One-pot synthesis of highly functionalized morphans from C-glycosides

Article abstract of DOI:10.1016/j.carres.2009.08.028

Highly functionalized morphan derivatives were synthesized from nitroalkene 2′-(oxoalkyl)-C-glycosides by a tandem reaction that created three (two C-N and one C-C) new bonds and four stereogenic centers in a one-pot procedure under very mild conditions w

Full text of DOI:10.1016/j.carres.2009.08.028

Carbohydrate Research 344 (2009) 2144–2150
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
One-pot synthesis of highly functionalized morphans from C-glycosides
*
Wei Zou , Kannan Vembaiyan, Milan Bhasin, Dean T. Williams
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6
a r t i c l e i n f o
a b s t r a c t
Highly functionalized morphan derivatives were synthesized from nitroalkene 20-(oxoalkyl)-C-glycosides
by a tandem reaction that created three (two C–N and one C–C) new bonds and four stereogenic centers
in a one-pot procedure under very mild conditions without the use of expensive reagents. The transfor-
mation was achieved from a b-elimination/Michael addition cascade, followed by Michael addition of the
amine and intramolecular enamination. In the presence of sodium cyanoborohydride the iminium inter-
mediate was reduced in situ to afford the desired morphans.
Article history:
Received 14 July 2009
Received in revised form 21 August 2009
Accepted 24 August 2009
Available online 27 August 2009
Keywords:
Synthesis
Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
Morphan
Tandem reaction
C-Glycoside
1. Introduction
uration are present. Although there were other potential compet-
ing reactions, we report here the chemo- and stereoselective
Morphine, with a morphan substructure, is the best-known opi-
oid analgesic. Subtle changes in substitutions on morphan ring and
N-alkyl group may lead to dramatic differences in binding specific-
reaction of nitroalkene C-glycosides 1 and 12 with various amines
leading to a class of highly functionalized morphan analogues.
ity to l, j, and d opioid receptors, consequently providing different
pharmacologic effects.1 Much effort has been made in the synthe-
sis of a variety of compounds including 5-phenylmorphan and
other morphan analogues to discover effective opioid receptor ago-
nists as analgesics that do not produce physical dependence and
antagonists to treat such dependence.2 New efficient synthetic
methods to access novel morphan derivatives with diverse ring
and N-substitutions are still desirable to advance structure–activ-
ity relationship studies.
2. Results and discussion
Nitroalkene C-glycosides 1 and 12 were synthesized from the
respective allyl-C-glycoside intermediates of
nose by performing 20-oxidation prior to b-elimination at C5.7 The
ribosyl substrate 1 was anomerically pure in the -configuration
and the arabinosyl substrate 12 was an anomeric mixture ( /b
D-ribose and D-arabi-
a
a
1:1). As the Michael addition of amines has been reported under
non-solvent conditions (NSCs),8 nitroalkene 1 was first treated
with allylamine at room temperature for two days, which gave
bridged azabicycle 2a (65%), an enamine possessing a morphan
skeleton as the major product (Scheme 1). Additionally, small
amounts of nitrocyclohexene 4 and cyclohexylamine 5a (R = allyl)
were also isolated as intermediates. In contrast to the reaction with
allylamine, when 1 was similarly treated with benzylamine and
cyclohexylamine the respective bridged azabicycles 2b and 2c
were obtained as minor products (ca. 10%) and the cyclohexyl-
amine intermediates (5b R = Bn and 5c R = C6H11) were isolated
as the major products (50–70%), which could be converted to 2b
and 2c, respectively, upon base treatment.
Because various azabicyclic compounds such as hydroxylated
quinolizidines,3 indolines, and oxindoles4 have been synthesized
from C-glycosides by tandem b-elimination and intramolecular
Michael additions, we envisioned that a morphan ring system
could be constructed by reaction of nitroalkene 20-(oxoalkyl)-C-
glycosides (e.g., 1 and 12) with amines. As a base, an amine may
instigate b-elimination leading to a conjugated ketone,5 and as a
nucleophile an amine may attack the nitroalkene at C5 via Michael
addition.6 These reactions might occur spontaneously or stepwise,
and could be followed by an intramolecular Michael addition of the
nitroalkyl anion to conjugated ketone to form highly functional-
ized cyclohexane derivatives. These intermediates may allow an
intramolecular cyclization to form an enamine between amino
and carbonyl groups when proper conformation and stereo config-
Two possible reaction pathways are illustrated in Scheme 1. The
first involves a tandem sequence of b-elimination, concurrent
Michael addition of the alkoxide anion to the nitroalkene (epoxida-
tion to 3), an intramolecular Michael addition of the nitroalkyl
anion to the
a,b-unsaturated ketone followed by base catalyzed
* Corresponding author. Tel.: +1 613 990 0821; fax: +1 613 952 9092.
E-mail address: wei.zou@nrc-cnrc.gc.ca (W. Zou).
b-elimination and epoxide ring opening to give cyclic nitroalkene
0008-6215/$ - see front matter Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.08.028

W. Zou et al. / Carbohydrate Research 344 (2009) 2144–2150
2145
NO
2
3
2
6
5
N R
7
1
4
O
1
4
R NH
NSC
2
O
2a R = Allyl (65%)
2b R = Bn (10%)
BnO
8
NO
2
3OBn 2OBn
OH5
6
9
2c R = Cyclohexyl (10%)
BnO
1
2
Pathway A
NO
NHR
2
NO
2
O
6
NO
2
O
5
HO
O
1
1
O
4
HO
3
2 OBn
OBn
BnO
BnO
OBn
OBn
5
4
3
O
+
N
R
HN
R
NO
BnO
BnO
BnO
BnO
2
NO
2
2
OH
OH
7
6
Pathway B
R
R
NO
2
O
N
O
2
NH
HO
NH
O
OH
1
5
2
+
OBn
OBn
9
BnO
OBn
8
4
Scheme 1.
4. Addition of an amine to 4 then produced 5 in the 4C1 conforma-
tion. The subsequent conformational change may be initiated or
followed immediately by C6-epimerization, leading to 6 with a
highly strained 1,5-diaxial configuration stabilized by an equato-
rial 6-nitro group. Reaction of the imino and carbonyl groups of 6
produced iminium 7 that was followed by isomerization to enam-
ine 2. The second pathway involves initial Michael addition of the
amine to nitroalkene followed by b-elimination to produce 8.
Because nitroalkanes have a pKa around 8.6, lower than that of
secondary amines (9.5–11),9 and the nitroalkyl anion is a softer
nucleophile than the secondary amine, thus an intramolecular
Michael addition of a nitroalkyl anion to the conjugated ketone is
likely favored to produce two diastereomers, 5 and 9. The former
can be converted to 2 directly while the latter has to go through
a retro-Michael addition to 4 en route to 2.
