The nitrile oxide-isoxazoline approach to 11-carbon monosaccharides. Conversion of 3-(tetritol-1-yl)-5-(tetrofuranos-4-yl)-2-isoxazolines into 6-deoxyundecoses

Article abstract of DOI:10.1016/S0008-6215(99)00168-8

Hydrogenolysis of (5R)-3-(1,2:3,4-di-O-isopropylidene-D-arabino-tetritol-1-yl)-5-(3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-tetrofuranos-4-yl)-4,5-dihydroisoxazole afforded the 7-ulose derivative, from which 6-deoxy-D-gluco-D-gluco- and D-manno-D-gluco-undecose derivatives 17 and 18 were prepared by reduction with sodium borohydride or L-Selectride. The configuration of the new stereogenic centre (C-7) in compounds 17 and 18 was established by NMR analysis of their 5,7-O-isopropylidene derivatives. 6-Deoxy-L-manno-D-gluco- and L-gluco-D-gluco-undecose analogues 19 and 20 were prepared similarly from the isomeric 3-(L-arabino-tetritolyl)-4,5-dihydroisoxazole. Removal of the isopropylidene protecting groups from compounds 17 and 20 yielded 3-O-benzyl-6-deoxy-D-gluco- and L-manno-D-gluco-undecopyranoses, which were characterised as their octa-acetate derivatives. The corresponding reaction sequence from 3-(D- and L-arabino-tetritol-1-yl)-5-(2,3-O-isopropylidene-3-O-methyl-α-D-lyxo-tetrofuranos-4-yl)-4,5-dihydroisoxazoles afforded 6-deoxy-D/L-gluco-D-manno and D/L-manno-D-manno-undecose derivatives. Copyright (C) 1999 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00168-8

www.elsevier.nl/locate/carres
Carbohydrate Research 321 (1999) 24–41
The nitrile oxide–isoxazoline approach to 11-carbon
monosaccharides. Conversion of
3-(tetritol-1-yl)-5-(tetrofuranos-4-yl)-2-isoxazolines into
6-deoxyundecosesꢀ
Karen E. McGhie, R. Michael Paton *
Department of Chemistry, The Uni6ersity of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK
Received 15 April 1999; accepted 19 June 1999
Abstract
Hydrogenolysis of (5R)-3-(1,2:3,4-di-O-isopropylidene-
-xylo-tetrofuranos-4-yl)-4,5-dihydroisoxazole afforded the 7-ulose derivative, from which 6-deoxy-
-gluco- and -manno- -gluco-undecose derivatives 17 and 18 were prepared by reduction with sodium borohydride
-Selectride. The configuration of the new stereogenic centre (C-7) in compounds 17 and 18 was established by
-manno- -gluco- and -gluco- -gluco-undecose
-arabino-tetritolyl)-4,5-dihydroisoxazole. Removal
of the isopropylidene protecting groups from compounds 17 and 20 yielded 3-O-benzyl-6-deoxy- -gluco- and
-manno- -gluco-undecopyranoses, which were characterised as their octa-acetate derivatives. The corresponding
reaction sequence from 3-( - and -arabino-tetritol-1-yl)-5-(2,3-O-isopropylidene-3-O-methyl-a- -lyxo-tetrofuranos-
4-yl)-4,5-dihydroisoxazoles afforded 6-deoxy- -gluco- -manno and -manno- -manno-undecose derivatives.
© 1999 Elsevier Science Ltd. All rights reserved.
D
-arabino-tetritol-1-yl)-5-(3-O-benzyl-1,2-O-isopropyli-
dene-a-
D
D
-gluco-
D
D
D
or
L
NMR analysis of their 5,7-O-isopropylidene derivatives. 6-Deoxy-
L
D
L
D
analogues 19 and 20 were prepared similarly from the isomeric 3-(
L
D
L
D
D
L
D
D
/L
D
D
/
L
D
Keywords: 2-Isoxazolines (4,5-dihydroisoxazoles); 6-Deoxyundecos-7-uloses; 6-Deoxyundecoses
1. Introduction
involves chain elongation at the non-reducing
terminus of readily accessible v-unsaturated
monosaccharides by 1,3-dipolar cycloaddition
with a nitrile oxide, followed by reductive
cleavage of the resulting 2-isoxazoline (4,5-di-
hydroisoxazole) cycloadducts. In the previous
paper in this series [8] we reported that the
undecose framework could be constructed by
cycloaddition of a five-carbon nitrile oxide to
a six-carbon alkene, and that such reactions
proceeded stereoselectively and in satisfactory
yield. For example, isoxazoline 1 was obtained
The identification of 11-carbon monosac-
charide structural subunits in the hikizimycin
[2,3], tunicamycin [4] and herbicidin [5] antibi-
otics has stimulated widespread interest in the
synthesis of such higher-carbon sugars [6]. We
are developing a route (Scheme 1) based on
nitrile oxide–isoxazoline chemistry [7], which
ꢀ For a preliminary description of part of this work, see
Ref. [1].
* Corresponding author. Tel.: +44-131-650-4714; fax: +
44-131-650-4743.
by combination of
D
-arabinononitrile oxide 2
E-mail address: r.m.paton@ed.ac.uk (R.M. Paton)
and the -Glc-derived alkene 3. We now de-
D
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00168-8

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
25
Scheme 1.
scribe the conversion of the isoxazoline cy-
cloadducts into undecose derivatives.
tion, retro-aldol reactions, and competing
over-reduction to g-aminoalcohols.
Initial experiments were carried out with
isoxazoline 1 using the conditions previously
used successfully in the nonose/decose series
[9], involving hydrogenolysis over a palla-
dium–charcoal catalyst. However, the reac-
tion proved to be slower in this case and TLC
examination after 18 h showed the presence of
significant amounts of unreacted starting ma-
terial as well as a new more polar material
that gave a positive stain with Brady’s
reagent, consistent with the target b-hydrox-
yketone 4 (Scheme 3). Continuing the reaction
for a further 20 h afforded, after preparative
TLC, unreacted isoxazoline (51%) and the
more polar component (19%), which was iden-
tified by its spectroscopic properties as the
2. Results and discussion
The chemistry of 2-isoxazolines is well doc-
umented [7]. They are readily prepared by
nitrile oxide/alkene cycloaddition reactions,
they are often sufficiently robust as to allow
the introduction and/or manipulation of sub-
stituents, but under reducing conditions they
can undergo cleavage at the NꢀO bond to
afford b-hydroxyimines and products derived
therefrom. Of particular relevance to higher-
sugar synthesis is their ability to undergo hy-
drogenolysis to yield b-hydroxyketones [7a],
which can subsequently be converted into 1,3-
diols, and we have previously exploited this
chemistry to provide access from carbohy-
drate isoxazolines to 7-deoxy-nonoses and -de-
coses [9]. An isoxazoline, such as compound 1,
can thus be regarded as a masked form of an
undecose (Scheme 2).
Isoxazoline ring opening.—Of the various
established methods for cleavage of the NꢀO
bond, we selected hydrogenation with a palla-
dium/charcoal or Raney nickel catalyst in the
presence of boric acid, methanol and water.
This protocol, developed by Curran and oth-
ers [7], is designed to achieve conversion to the
b-hydroxyketone, while minimising epimerisa-
D
-arabino- -gluco-6-deoxyundecos-7-ulose 4.
D
The presence of the carbonyl group was confi-
rmed by an IR peak at 1724 cm−1 and a C
13
NMR signal at lC 210 ppm. In other respects,
its NMR spectra (Tables 1–3) are broadly
similar to those of the isoxazoline precursor;
the only significant variations are associated
with the replacement of the isoxazoline moiety
by the target b-hydroxyketone. The signals for
C-6 and C-8 adjacent to the carbonyl group in
the product are shifted to higher frequency,
and there are corresponding shifts to lower
frequency for C-5 and, in the proton spec-
trum, for the ABX pattern attributable to H-5
and H-6ab, and for H-8 adjacent to the car-
bonyl. Proton 5-H shows distinct trans–diax-
ial and axial–equatorial couplings of 9.1 and
2.6 Hz to H-6a and H-6b, consistent with the
target b-hydroxyketone adopting a hydrogen-
bonded half-chair conformation (Fig. 1),
Scheme 2.

