, 2: 20%, 3: 62%.

S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
273
Reaction of the amines 7 and 13 with ten
equivalents of succinic or glutaric anhydride,
respectively, in dichloromethane in the pres-
ence of N-ethyldiisopropylamine as auxiliary
base led to the corresponding succinamidic
and glutaramidic acids, respectively, which
were transformed without isolation.12 Cyclisa-
tion in the presence of acetic anhydride in
pyridine afforded the saccharide succinimides
8 and 14 and glutarimides 9 and 15 in moder-
ate to good yields. In the formation of these
derivatives, the chain length of the dicarbonic
acid showed a significant influence on the
reaction conditions. Whereas the cyclisation
of the succinamidic acids took place at room
temperature, the generation of the glutarim-
ides required higher temperatures. This effect
was also observed when TBDMS ethers in-
stead of isopropylidene acetals were applied as
protecting groups (unpublished result). 1H and
13C NMR data for the unequivocal structural
assignments of all new compounds 6–9 and
12–15 are summarised in Tables 1 and 2.
Irradiations.—All irradiations were per-
formed with a low pressure mercury lamp at
254 nm under argon atmosphere in a solution
of acetonitrile. In these transformations, up to
a 1.5 g scale, no direct connection between the
concentration of the solution and conversion
and yield could be observed. Impurities in the
starting materials may have a significant effect
as inhibitors of the photoreaction though,
leading to longer reaction times due to re-
duced rate of conversion and resulting in
lower yields. Due to two other photolabile
carbonyl functions, the original products were
of limited stability under the reaction condi-
tions. Thus longer reaction times resulted in
an increase in decomposition products and the
reaction was usually stopped after 7–9 h.
Including the recovery of starting materials—
usually ranging from 0 up to 20%—the yields
do not exceed 90% because these reactions
were always accompanied by the formation of
minor amounts of side products, formed, e.g.,
by elimination after hydrogen abstraction to
give the unsaturated saccharide and free
imide. All main photoproducts crystallised
very well and allowed studies of the X-ray
structures of 16, 17 and 19. Data of these
X-ray analyses are summarised in Table 3.
Scheme 2. (i) 2,2-Dimethoxypropane, acetone, pTsOH, RT,
20 h, 73%; (ii) H2, Pd/C, EtOAc–MeOH, rt, 48 h, 97%; (iii)
(a) succinic anhydride, NEt(Pri)2, rt, 20 h; (b) glutaric anhy-
dride, NEt(Pri)2, rt, 20 h, (iv) pyridine, Ac2O (a) rt, 20 h, 64%;
(b) 100 °C, 20 h, 75%.
Scheme 3. (i) 2,2-Dimethoxypropane, acetone, pTsOH, rt, 20
h, 80%; (ii) H2, Pd/C, EtOAc–MeOH, rt, 48 h, 98%; (iii) (a)
succinic anhydride, NEt(Pri)2, rt, 20 h; (b) glutaric anhydride,
NEt(Pri)2, rt, 20 h; (iii) pyridine, Ac2O (a) rt, 20 h, 69%; (b)
90 °C, 20 h, 58%.
hydrogenolysis using palladium on activated
charcoal afforded the amines 7 and 13
in almost quantitative yield (Schemes 2 and
3).