The limited conversion to 2b and 2c from 1 under NSC suggests
that benzylamine and cyclohexylamine behaved more like a nucle-
ophile and to less extent a base, because of their inability to induce
a C6-epimerization to stabilize the 1,5-diaxial conformation (6)
needed for enamine formation. Thus, we reasoned out, regardless
of the reaction pathways, that the addition of base should facilitate
the formation of 4 and the subsequent transformation.
gether with small amount of cyclohexene 4. Further experiments
revealed that 4, 10, and 11 were in equilibrium under basic
conditions through b-elimination of nitroalkane and addition of
methoxide to the nitroalkene. The reversible reaction between dia-
stereomers 10 and 11 also indicates that these basic conditions (1%
sodium methoxide) are able to facilitate the C6-epimerization.
Consequently, we treated 1 with 1% sodium methoxide–methanol
prior to the addition of representative amines, including allyla-
mine, cyclohexylamine, benzylamine, hexylamine and uridine
amine, as expected the respective azabicycles (2a–e) were ob-
tained overnight in consistent yield (Scheme 2).
To demonstrate the generality of this reaction,
D-arabinosyl
substrate 12 was also treated with allylamine and benzylamine
in 1% sodium methoxide. In addition to the expected bridged aza-
bicycles (13a and 13b, see Scheme 3), caged compounds, 14a and
14b were also isolated as minor products. Apparently, two C1-iso-
mers (4-like cyclohexenes) were obtained from Michael addition,
which is in agreement with the previous observation of a similar
intramolecular Michael addition of amine3 and nitroalkyl anion4
to conjugated ketones. Complete stereoselectivity was achieved
on
whereas a mixture of 1,4-trans (major) and 1,4-cis (minor) diaste-
reoisomers was produced from -arabinosyl substrates. It was
D-ribosyl substrates giving 1,4-trans configured products,
In fact, when 1 was treated with base (1% sodium methoxide)
overnight in the absence of amine, we were able to isolate 5-O-
methyl-6-nitrocyclohexanes,10 10 and 11, as major products to-
D
hypothesized that steric hindrance, disfavored 1,3-diaxial interac-
tions and a proposed 4-hydroxy group directing effect were all

2146
W. Zou et al. / Carbohydrate Research 344 (2009) 2144–2150
Because the iminium moiety in intermediate 7 can be reduced
NO
2
MeO
HO
O
in situ, treatment of nitroalkene 1 with amines in 1% sodium meth-
oxide–methanol in the presence of sodium cyanoborohydride was
attempted. As expected, morphans 17a–c were obtained stereose-
lectively in good yield. Similarly, reaction of 12 with amines (allyl-
amine and benzylamine) also gave respective morphans 18a and
18b as the major products, but the respective caged derivatives
14a and 14b remained (see Scheme 4). Although 18 and 14 were
inseparable by chromatography, but pure 18a was obtained from
15 and allylamine under basic conditions.
The stereochemistry and conformation of morphan derivatives
(17 and 18) and caged derivatives 14a–b were established based
on the NOEs observed from NOESY experiments (see Fig. 1). For
example, NOEs between H7/H6 and H4a, H3 and H4b, H4b and
H5 were observed in 17a but not between H7 and C3–Me or H3.
Therefore, the piperidine ring of 17 and 18 likely adopts a boat con-
formation in which the methyl group is equatorially attached to
C3. The conformation of 14 was proposed based on the diagnostic
NOE between H7 and H9.
OBn
H NR
2
OBn
O
10
1% NaOMe
BnO
+
1
OH
O N
2
OBn
NO
2
MeO
HO
O
4
OBn
OBn
NH
R
2
11
2
O
N
NH
2e R =
O
2a R = Allyl (70%)
2b R = Bn (66%)
O
2c R = Cyclohexyl (60%)
2d R = n-Hexyl (62%)
O
O
(55%)
In summary, we have developed a tandem reaction that allowed
quick access to morphan analogues with structural diversity from
C-glycosides. The reaction of nitroalkene 20-(oxopropyl)-C-glyco-
sides with variety of primary amines was achieved under basic
conditions involving b-elimination/Michael addition cascade, fol-
lowed by Michael addition of the amine and intramolecular enam-
ination. In addition to flexibility of choosing different sugar
substrates and amines, various other modifications on the enam-
ine,12 nitro,13 and N/O-acetal14 functionalities can further provide
molecular complexity. The chemistry described here should thus
be very useful for morphan scaffold based drug development for
pain and addiction treatment.
Scheme 2.
contributing factors to the stereoselectivities.4 The subsequent
addition reaction of the amine to the two nitrocyclohexene diaste-
reomers was highly stereoselective and could be directed by the
ketone functionality via amino/carbonyl H-bonding,11 which over-
came steric hindrance of the neighboring hydroxyl group. During
the final enamination reaction, the azabicyclic compounds 13a
and 13b were synthesized through 1,4-trans configured intermedi-
ates, whereas iminium intermediates from 1,4-cis configured
nitrocyclohexene underwent an intramolecular addition of the
4-hydroxy group to the iminium moiety giving respective caged
N/O-acetals 14a and 14b.
3. Experimental
The above-mentioned mechanism was supported by the fact
that we were able to isolate pure 1,4-trans and 1,4-cis 5-O-
methyl-6-nitrocyclohexanes (15 and 16) by treatment of 12 with
1% sodium methoxide (see Scheme 3). Furthermore, reaction of
15 and 16 with allylamine under 1% sodium methoxide produced
13a and 14a via nitrocyclohexene intermediates as illustrated in
Scheme 3.
3.1. General method
1H and 13C NMR spectra were recorded in CDCl3 at 400 MHz and
100 MHz, respectively, with a Varian instrument at 298 K. Chemi-
cal shifts were given in ppm downfield to the signal of internal
TMS, and were assigned on the basis of 2D 1H–1H COSY and
NO
NO
2
2
O
O
MeO
MeO
HO
OBn
OBn
OBn
HO
OBn
16
15
NH R
2
NO
2
OBn
O
O N
2
1% NaOMe
OBn
+
OBn
BnO
O
O
OH
NH R
BnO
O N
O
OH
2
2
OBn
12 (α/β 1:1)
N R
NO
O N
R
BnO
BnO
BnO
BnO
2
NO
2
OH
14a R = Allyl (19% )
14b R= Bn (22 %)
13a R = Allyl (52%)
13b R = Bn (54%)
Scheme 3.

W. Zou et al. / Carbohydrate Research 344 (2009) 2144–2150
2147
128.36 (Bn), 128.76 (Bn), 128.79 (Bn), 133.2 (C5), 137.4 (Bn),
137.6 (Bn), 150.0 (C6), 205.1 (C20). ESIMS: calcd for C23H26NO6
[M+H]+ 412.1760, found 412.1732.