Table 1
1H NMR chemical shifts (lH/ppm) a for undecos-7-uloses 4, 5/6, 13, 15 and 16, and undecose derivatives 17–32, 35–38
b
1-H
5.87
2-H
4.59
4.55
4.59
4.53
4.50
4.58
4.60
4.57
4.60
4.50
4.50
4.54
4.54
4.54
3-H
4.07
4-H
4.02
5-H
4.44
4.27
4.43
4.42
4.38
4.22
4.27
4.23
4.27
6-H
7-H
8-H
4.35
4.32
4.36
4.37
4.37
3.9 c
3.78
3.8 c
3.86
9-H
4.15
4.37
4.19
4.17
4.18
3.9 c
3.75
3.8 c
3.90
10-H
4.12
4.05
4.15
4.15
4.12
4.0 c
4.07
4.06
4.0 c
11-H
PhCH2
OMe
OH
Me
4
2.89
3.14
1.77
1.86
2.91
3.10
2.91
3.08
2.92
2.98
1.72
2.08
1.93
1.93
1.59
2.29
1.92
1.68
1.71
2.03
1.91
1.91
1.64
2.22
1.93
1.79
1.69
1.77
3.94
4.10
3.96
4.14
4.10
3.95
3.93
4.08
4.05
3.91
3.93
4.12
3.99
4.17
4.17
3.99
4.11
3.92
3.91
4.59
4.70
2.91
1.30, 1.33, 1.36
1.40, 1.43, 1.47
1.30, 1.33, 1.37
1.40, 1.41, 1.50
1.30, 1.32, 1.33
1.41, 1.43, 1.46
1.29, 1.31, 1.36
1.39, 1.42, 1.43
1.26, 1.29, 1.30
1.37, 1.40, 1.41
1.29, 1.32, 1.35
1.39, 1.41, 1.46
1.30, 1.33, 1.34
1.42, 1.46, n.d. d
1.29, 1.33, 1.36
1.44, 1.47, n.d.
1.30, 1.31, 1.34
1.37, 1.38, 1.45
1.28, 1.33, 1.37
1.43, n.d., n.d.
1.27, 1.30, 1.32
1.39, 1.42, n.d.
1.23, 1.31, 1.34
1.35, 1.43, 1.47
1.29, 1.30, 1.35
1.39, 1.45, n.d.
1.28, 1.32, 1.35
1.36, 1.37, 1.38
1.45, n.d., n.d.
1.29, 1.33, 1.34
1.37, 1.40, 1.47
c
5/6 5.91
13
3.91–3.98
2.0
3.66
3.03
5.88
4.83
4.81
5.88
5.93
5.90
5.92
4.82
4.85
4.87
4.88
5.86
4.08
4.79
4.75
4.09
4.11
4.11
4.08
4.78
4.80
4.82
4.81
4.0 c
4.02
3.79
3.76
3.97
4.07
3.98
4.03
4.58
4.69
15
16
17
18
19
20
21
22
23
24
25
3.27
3.24
3.10
3.10
4.0 c
3.97
3.92
4.0 c
4.64
4.70
4.58
4.70
4.70
4.70
4.52
4.70
3.24
3.0
3.6
/
3.11
3.67
2.83
4.06
2.54
2.78
3.10
3.70
3.71
4.15
4.0 c
3.9 c
3.9 c
4.0 c
321
4.08
(
e
e
e
e
e
e
e
3.25
3.30
3.28
2.09
e
2
f
f
f
f
f
f
f
3.76
3.81
4.0 c
4.25
4.24
4.0 c
4.0 c
3.9 c
3.86
3.9 c
4.0 c
4.0 c
4.0 c
4.11
3.93
3.96
4.11
2.5
3.0
4.56
4.63
g
g
g
g
g
26
5.88
4.55
4.00
4.24
2.19
1.87
3.78
4.55
4.63

Table 1 (Continued)
1H NMR chemical shifts (lH/ppm) a for undecos-7-uloses 4, 5/6, 13, 15 and 16, and undecose derivatives 17–32, 35–38
b
1-H
5.88
2-H
4.55
3-H
4.03
4-H
3.96
5-H
4.23
6-H
7-H
8-H
9-H
3.81
10-H
4.13
11-H
PhCH2
OMe
OH
Me
g
g
27
28
29
1.53
1.92
4.06
3.95
4.57
4.64
1.29, 1.33, 1.35
1.36, 1.37, 1.41
1.46, n.d.
1.29, 1.32, 1.33
1.36, 1.38, 1.48
n.d., n.d.
1.28, 1.30, 1.31
1.37, 1.38, 1.40
n.d., n.d.
g
g
g
5.88
4.80
4.54
4.48
3.99
4.69
4.08
3.71
4.25
4.20
2.16
1.84
4.03
4.10
4.12
3.93
4.55
4.63
1.62
1.73
3.96 c
3.88
4.03 c
3.96 c
4.03 c
3.24
30
31
4.82
4.81
4.49
4.49
4.67
4.70
3.79
3.68
n.d.
n.d.
n.d.
n.d.
1.85
2.16
1.75
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
3.26
3.26
1.26–1.40
1.22–1.47
32
35
36
37
38
4.82
6.23
5.56
6.17
5.51
4.50
4.98 c
5.08
4.99
5.07
4.69
3.90
3.67
3.87
3.66
3.80
4.85
4.87
4.86
4.89
4.17
3.94
3.61
3.66
3.46
3.92
3.97
3.91
5.32
5.36
5.37
5.34
4.03
4.97 c
4.98
5.01
5.02
4.12
3.93
3.25
1.27, 1.32, 1.33
1.36, 1.37, 1.39
1.41, n.d.
1.95, 1.97, 2.00
2.01, 2.04, 2.10
2.09, n.d.
1.93, 1.98, 1.99
2.02, 2.03, 2.05
2.09, n.d.
1.95, 1.91, 2.00
2.01, 2.03, 2.05
2.09, 2.12
/
1.74
1.85
5.03
5.23
4.13
4.13
4.59
4.67
1.81 c
5.07
5.25
4.15
4.56
321
1.59
1.69
5.18 c
5.17 c
5.18 c
5.17 c
4.04
4.19
4.58
4.67
)
h
2
4.06
4.23
4.55
1.91, 1.97, 1.99
2.00, 2.02, 2.03
2.04, n.d.
a Recorded in CDCl3 at 360 or 600 MHz.
b Also l 7.2–7.5 (Ph).
c Overlapping multiplets.
d n.d., not determined.
e 3.68–4.18 (complex multiplet).
f 3.70–4.26 (complex multiplet).
g 3.91–4.11 (complex multiplet).
h 1.63–1.87 (complex multiplet).

28
K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
Scheme 3.
which allows the bulky furanosyl substituent
to occupy the sterically less demanding quasi-
equatorial position.
peak at 97.3 ppm attributable to the hemiketal
carbon (C-7), and one at 33.5 ppm for the
adjacent methylene carbon (C-6). Supporting
evidence is provided by two OH signals at lH
2.0 and 3.66 ppm, and peaks at 1.77 and 1.86
ppm for the methylene protons 6a and 6b. In
previous work [9] involving hydrogenolysis of
higher-sugar isoxazolines debenzylation was
not observed, presumably due to the shorter
reaction times.
A repeat experiment over a longer period
(63 h) yielded unreacted starting material
(9%), the 6-deoxyundecos-7-ulose 4 (37%), to-
gether with a mixture of more polar com-
pounds, which NMR analysis showed not to
contain the benzyl group. The major compo-
nent of the latter mixture was tentatively as-
signed, on the basis of its spectroscopic
properties, hemiketal structure 5, which is pre-
sumably formed by debenzylation at C-3
yielding b,d-dihydroxyketone 6, followed by
intramolecular addition of the d-hydroxyl
group to the ketone at C-7. In the 13C NMR
spectrum there is a characteristic quaternary
In order to shorten the reaction times and
minimise the debenzylation, the alternative
Raney nickel-catalysed procedure was investi-
gated. Isoxazoline 1 was subjected to the same
set of standard hydrogenolysis conditions de-
scribed above, but with Raney nickel in place
of the Pd–C catalyst. Complete consumption
of the starting material was achieved after
only 7 h, and preparative TLC afforded the
target b-hydroxyketone 4 in 66% yield, to-
gether with an inseparable mixture of g-
aminoalcohols 7 (25%). The latter amines
13
were identified by the characteristic C NMR
signals for C-7 at 50.7 and 52.3 ppm, as
expected [10] for the CHNH2 group; further
evidence was provided by high-resolution
mass spectrometry and a positive ninhydrin
TLC stain. The amino compounds are pre-
sumed to arise from hydrogenation of b-hy-
droxyimine 8, the putative intermediate on the
pathway to the b-hydroxyketone, competing
with its hydrolysis (Scheme 3). In an attempt
Fig. 1. Half-chair arrangement for b-hydroxyketone 4.