Table 1
1H NMR chemical shifts (l in ppm) and coupling constants (J in Hz)
Compound H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
-CH2-, succinimide
-CH2-, glutarimide
ꢀCH3, isopropylidene
6 a
7 a
5.45, s
3.55, s
3.14, s
4.37, s
5.15, s
4.26, d
J3,4 6.6
4.10, d
J3,4 6.6
4.55, d
J3,4 6.6
4.45, d
J3,4 6.6
4.23, d
4.42, t
4.53, t
4.11, d
J6a,6b 7.6
4.14, d
J6a,6b 7.6
4.22, d
J6a,6b 7.6
4.16, d
J6a,6b 7.6
4.00, dd
J6a,6b 7.2
3.62, dd
3.59, dd
1.54, s
1.37, s
1.53, s
1.33,s
1.55, s
1.34, s
1.55, s
1.34, s
1.52, s
1.32, s
J4,5 5.6 J5,6b 5.6
4.38, t 4.43, t
J4,5 5.6 J5,6b 5.6
4.80, t 4.61, t
J4,5 5.6 J5,6b 5.6
4.78, t 4.62, t
J4,5 5.6 J5,6b 5.6
5.29, s
5.14, s
5.29, s
/
8 a
3.60, dd 2.75, s
4 H
3.58, dd
9 a
2.70, t, 4 H
1.96, quint, 2 H
12 a
5.35, d
J1,2 3.1
4.05, dd
J2,3 6.3
3.62, s
4.61, dd
J5,6a 1.0
J5,6b 6.3
4.41, dd
J5,6a 1.0
J5,6b 6.6
4.39, d
J5,6b 6.3
4.26, d
J5,6b 6.3
3.78, t
13 a
5.31, d
J1,2 2.5
4.06–4.03,
m
4.10, d
J2,3 6.1
3.21, s
4.06–4.03,
m
3.76, t,
J6a,6b 6.6
1.54, s
1.31, s
6
)
14 b
15 a
5.40, d
J1,2 2.8
5.42, d
J1,2 3.1
4.35, dd
J2,3 6.0
4.51, dd
J2,3 6.3
4.50, d,
4.43, d
4.17, s
4.78, s
3.95, d,
J6a,6b 7.1
4.04, d
3.67, dd 2.67, s
1.48, s
1.27, s
1.50, s
1.27, s
271
4 H
2
3.72, t
2.68, t, 4 H
1.95, quint, 2 H
J6a,6b 6.3
a Solvent: CDCl3.
b Solvent: d6-Me2SO.

S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
275
NMR displayed the typical signals of the
amide group (lC 174.81) and the keto function
(lC 207.14). Furthermore, there was a new
quaternary carbon atom at lC 83.46 (C-8),
and the former identical secondary carbon
atoms of the succinimide now gave two signals
at lC 36.48 (C-6) and lC 29.97 (C-5). The
coupling constants of the sugar system (J1,2
and J9,10) in the tricyclic structure were un-
changed compared to the starting bicyclic
Considering the synthesised imido deriva-
tives of -galactosan (8, 9) and -mannosan
D
D
(14, 15) and assuming g-hydrogen abstraction,
there are in each case two suitable hydrogen
atoms which could react with the excited car-
bonyl function. One of these is bound to a
bridgehead atom (H-1 for the galacto cases,
H-5 for the manno cases) which makes an
abstraction less favourable compared to the
other one, the H-3 in both configurations.
However, a d-hydrogen abstraction of H-4 for
the galacto cases and H-2 for the manno cases
cannot entirely be excluded. Again, there is no
significant polarisation of these CꢀH bonds
which could render such a remote hydrogen
abstraction favoured. Thus, the alkylation at
C-3 for both sugar configurations is expected
to be the most probable course of these pho-
toreactions (Scheme 4).
form, which indicated that the pyranose ring
1
still adopted a C4(
D
) chair conformation.
This was confirmed by the X-ray structure
shown as an ORTEP drawing in Fig. 1. At-
tached to this chair, the seven-membered ring
adopted a boat conformation.
In case of the irradiation of the glutarimido
derivative 9, TLC indicated the formation of
two products with very similar Rf-values and
little elimination product. Again, 12% of the
starting material was recovered. The azocane-
dione 17, expected as the product of g-hydro-
gen abstraction and cis-alkylation at C-3 of
the galactosan, was found to be the main
product, and was obtained in a yield of 58%.