N
R
1% NaOMe
1
BnO
NO
2
RNH /NaCNBH
2
3
3.4. (1R,2S,3R,4R,5S,6R)-1-Acetylmethyl -5-allylamino-2,3-di-O-
benzyl-4-hydroxy-6-nitrocyclohexane (5a)
OH
BnO
17a R = Allyl (67%)
17b R = Bn (54%)
17c R = Cyclohexyl (45%)
1
Syrup, [
a]
ꢀ61 (c 1.5, CHCl3); H NMR: d 2.01 (s, 3H, 30-Me),
D
2.30 (dd, 1H, H10b, J1 b,1 = 5.2 Hz, J1 b,1 a = 18.4 Hz), 2.79 (dd, 1H,
0
0
0
H10a, J1 a,1 = 3.2 Hz, J1 a,1 b = 18.4 Hz), 2.94 (m, 1H, H1), 3.23 (d, 1H,
N–CH2, J = 6.0 Hz), 3.40 (dd, 1H, H4, J3,4 = 2.0 Hz, J4,5 = 10.0 Hz),
3.50 (dd, 1H, H5, J4,5 = J5,6 = 10.0 Hz), 3.73 (dd, 1H, H2,
J2,3 = 2.0 Hz, J1,2 = 11.2 Hz), 4.18 (br s, 1H, H3), 4.32 (d, 1H, Bn,
J = 11.6 Hz), 4.56 (d, 1H, Bn, J = 11.6 Hz), 4.72–4.78 (m, 2H, H6,
Bn) 4.95 (d, 1H, Bn, J = 11.6 Hz), 5.06 (m, 2H, CH2@), 5.79 (m, 1H,
0
0
0
N
R
1% NaOMe
12
14
+
RNH /NaCNBH
2
3
BnO
BnO
NO
2
OH
18a R = Allyl (69%) 18a/14a 7:3
18b R = Bn (62%) 18b/14b 2:1
13
CH@), 7.22–7.39 (m, 10H, Ph); C NMR: d 30.7 (C30), 38.0 (C1),
39.1 (C10), 48.4 (N–CH2), 59.6 (C5), 70.7 (C4), 72.2 (Bn), 74.8 (Bn),
75.1 (C3), 77.1 (C2), 88.9 (C6), 116.6 (CH2@), 128.0 (Bn), 128.2
(Bn), 128.3 (Bn), 128.7 (Bn), 128.8 (Bn), 136.5 (CH@), 137.4 (Bn),
137.6 (Bn), 207.4 (C20). ESIMS: calcd for C26H33N2O6 [M+H]+
469.2338, found 469.2333.
Scheme 4.
Me
3
O
N
N
3.5. (1R,2S,3R,4R,5S,6R)-1-Acetylmethyl-5-benzylamino-2,3-di-
O-benzyl-4-hydroxy-6-nitrocyclohexane (5b)
H
7
4
H
BnO
BnO
Ha
H
b
NO
2
BnO
5
7
9
NO
2
ꢀ16 (c 2.0, CHCl3); 1H NMR: d
H
H
6
Crystals, mp 114–115 °C; [a]
D
9
H
1.98 (s, 3H, 30-Me), 2.30 (dd, 1H, H10b, J1 b,1 = 4.8 Hz,
0
OH
0
BnO
J1 b,1 a = 18.4 Hz), 2.67 (d, 1H, OH, J = 6.4 Hz), 2.78 (dd, 1H, H10a,
0
17a
14a
0
0
0
J1 a,1 = 3.2 Hz, J1 a,1 b = 18.4 Hz), 2.93 (m, 1H, H1), 3.40 (m, 1H, H4),
3.53 (dd, 1H, H5, J4,5 = J5,6 = 10.8 Hz), 3.71 (s, 2H, N–CH2), 3.73
(dd, 1H, H2, J2,3 = 2.0 Hz, J1,2 = 11.2 Hz), 4.14 (dd, 1H, H3,
J2,3 = J3,4 = 2.4 Hz), 4.30 (d, 1H, Bn, J = 11.2 Hz), 4.55 (d, 1H, Bn,
J = 11.2 Hz), 4.68 (d, 1H, Bn, J = 11.6 Hz), 4.80 (dd, 1H, H6,
J1,6 = J5,6 = 10.8 Hz), 4.92 (d, 1H, Bn, J = 11.6 Hz), 7.20–7.36 (m,
Figure 1.
1H–13C chemical-shift correlated experiments. For high resolution
mass spectroscopic analysis, samples in CH2Cl2–CH3OH 1:1 were
mixed with Agilent ES tuning mix for internal mass calibration
and infused into a QSTAR mass spectrometer at a flow rate of
4 lL/min. Optical rotations were measured on a Perkin–Elmer
spectrometer. All chemicals were used without further
13
15H, Ph); C NMR: d 30.7 (C30), 37.9 (C1), 39.1 (C10), 50.1 (N–
CH2), 59.8 (C5), 70.7 (C4), 72.2 (Bn), 74.8 (Bn), 75.3 (C3), 77.5
(C2), 88.8 (C6), 127.5 (Bn), 127.97 (Bn), 128.01(Bn), 128.2 (Bn),
128.3 (Bn), 128.5 (Bn), 128.7(Bn), 128.8 (Bn), 137.4 (Bn), 138.6
(Bn), 139.8 (Bn), 207.4 (C20). ESIMS: calcd for C30H35N2O6 [M+H]+
519.2495, found 519.2474.
purification.
3.2. General synthetic procedures
3.6. (1R,2S,3R,4R,5S,6R)-1-Acetylmethyl-5-cyclohexylamino-
2,3-di-O-benzyl-4-hydroxy-6-nitrocyclohexane (5c)
(a) Substrate (1 or 12, 50–100 mg) was dissolved in 1%
NaOCH3–CH3OH (1–2 mL) at room temperature. To the solution
after 2 h was added amine (50–100 lL) and the reaction solution
was kept overnight. EtOAc was added and the organic solution
was washed with water, dried, and purified by column chromatog-
raphy to give product(s) (2, 13, and 14). (b) Substrate (1 or 12, 50–
100 mg) was dissolved in 1% NaOCH3–CH3OH (1–2 mL) at room
temperature. To the solution after 2 h were added amine (50–
Crystals, mp 105–106 °C; [a]
D
ꢀ21 (c 1.7, CHCl3); 1H NMR: d
0.82–1.30 (m, 5H, CH2 cyclohexyl), 1.50–1.89 (m, 5H, CH2 cyclo-
hexyl), 1.98 (s, 3H, 30-Me), 2.26 (dd, 1H, H10b, J1 b,1 = 5.2 Hz,
0
J1 b,1 a = 18.4 Hz), 2.37 (m, 1H, N–CH), 2.76 (dd, 1H, H10a,
0
0
0
0
0
J1 a,1 = 3.2 Hz, J1 a,1 b = 18.0 Hz), 2.97 (m, 1H, H1), 3.19 (dd, 1H, H4,
J3,4 = 1.2 Hz, J4,5 = 10.4 Hz), 3.53 (dd, 1H, H5, J4,5 = J5,6 = 10.4 Hz),
3.69 (dd, 1H, H2, J2,3 = 2.0 Hz, J1,2 = 11.6 Hz), 4.18 (br s, 1H, H3),
4.27 (d, 1H, Bn, J = 11.6 Hz), 4.52 (d, 1H, Bn, J = 11.6 Hz), 4.60
(dd,1H, H6, J1,6 = J5,6 = 10.8 Hz) 4.81 (d, 1H, Bn, J = 11.6 Hz), 4.92
(d, 1H, Bn, J = 11.6 Hz), 7.20–7.41 (m, 10H, Ph); 13C NMR: d 24.8
(CH2), 25.1 (CH2), 26.0 (CH2), 30.7 (C30), 34.6 (CH2), 35.0 CH2),
38.2 (C1), 39.2 (C10), 54.7 (N–CH), 58.0 (C5), 72.0 (Bn), 72.5 (C4),
74.6 (C3), 74.7 (Bn), 77.0 (C2), 90.7 (C6), 127.9 (Bn), 128.0 (Bn),
128.1(Bn), 128.2 (Bn), 128.6 (Bn), 128.7 (Bn), 128.8(Bn), 137.5
(Bn), 138.9 (Bn), 139.8, 207.5 (C@O). ESIMS: calcd for C29H39N2O6
[M+H]+ 511.2808, found 511.2791.