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
29
to increase the proportion of b-hydroxyketone
the concentration of boric acid was varied, but
with little effect. Indeed, the overriding influ-
ence on the yield of product was the nature of
the Raney nickel. The best results were
achieved when the catalyst had been pre-
Table 2
a
1H NMR couplings (Jx–y/Hz) for undecos-7-uloses 4, 5/6, 13, 15 and 16, and undecose derivatives 17–32, 35–38
1–2
3.8
2–3
3–4
3.1
n.d.
3.2
3.7
3.7
3.0
3.3
3.0
3.5
3.6
4–5
8.6
n.d.
8.6
8.5
8.2
8.3
7.7
8.3
8.0
8.4
5–6
9.1
6a–6b
6–7
7–8
8–9
5.8
2.1
5.5
5.6
5.6
n.d.
7.8
n.d.
7.3
n.d.
9–10
n.d.
3.4
10–11
4.5
11a–11b
PhCH2
b
4
B1
18.3
2.6
12.5
8.4
7.1
8.5
11.8
5/6
3.6
3.8
n.d.
B1
5.9
5.9
B1
5.0
11.6
9.1
2.7
8.9
3.0
7.8
4.1
10.2
2.1
4.9
7.1
10.1
1.7
2.7
9.2
10.1
2.4
n.d.
10.1
2.2
2.8
9.1
11.6
3.0
6.3
8.9
11.8
2.5
6.3
8.6
11.8
2.6
n.d.
11.7
2.4
6.3
9.1
8.9
1.9
4.8
6.0
6.2
4.5
4.5
6.1
6.2
4.8
5.0
6.0
5.3
6.2
6.0
5.3
6.0
5.1
4.9
6.0
n.d.
n.d.
13
18.1
17.9
17.4
14.7
n.d.
14.5
14.5
14.5
6.6
8.5
8.5
8.5
8.4
8.7
8.4
8.3
8.3
11.8
15
16
17
18
19
20
21
B1
B1
3.8
6.8
6.8
10.4
2.4
n.d. n.d.
n.d.
n.d.
7.3
11.8
11.7
3.7
3.8
3.8
B1
B1
B1
10.1
7.0
2.6
n.d.
7.5
1.7
10.1
2.6
10.1
2.4
n.d. n.d.
10.1
2.2
9.9
2.8
11.6
3.0
9.6
5.9
11.8
2.5
9.8
5.7
11.8
2.6
n.d. n.d.
7.6
11.8
B1
5.9
n.d.
22
23
B1
B1
5.9
6.0
3.7
3.3
n.d.
8.1
n.d.
14.5
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
3.1
24
25
26
27
28
29
B1
6.0
3.7
3.0
3.6
2.6
3.1
3.5
7.9
8.6
8.5
8.7
8.5
8.4
14.5
13.1
13.2
13.2
13.2
12.8
n.d.
n.d.
6.7
n.d.
n.d.
6.7
6.0
4.6
4.2
5.7
n.d.
8.3
8.1
n.d.
8.3
8.2
n.d.
3.7
B1
11.9
11.7
11.9
11.7
3.8
3.7
3.8
B1
B1
B1
5.3
6.3
6.3
5.6
6.2
5.3
4.2
8.1
n.d.
n.d.
n.d.
6.5
n.d.
1.9
B1
5.9
30
31
B1
B1
5.9
5.9
3.9
3.5
8.3
8.3
n.d.
13.0
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
11.7
n.d.
4.4
8.0
2.4
10.0
5.8
8.9
1.9
32
35
36
37
38
B1
5.9
10.0
9.4
3.6
9.4
9.4
9.3
9.3
8.5
10.0
9.5
13.1
15.1
n.d.
14.0
n.d.
6.1
3.2
3.9
3.4
4.3
7.9
8.0
7.4
7.6
6.7
6.1
5.3
n.d.
8.3
3.7
n.d.
11.9
11.8
8.3
3.9
8.3
n.d.
n.d. 3.9
4.1
4.1
5.2
3.5
5.9
3.1
10.0
9.4
10.1
9.6
10.1
1.7
9.6
2.4
9.0
B2
n.d. n.d.
n.d.
12.4
12.5
a Recorded in CDCl3 at 360 or 600 MHz.
b n.d., not determined.

Table 3
13C NMR chemical shifts (lC/ppm) a for undecos-7-uloses 4, 5/6, 13, 15 and 16, and undecose derivatives 17–32
C-1
C-2–C-4
C-5
C-6 C-7
C-11 CMe2
CMe2
CH2Ph PhC
PhCH
OMe
C-8–C-10
4
104.9 76.3, 78.0, 81.1, 81.7, 64.6
82.4, 82.9
43.4 210.2
66.5 109.8, 111.4,
111.6
67.4 110.1, 111.0,
111.9
66.5 109.8, 111.3,
111.6
66.5 109.7, 111.4,
112.5
24.8, 25.9, 26.2, 26.4, 26.5, 26.7
72.3
72.2
137.3 127.7, 128.0,
128.5
5/6 105.0 75.0, 76.3, 77.1, 77.9, 63.6
33.5
97.3
25.0, 26.1, 26.3, 26.6, 26.8, 27.9
25.0, 26.0, 26.1, 26.3, 26.6, 26.9
24.5, 25.0, 25.8, 26.1, 26.3, 26.9
24.5, 24.9, 25.8, 26.1, 26.3, 26.9
25.6, 26.1, 26.4, 26.6, 26.9, 27.0
25.0, 26.2, 26.6, 26.7, n.d. c, n.d.
25.0, 26.2, 26.3, 26.6, 26.8, n.d.
25.1, 26.1, 26.5, 26.7, 26.9, 27.0
24.3, 24.9, 25.7, 26.3, 26.7, 27.0
84.2, 84.5
13 104.9 76.4, 77.8, 81.1, 81.8, 64.8
43.4 209.9
43.4 209.1
43.3 208.9
137.2 127.7, 127.9,
128.4
/
82.3, 83.0
15 107.0 76.3, 78.0, 79.4, 81.1, 65.5
54.4
54.4
82.9, 84.7
16 106.9 76.3, 77.7, 79.3, 81.2, 65.7
66.5 109.7, 111.2,
112.5
83.0, 84.6
17 104.8 77.0, 77.1, 81.3, 82.3, 69.1 b 37.9
71.2 b 67.7 109.4, 109.7,
72.3
72.0
72.3
71.8
137.4 127.7, 127.8,
128.4
137.2 127.7, 127.9,
128.4
137.7 127.6, 127.7,
128.4
137.0 127.8, 128.1,
128.6
82.6, 82.9
111.5
66.2 b 67.7 109.2, 110.0,
111.4
18 105.0 76.3, 80.8, 82.0, 82.1, 69.6 b 37.9
321
82.2, 82.9
19 104.9 76.1, 80.8, 81.3, 82.5, 69.2 b 37.4
73.5 b 67.6 109.2, 110.1,
111.5
)
82.7, 82.9
20 105.0 77.0, 77.3, 81.6, 82.0, 67.1 b 38.2
82.1, 83.0
66.2 b 67.6 109.3, 109.6,
111.5
2
21 106.8 76.8, 76.9, 79.3, 81.8, 69.8 b 37.5
82.9, 84.4
70.9 b 67.4 109.3, 109.4,
112.1
54.1