Unfortunately, a second product in a 1H
NMR estimated amount of 14% could not be
separated from 17 in a state pure enough to
Irradiation of the succinimido derivative 8
was not completed after 9 h, and in addition
to 75% of the expected azepanedione 16, 14%
of starting material was recovered. Further-
more, a small amount of elimination product
1
was indicated by TLC. The H NMR of 16
showed the NH-signal at l 6.19, the splitting
of the succinimide CH2-groups into an ABCD
spin system and no signal for H-8. The 13C
Table 2
13C NMR chemical shifts (l in ppm)
Compound C-1
C-2
C-3
C-4
C-5
C-6
Succinimide
Glutarimide
Isopropylidene
a
6
99.86 61.40
102.74 53.81
100.12 54.00
101.15 54.98
73.62 69.40 72.28 63.59
77.68 69.30 72.52 63.55
109.07
25.71, 24.38, ꢀCH3
108.55
25.80, 24.40, ꢀCH3
25.84, 24.42, ꢀCH3
7 a
8 a
9 a
72.54 69.44 71.38 63.54 176.26, CꢁO
28.09, ꢀCH2ꢀ
72.83 69.34 72.21 62.74
172.19, CꢁO
33.30, 2 C, ꢀCH2ꢀ
16.87, ꢀCH2
108.15
25.80, 24.40, ꢀCH3
12 a
13 a
14 b
15 a
99.47 72.19
99.57 72.11
98.77 72.32
99.57 72.30
73.73 60.17 73.97 65.31
78.06 52.34 76.52 65.51
110.31
25.90, 25.81, ꢀCH3
109.99
25.94, 25.87, ꢀCH3
108.74
26.12, 26.03, ꢀCH3
109.04
71.91 52.12 74.10 65.91 177.41, CꢁO
28.21, ꢀCH2ꢀ
73.60 54.25 75.77 67.03
172.43, CꢁO
33.38, 2 C, ꢀCH2ꢀ
16.86, ꢀCH2ꢀ
25.95, 25.85, ꢀCH3
a Solvent: CDCl3.
b Solvent: d6-Me2SO.

276
S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
Table 3
former glutarimide system (C-7 lC 37.25, C-5
lC 34.08 and C-6 lC 23.27).
Crystal data, data collection parameters and refinement re-
sults
Again, no significant changes concerning
the coupling constants of the sugar system J1,2
and J10,11 were observed, which indicated a
pyranose chair conformation. The structure of
17 elucidated by NMR experiments was
proven by X-ray structure analysis, the ORTEP
drawing shown in Fig. 2. Inspection revealed a
kind of chair–boat conformation for the
eight-membered ring annelated to the sugar
b
16
17 a
19 a
Formula
Formula
weight
Crystal
dimension
(mm)
C13H17NO6 C14H19NO6
283.28
C14H19NO6
297.30
297.30
0.7×0.5×0.2 0.7×0.3×0.3
Crystal
system
monoclinic
monoclinic
orthorhombic
1
ring in C4 chair conformation.
Space group P21 (no.4)
P21 (no.4)
P212121 (no.
19)
8.5471(7)
10.7122(13)
15.187(3)
90
The photoreaction of the succinimido-sub-
stituted mannosan derivative 14 proved to be
more straightforward. After 7 h, complete
conversion of the starting material was ob-
served and the azepandione 18 was obtained
in 85% yield. The structure was elucidated by
NMR experiments, displaying the typical sig-
nals of the amide group (NHꢀCꢁO doublet at
l 5.77, lC 173.36) and the keto function (lC
204.77). The signal of a new quaternary centre
(C-8 lC 84.37) was in keeping with the ab-
sence of the signal of H-8. Furthermore, the
singlet of the succinimide protons split into an
ABCD-system, their carbon centres appearing
at lC 33.39 (C-6) and lC 29.96 (C-5). The
unchanged coupling constants of the sugar
system (J1,2 and J9,10) indicated that the chair
conformation of the pyranose ring was not
affected by the annelated seven-membered
ring (Scheme 5).
,
a (A)
8.6124(18)
7.6762(16)
10.883(2)
90
111.456(3)
90
8.4493(13)
9.6356 (14)
9.2656(11)
90
114.704(12)
90
685.31(17)
594.60
2
1.441
316
Cu Ka
154.178
0.954
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
90
90
3
,
V (A )
669.6(2)
566.55
2
1390.5(3)
1189.21
4
1.4202(3)
632
Cu Ka
154.178
0.940
Cell weight
Z
zcalcd (g cm−3) 1.4050(4)
F(000)
300
Radiation
u (pm)
Mo Ka
71.073
0.112
−120
54.90
2949
v (mm−1
T (°C)
)
−100
152.80
1527
20
152.85
2155
2qmax (°)
Unique
reflexions
Observed
reflexions
R
2869
1525
2126
0.0467
0.1185
−0.2(8)
0.0385
0.1025
0.0492
0.0389
0.1008
0.0371
wR2
Flack
parameter
S=Goodness- 1.053
of-fit
1.057
1.087
a Enraf–Nonius CAD-4 diffractometer.
b Bruker Apex-diffractometer.
get proper NMR spectra. Although it has not
been identified so far, the 13C NMR tenta-
tively referred to a system with both a lactam
structure and a keto function as well. Thus,
hydrogen abstraction and cyclisation at the
bridgehead C-1 must be assumed.