100 lL) and sodium cyanoborohydride (5–10 equiv) and the mix-
ture was kept at room temperature for 16 h. EtOAc was added
and the organic solution was washed with water, dried, and puri-
fied by column chromatography to give product(s) (17, 18, and 14).
3.3. (1R,2S,3R,4R)-1-Acetylmethyl-2,3-di-O-benzyl-4-hydroxy-
6-nitrocyclohex-5-ene (4)
Syrup, [
a
]
D ꢀ2 (c 2.0, CHCl3); 1H NMR: d 2.03 (s, 3H, 30-Me), 2.23
(dd, 1H, H10b, J1 b,1 = 9.6 Hz, J1 b,1 a = 18.4 Hz), 2.69 (dd, 1H, H10a,
0
0
0
0
0
0
J1 a,1 = 2.4 Hz, J1 a,1 b = 18.4 Hz), 3.45 (d, 1H, OH, J = 10.4 Hz), 3.60
(d, 1H, H3, J = 3.6 Hz), 3.77 (br d, 1H, H1, J = 9.6 Hz), 3.89 (br s,
1H, H2), 4.45 (m, 1H, H4), 4.60 and 4.65 (d and d, 1H each, Bn,
J = 12.0 Hz), 4.70 (s, 2H, Bn), 7.22–7.39 (m, 11H, H5, Bn); 13C
NMR: d 30.1 (C30), 35.1 (C1), 42.4 (C10), 64.4 (C4), 71.4 (Bn), 72.2
(C3), 72.6 (Bn), 78.3 (C2), 128.1 (Bn), 128.30 (Bn), 128.32 (Bn),
3.7. (1R,2S,3R,4R,5S,6S)-1-Acetylmethyl-2,3-di-O-benzyl-4-
hydroxy-5-methoxy-6-nitrocyclohexane (10)
1
Syrup, [
a]
ꢀ15 (c 0.8, MeOH); H NMR: d 2.09 (s, 3H, 30-Me),
D
2.16 (m, 1H, H10b), 2.41 (d, 1H, OH, JOH,4 = 6 Hz), 2.92 (d, 1H,

2148
W. Zou et al. / Carbohydrate Research 344 (2009) 2144–2150
H10a, J1,1 b = 18.8 Hz), 3.03 (m, 1H, H1), 3.52 (s, 3H, OCH3), 3.71 (m,
1H, H5), 3.89 (d, 1H, H2, J1,2 = 11.6 Hz), 4.23 (m, 2H, H3, H4), 4.42
(d, 1H, Bn, J = 11.6 Hz), 4.62 and 4.66 (d and d, 1H each, Bn,
J = 11.6 Hz), 4.90 (d, 1H, Bn, J = 11.6 Hz), 5.42 (br s, 1H, H6) 7.20–
(m, 1H, H1), 4.50 (d, 1H, Bn, J = 11.2 Hz), 4.61 (d, 1H, Bn,
J = 11.2 Hz), 4.69 (s, 2H, Bn), 5.18 (br s, 1H, H9), 7.26–7.36 (m,
10H, Ph); 13C NMR: d 20.4 (Me), 25.6 (CH2), 26.0 (CH2), 26.7
(CH2), 30.9 (CH2), 33.1 (CH2), 35.8 (C5), 55.2 (C1), 57.3 (N–Bn),
70.8 (Bn), 73.42 (C9), 73.45 (Bn), 73.48 (C8), 74.9 (C7), 81.2 (C6),
87.9 (C4), 127.87 (Bn), 127.96 (Bn), 128.01 (Bn), 128.1 (Bn), 128.6
(Bn), 128.7 (Bn), 137.8 (Bn), 138.1 (Bn), 140.7 (C3). ESIMS: calcd
for C29H37N2O5 [M+H]+ 493.2702, found 493.2679.
0
13
7.39 (m, 10H, Ph); C NMR: d 30.6 (C30), 33.8 (C1), 41.1 (C10),
58.9 (OCH3), 70.3 (C4), 72.3 (Bn), 75.3 (Bn), 76.1 (Bn), 77.4 (C2),
78.6 (C5), 86.2 (C6),128.0 (Bn), 128.1 (Bn), 128.3 (Bn), 128.6 (Bn),
128.8 (Bn), 137.5 (Bn), 138.6 (Bn), 206.6 (C@O). ESIMS: calcd for
C24H30NO7 [M+H]+ 444.2022, found 444.2020.
3.12. (1S,5R,6S,7R,8R,9S)-2-Hexyl-6,7-di-O-benzyl-8-hydroxy-3-
3.8. (1R,2S,3R,4R,5S,6R)-1-Acetylmethyl-2,3-di-O-benzyl-4-
methyl-9-nitro-2-azabicyclo[3,3,1]nonan-3-ene (2d)
hydroxy-5-methoxy-6-nitrocyclohexane (11)
Syrup, [a]
+3 (c 1, CHCl3); 1H NMR: d 0.90 (t, 3H, n-hex–CH3,
D
1
Syrup, [
a]
ꢀ24 (c 0.5, CHCl3); H NMR: d 1.99 (s, 3H, 30-Me),
J = 7.2 Hz), 1.18–1.36 (m, 6H, CH2), 1.40–1.57 (m, 2H, CH2), 1.67
(s, 3H, Me), 3.05 (t, 2H, N–CH2, J = 8.4 Hz), 3.42 (m, 1H, H5), 3.53
(br s, 1H, OH), 3.59 (dd, 1H, H7, J6,7 = J7,8 = 3.2 Hz), 3.91–3.96 (m,
2H, H4, H6), 4.16 (br s, 1H, H8), 4.21 (m, 1H, H1), 4.50 (d, 1H, Bn,
J = 11.6 Hz), 4.63 (d, 1H, Bn, J = 11.6 Hz), 4.68 and 4.72 (d and d,
1H each, Bn, J = 14.4 Hz), 5.15 (dd, 1H, H9, J = 2.4 Hz, J = 4.0 Hz),
7.26–7.38 (m, 10H, Ph); 13C NMR: d 14.2 (CH3 n-hex), 19.9 (Me),
22.9 (CH2), 26.6 (CH2), 30.0 (CH2), 31.8 (CH2), 36.8 (C5), 51.0 (N–
CH2), 59.7 (C1), 70.8 (Bn), 73.2 (C8), 73.3 (C7), 73.39 (C9), 73.44
(Bn), 81.4 (C6), 86.6 (C4), 127.9 (Bn), 128.99 (Bn), 128.03 (Bn),
128.1 (Bn), 128.6 (Bn), 128.7 (Bn), 137.8 (Bn), 138.1 (Bn), 141.5
(C3). ESIMS: calcd for C29H39N2O5 [M+H]+ 495.2858, found
495.2851.
