Full acetals of β-D-glycopyranosylnitromethanes and a 1,2-dideoxy-1- nitroalk-1-enitol derived from common hexoses

Article abstract of DOI:10.1016/S0008-6215(97)00203-6

Kinetically controlled O-isopropylidenation of common 2,6-anhydro-1- deoxy-1-nitroalditols (β-D-glycopyranosylnitromethanes) derived from D- glucose, D-galactose, and D-mannose with 2-methoxypropene in 1,2- dimethoxyethane catalyzed with 4-toluenesulfonic

Full text of DOI:10.1016/S0008-6215(97)00203-6

Ž
.
Carbohydrate Research 306 1998 45–55
Full acetals of b-D-glycopyranosylnitromethanes
and a 1,2-dideoxy-1-nitroalk-1-enitol derived from
1
common hexoses
a
a
b
Duy-Phong Pham-Huu , Maria Petrusova , James N. BeMiller ,
´
ˇ ´
d
Peter Koll c,), Jungen Kopf , Ladislav Petrus
Institute of Chemistry, SloÕak Academy of Sciences, 84238 BratislaÕa, SloÕakia
The Whistler Center for Carbohydrate Research, Purdue UniÕersity, West Lafayette, IN 47907-1160,
a
¨
¨
ˇ
a
b
d
USA
c
Department of Chemistry, UniÕersity of Oldenburg, Carl-Õon-Ossietsky-str. 9-1, 26111 Oldenburg,
Germany
Department of Inorganic and Applied Chemistry, UniÕersity of Hamburg, 20146 Hamburg, Germany
Received 25 February 1997; accepted 17 June 1997
Abstract
Kinetically controlled O-isopropylidenation of common 2,6-anhydro-1-deoxy-1-nitroaldi-
Ž
.
tols b-D-glycopyranosylnitromethanes derived from D-glucose, D-galactose, and D-mannose
with 2-methoxypropene in 1,2-dimethoxyethane catalyzed with 4-toluenesulfonic acid af-
forded high yields of 2,3;4,6-di-O-isopropylidene acetals. With D-mannose, the bisacetal was
also obtained in quantitative yield by reaction with 2,2-dimethoxypropane. Mono-O-benzyl-
idenation of the starting compounds with benzaldehyde dimethyl acetal followed by O-isopro-
pylidenation led to 4,6-O-benzylidene-2,3-O-isopropylidene acetals having better solubilities
in non-polar solvents than the di-O-isopropylidene acetals. Di-O-benzylidenation of b-D-man-
Ž
.
Ž
.
nopyranosylnitromethane gave both endo-2,3 :4,6- and exo-2,3 :4,6-di-O-benzylidene ac-
etals. Transacetalation of 1-deoxy-1-nitro-D-mannitol with 2,2-dimethoxypropane followed by
Ž
.
2-O-acetylation and b-elimination of the acetoxy group afforded E -1,2-dideoxy-2,4:5,6-di-
O-isopropylidene-1-nitro-D-arabino-hex-1 -enitol. q 1998 Published by Elsevier Science Ltd.
All rights reserved.
Keywords: Carbohydrate acetals; D-arabino-Hex-1-enitol; 1,2-dideoxy-1-nitro-; C-Glycosyl compounds; b-D-Gly-
copyranosylnitromethanes; Isopropylidenation
1. Introduction
Ž
2,6-Anhydro-1-deoxy-1-nitroalditols glyco-
.
) Corresponding author.
pyranosylnitromethanes are convenient precursors for
the synthesis of C-glycosyl mimics of naturally oc-
curring carbohydrates 1–3 . However, a precondition
1 Dedicated to Professor Dr. Hans Paulsen on occasion
of his 75th birthday.
w
x
0008-6215r98r$19.00 q 1998 Published by Elsevier Science Ltd. All rights reserved.

(
)
46
D.-P. Pham-Huu et al.rCarbohydrate Research 306 1998 45–55
for their use as C-glycosyl donors in nucleophilic
additions is good solubility and stability of their
nitronate forms generated with bases in anhydrous
solvents, a condition not fulfilled by their per-O-
acetates. Here, we introduce full acetals as a new
group of b-D-glycopyranosylnitromethanes fully pro-
tected with O-isopropylidene groups. Such acetals
have previously been prepared from O-glycosides of
Therefore, preparation of a fully O-acetalated nitro-
hexenitol as a base-stable equivalent to 3,4,5,6-tetra-
O-acetyl-1,2-dideoxy-1-nitro-D-arabino-hex-1-enitol
w
x
10 is also described.
2. Results and discussion
w
x
D-glucose and D-galactose 4–6 , but only partial
acetals of b-D-glycopyranosylnitromethanes have
Kinetically controlled acetonation was performed
essentially under the same conditions applied for
di-O-isopropylidenation of D-gluco- and D-galac-
w
x
been described 7,8 .
w
x
1,2-Dideoxy-1-nitroalk-1-enitol peracetates as
acyclic glycose precursors are useful reactive species
applicable as acceptors in nucleophilic additions e.g.,
Ref. 9 . Their use, however, is limited because of
instability of the protecting groups in basic media.
topyranosides 4,5 , except for using a more conve-
nient solvent, 1,2-dimethoxyethane, in place of
N,N-dimethylformamide. Treatment of 2,6-anhydro-
Ž
w x.
w x Ž
1-deoxy-1-nitro-D-glycero-D-gulo-heptitol 11 b-D-
.
glucopyranosylnitromethane, 1 , 2,6-anhydro-7-de-
Scheme 1.