NMR data for a decisive structural assign-
ment of 17 were the signals of the lactam and
carbonyl function (NHꢀCꢁO doublet at l
5.41, lC 174.22, CꢁO lC 210.07), the signal of
the new quaternary centre C-9 at lC 87.61 and
the splitting of the methylene groups of the
Scheme 4. (i) 254 nm, MeCN, 18 °C, 16: 9 h, 75%, 17: 7.5 h,
58%.

S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
277
Fig. 1. ORTEP drawing of 16.
Fig. 2. ORTEP drawing of 17.
173.93). Furthermore, the new quaternary
centre C-9 gave a signal at lC 87.75 and the
secondary centres of the former glutarimide
system appeared at lC 36.46 (C-7), lC 34.39
(C-5) and lC 24.09 (C-6). Likewise all other
tricycles examined, the coupling constants (J1,2
and J10,11) displayed that the annelated ring
did not have significant influence on the con-
formation of the pyranose chair. X-ray struc-
Irradiation of the glutarimido derivative 15
was terminated after 8 h and afforded 73% of
the azocanedione system 19 as well as 16% of
recovered starting material. Elimination only
led to trace amounts of unsaturated man-
nosan derivative. Characteristic NMR data of
the tricyclic system 19 were the signals of the
carbonyl group at lC 208.52 and the lactam
system (NHꢀCꢁO, doublet at l 5.80 and lC

278
S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
significantly diverse effects.13,14 Additionally,
these heterotricycles constitute interesting ob-
jects as precursors to branched chain sugars.15
The chemical transformations of the azepane-
diones 16 and 18 and the azocanediones 17
and 19 such as N-protection with subsequent
lactam opening or cleavage of the 1,6-anhydro
bridge bear some exciting structures, which in
turn open new potentials of chemical modifi-
cations and structure design, and offer ver-
satile access to variably functionalised
heterocycles and higher sugar derivatives.
3. Experimental
Scheme 5. (i) 254 nm, MeCN, 18 °C, 18: 7 h, 85%, 19: 8 h,
General methods.—TLC was performed on
Silica Gel 60-coated aluminium sheets (E.
Merck) using the given eluent mixtures. Spots
were visualised under UV light at 366 nm and
by spraying with 10% H2SO4 in EtOH and
subsequent heating. Column chromatography
was performed on Silica Gel 60 (230–240
mesh, grain size 0.040–0.063 nm, E. Merck).
Petroleum ether refers to the fraction with
distillation range 50–70 °C. All irradiations
were performed in commercial dry MeCN
(Fluka), deoxygenated by 30 min degassing
with Ar in an ultrasonic bath. A 60 Watt
73%.
ture analysis of 19 verified these results and is
shown as an ORTEP drawing in Fig. 3. Again,
1
the C4 pyranose chair is annelated to the
eight-membered ring, however, in this case a
sort of crown (chair–chair) conformation was
observed.
The azepanedione system in principle is an
interesting structural element as it is wide-
spread in physiologically active compounds in
which only minor structural changes induce
Fig. 3. ORTEP drawing of 19.

S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
279
quoted temperature. The reaction mixture was
concentrated under reduced pressure and
codestilled twice with toluene. The residue was
taken up in CH2Cl2, neutralised with aq satd
NaHCO3 solution and washed with brine.