D
2.26–2.35 (m, 2H, H10b,OH), 2.73 (dd, 1H, H10a, J1 a,1 a = 3.6 Hz,
0
0
0
J1,1 a = 18.4 Hz), 2.89 (m, 1H, H1), 3.45 (s, 3H, OCH3), 3.51 (dd, 1H,
H4, J4,5 = 7.2 Hz, J4,OH = 5.2 Hz), 3.74 (d, 1H, H2, J1,2 = 11.2 Hz),
3.96 (dd, 1H, H5, J4,5 = J5,6 = 10.0 Hz), 4.08 (br s, 1H, H3), 4.33 (d,
1H, Bn, J = 11.6 Hz), 4.58 and 4.64 (d and d, 1H each, Bn,
J = 11.6 Hz), 4.65 (s, 1H, H6) 4.97 (d, 1H, Bn, J = 11.6 Hz), 7.20–
13
7.39 (m, 10H, Ph); C NMR: d 30.7 (C30), 37.1 (C1), 39.0 (C10),
61.2 (OCH3), 72.5 (Bn), 73.0 (C4), 75.0 (Bn), 76.2 (Bn), 77.6 (C2),
82.0 (C5), 88.6 (C6),128.1 (Bn), 128.2 (Bn), 128.4 (Bn), 128.8 (Bn),
128.9 (Bn), 137.3 (Bn), 138.4 (Bn), 206.9 (C@O). ESIMS: calcd for
C24H30NO7 [M+H]+ 444.2022, found 444.2025.
3.9. (1S,5R,6S,7R,8R,9S)-2-Allyl-6,7-di-O-benzyl-8-hydroxy-3-
methyl-9-nitro-2-azabicyclo[3,3,1]nonan-3-ene (2a)
3.13. (1S,5R,6S,7R,8R,9S)-2-(Uridine 20,30-di-O-isopropylidene-
50-deoxy-50-amino)-6,7-di-O-benzyl-8-hydroxy-3-methyl-9-
nitro-2-azabicyclo[3,3,1]nonan-3-ene (2e)
Syrup, [a]
D ꢀ61 (c 1.5 , CHCl3); 1H NMR: d 1.71 (s, 3H, Me), 3.43
(m, 1H, H5), 3.49 (d, 1H, OH, J = 6.0 Hz), 3.60 (dd, 1H, H7,
J6,7 = J7,8 = 3.2 Hz), 3.65 (dd, 1H, N–CH2, J = 7.2 Hz, J = 16.0 Hz),
3.84 (dd, 1H, N–CH2, J = 4.8 Hz, J = 16.0 Hz), 3.93–3.99 (m, 2H, H4,
H6), 4.16 (m, 1H, H8), 4.20 (br s, 1H, H1), 4.51 (d, 1H, Bn,
J = 11.6 Hz), 4.62 (d, 1H, Bn, J = 11.6 Hz), 4.69 and 4.73 (d and d,
1H each, Bn, J = 12.4 Hz), 5.12–5.21 (m, 3H, CH2@, H9), 5.74 (m,
1H, CH@), 7.26–7.39 (m, 10H, Ph); 13C NMR: d 19.8 (Me), 37.0
(C5), 54.2 (N–CH2), 59.8 (C1), 70.8 (Bn), 72.9 (C8), 73.2 (C7), 73.3
(C9), 73.5 (Bn), 81.2 (C6), 87.4 (C4), 117.5 (CH2@), 127.9 (Bn),
128.01 (Bn), 128.03 (Bn), 128.2 (Bn), 128.6 (Bn), 128.7 (Bn), 135.7
(CH@), 137.8 (Bn), 138.1 (Bn), 141.4 (C3). ESIMS: calcd for
C26H31N2O5 [M+H]+ 451.2233, found 451.2225.
Syrup, [a]
D +24 (c 2, CHCl3); 1H NMR: d 1.32 (s, 3H, U-Me), 1.55
(s, 3H, U-Me), 1.60 (s, 3H, Me), 3.36 (br s, 1H, H5), 3.40 (dd, 1H, U-
H5, J4,5 = 3.2 Hz, Jgem = 15.5 Hz), 3.53–3.62 (m, 2H, H7, U-H5), 3.88
(dd, 1H, H6, J5,6 = J6,7 = 4.0 Hz), 3.95 (d, 1H, H4, J = 6.4 Hz), 4.17 (m,
1H, U-H4), 4.25 (br s, 2H, H1, H8), 4.45 (d, 1H, Bn, J = 11.6 Hz), 4.60
(d, 1H, Bn, J = 11.6 Hz), 4.64 and 4.68 (d and d, 1H each, Bn,
J = 13.2 Hz), 4.70 (dd, 1H, U-H3, J = 4.8 Hz, J = 6.4 Hz), 5.05 (d, 1H,
U-H2, J = 6.4 Hz), 5.14 (br s, 1H, H9), 5.44 (br s, 1H, U-H1), 5.69
(d, 1H, U-H7, J6,7 = 8.0 Hz), 7.14 (d, 1H, U-H6, J6,7 = 8.0 Hz), 7.23–
7.34 (m, 10H, Ph); 13C NMR: d 20.4 (Me), 25.4 (U-Me), 27.3 (U-
Me), 36.9 (C5), 53.9 (U-C5), 60.4 (C1), 70.7 (Bn), 72.7 (C9), 73.1
(Bn), 73.2 (C7), 73.4 (C8), 81.0 (C6), 82.5 (U-C3), 84.4 (U-C2), 87.6
(U-C4), 88.5 (C4), 96.4 (U-C1), 102.8 (U-C7), 114.9 (C-Me2), 127.9
(Bn), 128.0 (Bn), 128.1 (Bn), 128.6 (Bn), 128.7 (Bn), 137.7 (Bn),
138.1 (Bn), 141.4 (C3), 143.6 (U-C6), 150.0 (C@O), 163.3 (C@O).
ESIMS: calcd for C35H41N4O10 [M+H]+ 677.2822, found 677.2818.