(
)
D.-P. Pham-Huu et al.rCarbohydrate Research 306 1998 45–55
47
w
x Ž
oxy-7-nitro-L-glycero-L-galacto-heptitol 11
b-D-
reaction time of 1 and 2 led to complex mixtures of
products which were not analyzed in detail; only the
prevailing product from the reaction of 2, character-
.
galactopyranosylnitromethane, 2 , and 2,6-anhydro-
w
x Ž
1-deoxy-1-nitro-D-glycero-D-galacto-heptitol 12 b-
D-manno-pyranosylnitromethane, 3 with an excess of
2-methoxypropene and a catalytic amount of 4-
toluenesulfonic acid in 1,2-dimethoxyethane under
anhydrous conditions resulted in almost complete
formation of the respective 2,3:4,6-di-O-isopropyli-
dene acetals 5–7 Scheme 1 . The reactions were
rapid; starting glycosylnitromethanes dissolved within
1 min and reaction was complete by TLC in 10–15
min. Diacetals 5–7 were isolated after purification by
flash chromatography in 80–90% yields. Prolonged
.
Ž
ized as the 3,4-O-isopropylidene-6-O- 1-methoxy-1-
.
Ž .
Ž
.
methylethyl derivative 8 , was isolated 46% yield .
Comparative thermodynamically controlled iso-
propylidenation of 1 and 2 with 2,2-dimethoxy-
propane did not afford appreciable amounts of bisac-
etals. Rather, 4,6-mono-O-isopropylidene derivative
9 was a single product from starting 1, and a mixture
of products not further identified resulted from start-
ing 2. This acetonation is, however, more convenient
and unambiguous for preparation of diacetal 7, which
was obtained from 3 in almost quantitative yield,
confirming that trans-2,3-diequatorial isopropylide-
nation is not favorable when 2,2-dimethoxypropane,
Ž
.
Ž
.
Table 1
Crystallographic data for 14a,b
w x
as opposed to 2-methoxypropene, is used 4 .
Similar transacetalation reactions of benzaldehyde
dimethyl acetal with glycosylnitromethanes 1–3 re-
sulted in the formation of expected 4,6-O-benzyl-
idene acetals 10–12. With starting 3, the acetalation
occurred further at its cis diol site and two di-O-ben-
zylidene acetals 13 and 14 which differed in their
stereochemistry at the five-membered ring acetal car-
bon atom were separated by flash chromatography
and isolated in respective 50% and 32% yields. Com-
pound 14 was obtained from ether in a form conve-
nient for X-ray crystal structural analysis and mea-
surements were performed at y1008C. The structure
was solved by direct methods with the SHELXS-96
14
Formula
Mol wt
Crystal dimensions mm
C21H21NO7
399.39
0.5=0.4=0.2
195–198
P21
Ž
.
Ž
.
mp 8C
Space group
Ž
.
Cell parameters pm, degrees
Ž .
545.4 1
a
b
c
Ž .
1123.8 1
Ž .
1557.5 1
Ž .
95.54 1
b
3
950.2=106
2
Ž
.
Volume V pm
Z
Ž
.
F 000
Calculated density, Dx g cm
m cm
420
1.396
8.9
154.178
5.7–152.1
4519
3858
3777
284
y3
Ž
.
y1
w
x
w x
program 13 and refined with SHELXL-96 14 . The
Ž
Ž
.
refinement was done on F2 for all reflections. The
. Ž .
l Cu Ka pm
Ž
.
2Q range degrees
Reflections measured
Symmetry independent reflections
Ž ..
Ž
.
validated threshold F)2s F was used for calcu-
lating Robsd only. All atoms, including hydrogens
introduced at theoretical positions using the AFIX
Reflections with F)2s F
Number of refined parameters
w
x
option 14 , were refined. Table 1 gives the relevant
crystallographic data of 14. The final fractional
2
Ratio of valued reflections to parameters 13.6
Final residual factors Rc,d
R1Žobsd.
wR2Žall.
wR2Žobsd.
Goodness of fit Se
Sall
coordinates of C and O with equivalent thermal
parameters are given in Table 2. An ORTEP equiva-
lent illustration of the title compound including the
numbering scheme was obtained with PLATON96
0.050
0.144
0.141
w
x
15 and is presented in Fig. 1. It can be seen that 14
is the 2,3-exo diastereomer, leaving the correspond-
1.04
1.04
Sobsd
y3
0.26=10y6
y0.19=10y6
Ž
Ž
.
Largest difference peak e pm
Largest difference hole e pm
Flack parameter
y3
.
Ž .
0.2 2
aStandard deviations in parentheses.
2 Tables of atomic coordinates including anisotropic
thermal parameters for the heavy atoms and isotropic ones
for the hydrogen atoms, bond lengths, and bond angles
have been deposited with the Cambridge Crystallographic
Data Centre. These tables may be obtained, on request,
from the Director, Cambridge Crystallographic Data Cen-
tre, 12 Union Road, Cambridge, CB2 1EZ, UK.
b Diffractometer Enraf–Nonius CAD4.
c
2
5
<
<
<
<
<
w
Ž
Definitions: R11sr2 Ý F0 y F0 rÝ F0 ; wR2 s Ýw F0 y
F2 rÝw F0
.
2
.