Drying and evaporation of the solvent af-
forded the crude product, which was purified
by column chromatography using the quoted
eluent and if necessary by subsequent
recrystallisation.
low-pressure mercury vapour lamp of the
company Heraeus (u=254 nm) was used. The
photo reactor was made of quartz glass and
measured 35 cm in length and 4.5 cm in
diameter, and the temperature was maintained
at 18 °C by water cooling. Melting points were
measured on a ST-apotec and are reported
uncorrected. Optical rotations were measured
on a Perkin–Elmer Polarimeter 243, with [h]D
values given in units of 10−1 deg cm2 g−1
.
Elemental analyses were performed by the mi-
croanalytical laboratory of the Institute of
Organic Chemistry of the University of Ham-
burg. IR absorptions were recorded on a ATI
Matteson FTIR (Genesis Series). NMR spec-
tra were recorded on a Bruker AMX-400
NMR spectrometer. Chemical shifts are re-
ferred to the solvent used.
Procedure A: isopropylidenation.—The diol
(50 mmol) was dissolved in acetone (100 mL)
and 2,2-dimethoxypropane (50 mL) and
treated with catalytic amounts of 4-toluene
sulfonic acid. After stirring overnight at rt, the
reaction was quenched by addition of triethy-
lamine (5 mL) and concentrated under re-
duced pressure. The residue was taken up in
CH2Cl2 or Et2O and washed with aq satd
NaHCO3 solution and brine. Drying and
evaporation of the solvent left the crude
product, which was purified by column chro-
matography using the quoted eluent.
Procedure B: hydrogenation.—The azide (20
mmol) was dissolved in a mixture of dry
EtOAc (100 mL) and dry MeOH (25 mL) and
hydrogenated using Pd/C (10 %) (10% by
weight) by stirring at rt under one atmosphere
of hydrogen for 2 days. Removal of the cata-
lyst by filtration through a short pad of Celite
and evaporation of the solvents yielded the
amine, which was transformed without further
purification.
Procedure C: imide formation.—A suspen-
sion of the amine (10.0 mmol), succinic anhy-
dride (10.0 g, 100.0 mmol) or glutaric
anhydride (11.4 g, 100.0 mmol) and N-ethyldi-
isopropylamine (1.7 mL, 10.0 mmol) in dry
CH2Cl2 (75 mL) was stirred overnight at rt.
After addition of MeOH (10 mL), the solvents
were evaporated under reduced pressure. The
residue was dissolved in dry pyridine (30 mL)
and Ac2O (30 mL) and stirred overnight at the
Procedure D: irradiation.—The imido-sub-
stituted sugar (0.5–1.0 g) was dissolved in dry,
deoxygenated MeCN (200 mL) and irradiated
at 18 °C under an Ar atmosphere for 7–9 h.
Purification was performed by column chro-
matography using the quoted eluent and by
subsequent recrystallisation.
1,6-Anhydro-2-azido-2-deoxy-3,4-O-iso-
propylidene-i-
Anhydro-2-azido-2-deoxy-b-
D
-galactopyranose
(6).—1,6-
D
-galactopyranose
(5, 5.70 g, 30.39 mmol) was protected follow-
ing Procedure A. Column chromatography
with 12:1 petroleum ether–EtOAc yielded
compound 6 (5.01 g, 73%) as white crystals:
mp 38 °C, [h]2D0 −25.8° (c 1.0, CHCl3). Anal.
Calcd for C9H13N3O4: C, 47.57; H, 5.77; N,
18.49. Found: C, 48.00; H, 5.84; N, 17.96.
2-Amino-1,6-anhydro-2-deoxy-3,4-O-iso-
propylidene-i-
D
-galactopyranose
(7).—Re-
duction of azide 6 (4.0 g, 17.60 mmol)
according to Procedure B provided the amine
7 (3.43 g, 97%) as a hygroscopic, colourless
solid which was transformed without further
purification.
1,6-Anhydro-2-deoxy-3,4-O-isopropylidene-
2-N-succinimido-i- -galactopyranose (8).—
D
The amine 7 (2.0 g, 9.94 mmol) was reacted
with succinic anhydride according to Proce-
dure C, with the cyclisation step completed
after stirring overnight at room temperature.
Column chromatography using 3:1 petroleum
ether–ethylacetate as eluent yielded the pure
product, which was furthermore recrystallised
from 2-propanol to give compound 8 (1.80 g,
64%) as white needles: mp 209–211 °C, [h]D20
+21.5° (c 1.0, CHCl3). Anal. Calcd for
C13H17NO6: C, 55.12; H, 6.05; N, 4.94. Found:
C, 54.74; H, 5.99; N: 4.69.