Table 3 (Continued)
C-1
C-2–C-4
C-5
C-6 C-7
C-11 CMe2
CMe2
CH2Ph PhC
PhCH
OMe
C-8–C-10
22 106.6 76.3, 79.9, 80.6, 81.5, 69.8 b 37.6
67.1 b 67.8 108.8, 109.1,
109.5
25.3, 25.7, 26.5, 26.9, 27.3, 27.4
54.6
54.3
54.4
82.8, 84.6
23 107.0 76.2, 79.6, 80.2, 81.9, 69.9 b 37.3
66.8 b 67.3 109.3, 109.6,
112.2
24.9, 25.8, 26.2, 26.7, 26.8, n.d.
24.5, 25.1, 25.8, 26.4, 27.0, 27.1
82.8, 84.6
24 106.9 77.0, 77.4, 79.9, 81.5, 67.2 b 38.3
67.1 b 67.6 109.4, 109.6,
112.5
83.2, 84.6
25 104.8 76.0, 77.4, 80.6, 82.3, 67.8 b 31.1
65.7 b 67.4 98.5, 109.4,
109.5, 111.5
19.7, 25.0, 26.1, 26.4, 26.5, 26.6,
27.3, 29.7
24.7, 25.0, 25.2, 26.1, 26.5, 26.7,
27.1, 27.4
19.7, 25.2, 26.2, 26.4, 26.7, 27.4,
29.8, n.d.
24.9, 25.0, 25.1, 26.1, 26.5, 26.7,
26.8, 27.6
72.2
72.2
72.3
72.2
137.7 127.4, 127.6,
128.2
137.5 127.4, 127.7,
128.3
137.5 127.5, 127.7,
128.3
137.5 127.5, 127.7,
128.3
82.8 d
26 104.8 76.9, 78.2, 81.2, 81.4, 66.8 b 30.3
63.4 b 66.9 100.4, 109.4,
110.0, 111.5
/
82.1, 82.8
27
104.9 76.6, 78.5, 80.7, 81.5, 69.8 b 30.5
82.3, 83.0
65.6 b 66.3 98.4, 104.9,
110.0, 111.7
28 104.9 77.1, 77.2, 81.2, 82.0, 65.9 b 31.4
63.6 b 67.4 100.3, 109.5,
109.7, 111.4
82.2, 82.6
29 106.7 76.3, 77.5, 79.1, 81.7, 68.1 b 30.7
82.6, 84.7
66.4 b 67.5 98.7, 109.4,
112.0
19.4, 24.8, 25.1, 26.0, 26.5, 26.6,
27.5, 29.7
54.2
54.2
54.0
54.2
d
321
30
n.d. 64.2, 66.9, 76.8, 78.4,
81.4, 82.0
n.d.
30.7
n.d.
66.7 100.6, 109.4,
110.0, 112.1
24.5–27.5
(
31 106.7 76.5, 78.7, 78.9, 81.3, 69.9 b 30.3
66.1 b 66.1 98.4, 106.7,
110.0, 111.9
19.3, 24.7, 25.1, 25.8, 26.3, 27.3, 27.5,
29.6
24.2, 24.4, 24.8, 25.1, 25.9, 26.4, 26.8,
27.6
81.7, 84.5
2
32 106.8 77.3, 77.4, 79.2, 82.0, 66.2 b 32.1
64.1 b 67.5 106.8, 109.5,
109.7, 112.2
84.7 b
a Recorded in CDCl3 at 50 or 90 MHz.
b Alternative assignments.
c n.d., not determined.
d Overlapping signals.

32
K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
washed with water, as reported by Curran
[7a], and stored under methanol atB0 °C for
3–4 weeks prior to use.
bonyl function of the b-hydroxyketone to
provide the corresponding 1,3-diols (Scheme
2). A new asymmetric centre is created in this
Having established an effective procedure
for the conversion of isoxazoline 1 to b-hy-
droxyketone 4, the closely related undecose–
isoxazolines 9–11 were examined under
similar conditions. Isoxazoline 9, which is
step at C-7 and, as the
D
- and
L
-arabinose-
derived undecosuloses have opposite configu-
ration at C-8 adjacent to the carbonyl of the
b-hydroxyketone moiety, it was of interest to
establish the extent to which this influences
the stereochemical outcome. Two reducing
derived from alkene 3 and
L
-arabinononitrile
-gluco-6-de-
oxide 12, afforded -arabino-
L
D
agents, sodium borohydride and -Selectride,
L
oxyundecos-7-ulose 13 (54%), together with
27% of the corresponding g-aminoalcohol by-
products. No evidence for debenzylation was
observed for any of the Raney nickel-
catalysed reactions. Others [11,12] have
achieved similar success in this respect, and
the advantages of employing deactivated
Raney nickel have also been reported [11].
Similarly isoxazolines 10 and 11, which were
obtained [8] by combination of arabinonitrile
were used for this study. Treatment of b-hy-
droxyketone 4 with sodium borohydride in
ethanol–water afforded a mixture of 1,3-diols
17 and 18 in 79% combined yield (Scheme 5).
The products were separated by preparative
1
TLC and characterised by H and 13C NMR
spectroscopy, optical rotation and FABMS.
In the carbon spectrum the carbonyl peak at
210 ppm for the starting material is replaced
by a CHOH signal at ca. 70 ppm. The isomer
ratio (62:38; see Table 4) was measured from
oxides 2 and 12 with
D
-Man-derived hex-5-
- and -arabino- -
manno-6-deoxyundecos-7-uloses 15 (55%) and
16 (52%), respectively (Scheme 4).
enofuranoside 14, yielded
D
L
D
1
the H NMR spectrum of the product mixture
by comparison of the anomeric proton signals,
which are well separated (Dl=0.05 ppm) de-
spite the remoteness of this nucleus from the
centre of asymmetry. b-Hydroxyketones 13,
15, 16 reacted similarly yielding mixtures of
1,3-diols 19/20, 21/22 and 23/24 (72–82%).
The borohydride reductions were useful in
providing access to both isomers with ratios
typically ca. 2:3. Higher yields (76–98%) and
greater selectivity, however, were achieved
Reduction of 6-deoxyundecos-7-uloses.—
The next stage in the sequence from nitrile
oxide cycloaddition through to the target
higher sugars involves reduction of the car-
with
L
-Selectride in THF as reducing agent,
with d.e. values ranging from 72 to \94%.
Indeed, except in the case of ketone 13, the
signals attributable to the minor 1,3-diol iso-
mer were on the limits of NMR detection. For
all four ketones studied the major product was
the same for the two reducing agents. Whereas
the
D- and
L
-arabino- -gluco-deoxyundecos-7-
D
uloses 4 and 13 afforded chromatographically
separable diastereomeric 1,3-diols, the mix-
tures obtained from
manno-deoxyundecos-7-uloses 15 and 16
could not be separated; however, as -Selec-
D- and
L
-arabino-
D
-
L
tride gave essentially one product, this allowed
1
characterisation of one isomer, and partial H
and 13C NMR analyses of the minor isomers
from the spectra of the mixtures were also
obtained.
Scheme 4.

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
33
Scheme 5.
of the bulky substituents to occupy an unfa-
vourable axial position; distortion of the chair
is therefore expected, in accord with the ob-
served couplings. Therefore, the major isomer
is assigned the 5R,7R configuration 24, and
the minor product is assigned the 5R,7S
epimer 23. Similar characteristic patterns are
observed for the C-6 methylene protons of the
other pairs of 1,3-diols, and assignment of
configuration at C-7 for each isomer was
made using the arguments outlined above.
Confirmation of the configuration at C-7.—
In order to confirm the structural predictions
described above, the 5,7-O-isopropylidene ke-
tal derivatives were prepared. By this means
the C-5, C-6 and C-7 unit of the undecose is
locked in a six-membered 1,3-dioxane ring, for
which the vicinal proton–proton coupling
constants are predictable when it adopts a
chair conformation. Each of the individual
1,3-diols 17–20 and the inseparable mixtures
The individual 1,3-diols show distinctive
splitting patterns for the C-6 methylene pro-
tons, which enable the configuration at the
new stereogenic centre C-7 to be established.
This is illustrated for diols 23 and 24 in Fig. 2,
1
which shows the H NMR spectrum for this
region. In the major isomer 24 the signals for
6a-H and 6b-H appear as two clearly defined
doublet-of-doublet-of-doublets, each with two
large and one small coupling. In contrast the
spectrum for the minor isomer 23 has two
more widely separated doublet-of-triplet pat-
terns, with a small triplet coupling for 6a-H
and a large triplet coupling for 6b-H. These
observations are consistent with the minor
isomer adopting a hydrogen-bonded chair-
type conformation (Fig. 3), in which the bulky
furanose unit and the -arabino-tetrosyl sub-
L
stituent occupy the least sterically demanding
equatorial positions. Conformer A has the
hydrogen of the 5-OH group in hydrogen
bonding, whereas B represents the alternative
arrangement involving the 7-OH group. In
both of these structures 6ax-H would be ex-
pected to show two large axial–axial cou-
plings (10–13 Hz), with 6eq-H having two
smaller axial–equatorial couplings (2–4 Hz),
as observed. On the other hand the corre-
sponding hydrogen-bonded chair-type confor-
mations for the 7R epimer would require one
Table 4
Isomer ratios for 1,3-diols
Reducing agent
Isomer ratio
17:18
19:20
21:22
23:24
NaBH4
62:38
\97.3
40:60
12:88
62:38
\95:5
37:63
B3:97
L-Selectride