3.10. (1S,5R,6S,7R,8R,9S)-2-Benzyl-6,7-di-O-benzyl-8-hydroxy-
3-methyl-9-nitro-2-azabicyclo[3,3,1]nonan-3-ene (2b)
Syrup, [a]
D ꢀ43 (c 1.6, CHCl3); 1H NMR: d 1.78 (s, 3H, Me), 3.39
(d, 1H, OH, J = 5.6 Hz), 3.46 (m, 1H, H5), 3.65 (dd, 1H, H7,
J6,7 = J7,8 = 3.2 Hz), 3.76 (m, 1H, H8) 3.96 (m, 1H, H6), 4.07 (d, 1H,
H4, J4,5 = 6.8 Hz), 4.10 (d, 1H, N–Bn, J = 15.6 Hz), 4.20 (m, 1H, H1),
4.42 (d, 1H, Bn, J = 11.6 Hz), 4.52 (d, 1H, Bn, J = 11.6 Hz), 4.56 (d,
1H, N–Bn, J = 15.6 Hz), 5.14 (br s, 1H, H9), 7.18–7.40 (m, 15H,
Ph); 13C NMR: d 20.5 (Me), 37.2 (C5), 55.5 (N–Bn), 60.4 (C1), 70.5
(Bn), 72.6 (C8), 72.8 (C7), 73.3 (C9), 73.5 (Bn), 81.1 (C6), 88.3
(C4), 127.8 (Bn), 127.9 (Bn), 128.0 (Bn), 128.2 (Bn), 128.6 (Bn),
128.7 (Bn), 128.9 (Bn), 137.8 (Bn), 138.1 (Bn), 139.4 (Bn), 141.7
(C3). ESIMS: calcd for C30H33N2O5 [M+H]+ 501.2389, found
501.2400.
3.14. (1S,5R,6R,7R,8R,9S)-2-Allyl-6,7-di-O-benzyl-8-hydroxy-3-
methyl-9-nitro-2-azabicyclo[3,3,1]nonan-3-ene (13a)
Syrup, [
a]
D ꢀ139 (c 0.6, CHCl3); 1H NMR: d 1.78 (s, 3H, Me), 2.60
(s, 1H, OH), 3.48 (m, 1H, H5), 3.59 (dd, 1H, H7, J6,7 = 8.8 Hz,
J7,8 = 4.0 Hz), 3.62 (dd, 1H, N–CH2, J = 7.6 Hz, J = 16.0 Hz), 3.77
(dd, 1H, H6, J5,6 = 3.6 Hz, J6,7 = 8.8 Hz), 3.86 (dd, 1H, N–CH2,
J = 5.2 Hz, J = 16.0 Hz), 3.97 (dd, 1H, H8, J7,8 = J1,8 = 4.0 Hz), 4.10
(dd, 1H, H1, J1,8 = 2.8 Hz, J1,9 = 6.0 Hz), 4.22 (d, 1H, H4, J = 6.4 Hz),
4.62 (d, 1H, Bn, J = 11.2 Hz), 4.66 (d, 1H, Bn, J = 11.6 Hz), 4.73 (br
s, 1H, H9), 4.77 (d, 1H, Bn, J = 11.6 Hz), 4.80 (d, 1H, Bn,
J = 11.2 Hz), 5.14 (m, 2H, CH2@), 5.74 (m, 1H, CH@), 7.26–7.42
(m, 10H, Ph); 13C NMR: d 19.9 (Me), 35.6 (C5), 54.0 (N–CH2), 57.8
(C1), 71.6 (C8), 72.1 (Bn), 73.7 (Bn), 74.9 (C9), 79.2 (C7), 81.7
(C6), 87.9 (C4), 117.3 (CH2@), 127.77 (Bn), 127.83 (Bn), 127.9
(Bn), 128.0 (Bn), 128.4 (Bn), 128.5 (Bn), 135.7 (CH@), 138.1 (Bn),
138.2 (Bn), 140.3 (C3). ESIMS: calcd for C26H31N2O5 [M+H]+
451.2232, found 451.2212.
3.11. (1S,5R,6S,7R,8R,9S)-2-Cyclohexyl-6,7-di-O-benzyl-8-
hydroxy-3-methyl-9-nitro-2-azabicyclo[3,3,1]nonan-3-ene (2c)
Syrup, [
a
]
ꢀ92 (c 2.0, CHCl3); 1H NMR: d 0.80–1.94 (m, 13H,
D
cyclohexyl CH2, Me), 3.24 (m, 1H, N–CH), 3.34 (m, 1H, H5), 3.56
(d, 1H, OH, J = 5.6 Hz), 3.60 (dd, 1H, H7, J6,7 = J7,8 = 3.6 Hz), 3.93
(m, 1H, H6), 3.98 (d, 1H, H4, J4,5 = 6.0 Hz), 4.10 (m, 1H, H8), 4.38

W. Zou et al. / Carbohydrate Research 344 (2009) 2144–2150
2149
3.15. (1S,5R,6R,7R,8R,9S)-2-Benzyl-6,7-di-O-benzyl-8-hydroxy-
3-methyl-9-nitro-2-azabicyclo[3,3,1]nonan-3-ene (13b)
3.19. (1S,2R,3R,4R,5R,6S)-1-Acetylmethyl-2,3-di-O-benzyl-4-
hydroxy-5-methoxy-6-nitrocyclohexane (16)
Syrup, [
a
]
ꢀ6 (c 0.8, CHCl3); 1H NMR: d 1.86 (s, 3H, Me),
Crystals, mp 166–168 °C; [a]
D +33 (c 2, CHCl3); 1H NMR: d 1.92
D
3.49 (m, 1H, H5), 3.58–3.63 (m, 2H, H7, H8), 3.72 (dd, 1H, H6,
J5,6 = 2.8 Hz, J6,7 = 8.0 Hz), 4.06 (m, 1H, H1), 4.09 (d, 1H, N–CH2,
J = 15.6 Hz), 4.29 (d, 1H, H4, J = 6.4 Hz), 4.50 (d, 1H, Bn,
J = 11.6 Hz), 4.54 (d, 1H, N–CH2, J = 15.6 Hz), 4.64 (d, 1H, Bn,
J = 11.6 Hz), 4.70 (d, 1H, Bn, J = 11.6 Hz), 4.72 (br s, 1H, H9),
4.76 (d, 1H, Bn, J = 11.6 Hz), 7.19–7.38 (m, 15H, Ph); 13C NMR:
d 20.7 (Me), 35.9 (C5), 54.4 (N–CH2), 58.5 (C1), 71.4 (C8), 72.3
(Bn), 73.6 (Bn), 75.0 (C9), 79.2 (C7), 81.8 (C6), 89.0 (C4), 127.7
(Bn), 127.9 (Bn), 128.0 (Bn), 128.1 (Bn), 128.2 (Bn), 128.65
(Bn), 128.67 (Bn), 128.8 (Bn), 138.2 (Bn), 138.4 (Bn), 139.6
(Bn), 140.7 (C3). ESIMS: calcd for C30H33N2O5 [M+H]+ 501.2389,
found 501.2370.