1,6-Anhydro-2-deoxy-2-N-glutarimido-3,4-
O-isopropylidene-i- -galactopyranose (9).—
D
The amine 7 (2.0 g, 9.94 mmol) was reacted

280
S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
compound 15 (1.71 g, 58%) as white needles:
mp 137–138 °C, [h]2D0 −118.9° (c 1.5, CHCl3).
Anal. Calcd for C14H19NO6: C, 56.56; H, 6.44;
N, 4.71. Found: C, 56.55; H, 6.67; N, 4.33.
(1R,2R,8R,9S,10R) - 8,9 - Isopropylidene-
dioxy - 12,13 - dioxa - 3 - aza - tricyclo[8.2.1.02,8]-
tridecan-4,7-dione (16).—The succinimido
derivative 8 (0.99 g, 3.49 mmol) was irradiated
according to Procedure D for 9 h. Purification
by column chromatography with 3:1–1:1
petroleum ether–EtOAc yielded recovered
starting material (0.13 g, 14%) and compound
16 (0.74 g, 75%) as a white solid, which can be
crystallised from 2-propanol to give colourless
needles: mp 272–275 °C, [h]2D0 +1.7° (c 1.0,
with glutaric anhydride according to Proce-
dure C, with the cyclisation step requiring 20
h at 100 °C. Column chromatography using
3:1 petroleum ether–ethylacetate yielded the
pure product 9 (2.21 g, 75%) which was fur-
thermore crystallised from 2-propanol to give
colourless, prismatic crystals: mp 213 °C, [h]D20
+3.7° (c 0.79, CHCl3). Anal. Calcd for
C14H19NO6: C, 56.56; H, 6.44; N, 4.71. Found:
C, 56.38; H, 6.45; N, 4.50.
1,6-Anhydro-4-azido-4-deoxy-2,3-O-iso-
propylidene-i-
Anhydro-4-azido-4-deoxy-b-
D
-mannopyranose
(12).—1,6-
D
-mannopyranose
(11, 6.0 g, 32.06 mmol) was protected accord-
ing to Procedure A. Column chromatography
using 12:1 petroleum ether–EtOAc afforded
compound 12 (5.83 g, 80%) as a white solid:
mp 49 °C, [h]2D0 −111.7° (c 1.0, CHCl3). Anal.
Calcd for C9H13N3O4: C, 47.57; H, 5.77; N,
18.49. Found: C, 47.97; H, 5.82; N, 18.16.
4-Amino-1,6-anhydro-4-deoxy-2,3-O-iso-
1
CHCl3), H NMR (CDCl3): l 6.19 (sb, 1 H,
NH), 5.38 (s, 1 H, H-1), 5.26 (d, 1 H, J9,10 7.1
Hz, H-9), 4.78 (dd, 1 H, J10,11b 4.6 Hz, H-10),
4.29 (d, 1 H,, J11a,11b 7.6 Hz, H-11a), 3.90 (d,
1 H, J2,NH 5.1 Hz, H-2), 3.57 (dd, 1 H, H-11b),
3.22–3.11 (m, 2 H, H-6a, H-5a), 2.67 (m, 1 H,
H-6b), 2.45 (m, 1 H, H-5b), 1.53, 1.19 (both s,
both 3 H, ꢀCH3, isopropylidene), 13C NMR
(CDCl3): l 207.14 (CꢁO), 174.81 (NHꢀCꢁO),
110.56 (isopropylidene, 99.78 (C-1), 83.46 (C-
8), 72.48 (C-10), 67.85 (C-9), 63.34 (ꢀCH2ꢀ,
C-11), 60.98 (C-2), 36.48 (ꢀCH2ꢀ, C-6), 29.97
(ꢀCH2ꢀ, C-5), 26.81, 25.81 (both ꢀCH3, iso-
propylidene). Anal. Calcd for C13H17NO6: C,
55.12; H, 6.05; N, 4.94. Found: C, 54.88; H,
6.08; N, 4.89.
propylidene-i- -mannopyranose (13).—The
D
azide 12 (3.6 g, 15.84 mmol) was hydro-
genated following Procedure B and the amine
13 (3.12 g, 98 %) was obtained as a hygro-
scopic, colourless solid which was transformed
without further purification: mp 77–79 °C,
[h]2D0 −40.3° (c 1.0, CHCl3).