Ž
2 .2 x
c
d Weighting scheme: w s 1r s F0 q 0.1147P 2 q
2
w
2Ž
.
Ž
.
2
2
x
Ž
.
c
2
0.0948 P where Ps F0 q2F r3.
e
2
2
c
1r2
w
Ž
.
Ž
.x
Definition: Ss Ýw F0 y F r ny p
.

(
)
48
D.-P. Pham-Huu et al.rCarbohydrate Research 306 1998 45–55
Table 2
ing endo structure for 13. The pyranoid ring is found
4
Fractional positional parameters of C, O and N atoms and
the temperature factors U for 14
Atom 104
Ž .
in a slightly flattened C1 D conformation with
puckering parameters according to Cremer and Pople
a
Ž
.
eq
x
104
y
104 z
Ž .
3350 1
3474 1
Ž .
2665 1
1801 1
Ž .
1574 1
5220 2
Ž .
4658 1
103 U
eq
w
x
Ž .
Ž .
16,17 of Qs54.5 2 pm, us20.4 2 8 and fs
Ž .
6515 3
Ž .
Ž .
42 1
O-2
O-3
O-4
O-5
y62 1
Ž .
316.5 6 8.
Ž .
Ž .
2578 1
Ž .
Ž .
44 1
7881 2
In order to obtain full and defined acetals of
Ž .
4439 3
Ž .
Ž .
44 1
3248 1
glycosylnitromethanes 1–3 as single products with
better solubilities of their nitronate forms in ben-
zenoid solvents, monobenzylidene acetals 10–12 were
treated with 2-methoxypropene. TLC analysis showed
that the treatment resulted in rapid formation of
4,6-O-benzylidene-2,3-O-isopropylidene derivatives
Ž .
Ž .
1141 1
Ž .
Ž .
45 1
1740 3
Ž .
2013 3
Ž .
Ž .
57 1
O-7
y902 1
Ž .
Ž .
y1143 2
Ž .
Ž .
74 1
O-11
O-12
N-1
C-1
C-2
C-3
C-4
C-5
C-6
7824 3
Ž .
11260 3
Ž .
Ž .
62 1
y1049 2
Ž .
Ž .
y612 2
Ž .
Ž .
46 1
9340 3
4849 1
Ž .
Ž .
8807 4
Ž .
Ž .
45 1
655 2
4600 1
Ž .
Ž .
728 2
Ž .
Ž .
37 1
6378 3
4054 1
Ž .
3780 1
3020 1
Ž .
2370 1
2813 1
Ž .
2129 2
2759 1
Ž .
1179 1
2891 1
Ž .
3429 2
3509 2
Ž .
3047 2
Ž
.
15–17 complete in 15 min . Derivatives 15–17 were
isolated by flash chromatography in 77–88% yields.
Derivative 17 was obtained in the same yield also by
controlled acid-catalyzed transacetalation reaction of
2,2-dimethoxypropane with 12. Attempted prepara-
tion of 17 by a direct, one-step, regioselective diac-
etalation of 3 using equimolar amounts of benzal-
dehyde dimethyl acetal and 2,2-dimethoxypropane
led to a complex mixture of products.
Ž .
5796 3
Ž .
Ž .
37 1
2009 2
Ž .
Ž .
2138 2
Ž .
Ž .
38 1
3823 3
Ž .
3941 4
Ž .
Ž .
38 1
1139 2
Ž .
Ž .
y63 2
Ž .
Ž .
41 1
4241 4
Ž .
4241 5
Ž .
Ž .
56 1
C-7
C-8
C-9
y1019 2
Ž .
Ž .
3325 2
Ž .
Ž .
40 1
7053 3
Ž .
1848 4
Ž .
Ž .
48 1
228 2
Ž .
Ž .
4605 2
Ž .
Ž .
42 1
C-81
C-82
C-83
C-84
C-85
C-86
C-91
C-92
C-93
C-94
C-95
C-96
7794 4
Ž .
6571 5
Ž .
Ž .
53 1
5333 2
Ž .
Ž .
6526 2
Ž .
Ž .
67 1
7240 6
Ž .
9051 6
Ž .
Ž .
72 1
6985 2
Finally, analogical trans-acetalation of 1-deoxy-
Ž .
Ž .
6258 3
Ž .
Ž .
77 1
10241 6
2516 3
Ž .
w
x Ž .
1-nitro-D-mannitol 18
propane afforded 1-deoxy-3,4:5,6-di-O-isopropyli-
4 with 2,2-dimethoxy-
Ž .
9629 4
Ž .
Ž .
57 1
5052 2
2435 2
Ž .
Ž .
295 2
Ž .
Ž .
52 1
y416 5
551 1
Ž .
157 2
Ž
.
dene-1-nitro-D-mannitol 18 in an isolated yield of
70%. Acetylation of 18 under conditions used for a
Ž .
y1434 6
Ž .
Ž .
Ž .
69 1
y722 3
Ž .
Ž .
Ž .
83 1
y3395 7
y625 4
y481 2
Ž .
y4375 6
Ž .
459 4
Ž .
Ž .
81 1
y710 2
w x
b-D-glucopyranosyl analog 2 , but without the cat-
Ž .
Ž .
Ž .
Ž .
81 1
y3433 7
1471 4
y300 2
alytic amount of DMAP, gave its 2-O-acetyl deriva-
Ž .
y1481 6
Ž .
1390 3
Ž .
331 2
Ž .