(s, 3H, Me), 2.32–2.42 (m, 2H, H1, H10a), 2.45 (s, 1H, OH), 2.57 (m,
1H, H10b), 3.34 (s, 3H, OCH3), 3.50 (dd, 1H, H3, J2,3 = 2.4 Hz,
J3,4 = 9.2 Hz), 3.67 (dd, 1H, H2, J1,2 = 10.0 Hz, J2,3 = 2.4 Hz), 3.96
(dd, 1H, H5, J4,5 = J5,6 = 9.2 Hz), 4.38 (m, 1H, H4), 4.48 (d, 1H, Bn,
J = 11.6 Hz), 4.70 (m, 2H, Bn), 4.87 (d, 1H, H6, J1, 6 = 11.6 Hz), 4.93
(d, 1H, Bn, J = 11.6 Hz), 7.20–7.38 (m, 10H, Ph); 13C NMR: d 30.2
(Me), 39.0 (C1), 40.9 (C10), 58.0 (OCH3), 65.8 (C4), 72.7 (Bn), 75.5
(Bn), 77.4 (C5), 80.3 (C2), 82.4 (C3), 87.6 (C6), 128.0 (Bn), 128.1
(Bn), 128.3 (Bn), 128.6 (Bn), 128.8 (Bn), 137.5 (Bn), 138.6 (Bn),
206.6 (C@O). ESIMS: calcd for C24H30NO7 [M+H]+ 444.2022, found
444.2053.
3.20. (1S,3S,5R,6S,7R,8R,9S)-2-Allyl-6,7-di-O-benzyl-8-hydroxy-
3.16. (1R,3R,5S,6R,7R,8S,9R)-2-Allyl-6,7-di-O-benzyl-3-methyl-
3-methyl-9-nitro-2-azabicyclo[3,3,1]nonane (17a)
9-nitro-3,8-oxy-2-azabicyclo[3,3,1]nonane (14a)
Syrup, [
a
]
ꢀ30 (c 1, CHCl3); 1H NMR: d 0.85 (d, 3H, Me,
D
Syrup, [
a]
+19 (c 0.5, CHCl3); 1H NMR: d 1.40 (s, 3H, Me), 1.68
J3,Me = 5.6 Hz), 0.91 (d, 1H, H4a, J4a,4b = 12.4 Hz), 2.04 (m, 1H,
H4b), 2.51 (m, 1H, H3), 3.09–3.32 (m, 4H, H5, OH, NCH2), 3.74
(br s, 1H, H6), 3.99 (m, 2H, H1, H8), 4.09 (br s, 1H, H7), 4.50 and
4.65 (d and d, 1H each, Bn, J = 12 Hz), 4.67 (s, 2H, Bn), 4.89 (br s,
1H, H9), 5.15 (m, 2H, CH2@), 5.80 (m, 1H, CH@), 7.27–7.39 (m,
10H, Ph); 13C NMR: d 22.0 (Me), 32.8 (C5), 33.1 (C4), 45.8 (C3),
57.0 (NCH2), 60.3 (C1), 70.7 (Bn), 71.1 (C7), 71.9 (C8), 73.5 (Bn),
78.0 (C9), 81.5 (C6), 118.3 (CH2@), 127.9 (Bn), 128.1 (Bn), 128.2
(Bn), 128.6 (Bn), 128.7 (Bn), 134.8 (CH@), 137.7 (Bn), 138.1 (Bn).
ESIMS: calcd for C26H33N2O5 [M+H]+ 453.2389, found 453.2380.
D
(d, 1H, H4a, J4a,4b = 14 Hz), 2.31 (dd, 1H, H4b, J4b,5 = 6.4 Hz), 2.82–
2.90 (m, 2H, H5, NCH2), 3.36–3.46 (m, 2H, H7, NCH2), 3.94 (d, 1H,
H6, J5,6 = 5.6 Hz), 4.18 (m, 1H, H1), 4.38 (d, 1H, H8, J1,8 = 6.4 Hz),
4.60–4.66 (m, 3H, H9, Bn), 4.63 and 4.72 (d and d, 1H each, Bn,
J = 12.4 Hz), 5. 14 (m, 2H, CH2@), 5.70 (m, 1H, CH@), 7.21–7.38
(m, 10H, Ph); 13C NMR: d 20.9 (Me), 36.2 (C5), 40.8 (C4), 52.0
(NCH2), 62.2 (C1), 71.8 (Bn), 72.0 (Bn), 73.6 (C8), 79.4 (C9), 80.3
(C7), 85.2 (C6), 98.0 (C3), 118.5 (CH2@), 127.9 (Bn), 128.1 (Bn),
128.2 (Bn), 128.6 (Bn), 128.7 (Bn), 135.5 (CH@), 137.7 (Bn), 138.0
(Bn). ESIMS: calcd for C26H31N2O5 [M+H]+ 451.2232, found
451.2259.
3.21. (1S,3S,5R,6S,7R,8R,9S)-2-Benzyl-6,7-di-O-benzyl-8-
hydroxy-3-methyl-9-nitro-2-azabicyclo[3,3,1]nonane (17b)
3.17. (1R,3R,5S,6R,7R,8S,9R)-2-Benzyl-6,7-di-O-benzyl-3-
methyl-9-nitro-3,8-oxy-2-azabicyclo[3,3,1]nonane (14b)
Syrup, [
a]
ꢀ44 (c 1, CHCl3); 1H NMR: d 0.91 (d, 3H, Me,
D
J3,Me = 5.6 Hz), 1.38 (m, 1H, H4a), 1.94 (m, 1H, H4b), 2.60 (m,
1H, H3), 3.00 (m, 1H, H5), 3.06 (d, 1H, OH, JOH,8 = 3.6 Hz), 3.56
(d, 1H, NCH2, J = 14.8 Hz), 3.81 (d, 1H, J = 14.8 Hz, NCH2), 3.83–
3.90 (m, 3H, H6, H7, H1), 4.36 (d, 1H, H8, J7,8 = 3.2 Hz), 4.56
and 4.68 (d and d, 1H each, Bn, J = 11.6 Hz), 4.66 (s, 2H, Bn),
5.05 (br s, 1H, H9), 7.20–7.40 (m, 15H, Ph); 13C NMR: d 23.7
(Me), 30.6 (C4), 34.4 (C5), 51.9 (C3), 55.7 (NCH2), 60.2 (C1),
66.2 (C8), 71.0 (Bn), 73.5 (Bn), 74.9 (C7), 77.8 (C9), 80.2 (C6),
127.2 (Bn), 127.9 (Bn), 128.0 (Bn), 128.1 (Bn), 128.2 (Bn), 128.3
(Bn), 128.4 (Bn), 128.6 (Bn), 128.8 (Bn), 137.7 (Bn), 137.9 (Bn),
139.5(Bn). ESIMS: calcd for C30H35N2O5 [M+H]+ 503.2545, found
503.2549.