1,6-Anhydro-4-deoxy-2,3-O-isopropylidene-
4-N-succinimido-i- -mannopyranose (14).—
D
Compound 13 (2.5 g, 12.42 mmol) was reacted
with succinic anhydride according to Proce-
dure C, with the cyclisation step carried out
by stirring overnight at rt. The crude product
was purified by column chromatography using
3:1 petroleum ether–EtOAc as eluent and
subsequent crystallisation from 2-propanol to
give compound 14 (2.43 g, 69%) as white
crystals: mp 187–189 °C, [h]2D0 −93.5° (c 1.0,
CHCl3). Anal. Calcd for C13H17NO6: C, 55.12;
H, 6.05; N, 4.94. Found: C, 55.20; H, 6.09; N,
4.79.
(1R,2R,9R,10S,11R) - 9,10 - Isopropylidene-
dioxy - 13,14 - dioxa - 3 - aza - tricyclo[9.2.1.02,9]-
tetradecan-4,8-dione (17).—Irradiation of the
glutarimido derivative 9 (0.99 g, 3.33 mmol)
according to Procedure D for 7.5 h and purifi-
cation by column chromatography using 3:1–
1:2 petroleum ether–EtOAc gave recovered
starting material (0.12 g, 12%), impurified,
unidentified side product (0.14 g, 14%) and
compound 17 (0.57 g, 58%) as a white solid,
which was crystallised from 2-propanol as
colourless, prismatic crystals: mp 218 °C, [h]D20
1,6-Anhydro-4-deoxy-4-N-glutarimido-2,3-
1
O-isopropylidene-i-
D
-mannopyranose (15).—
+44.9° (c 0.65, CHCl3), H NMR (CDCl3): l
Compound 13 (2.0 g, 9.94 mmol) was reacted
with glutaric anhydride according to Proce-
dure C, with the cyclisation step requiring
90 °C for 20 h. The crude product was purified
by column chromatography using 3:1
petroleum ether–EtOAc as eluent and subse-
quent crystallisation from 2-propanol to give
5.41 (d, 1 H, J2,NH 10.7 Hz, NH), 5.38 (s, 1 H,
H-1), 5.09 (d, 1 H, J10,11 6.6 Hz, H-10), 4.62
(dd, 1 H, J11,12b 4.5 Hz, H-11), 4.37 (d, 1 H,
J12a,12b 7.6 Hz, H-12a), 4.08 (d, 1 H, H-2), 3.64
(dd, 1 H, H-12b), 3.42 (m, 1 H, H-7a), 2.54–
2.40 (m, 2 H, H-5a, H-5b), 2.26 (m, 1 H,
H-7b), 2.15 (m, 1 H, H-6a), 2.03 (m, 1 H,

S. Thiering et al. / Carbohydrate Research 336 (2001) 271–282
281
(d, 1 H, J1,13b 6.3 Hz, H-1), 4.21 (dd, 1 H,
H-13a), 4.13 (d, H-2), 3.83 (dd, 1 H, J13a,13b
7.5 Hz, H-13b), 3.38 (m, 1 H, H-7a), 2.52–
2.42 (m, 2 H, H-5a, H-5b), 2.26 (m, 1 H,
H-7b), 2.10–1.99 (m, 2 H, H-6a, H-6b), 1.61,
1.16 (both s, both 3 H, ꢀCH3, isopropylidene),
13C NMR (CDCl3): l 208.52 (CꢁO), 173.93
(NHꢀCꢁO), 112.41 (isopropylidene), 99.28 (C-
11), 87.75 (C-9), 75.47 (C-1), 70.96 (C-10),
64.85 (ꢀCH2ꢀ, C-13), 53.01 (C-2), 36.46
(ꢀCH2ꢀ, C-7), 34.39 (ꢀCH2ꢀ, C-5), 27.97,
26.17 (both ꢀCH3, isopropylidene), 24.09
(ꢀCH2ꢀ, C-6). Anal. Calcd for C14H19NO6: C,
56.56; H, 6.44; N, 4.71. Found: C, 56.56; H,
6.38; N, 4.71.