66 1
Ž
.
tive 19 in addition to the expected nitroalkene, E -
1,2-dideoxy-3,4:5,6-di-O-isopropylidene-1-nitro-D-
aStandard deviations in parentheses.
w
x
Ž
.
Fig. 1. ORTEP equivalent representation 15 of 2,6-anhydro-1-deoxy- exo-3,4 :5,7-di-O-benzylidene-1-nitro-D-glycero-D-
galacto-heptitol 14 .
Ž
.

Table 3
13C chemical shifts of prepared compounds
c
c
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
Compd)
C-1
C-7
C-2–C-6
C A5
C A6
C Ph ; C Me ; C OMe
5a
6a
77.5
65.2
75.9
62.8
77.9
78.2
69.2
77.8
77.3
77.6
78.9
70.3
69.0
75.8
62.5
79.0
61.6
79.1
62.9
69.0
77.8
61.7
68.9
68.9
68.4
77.9
76.4
68.3
79.9, 76.4, 76.2, 73.7, 73.6
81.9, 78.1, 72.7, 71.9, 69.2
76.1, 73.7, 73.0, 72.6, 69.4
81.8, 78.1, 77.6, 76.5, 72.3
78.7, 76.2, 74.7, 72.9, 72.7
81.9, 78.0, 75.5, 72.6, 71.3
78.2, 77.2, 74.8, 70.7, 69.7
79.6, 75.6, 71.6, 70.9, 68.9
81.8, 76.9, 75.9, 73.9, 69.2
77.7, 77.3, 74.9, 74.3, 69.3
80.1, 76.2, 75.6, 75.3, 72.0
80.2, 76.8, 74.5, 71.2, 70.5
79.8, 75.8, 73.6, 70.2, 69.2
80.1, 75.5, 73.6, 73.1, 68.6
112.3
113.4
110.4
111.9
100.0
100.9
99.7
28.9, 27.0, 26.5, 19.5
30.6, 28.0, 27.9, 20.1
28.9, 28.2, 26.3, 18.7
29.6, 27.7, 25.9, 25.8; 50.0
29.3, 19.2
139.0, 129.5, 128.7, 127.2
139.7, 129.3, 128.6, 127.2
139.1, 129.4, 128.7, 127.2
138.9, 138.4, 130.2, 129.5, 129.2, 128.8, 127.6, 127.1
139.9, 138.4, 129.9, 129.6, 129.1, 128.8, 127.1
136.6, 129.2, 128.2, 126.3; 26.7, 26.3
139.5, 129.5, 128.7, 127.2; 26.8, 26.7
137.4, 129.0, 128.3, 126.1; 26.6, 26.4
138.0, 129.0, 128.1, 126.2; 28.2, 26.3
7b
8a
102.4d
100.7
102.1
101.4
102.4
102.2
102.3
101.6
100.8
100.4
101.8
9a
10a
11a
12a
13b
14b
15b
16a
16b
17b
105.3
104.1
112.6
111.5
111.6
110.5
c
Ž . Ž
.
Ž .
Ž
.
)Recorded in a CD3d 2CO or in b CDCl3 with TMS as an internal standard. Acetal carbon atom in a five-membered 1,3-dioxolane ring A5 or six-membered
Ž
.
1,3-dioxane ring A6 . Carbon atom of the acyclic acetal.

Table 4
1H chemical shifts of prepared compounds
X
Ž
.
Ž
.
Ž
.
Compd) H-1
H-1
H-2
H-3
H-4
H-5
H-6
H-7
H-7X
H–CPh
H Ph ; H Me ; H OMe
5a
6a
4.86 dd 4.59 dd
4.42 dd 3.87 dd
4.72 dd 4.60–4.53 m
3.62 d
4.93 dd 4.45 dd
4.96 dd 4.59 dd
4.45 dt 3.95 dd 3.80 m
3.36 m 4.60 dd 3.77 dd
4.24 dd 4.14 dd
3.36 t
3.85 t
3.34 dt 3.82–3.75 m
4.38 dt 4.80 dd
1.49, 1.41, 1.39, 1.32 s
1.53, 1.48, 1.44, 1.42 s
1.54, 1.51, 1.42, 1.34 s
1.52, 1.37, 1.35, 1.34 s; 3.21 s
1.30, 1.28 s
7.51–7.33 m
7.52–7.33 m
4.68 dd
3.70 dd
4.55 dd
3.63 t
3.45 m 5.58 s
4.63 dd 5.60 s
3.72 t
3.72 t
3.78 t
3.30 dd 5.57 s
4.73 dd 5.66 s
7b
3.72 dd 3.19 dt 3.91 dd
3.50 dd 3.96 m 4.87 dd
3.45 t
4.20 dd 3.52 m 3.68 t
4.06 m 4.98 dd
4.69 dd 3.43 m 4.14 dd
3.83 dd 3.57 td 4.24 dd
4.00 dd 3.56 td 4.29 dd
4.35 dd 3.51 m 3.80 m
4.43 dt 4.88 dd
8a
3.62 d
3.94 m 4.29 dd 4.12 dd
4.07 dt 3.53 m 3.34 m
4.17 m 3.75 m 3.49 m
3.62 m 4.30 dd 3.73–3.64 m
3.90 m 4.07 m 4.46 m
4.93 dt 4.59 dd 4.53 dd
4.82 dt 4.46 dd 4.74 dd
4.42 m 3.89–3.77 m
9a
3.29 dt 3.77 dd
10a
11a
12a
13b
14b
15b
16a
16b
17b
4.09 d
4.09 d
4.82 dd 4.71 dd
5.06 dd 4.74 dd
5.02 dd 4.70 dd
4.69 dd 4.49 dd
4.16d
4.31 dd 4.07 dd
4.98 dd 4.66 dd
5.59 s
7.50–7.34 m
5.98, 5.65 s 7.59–7.34 m
6.27, 5.73 s 7.52–7.36 m
7.33–7.51 m; 1.48, 1.47 s
7.51–7.32 m; 1.41, 1.29s
7.50–7.32 m; 1.47, 1.45 s
7.50–7.34 m; 1.35, 1.32 s
4.18 d
3.65 m 4.67 dd 3.95–3.86 m
3.47 m 4.54 dd 3.70 dd
4.82 dt 4.49 dd 4.35 dd
3.92 t
4.40 m 4.66 d
4.65 d
3.73 t
5.56 s
5.68 s
3.78 dd 3.46 td 4.23 dd
Ž . Ž
.