34
K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
1
Fig. 2. H NMR signals for 6a-H/6b-H for compounds 23 and 24.
21/22 and 23/24 were treated with acetone and
2,2-dimethoxypropane in the presence of a
catalytic amount of p-toluenesulfonic acid to
afford the corresponding ketals 25–32.
accommodated only by the 5R,7S isomer in
which the sugar substituents (R1 and R2) can
occupy the equatorial positions. The other
isomer must therefore have 5R,7R stereo-
chemistry for which a chair structure would
necessitate one of these substituents being lo-
cated in an unfavourable axial position. The J
values observed for the latter isomer are in-
deed indicative of a non-chair structure and
may best be explained by the 1,3-dioxane ring
adopting a twist-boat/skew conformation D,
which allows both bulky substituents (R1 and
R2) to occupy pseudo-equatorial positions.
Similar spectral features were observed for the
other pairs of isomers 27/28, 29/30 and 31/32.
Further support for these assignments is pro-
vided by their 13C NMR data. Distinctive
The diol mixtures 21/22 and 23/24 provided
inseparable mixtures of ketals, and it therefore
did not prove possible to fully characterise the
1
minor isomers. Examination of the H NMR
spectra in the region of the C-6 methylene
protons for compounds 25 and 26 revealed
patterns that closely paralleled those of the
diols from which they had been prepared. One
isomer has characteristic chair couplings: 6a-
H shows two ca. 12 Hz axial–axial couplings,
whereas 6b-H has two small (ꢀ3 Hz) axial–
equatorial couplings. Such a chair arrange-
ment (Fig. 4, structure C) may be

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
35
Table 5
Characteristic 13C NMR signals for isopropylidene carbons of
1,3-dioxane ring in compounds 25–32
Ketal Assignment
Conforma-
tion
lC (ppm)
CMe2 2×Me
25
27
29
31
26
28
30
32
5R,7S
5R,7S
5R,7S
5R,7S
5R,7R
5R,7R
5R,7R
5R,7R
chair
chair
chair
chair
skew
skew
skew
skew
98.5 19.7, 29.7
98.4 19.7, 29.8
98.7 19.4, 29.7
98.4 19.3, 29.6
100.4 24.7–27.4
100.3 24.9–27.6
100.6 24.5–27.5
100.7 24.2–27.6
Fig. 3. Hydrogen-bonded chair conformations for compound
23.
98.4–98.7 ppm, whereas the corresponding
peaks for the skew conformation are at
100.7–100.3 ppm. Previous studies by
Buchanan et al. have shown [13] that such
values are typical of chair and skew arrange-
ments in 1,3-dioxanes.
Rationalisation of y-facial selecti6ity.—The
following conclusions are evident from the
above structural assignments: (a) the predomi-
nant 1,3-diol is dependent on the starting b-
hydroxyketone and independent of the
signals are observed for the methyl carbons of
the 5,7-O-isopropylidene moiety (Table 5).
For compounds 25, 27, 29 and 31 the axial
and equatorial methyl carbon peaks are well
separated at 19.3–19.7 and 29.6–29.8 ppm
(Dl ꢀ10 ppm), whereas for the isomers com-
pounds 26, 28, 30 and 32 both fall within the
range 24.2–27.6 ppm. The signals for the qua-
ternary CMe2 are also distinctive: for the
chair conformation this carbon absorbs at
reducing agent used; (b)
greatly increased levels of selectivity relative to
sodium borohydride; (c) the -arabinose-
L
-Selectride provided
D
derived b-hydroxyketones 4 and 10 provided
the 7S isomers predominantly; and (d) the
L
-arabinose-derived b-hydroxyketones 9 and
11 mainly the 7R isomers. Hence the configu-
Fig. 4. Chair and skew conformations for compounds 25 and
26.
Fig. 5. Felkin–Anh model for reduction of 6-deoxyundecos-7-
uloses.

36
K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
ration at C-8, the position adjacent to the
carbonyl function, determines the stereochem-
istry of major product, which in all cases
possesses a threo relationship about the C-7/
C-8 bond. In the absence of chelating reagents
these results can best be explained in terms of
a Felkin–Anh transition-state model [14] (Fig.
5), which involves hydride ion attack on a
staggered orientation of substituents with the
anti alkoxy group. Similar results have been
anose derivatives 39 and 40, which would be
readily distinguished from the
D
-gluco prod-
1
ucts by their H NMR parameters.
reported for the related reduction of -glycer-
D
aldehyde-derived compounds 33 and 34 for
which the preferential formation of threo/anti
products was ascribed to the Felkin–Anh
model [15]. The substantially higher levels of
selectivity observed for the -Selectride reduc-
L
tions may be attributed to the greater bulk of
this reagent.
3. Conclusions
Con6ersion of 6-deoxyundecofuranoses 17
and 20 into octa-O-acetylpyranose deri6a-
The present work, taken with the results
reported in the previous paper in this series
[8], demonstrates that nitrile oxide/isoxazoline
chemistry is well suited for the construction of
11-carbon monosaccharides. The route is
sufficiently flexible as to allow combination of
various sugar alkene and sugar nitrile oxides
in the cycloaddition step, the resulting isoxa-
zolines can be modified while leaving the hete-
rocyclic ring intact, and their ring-opening
reactions can provide access to various func-
tionality including b-hydroxyketones and g-
aminoalcohols. It is anticipated that a wide
range of higher monosaccharides and ana-
logues may be accessible by combination of
the appropriate sugar alkene and sugar nitrile
oxide precursors.
ti6es.—
D
-gluco- -gluco-Undecofuranose 17
D
was subjected to isopropylidene deprotection
(TFA–H2O) followed by treatment with acetic
anhydride–pyridine–DMAP to afford a mix-
ture of a- and b-octaacetylpyranosides 35 and
36, which were readily separable by chro-
matography.
L
-Gluco- -gluco-undecofuran-
D
oside 20 reacted similarly to yield octa-acetate
1
derivatives 37 and 38. The H NMR spectra
of each product showed the same general fea-
tures (Tables 1 and 2). As reported for penta-
O-acetyl- -glucose [16], the a and b forms are
D
readily identified from the anomeric proton
resonances; H-1 for the a isomer has the
greater chemical shift (Dl=0.06 ppm) and
has smaller J1,2 coupling (3.7–3.9 Hz cf. 8.3
Hz for the b isomer). The observed J2,3, J3,4
and J4,5 values (9.3–10.1 Hz) are typical of the
axial–axial couplings associated with a pyra-
4. Experimental
nose ring of
D
-gluco configuration. This fur-
General methods and materials.—The ana-
lytical methods, instrumentation and proce-
dures for preparative chromatography were as
previously described [8,9]. The purity of new
compounds was established by NMR spec-
troscopy and by TLC (silica: hexane–Et2O).
(5R)-5-(3-O-Benzyl-1,2-O-isopropylidene-a-
ther reinforces the assignment of
R
configuration to the chiral centre C-5 in the
major adducts formed in the nitrile oxide cy-
cloaddition reactions [8]. In contrast the isoxa-
zoline isomers with opposite configuration at
C-5 would yield the corresponding -idopyr-
L