Syrup, [a]
+37 (c 0.5, CHCl3); 1H NMR: d 1.39 (s, 3H, Me), 1.71
D
(d, 1H, H4a, J4a,4b = 14 Hz), 2.43 (dd, 1H, H4b, J4b,5 = 6.4 Hz), 2.82 (d,
1H, H5, J4b,5 = 6.4 Hz), 3.28 (d, 1H, NCH2, J = 13.2 Hz), 3.41 (d, 1H,
H7, J7,8 = 5.2 Hz), 3.92–3.98 (m, 2H, H1, H6), 4.02 (d, 1H, NCH2,
J = 13.2 Hz), 4.42–4.51 (m, 3H, H9, H8, Bn), 4.62 (d, 1H, Bn,
J = 12 Hz), 4.64 and 4.72 (d and d, 1H each, Bn, J = 12 Hz), 7.18–
7.37 (m, 15H, Ph); 13C NMR: d 21.5 (Me), 36.1 (C5), 40.8 (C4),
53.6 (NCH2), 63.6 (C1), 71.8 (Bn), 72.1(Bn), 73.5 (C9), 79.3 (C8),
80.2 (C7), 85.2 (C6), 98.6 (C3), 127.6 (Bn), 127.9 (Bn), 128.0 (Bn),
128.1 (Bn), 128.2 (Bn), 128.5 (Bn), 128.6 (Bn), 128.7 (Bn), 128.9
(Bn), 137.7 (Bn), 138.0 (Bn), 138.1 (Bn). ESIMS: calcd for
C30H33N2O5 [M+H]+ 501.2389, found 501.2389.
3.22. (1S,3S,5R,6S,7R,8R,9S)-2-Cyclohexyl-6,7-di-O-benzyl-8-
3.18. (1R,2R,3R,4R,5S,6R)-1-Acetylmethyl-2,3-di-O-benzyl-4-
hydroxy-3-methyl-9-nitro-2-azabicyclo[3,3,1]nonane (17c)
hydroxy-5-methoxy-6-nitrocyclohexane (15)
Syrup, [
a
]
ꢀ31 (c 1, CHCl3); 1H NMR: d 0.83 (d, 3H, Me,
D
Syrup, [
a
]
D ꢀ60 (c 1.5, CHCl3); 1H NMR: d 1.87 (s, 3H, Me), 2.11
J3,Me = 5.6 Hz), 0.89 (m, 1H, H4a), 1.02–1.84 (m, 10H, CH2), 2.06
(m, 1H, H4b), 2.58–2.73 (m, 2H, H3, NCH), 3.17 (m, 1H, H5), 3.28
(d, 1H, OH, JOH,8 = 5.2 Hz), 3.73 (m, 1H, H6), 3.96 (m, 1H, H1),
4.01 (m, 1H, H8), 4.15 (dd, 1H, H7, J6,7 = J7,8 = 3.6 Hz), 4.47 and
4.63 (d and d, 1H each, Bn, J = 11.6 Hz), 4.65 (s, 2H, Bn), 4.91 (m,
1H, H9), 7.27–7.39 (m, 10H, Ph); 13C NMR: d 21.8 (Me), 23.5,
25.7, 26.1, 26.9, 32.2, 33.2 (C4), 33.5 (C5), 43.0 (C3), 56.0 (C1),
57.1 (NCH2), 64.0 (C8), 70.5 (C7), 70.9 (Bn), 73.3 (Bn), 74.9 (C7),
78.2 (C9), 81.4 (C6), 127.2 (Bn), 127.8 (Bn), 127.9 (Bn), 128.4
(Bn), 128.5 (Bn), 137.6 (Bn), 137.9 (Bn). ESIMS: calcd for
C29H39N2O5 [M+H]+ 495.2858, found 495.2837.
(m, 1H, H10a), 2.37 (d,1H, OH, JOH,4 = 8.4 Hz), 2.63 (dd, 1H, H10b,
0
0
0
J1 a,1 b = 10.8 Hz, J1,1 b = 18.4 Hz), 2.97 (m, 1H, H1), 3.47 (s, 3H,
OCH3), 3.80–3.92 (m, 4H, H2, H3, H4, H5), 4.18 (d, 1H, Bn,
J = 12.0 Hz), 4.40 (dd, 1H, H6, J5,6 = 9.6 Hz, J1,6 = 12.4 Hz), 4.46,
4.54 and 4.73 (d, d and d, 1H each, Bn, J = 11.6 Hz), 7.18 (m, 2H,
Ph), 7.27–7.33 (m, 8H, Ph); 13C NMR: d 30.2 (Me), 35.0 (C1), 39.9
(C10), 61.3 (OCH3), 71.9 (C4), 73.0 (Bn), 73.6 (C3), 75.8 (C2), 82.2
(C5), 89.2 (C6),128.5 (Bn), 128.6 (Bn), 128.7 (Bn), 128.9 (Bn),
137.2 (Bn), 137.3 (Bn), 205.8 (C@O). ESIMS: calcd for C24H30NO7
[M+H]+ 444.2022, found 444.2016.

2150
W. Zou et al. / Carbohydrate Research 344 (2009) 2144–2150
3.23. (1S,3S,5R,6R,7R,8R,9S)-2-Allyl-6,7-di-O-benzyl-8-hydroxy-
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453.2389, found 453.2352.
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3.24. (1S,3S,5R,6R,7R,8R,9S)-2-Benzyl-6,7-di-O-benzyl-8-
hydroxy-3-methyl-9-nitro-2-azabicyclo[3,3,1]nonane (18b)
Syrup, 1H NMR: d 1.03 (d, 3H, Me, J3,Me = 5.6 Hz), 1.74 (m, 1H,
H4a), 1.89 (m, 1H, H4b), 2.61 (m, 1H, H3), 3.33 (m, 1H, H5), 3.46
(d, 1H, NCH2, J = 13.6 Hz), 3.63 (dd, 1H, H6, J6,7 = 4.8 J5,6 = 9.6 Hz),
3.85–4.05 (m, 4H, H7, H8, H1, NCH2), 4.42–4.75 (m, 5H, Bn, H9),
7.17–7.38 (m, 10H, Ph); 13C NMR: d 23.2 (Me), 29.6 (C4), 31.7
(C5), 47.5 (C3), 59.8 (NCH2), 60.0 (C1), 70.1 (C8), 71.8 (Bn), 73.2
(Bn), 77.0 (C7), 79.2 (C9), 79.4 (C6), 127.8 (Bn), 127.9 (Bn), 128.0
(Bn), 128.1 (Bn), 128.4 (Bn), 128.5, 128.6 (Bn), 138.4, 140.2 (Bn).
ESIMS: calcd for C30H35N2O5 [M+H]+ 503.2545, found 503.2546.
Acknowledgments
This is NRC-CNRC publication No. 50005. We thank Ken Chan
and Jacek Stupak for MS analysis and Nam Khieu for the assistance
in NMR analysis.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2009.08.028.