Ž .
)Recorded in a CD3 2CO or in b CDCl3 with TMS as an internal standard.

Table 5
Proton coupling constants of prepared compounds
X
X
X
X
Compd)
J1,1
J1,2
J1 ,2
J2,3
J3,4
J4,5
J5,6
J6,7
J6,7
J7,7
n
5a
6a
13.3
13.0
14.1
0.0
13.2
13.3
0.0
13.5
13.6
13.3
12.6
0.0
12.7
13.4
2.4
2.2
9.9
6.2
2.5
2.5
1.7
3.0
2.5
2.1
1.7
1.7
1.3
2.4
9.3
1.6
2.9
6.2
9.3
9.3
1.7
9.2
9.7
9.8
9.1
1.5
2.0
9.8
9.3
1.3
2.5
2.2
n
n
1.2
n
2.6
2.2
10.6
1.3
1.2
2.6
9.2
2.6
5.4
5.4
n
9.1
9.3
7.9
7.1
9.4
10.1
n
6.1
7.4
8.1
10.5
n
9.1
9.3
10.1
9.7
9.7
4.5
n
4.6
9.8
9.7
4.8
9.3
9.4
9.8
6.3
2.6
5.7
2.7
5.4
9.5
2.4
5.0
5.1
5.1
n
9.1
9.3
10.1
9.3
10.0
n
9.5
10.2
10.1
10.1
8.6
9.4
6.2
13.5
10.9
13.2
10.6
10.1
13.2
10.3
10.2
10.3
9.5
7b
8a
9a
10a
11a
12a
13b
14b
15b
16a
16b
17b
n
3.2
1.4
5.9
5.2
n
2.3
2.7
5.5
2.6
5.5
5.2
13.4
0.0
10.3
9.2
7.9
10.1
Ž . Ž
.
Ž .
)Recorded in a CD3 2CO or in b CDCl3 with TMS as an internal standard.
n—Not determined.

(
)
52
D.-P. Pham-Huu et al.rCarbohydrate Research 306 1998 45–55
Ž
. Ž
arabino-hex-1-enitol 20 20:19 ratio ca. 1:5 by
chromatograms with 10% ethanolic sulfuric acid and
charring them on a hot plate. Flash chromatography
13
.
C-NMR . Complete elimination of the acetoxy
Ž
group under formation of nitroalkene 20 was achieved
only after 14 h heating at the reflux temperature of
the benzene solution.
was performed using silica gel 0.040–0.100 mm,
.
Lachema .
Commercial benzylidene dimethyl acetal, 2,2-di-
1Hy and 13C-NMR data for all prepared acetals
methoxypropane, 2-methoxypropene, and 1,2-di-
methoxyethane were obtained from Aldrich. b-D-
provided proof of their structures. The 13C chemical
Ž
.
Ž .
shifts Table 3 of the isopropylidene methyl groups
clearly indicated the presence of both 1,3-dioxane
and 1,3-dioxolane rings. In accordance with detailed
Galactopyranosylnitromethane 1 , b-D-gluco-
Ž .
pyranosylnitromethane 2 , b-D-mannopyranosyl-
Ž . Ž .
nitromethane 3 , and 1-deoxy-1-nitro-D-mannitol 4
w
x
w
x
studies by Buchanan et al. 19 , 1,3-dioxane struc-
tures gave an acetal carbon signal at d ca. 99–101
and two methyl signals at d ca. 29–30 and d ca.
19–20. Corresponding signals in the 1,3-dioxolane
were prepared by published procedures 11,12,18 .
Isopropylidenation of glycosylnitromethanes with
2-methoxypropene.—A mixture of a glycosylni-
Ž
.
Ž
.
tromethane 1–3; 0.22 g, 1 mmol , Drierite 0.5 g ,
Ž
Ž .
arrangement were observed at d ca. 110–112 acetal
4-toluenesulfonic acid 20 mg , and 1,2-di-
.
Ž
Ž
.
carbon and dsca. 26–28 both methyl carbon
methoxyethane 10 mL was stirred 15 min under
nitrogen at rt. After addition of 2-methoxypropene
1.0 mL, 10.4 mmol , the reaction mixture was stirred
15 min. Then, NaHCO3 0.1 g was added. After
stirring 10 min, the neutral mixture was filtered with
suction and washed with MeOH 2=5 mL . Concen-
tration of filtrates in vacuo afforded a residue which
was purified by flash chromatography eluent: 1:2
vrv ethyl acetate–petroleum ether . Compounds 5–7
.
atoms . One signal of the methyl group of the termi-
Ž
.
nal isopropylidene group was observed at d ca.