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
37
D
-xylo-tetrofuranos-4-yl)-3-(1,2:3,4-di-O-iso-
propylidene- -arabino-tetritol-1-yl)-2-isoxa-
zoline 1, (5R)-5-(3-O-benzyl-1,2-O-isopropyli-
dene-a- -xylo-tetrofuranos-4-yl)-3-(1,2:3,4-di-
O-isopropylidene- -arabino-tetritol-1-yl)-2-
isoxazoline 9, (5R)-5-(2,3-O-isopropylidene-1-
O-methyl-a- -lyxo-tetrofuranos-4-yl)-3-(1,2:3,
4-di-O-isopropylidene- -arabino-tetritol-1-yl)-
2-isoxazoline 10, and (5R)-5-(2,3-O-isopropyl-
idene-1-O-methyl-a- -lyxo-tetrofuranos-4-yl)-
3-(1,2:3,4-di-O-isopropylidene- -arabino-tetri-
Raney nickel-catalysed hydrogenolysis of
isoxazolines: general procedure.—The isoxazo-
line (1 M equiv) and boric acid (6 M equiv)
were dissolved in a mixture of MeOH and
water (5:1) (8–12 mL per 100 mg of isoxazo-
line) and Raney nickel (three spatula tips per
100 mg of isoxazoline) added. The mixture
was degassed, flushed with hydrogen, and left
to stir vigorously under a hydrogen atmo-
sphere. Upon completion of the reaction
(monitored by TLC), the mixture was filtered
through Celite and concd in vacuo at B
25 °C. The excess boric acid was removed by
repeated cycles of MeOH addition and evapo-
ration. The resulting oil was purified by
preparative TLC on silica (70–90% Et2O in
hexane).
D
D
L
D
D
D
L
tol-1-yl)-2-isoxazoline 11 were prepared as
previously reported [8]. Raney nickel was
washed with water (stir and decant×20) and
then stored under MeOH in a freezer for 3–4
weeks prior to use. NMR data for the prod-
ucts are given in Tables 1–3.
Palladium on charcoal-catalysed hydrogenol-
ysis of isoxazoline 1.—Isoxazoline 1 (100 mg,
0.19 mmol) and boric acid (72 mg, 1.16 mmol)
were dissolved in MeOH (15 mL) and water (3
mL). 10% Pd–C (19 mg) was added and the
mixture degassed using a water pump, flushed
with hydrogen (×5), and left to stir vigor-
ously under the hydrogen atmosphere for 38
h. The mixture was filtered through a Celite
pad and evaporated in vacuo at B25 °C.
MeOH was added and evaporated several
times to remove the excess of boric acid as
trimethyl borate. Preparative TLC (silica, 60%
Et2O in hexane) afforded, in order of elution,
unreacted isoxazoline 1 (52 mg, 51%) and a
more polar component, which stained with
Brady’s reagent and was identified as 3-O-
benzyl-6-deoxy-1,2:8,9:10,11-tri-O-isopropyli-
Hydrogenolysis of isoxazoline 1.—Accord-
ing to the general procedure, isoxazoline 1
(300 mg, 0.56 mmol) yielded undecos-7-ulose-
(1,4) (4) (194 mg, 66%) after 7 h, and a
colourless oil, which gave a positive ninhydrin
stain on TLC and was identified as an insepa-
rable mixture (ca. 1:1) of g-aminoalcohols 7-
amino-3-O-benzyl-6,7-dideoxy-1,2:8,9:10,11-
tri-O-isopropylidene-
D
-gluco-and
D-manno-a-
D-gluco-undeco-1,4-furanose (7) (73 mg, 25%);
1H NMR (200 MHz, CDCl3): 7.39–7.23 (m, 5
H, Ph), 5.87, 5.89 (2×d overlapping, 1 H, J1,2
3.7, J1,2 3.7 Hz, 1-H), 4.68, 4.79 (2×d, 1 H, J
11.9 Hz, CH2Ph), 4.67 (d, s, CH2Ph), 4.57 (d,
ꢀ0.5 H, J2,1 3.8 Hz, 2-H), 4.55 (d, ꢀ0.5 H,
J2,1 3.5 Hz, 2-H), 3.54–4.30 (m, 9 H), 3.16–
3.28 (m, 1 H), 2.92 (br s, 2 H, NH2), 2.09–
1.71 (m, 2 H, 6-H2), 1.46, 1.40, 1.39, 1.38,
1.35, 1.33, 1.32, 1.29, 1.28, 1.24 (s, 18 H,
6×Me); 13C NMR (50 MHz, CDCl3): 138.0,
137.6 (3×PhC), 128.3, 128.2, 127.6, 127.5
(5×PhCH), 111.4, 111.3, 109.7, 109.6, 109.1
(3×CMe2), 105.0, 104.8 (C-1), 84.5, 84.2,
83.5, 82.7, 82.4, 82.0, 81.8, 81.1, 79.9, 77.3,
77.0, 76.9, 69.5, 66.5 (C-2, C-3, C-4, C-5, C-8,
C-9, C-10), 72.5, 72.3 (CH2Ph), 67.8 (C-11),
52.3, 50.7 (C-7), 37.5, 34.6 (C-6), 26.9, 26.8,
26.6, 26.4, 26.1, 25.1, 25.0 (6×Me); HRMS
(FAB): Calcd for C27H42NO9 [M+H]: m/z
524.28593. Found: m/z 524.2859.
dene-D
-arabino-a- -gluco-undecos-7-ulose-(1,4
D
) (4) (19 mg, 19%) as a colourless oil; wmax
/
cm−1 (neat): 3490 (OH), 1724 (CꢁO); HRMS
(FAB): Calcd for C27H40O10 [M+H]: m/z
524.26213. Found: m/z 524.26217. For NMR
data, see Tables 1–3.
A repeat reaction on twice the scale, with
THF added to aid dissolution of the isoxazo-
line, afforded unreacted isoxazoline 1 (17 mg,
9%), undecosulose 4 (74 mg 37%) and a more
polar fraction (61 mg), which comprised a
mixture of debenzylated compounds, after 63
h. The major component of this mixture was
attributed to 6-deoxy-1,2:8,9:10,11-tri-O-iso-
Hydrogenolysis of isoxazoline 9.—Accord-
ing to the general procedure isoxazoline 9 (223
mg, 0.43 mmol) afforded the following com-
pounds after 3 h in order of elution: 3-O-ben-
zyl-6-deoxy-1,2:8,9:10,11-tri-O-isopropylidene-
propylidene-
D
-arabino-a- -gluco-undeco-7-
D
ulo-1,4-furanose (6) in its hemiketal form 5.
For NMR data, see Tables 1–3.

38
K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
L
-arabino-a-
D
-gluco-undecos-7-ulo-1,4-fur-
112.4, 112.2, 109.8, 109.6, 109.3, 109.1 (3×
CMe2), 107.4, 107.2 (C-1), 84.7, 84.2, 82.6,
81.5, 80.3, 79.9, 79.5, 77.0, 76.9, 70.5, 67.3
(C-2, C-3, C-4, C-5, C-8, C-9, C-10), 67.9, 67.8
(C-11), 52.5, 51.1 (OMe), 52.7, 51.1 (C-7),
37.2, 35.1 (C-6), 27.0, 26.9, 26.6, 26.4, 25.9,
25.2, 25.1, 25.0, 24.6, 24.5, 23.2, 22.9 (6×
Me); HRMS (FAB): Calcd for C21H36NO9
[M+H]: m/z 448.25464. Found: m/z
448.25467.
Hydrogenolysis of isoxazoline 11.—Accord-
ing to the general procedure isoxazoline 11
(300 mg, 0.68 mmol) afforded the following
compounds after 5.5 h in order of elution:
methyl 6-deoxy-2,3:8,9:10,11-tri-O-isopropyli-
anose (13) as a clear oil (122 mg, 54%) [wmax
/
cm−1 (neat): 3516 (OH), 1719 (CꢁO); HRMS
(FAB): Calcd for C27H40O10 [M+2H]: m/z
524.26213. Found: m/z 524.26210; for NMR
data, see Tables 1–3] and an oil, which gave a
positive ninhydrin stain on TLC and was
identified as an inseparable mixture of g-
aminoalcohols 7-amino-3-O-benzyl-6,7-dide-
oxy1,2:8,9:10,11-tri-O-isopropylidene-
and -manno-a- -gluco-undeco-1,4-furanose
L
-gluco-
L
D
1
(60 mg, 27%). H NMR (200 MHz, CDCl3):
7.37–7.21 (m, 5 H, Ph), 5.87 (d, 1 H, J1,2 3.7
Hz, 1-H), 4.78–4.59 (m, 2 H, CH2Ph), 4.56 (d,
1 H, J2,1 3.8 Hz, 2-H), 4.28–3.60 (m, 9 H),
3.31–3.22, 3.13–3.05 (2×m, 1 H), 2.83 (br s,
2 H, NH2), 2.26–2.18, 1.91–1.77 (m, 2 H,
6-H2), 1.44, 1.36, 1.33, 1.31, 1.29 (s, 18 H,
6×Me); 13C NMR (50 MHz, CDCl3): 138.0,
137.6 (3×PhC), 128.3, 127.7, 127.5 (5×
PhCH), 111.3, 109.5, 109.1 (3×CMe2), 105.0
(C-1), 85.3, 84.0, 83.5, 82.5, 81.6, 81.3, 79.5,
77.8, 76.9, 69.6, 66.5 (C-2, C-3, C-4, C-5, C-8,
C-9, C-10), 72.5, 72.3 (CH2Ph), 67.9, 67.6
(C-11), 54.3, 48.9 (C-7), 35.8, 35.4 (C-6), 27.1,
26.8, 26.6, 26.2, 25.0 (6×Me); HRMS (FAB):
Calcd for C27H42NO9 [M+H]: m/z 524.28593.
Found: m/z 524.28597.
dene-
L
-arabino-a- -manno-undecos-7-ulo-1,4-
D
furanose (16) as a clear oil (156 mg, 52%)
[wmax/cm−1 (neat): 3498 (OH), 1727 (CꢁO);
HRMS (FAB): Calcd for C21H35O10 [M+2H]:
m/z 448.23082. Found: m/z 448.23083; for
NMR data, see Tables 1–3] and an oil, which
gave a positive ninhydrin stain on TLC and
was identified as an inseparable mixture of
g-aminoalcohols methyl 7-amino-6-deoxy-
2,3:8,9:10,11 - tri - O - isopropylidene -
L
- gluco -
and -manno-a- -manno-undecofuranoside
L
D
1
(54 mg, 18%). H NMR (200 MHz, CDCl3):
4.91–4.71 (m, 2 H, 1-H, 3-H), 4.52, 4.51 (2×
d, 1 H, J2,3 6.0, J2,3 6.0 Hz, 2-H), 4.24–3.62
(m, 8 H), 3.27, 3.26 (2×s, 3 H, OMe), 2.76
(br s, 3 H, OH, NH2), 1.85–1.79 (m, 2 H,
6-H2), 1.44, 1.40, 1.37, 1.35, 1.33, 1.30, 1.28 (s,
18 H, 6×Me); 13C NMR (50 MHz, CDCl3):
112.3, 109.5, 109.2 (3×CMe2), 107.1 (C-1),
84.7, 84.1, 80.8, 79.8, 78.0, 77.0, 67.3 (C-2,
C-3, C-4, C-5, C-8, C-9, C-10), 67.6 (C-11),
54.2, 54.3 (OMe), 49.1 (C-7), 35.9 (C-6), 27.2,
26.9, 26.5, 25.9, 25.1, 24.5 (6×Me); HRMS
(FAB): Calcd for C21H36NO9 [M+H]: m/z
448.25464. Found: m/z 448.25467.
Hydrogenolysis of isoxazoline 10.—Accord-
ing to the general procedure isoxazoline 10
(168 mg, 0.38 mmol) afforded the following
compounds after 5 h in order of elution:
methyl 6-deoxy-2,3:8,9:10,11-tri-O-isopropyli-
dene-
D
-arabino-a- -manno-undecos-7-ulo-1,4-
D
furanose (15) as a clear oil (55 mg, 55%)
[wmax/cm−1 (neat): 3497 (OH), 1725 (CꢁO);
HRMS (FAB): Calcd for C21H35O10 [M+H]:
m/z 447.22300. Found: m/z 447.22301; for
NMR data, see Tables 1–3] and an oil, which
gave a positive ninhydrin stain on TLC and
was identified as an inseparable mixture of
g-aminoalcohols methyl 7-amino-6-deoxy-
Reduction of i-hydroxyketones 4, 13, 15 and
16 to 1,3-diols 17–24.—The reductions were
performed using either sodium borohydride
2,3:8,9:10,11 - tri - O - isopropylidene -
and -manno-a- -manno-undecofuranoside
D
- gluco-
D
D
(Method A) or
L
-Selectride (Method B), as
1
(34 mg, 34%) H NMR (200 MHz, CDCl3):
4.86, 4.83 (2×s, 1 H, 1-H), 4.84–4.81 (m, 1
H), 4.53, 4.52 (2×d, 1 H, J2,3 6.0, J2,3 6.0 Hz,
2-H), 4.28–3.56 (m, 8 H), 3.28 (s, 3 H, OMe),
2.92 (br s, 3 H, OH, NH2), 2.03–1.75 (m, 2 H,
6-H2), 1.44, 1.38, 1.37, 1.35, 1.32, 1.30 (s, 18
H, 6×Me); 13C NMR (50 MHz, CDCl3):
described below. All the products were oils
and were purified by preparative TLC on sil-
ica (70–100% Et2O in hexane). The isomer
ratios (Table 4) were measured by comparison
of the integrals for corresponding signals in
1
the H NMR spectra of the mixtures. NMR
data for the products are given in Tables 1–3.