H-6b), 1.60, 1.17 (both s, both 3 H, ꢀCH3,
isopropylidene), 13C NMR (CDCl3): l 210.07
(CꢁO), 174.22 (NHꢀCꢁO), 110.74 (isopropyli-
dene), 100.40 (C-1), 87.61 (C-9), 72.45 (C-11),
68.15 (C-10), 65.02 (ꢀCH2ꢀ, C-12), 54.75 (C-
2), 37.25(ꢀCH2ꢀ, C-7), 34.08 (ꢀCH2ꢀ, C-5),
27.19, 26.74 (both ꢀCH3, isopropylidene),
23.27 (ꢀCH2ꢀ, C-6). Anal. Calcd for
C14H19NO6: C, 56.56; H, 6.44; N, 4.71. Found:
C, 56.17; H, 6.45; N, 4.51.
(1R,2R,8S,9S,10R) - 8,9 - Isopropylidene-
dioxy - 11,13 - dioxa - 3 - aza - tricyclo[8.2.1.02,8]-
tridecan-4,7-dione (18).—The succinimido
derivative 14 (0.73 g, 2.59 mmol) was irradi-
ated according to Procedure D for 7 h. Purifi-
cation by column chromatography with
1:1–1:2 petroleum ether–EtOAc yielded com-
pound 18 (0.62 g, 85%) as a white solid, which
can be crystallised from 2-propanol or MeOH
to give fine white needles: mp 265–269 °C
4. Supplementary material
Complete crystallographic data for the
structural analysis have been deposited with
the Cambridge Crystallographic Data Centre,
CCDC no. 163492 (19), 163493 (16) and
163494 (17). Copies of this information may
be obtained free of charge from The Director,
CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (fax: +44-1223-336033, e-mail: de-
posit@ccdc.cam.ac.uk or www: http://www.
ccdc.cam.ac.uk).
1
(dec), [h]2D0 −47.6° (c 0.72, MeOH), H NMR
(CDCl3): l 5.77 (d, 1 H, J2,NH 5.0 Hz, NH),
5.54 (d, 1 H, J9,10 3.8 Hz, H-10), 4.87 (d, 1 H,
H-9), 4.55 (d, 1 H, J1,12b 6.3 Hz, H-1), 4.09–
4.05 (m, 2 H, H-2, H-12a), 3.91 (dd, 1 H,
J12a,12b 7.6 Hz, H-12b), 3.28 (m, 1 H, H-6a),
3.12 (m, 1 H, H-5a), 2.67 (m, 1 H, H-6b), 2.57
(m, 1 H, H-5b), 1.56, 1.19 (both s, both 3 H,
ꢀCH3, isopropylidene), 13C NMR (CDCl3) l
204.77 (CꢁO), 173.36 (NHꢀCꢁO), 112.55 (iso-
propylidene), 99.50 (C-10), 84.37 (C-8), 73.97
(C-1), 70.95 (C-9), 66.23 (ꢀCH2ꢀ, C-12), 57.09
(C-2), 33.39 (ꢀCH2ꢀ, C-6), 29.96 (ꢀCH2ꢀ, C-
5), 27.25, 26.79 (both ꢀCH3, isopropylidene).
Anal. Calcd for C13H17NO6: C, 55.12; H, 6.05;
N, 4.94. Found: C, 55.35; H, 6.18; N, 4.70.
(1R,2R,9S,10S,11R) - 9,10 - Isopropylidene-
dioxy - 12,14 - dioxa - 3 - aza - tricyclo[9.2.1.02,9]-
tetradecan-4,8-dione (19).—Application of
Procedure D to the glutarimido derivative 15
(0.55 g, 1.86 mmol) for 8 h and subsequent
Acknowledgements
Support of this work by the Fonds der
Chemischen Industrie and the Deutsche
Forschungsgemeinschaft (GRK 464) is grate-
fully acknowledged.
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