24–25 for each compound 18–20. In agreement with
another study by Liptak et al. 20 , the size of the
Ž
.
w
x
´
Ž
.
acetal rings of benzylidene acetals 10–17 was also
apparent from their 13C chemical shifts; respective
acetal carbon atoms in 1,3-dioxolane and 1,3-dioxane
rings resonated at d ca. 104–105 and ca. 100–102.
Conversion of acetate 19 to nitroalkene 20 was clearly
indicated by disappearance of the signals of the acetyl
carbon atoms at d 20.0 and 168.7 and appearance of
those of the double bond at d 138.7 and 139.2.
Values of the chemical shifts of the double bond
protons of 20, d 7.24 and 7.36, are diagnostic of its
Ž
.
were thus prepared.
2,6-Anhydro-1-deoxy-3,4:5,7-di-O-isopropylidene-
Ž
1-nitro-D-glycero-D-gulo-heptitol 2,3:4,6-di-O-iso-
Ž .
.
propylidene-b-D-glucopyranosylnitromethane
5 :
Ž
Ž
.
w x
yield 0.26 g 87% ; mp 71–728C; a y18.08 c
D
.
Ž
1.0, acetone ; Rf 0.44 1:2 vrv ethyl acetate–petro-
w
x
.
Ž
.
E configuration 21,22 . The corresponding coupling
constant, J1,2 s13.3 Hz, also proved this stereochem-
leum ether . Anal. Calcd for C13H21NO7 303.32 : C,
51.48; H, 6.98; N, 4.62. Found: C, 51.33; H, 6.99; N,
4.35.
1
istry. H-NMR data of acetals 5–17 given in Table 4
Ž
.
Ž
.
chemical shifts and Table 5 coupling constants
support the assigned structures.
2,6-Anhydro-7-deoxy-1,3:4,5-di-O-isopropylidene-
Ž
7-nitro-L-glycero-L-galacto-heptitol 2,3:4,6-di-O-iso-
Ž .
.
Use of the full acetals of b-D-glycopyranosyl-
nitromethanes and 1,2-dideoxy-1-nitro-D-arabino-
hex-1-enitol for Michael additions is in progress.
propylidene-b-D-galactopyranosylnitromethane
6 :
Ž
.
w x Ž
yield 0.24 g 80% ; solid foam; a q12.08 c 1.0,
D
.
Ž
acetone ; Rf 0.39 1:2 vrv ethyl acetate–petroleum
.
Ž
.
ether . Anal. Calcd for C13H21NO7 303.32 : C,
51.48; H, 6.98; N, 4.62. Found: C, 51.79; H, 7.00; N,
4.26.
3. Experimental
2,6-Anhydro-1-deoxy-3,4:5,7-di-O-isopropylidene-
Ž
General methods and materials.—Melting points
were measured on a Kofler stage and are uncorrected.
Optical rotations were measured with a Perkin–Elmer
141 polarimeter at 208C. Microanalyses were ob-
tained using a Perkin–Elmer 240 instrument. NMR
1-nitro-D-glycero-D-galacto-heptitol 2,3:4,6-di-O-
. Ž .
isopropylidene-b-D-mannopyranosylnitromethane 7
was obtained directly by crystallization of the evapo-
ration residue: yield 0.27 g 90% ; mp 148–1508C;
y107.08 c 1.0, acetone ; Rf 0.48 1:2 vrv
ethyl acetate–petroleum ether . Anal. Calcd for
C13H21NO7 303.32 ; C, 51.48; H, 6.98; N, 4.62.
Ž
.
w x
a
Ž
.
.
Ž
D
spectra were recorded at 295 K on a Bruker AM 300
1
Ž
Ž
.
spectrometer 300.13 MHz for H and 75.47 MHz for
13
.
C . TLC was run on glass plates precoated with
silica gel L 0.005–0.040 mm, Lachema, Brno, Czech
Republic ; detection was effected by spraying the
Found: C, 51.66; H, 7.14; N, 4.44.
Ž
2,6-Anhydro-7-deoxy-3,4-O-isopropylidene-1-O-
1-methoxy-1-methylethyl -7-nitro-L-glycero-L-galacto-
.
(
)

(
)
D.-P. Pham-Huu et al.rCarbohydrate Research 306 1998 45–55
53
31
(
(
.
w x
w x
petroleum ether . Lit. 7 mp 211–2128C,
20
heptitol 3,4-O-isopropylidene-6-O- 1-methoxy-1-
a
D
)
) Ž .
Ž
.
w x w x
y35.48 c 1.3, MeOH ; lit. 8 mp 213–2148C, a
methylethyl -b-D-galactopyranosylnitromethane 8 .
—Treatment of b-D-galactopyranosylnitromethane
with 2-methoxypropene according to the procedure
given above, but prolonged for 2 days, gave 8 as the
major product isolated as a solid foam: yield 0.18 g
D
Ž
.
y42.68 MeOH .
2,6-Anhydro-1,3-O-benzylidene-7-deoxy-7-nitro-
L-glycero-L-galacto-heptitol 4,6-O-benzylidene-b-
D-galactopyranosylnitromethane 11 : yield 0.28 g
Ž
. Ž
.