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
39
3-O-Benzyl-6-deoxy-1,2:8,9:10,11-tri-O-iso-
General procedure using sodium borohydride:
Method A.—A solution of sodium borohy-
dride (0.4 M equiv) in water (2 mL per 100 mg
of ketone) was added dropwise to an ice-
chilled, stirred solution of the b-hydroxyke-
tone (1 equiv) in EtOH and water (3:1, ꢀ4
mL per 100 mg of ketone). The resulting
solution was stirred overnight while warming
to room temperature (rt). The EtOH was re-
moved in vacuo, acetone (two to three drops)
was added to decompose any remaining
reagent and the solution extracted with
CHCl3. The combined extracts were dried
(MgSO4), filtered and evaporated to afford the
crude mixture of diastereomeric diols.
propylidene-
L
-gluco-a- -gluco-undecofura-
D
nose (20); [h]2D7 −28.8° (c 1.33 in CHCl3);
HRMS (FAB): Calcd for C27H41O10 [M+H]+:
m/z 525.26995. Found: m/z 524.26996. Yield:
Method A, 46%; Method B, 59%.
Methyl 6-deoxy-2,3:8,9:10,11-tri-O-iso-
propylidene-
ose (21) and methyl 6-deoxy-2,3:8,9:10,11-tri-
O-isopropylidene- -manno-a- -manno-unde-
D
-gluco-a- -manno-undecofuran-
D
D
D
cofuranose (22) as an inseparable mixture;
HRMS (FAB): Calcd for C21H37O10 [M+H]+:
m/z 449.23865. Found: m/z 449.293868.
Combined yield: Method A, 72%; Method B,
94%.
Methyl 6-deoxy-2,3:8,9:10,11-tri-O-iso-
General procedure using
L
-Selectride:
propylidene-
nose (23)
2,3:8,9:10,11-tri-O-isopropylidene-
-manno-undecofuranose (24) as an insepara-
L
-gluco-a- -manno-undecofura-
D
Method B.—1 M -Selectride in THF (1.4
L
and
methyl
6-deoxy-
equiv) was added dropwise to a solution of
the b-hydroxyketone (1 M equiv) in dry THF
(ꢀ10 mL per 100 mg of b-hydroxyketone) at
−78 °C under nitrogen. The resulting solu-
tion was stirred for 30 min at −78 °C and for
45 min at rt. After cooling to 0 °C, the reac-
tion was quenched by the successive slow ad-
L
-manno-a-
D
ble mixture; HRMS (FAB): Calcd for
C21H37O10 [M+H]+: m/z 449.23865. Found:
m/z 449.293862. Combined yield: Method A,
82%; Method B, 76%.
Preparation of 5,7-isoproplidene ketals 25–
32: general procedure.—The 1,3-diol (35–165
mg) was dissolved in 1:1 dry acetone and
2,2-dimethoxypropane (ꢀ3 mL per 40 mg of
diol), a catalytic amount of p-toluenesulfonic
acid was added, and the mixture stirred for 16
h at rt. Satd aq NaHCO3 was added and the
mixture extracted with CH2Cl2. The combined
organic layers were dried (MgSO4) and evapo-
rated in vacuo to afford the crude ketal, which
was purified by preparative TLC on silica.
NMR data for the products are given in Ta-
bles 1–3.
ditions of water (0.3 mL per mL
EtOH (1.3 mL per mL -Selectride), 3 M
NaOH (1.7 mL per mL -Selectride) and 30%
hydrogen peroxide (1.3 mL per mL -Selec-
tride). The aq layer was satd with K2CO3 and
extracted with 1:1 Et2O–THF (3×6 mL). The
combined organic layers were dried (MgSO4)
and concd in vacuo to afford the products.
3-O-Benzyl-6-deoxy-1,2:8,9:10,11-tri-O-iso-
L
-Selectride),
L
L
L
propylidene-
D
-gluco-a- -gluco-undecofura-
D
nose (17); [h]2D6 −13.1° (c 1.78 in CHCl3);
HRMS (FAB): Calcd for C27H40O10 [M]: m/z
524.26217. Found: m/z 524.26213. Yield:
Method A, 44%; Method B, 98%.
3-O-Benzyl-6-deoxy-1,2:5,7:8,9:10,11-tetra-
O-isopropylidene-
D
-gluco-a- -gluco-undeco-
D
furanose (25) (76%); [h]2D7 +3.0° (c 2.99 in
CHCl3); HRMS (FAB): Calcd for C30H45O10
[M+H]+: m/z 565.30125. Found: m/z
565.30129.
3-O-Benzyl-6-deoxy-1,2:8,9:10,11-tri-O-iso-
propylidene-
D
-manno-a- -gluco-undecofuran-
D
ose (18); [h]2D6 −11.0° (c 1.11 in CHCl3);
HRMS (FAB): Calcd for C27H41O10 [M+H]+:
m/z 525.26995. Found: m/z 524.26996. Yield:
Method A, 27%.
3-O-Benzyl-6-deoxy-1,2:5,7:8,9:10,11-tetra-
O-isopropylidene-
D
-manno-a- -gluco-undeco-
D
furanose (26) (72%); [h]2D7 +12.2° (c 1.4 in
CHCl3); HRMS (FAB): Calcd for C30H45O10
[M+H]+: m/z 565.30125. Found: m/z
565.30126.
3-O-Benzyl-6-deoxy-1,2:8,9:10,11-tri-O-iso-
propylidene-
L
-manno-a- -gluco-undecofura-
D
nose (19); [h]2D6 −20.3° (c 1.56 in CHCl3);
HRMS (FAB): Calcd for C27H40O10 [M]: m/z
524.26217. Found: m/z 524.26213. Yield:
Method A, 32%; Method B, 8%.
3-O-Benzyl-6-deoxy-1,2:5,7:8,9:10,11-tetra-
O-isopropylidene-
L
-manno-a- -gluco-undeco-
D