Ž
.
w x
Ž
.
Ž
Ž
.
w
Ž
.
52% ; a q46.08 c 1.0, acetone ; Rf 0.25 1:2
88% ; mp 157–1598C, aD q10.88 c 4, acetone ;
D
.
Ž
.
vrv ethyl acetate petroleum ether . Anal. Calcd for
Rf 0.32 5:1 vrv EtOAc–petroleum ether . Anal.
Ž
.
Ž
.
C14H25NO8 335.36 : C, 50.14; H, 7.51; N, 4.18.
Calcd for C14H17NO7 311.29 : C, 54.02; H, 5.50;
Found: C, 50.38; H, 7.40; N, 3.86.
N, 4.50. Found: C, 53.85; H, 5.76; N, 4.33.
Isopropylidenation of glycosylnitromethanes with
2,2-dimethoxypropane.—To a mixture of a glycosyl-
Ž
.
Ž
.
nitromethane 0.22 g, 1 mmol , Drierite 0.5 g ,
Ž
.
Ž
4-toluenesulfonic acid 20 mg and 1,2-di-
methoxyethane 10 mL prestirred 15 min at rt, 2,2-
dimethoxypropane 1 mL, 8.1 mmol was added and
stirring was continued for 24 h. Then, NaHCO3 0.1
g was added, and after stirring 10 min, the neutral
mixture was filtered and washed with MeOH 2=5
mL . Concentration of filtrates afforded a residue
Ž
.
Ž
.
Ž
.
Ž
.
which crystallized from ethanol. Compounds 7 and 9
were thus prepared.
a
Ž
2,6-Anhydro-1-deoxy-3,4:5,7-di-O-isopropylidene-
Ž
1-nitro-D-glycero-D-galacto-heptitol 2,3:4,6-di-O-
. Ž .
isopropylidene-b-D-mannopyranosylnitromethane 7
identical with the sample obtained by isopropylidena-
Ž
.
(
)
tion with 2-methoxypropene: yield 0.29 g 98% .
2,6-Anhydro-1-deoxy- exo-3,4 :5,7-di-O-benzyl-
w
Ž
2,6-Anhydro-1-deoxy-5,7-O-isopropylidene-1-
nitro-D-glycero-D-gulo-heptitol 4,6-O-isopropyli-
dene-b-D-glucopyranosylnitromethane 9 : yield 0.23
g 87% ; mp 144–1458C, a y27.08 c 1, MeOH ;
Rf 0.49 ethyl acetate . Lit. 8 mp 158–1598C, a
idene-1-nitro-D-glycero-D-galacto-heptitol
2,3 :4,6-di-O-benzylidene-b-D-mannopyranosylnitro-
methane 14 : yield 0.13 g 32% ; mp 195–1988C;
exo-
Ž
.
. Ž .
Ž
x
Ž
.
Ž
.
Ž
.
w x
.
w x
Ž .
a
y1178 c 1.0, acetone ; Rf 0.79 and 0.42
w Dx
w x
D
Ž
Ž
.
Ž
EtOAc–petroleum ether, 5:1 vrv and 1:2 vrv, re-
D
.
.
Ž
.
y27.68 c 2, MeOH .
spectively . Anal. Calcd for C21H21NO7 399.40 : C,
63.15; H, 5.30; N, 3.51. Found: C, 63.35; H, 5.49; N,
3.50.
Benzylidenation procedure.—A mixture of a gly-
Ž
.
cosylnitromethane 1–3 0.22 g, 1 mmol , Drierite
Ž
.
Ž
.
0.5 g , 4-toluenesulfonic acid 20 mg and 1,2-di-
methoxyethane 10 mL was stirred 15 min under
nitrogen at rt. After addition of benzaldehyde dimethyl
acetal 0.3 mL, 2.0 mmol for monobenzylidenation;
0.6 mL, 4.0 mmol for dibenzylidenation , stirring was
continued for 20 h. NaHCO3 0.2 g was added, and
after stirring 10 min, the neutral mixture was filtered
with suction and washed with MeOH 2=5 mL .
Concentration of filtrates in vacuo afforded a residue
which was purified by flash chromatography eluent:
5:1 vrv ethyl acetate–petroleum ether . Compounds
Isopropylidenation of 4,6-O-benzylidene-glyco-
sylnitromethanes.—A mixture of Drierite 0.25 g ,
4-toluenesulfonic acid 10 mg and 1,2-di-
methoxyethane 5 mL was stirred 15 min under
nitrogen at room temperature. After addition of 2-
methoxypropane 0.5 mL, 5.2 mmol and a 4,6-O-
benzylidene-glycosylnitromethane 10–12 0.16 g, 0.5
mmol , stirring was continued for 15 min. Then,
NaHCO3 0.1 g was added, and after stirring 10 min,
the neutral mixture was filtered with suction and
washed with MeOH 2=5 mL . Concentration of
filtrates in vacuo afforded a residue that was purified
Ž
.
Ž
.
Ž
.
Ž
Ž
.
.
Ž
.
Ž
.
Ž
Ž
.
.
Ž
.
Ž
.
Ž
.
10–13 were thus prepared.
Ž
by flash chromatography eluent: 1:2 vrv ethyl ac-
.
etate–petroleum ether . Compounds 15–17 were pre-
pared using this procedure.