40
K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
furanose (27) (89%); [h]2D7 −20.0° (c 2.13 in
CHCl3); HRMS (FAB): Calcd for C30H45O10
[M+H]+: m/z 565.30125. Found: m/z
565.30129.
127.3 (5×PhCH), 88.3 (C-1), 74.6 (CH2Ph),
77.0, 72.5, 71.3, 70.1, 69.7, 69.6, 68.3, 68.2
(C-2, C-3, C-4, C-5, C-7, C-8, C-9, C-10), 61.4
(C-11), 31.6 (C-6), 20.7, 20.6, 20.5, 20.3 (8×
CH3CꢁO); HRMS (FAB): Calcd for
C32H41O16 [M+CH3CO2]+: m/z 681.23943.
Found: m/z 681.23940.
3-O-Benzyl-6-deoxy-1,2:5,7:8,9:10,11-tetra-
O-isopropylidene-
L
-gluco-a- -gluco-undeco-
D
furanose (28) (76%); [h]2D6 −11.0° (c 2.39 in
CHCl3); HRMS (FAB): Calcd for C30H45O10
[M+H]+: m/z 565.30125. Found: m/z
565.30128.
3-O-Benzyl-6-deoxy-1,2,4,7,8,9,10,11-octa-
O-acetyl-
D
-gluco-b- -gluco-undecopyranose
D
(36) as an oil (30%); [h]2D1 +5.9° (c 1.1 in
CHCl3); wmax/cm−1 (neat): 1754 (CꢁO); 13C
NMR (90 MHz, CDCl3): 170.4, 169.9, 169.8,
169.64, 169.59, 169.0, 169.8 (8×CH3CꢁO),
137.5 (PhC), 128.3, 127.8, 127.6 (5×PhCH),
91.7 (C-1), 74.0 (CH2Ph), 79.2, 72.4, 72.1,
71.6, 71.0, 69.3, 68.5, 68.4 (C-2, C-3, C-4, C-5,
C-7, C-8, C-9, C-10), 61.4 (C-11), 31.7 (C-6),
20.67, 20.62, 20.60, 20.54, 20.34 (8×
CH3CꢁO); HRMS (FAB): Calcd for
C32H41O16 [M+CH3CO2]+: m/z 681.23943.
Found: m/z 681.23940.
Methyl 6-deoxy-1,2:5,7:8,9:10,11-tetra-O-
isopropylidene-
D
-gluco-a- -manno-undeco-
D
furanose (29) and methyl 6-deoxy-1,2:5,
7:8,9:10,11-tetra-O-isopropylidene- -manno-
-manno-undecofuranose (30) as an insepa-
D
a-D
rable mixture (92%); HRMS (FAB): Calcd for
C24H41O10 [M+H]+: m/z 489.26995. Found:
m/z 489.26992.
Methyl 6-deoxy-1,2:5,7:8,9:10,11-tetra-O-
isopropylidene-
L
-manno-a- -manno-undeco-
D
furanose (31) and methyl 6-deoxy-1,2:5,
7:8,9:10,11-tetra-O-isopropylidene- -gluco-a-
-manno-undecofuranose (32) as an insepara-
L
3-O-Benzyl-6-deoxy-1,2,4,7,8,9,10,11-octa-
D
O-acetyl-
L
-gluco-a- -gluco-undecopyranose
D
ble mixture (81%); HRMS (FAB): Calcd for
C24H41O10 [M+H]+: m/z 489.26995. Found:
m/z 489.26998.
(37) as an oil (31%); [h]2D1 +21.3° (c 1.8 in
CHCl3); wmax/cm−1 (neat): 1745 (CꢁO); 13C
NMR (90 MHz, CDCl3): 170.40, 169.75,
169.64, 169.61, 169.55, 169.52, 169.4, 168.9
(8×CH3CꢁO), 137.9 (PhC), 128.3, 127.6,
127.2 (5×PhCH), 88.3 (C-1), 74.5 (CH2Ph),
77.2, 72.5, 71.4, 70.8, 68.3, 68.0, 67.9, 67.6
(C-2, C-3, C-4, C-5, C-7, C-8, C-9, C-10), 61.3
(C-11), 32.7 (C-6), 20.69, 20.62, 20.60, 20.57,
20.51, 20.43, 20.32, 20.28 (8×CH3CꢁO);
HRMS (FAB): Calcd for C32H41O16 [M+
CH3CO2]+: m/z 681.23943. Found: m/z
681.23940.
Con6ersion of diols 17 and 20 to undecopyra-
nose deri6ati6es 35/36 and 37/38: general pro-
cedure.—The diol (ꢀ50 mg) in trifluoroacetic
acid (ꢀ1 mL) and water (0.1 mL) was stirred
for 30 min at rt. The mixture was evaporated
in vacuo, then water added and evaporated
several times. Pyridine (1 mL), Ac2O (1 mL)
and a catalytic amount of 4-dimethylaminopy-
ridine were added and the mixture stirred for
ꢀ18 h. The resulting solution was poured
into water (4 mL) and the product was ex-
tracted with CH2Cl2 (3×4 mL). The com-
bined organic layers were dried (MgSO4),
evaporated in vacuo, and the resulting oil
purified by preparative TLC on silica (80%
Et2O in hexane, double elution) to afford, in
order of elution, the a- and b-octaacetates.
NMR data for the products are given in Ta-
bles 1 and 2.
3-O-Benzyl-6-deoxy-1,2,4,7,8,9,10,11-octa-
O-acetyl-
L
-gluco-b- -gluco-undecopyranose
D
(38) as a white solid (48%); mp 104–105 °C
(from EtOH); [h]D21 −6.2° (c 0.41 in CHCl3);
wmax/cm−1 (neat): 1754, 1741 (CꢁO); 13C
NMR (90 MHz, CDCl3): 170.39, 169.76,
169.67, 169.53, 169.48, 169.36, 168.90, 168.71
(8×CH3CꢁO), 137.5 (PhC), 128.3, 127.7,
127.6 (5×PhCH), 91.7 (C-1), 73.8 (CH2Ph),
79.9, 72.4, 71.5, 71.1, 70.5, 68.8, 68.5, 68.1
(C-2, C-3, C-4, C-5, C-7, C-8, C-9, C-10), 61.4
(C-11), 32.0 (C-6), 20.67, 20.58, 20.56, 20.52,
20.48, 20.34, 20.30 (8×CH3CꢁO); HRMS
(FAB): Calcd for C32H41O16 [M+CH3CO2]+:
m/z 681.23943. Found: m/z 681.23940.
3-O-Benzyl-6-deoxy-1,2,4,7,8,9,10,11-octa-
O-acetyl-
D
-gluco-a- -gluco-undecopyranose
D
(35) as an oil (20%); [h]2D1 +8.0° (c 2.8 in
CHCl3); 13C NMR (90 MHz, CDCl3): 170.4,
170.3, 169.8, 169.7, 169.6, 169.5, 169.4, 169.0
(8×CH3CꢁO), 137.9 (PhC), 128.3, 127.7,

K.E. McGhie, R.M. Paton / Carbohydrate Research 321 (1999) 24–41
41
(Ed.), Studies in Natural Products Chemistry, Vol. 11,
Elsevier, Amsterdam, 1992, pp. 429–480.
Acknowledgements
[7] For reviews of nitrile oxide–isoxazoline methodology,
see for example: (a) D.P. Curran, Ad6. Cycloaddition, 1
(1988) 129–189. (b) K.B.G. Torssell, Nitrile Oxides, Ni-
trones and Nitronates in Organic Synthesis, VCH, Wein-
heim, 1988. (c) S. Kanemasa, O. Tsuge, Heterocycles, 30
(1990) 719–736. (d) P. Gru¨nanger, P. Vita-Finzi, Isoxa-
zoles: The Chemistry of Heterocyclic Compounds, Vol. 49,
Part 1, Wiley, New York, 1991. (e) V. Ja¨ger, R. Mu¨ller,
T. Leibold, M. Hein, M. Schwarz, M. Fengler, L.
Jaraskova, M. Pa¨tzel, P.-Y. LeRoy, Bull. Chim. Soc.
Belg., 113 (1994) 491–507.
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We are grateful to the SERC and DENI for
research and maintenance (K.E.McG.) grants,
and we thank Drs I.H. Sadler and D. Reed for
their assistance with the NMR spectra.
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