2,6-Anhydro-5,7-O-benzylidene-1-deoxy-3,4-O-
isopropylidene-1-nitro-D-glycero-D-gulo-heptitol
Ž

(
)
54
D.-P. Pham-Huu et al.rCarbohydrate Research 306 1998 45–55
Ž
Ž
4,6-O-benzylidene-2,3-O-isopropylidene-b-D-gluco-
. Ž
78.8, 78.7, 76.2, 74.6, 69.0, 66.9 C-1, C-2, C-3, C-4,
.
Ž
.
Ž
pyranosylnitromethane 15 as a solid foam: yield
C-5, C-6 , 26.5, 26.4, 25.9, 24.6 4 isopropylidene
Ž
.
w x
.
.
Ž
.
0.14 g 77% ; a D y24.08 c 1.5, acetone ; Rf 0.43
Me , 20.0 acetyl Me .
Ž
.
EtOAc–petroleum ether, 3:2 . Anal. Calcd for
The residue containing 19 and 20 was dissolved in
dry benzene 10 mL , and the solution was heated 14
h at the reflux temperature in the presence of NaHCO3
Ž
.
Ž
.
C17H21NO7 351.37 : C, 58.11; H, 6.02; N, 3.99.
Found: C, 58.19; H, 5.99; N, 3.78.
Ž
.
2,6-Anhydro-1,3-O-benzylidene-7-deoxy-4,5-O-
isopropylidene-7-nitro-L-glycero-L-galacto-heptitol
0.4 g . The cooled reaction mixture was filtered and
Ž
.
evaporated to give syrupy 20: yield 0.31 g 94% ;
Ž
w x
Ž . Ž
q5.08 c 1.4, acetone ; Rf 0.66 1:2 vrv
1
4,6-O-benzylidene-2,3-O-isopropylidene-b-D-galacto-
a
D
. Ž
.
Ž
.
.
Ž
.
pyranosylnitromethane 16 : yield 0.16 g 88% , had
mp 155–1568C,
0.39 EtOAc–petroleum ether, 3:2 . Anal. Calcd for
C17H21NO7 351.37 : C, 58.11; H. 6.02; N, 3.99.
EtOAc–petroleum ether . H-NMR CDCl3 : d 7.36
w x
Ž
.
Ž
.
Ž
a
q7.78 c 1.3, acetone ; Rf
dd, 1 H, J1,2 13.3 Hz, J2,3 3.6 Hz, H-2 , 7.24 dd, 1
D
Ž
.
.
Ž
H, J1,3 1.7 Hz, H-1 , 4.63 ddd, 1 H, J3,4 8.1 Hz,
H-3 , 4.16 m, 1 H, J5,6 6.05 Hz, H-6 , 4.11 m, 1 H,
J5,6 3.65 Hz, H-5 , 3.97 dd, 1 H, J6,6 8.3 Hz, H-6 ,
3.68 t, 1 H, J4,5 8.2 Hz, H-4 , 1.44, 1.43, 1.42, 1.36
Ž
Ž
Ž
.
.
Ž
.
Ž
X
.
Ž
.
X
X
Found: C, 58.14; H, 6.15; N, 4.00.
2,6-Anhydro-5,7-O-benzylidene-1-deoxy-3,4-O-
isopropylidene-1-nitro-D-glycero-D-galacto-heptitol
Ž
.
13
.
Ž
.
4 s, 12 H, 4 CH3 ; C-NMR CDCl3 : d 139.2
C-1 , 138.7 C-2 , 110.5, 109.6 2 CMe2 , 80.8,
Ž
.
Ž
.
Ž
.
4,6-O-benzylidene-2,3-O-isopropylidene-b-D-manno-
. Ž
.
Ž
.
Ž
Ž
.
Ž
.
pyranosylnitromethane 17 : yield 0.16 g 88% ; mp
76.6, 76.3 C-3, C-4, C-5 , 67.3 C-6 , 26.4, 26.3,
w x
Ž
.
.
132–1338C, a y95.08 c 1.0, acetone ; Rf 0.44
26.1, 24.8 4 Me . Anal. Calcd for C12 H19NO6: C,
52.74; H, 7.01, N, 5.13. Found: C, 52.51, H, 7.16, N,
4.87.
D
Ž
.
3:2 vrv EtOAc–petroleum ether . Anal. Calcd for
Ž
.
C17H21NO7 351.37 : C, 58.11; H, 6.02; N, 3.99.
Found: C, 57.94; H, 6.31; N, 3.66. The foregoing
isopropylidenation procedure with 12, with the excep-
Acknowledgements
Ž
.
tion of using 2,2-dimethoxypropane 0.5 mL in a 2 h
Ž
reaction in place of 2-methoxypropene, gave 17 yield
0.16 g, 88% identical with the sample described
This work was supported in part by Slovak
.
Academy of Sciences, Grant No. 1234r96.
above.
Ž
Treatment of 1-deoxy-1-nitro-D-mannitol 0.42 g,
.
2 mmol according to the procedure for isopropylide-
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Ž
.
Ž
.
Ž
.
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Ž
.
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Ž
.
Ž
Ž
.
.
Ž
.
Ž
.
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Ž
.
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.
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.
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.
Ž
.
Ž
.
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.
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.
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.
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.
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.
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´
.
Ž
.
roleum ether , and nitroalkene 20 0.4 g in an ap-
Ž
.
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Ž
.
x
¨
¨
Ž
.
Ž
.
Ž
.
Ž
.
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.
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