Synthesis and ring opening reactions of 2-glyco-1,4-dimethyl-3-nitro-7-oxabicyclo[2.2.1]hept-5-enes

Article abstract of DOI:10.1016/j.tet.2010.02.027

The high-pressure asymmetric Diels-Alder reactions of d-galacto- (1a) and d-manno-3,4,5,6,7-penta-O-acetyl-1,2-dideoxy-1-nitrohept-1-enitol (1b) with 2,5-dimethylfuran (2) afforded mixtures of cycloadducts, from which the (2S,3R)-3-exo-nitro (3a and 3b), (2R,3S)-3-exo-nitro (4a and 4b), and (2R,3S)-1′,2′,3′,4′,5′-penta-O-acetyl-1′-C-(1,4-dimethyl-3-endo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl)-d-galacto-pentitol (5b) were isolated pure. Deacetylation of these compounds led to new chiral mono-, bi-, and tricyclic ethers, being their asymmetric centers arising from the chiral inductor used in the cycloaddition reaction. A ring opening mechanism through a 1-nitro-1,3-cyclohexadiene intermediate has been proposed.

Full text of DOI:10.1016/j.tet.2010.02.027

Tetrahedron 66 (2010) 2664–2674
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and ring opening reactions of 2-glyco-1,4-dimethyl-3-nitro-
7
-oxabicyclo[2.2.1]hept-5-enes
*
Noelia Ara u´ jo, Mar ı´ a V. Gil, Emilio Rom a´ n , Jos e´ A. Serrano
Departamento de Qu ´ı mica Org a´ nica e Inorg a´ nica, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The high-pressure asymmetric Diels–Alder reactions of D-galacto- (1a) and D-manno-3,4,5,6,7-penta-
Received 13 January 2010
Received in revised form 2 February 2010
Accepted 3 February 2010
Available online 8 February 2010
O-acetyl-1,2-dideoxy-1-nitrohept-1-enitol (1b) with 2,5-dimethylfuran (2) afforded mixtures of
cycloadducts, from which the (2S,3R)-3-exo-nitro (3a and 3b), (2R,3S)-3-exo-nitro (4a and 4b), and
0
0
0
0
0
0
(
2R,3S)-1 ,2 ,3 ,4 ,5 -penta-O-acetyl-1 -C-(1,4-dimethyl-3-endo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-
exo-yl)- -galacto-pentitol (5b) were isolated pure. Deacetylation of these compounds led to new
D
chiral mono-, bi-, and tricyclic ethers, being their asymmetric centers arising from the chiral inductor
used in the cycloaddition reaction. A ring opening mechanism through a 1-nitro-1,3-cyclohexadiene
intermediate has been proposed.
Keywords:
Asymmetric synthesis
Carbohydrate nitroalkenes
Chiral 7-oxanitronorbornenes
Diels–Alder reaction
Oxygen heterocycles
Ring opening reactions
Ó 2010 Elsevier Ltd. All rights reserved.
1
. Introduction
and undecul-2-ose derivatives. These latter compounds could be
9
considered as higher sugars, being identified as fragments of bi-
10
Racemic 7-oxabicyclo[2.2.1]hept-5-ene-trans-3-nitro-2-carboxy-
lates1 are very useful compounds for the preparation of natural
products bearing multisubstituted cyclohexanol units after regiose-
lective cleavage of the ethereal C–O bond. However, although the
access to chiral derivatives of 7-oxabicyclo[2.2.1]heptenes seems also
promising, references about this type of compounds are rather
scarce, probably due to difficulties related to their asymmetric
synthesis. In particular, apart from papers of our group, we have not
found any reference about the preparation of chiral 7-oxani-
tronorbornenes; attempts to prepare these compounds by using
chiral nitroacrylates as dienophiles have failed, being obtained chiral
amino derivatives by reduction from racemic 7-oxani-
ologically interesting compounds, such as octosylic acids A and C,
antifungal C-glycoside malayamycin A, and ezomycins.
10
11
Following our research work on asymmetric synthesis with
2
12
sugar-derived nitro compounds, we describe in full details about
13
14
Diels–Alder reactions between nitroalkenes 1a and 1b with 2,5-
dimethylfuran (2). It is noteworthy that, by changing the solvent,
we have observed variations in both the rate and stereoselectivity
of the cycloadditions with 1a. In addition, we describe the ring
opening reactions and the products obtained from the new
cycloadducts.
3
4
2
c
tronorbornenes, followed by enzymatic resolution or chiral HPLC.
2. Results and discussion
In recent years, the seven-membered oxacycles and other me-
5
dium size rings have received a considerable attention. This fact is
mainly due to their biological and synthetic interest as well as their
occurrence in a wide variety of natural products, such as zoapata-
nol, hemibrevetoxin B, or ciguatoxins and brevetoxins A and B.
Among the methods described for their preparation, we reported
in a preliminary communication, a new one-pot ring opening
The high-pressure Diels–Alder reactions between the D-galacto-
4b
nitroalkene 1a and 2,5-dimethylfuran 2 afforded mixtures of
cycloadducts 3a, 4a, and 5a, in ratios that were dependent both on
the solvent and on the reaction time (Scheme 1 and Table 1, entries
6
7
8
1
–8). After fractional crystallization from the crude product, the
exo-nitro stereoisomers 3a and 4a were isolated pure. Similarly,
-manno-nitroalkene 1b and 2,5-dimethylfuran led, after 3 days, to
a 6.8:3.5:1.0 mixture of 3b, 4b, and 5b (Scheme 1 and Table 1, entry
4
b
reaction where the cycloadduct 3a led to an optically pure oxocine
D
1
1), that was separated by column chromatography and semi-
1
*
Corresponding author. Tel.: þ34924289381; fax: þ34924271149.
E-mail address: roman@unex.es (E. Rom a´ n).
preparative HPLC. Neither in this reaction nor in the previous, H
NMR signals were observed for the endo-nitro product 6.
0
040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.027

N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
2665
Scheme 1.
Table 1
Solvents, relative ratios between cycloadducts, facial diastereoselectivity, exo/endo ratios, and reaction times for reactions of nitroalkenes 1a and 1b with 2,5-dimehtylfurana
Entry
Nitroalkene
Solvent
Ratio of adductsb
(2R,3S)/(2S,3R) Ratioc
exo/endo Ratio
Time (days)
% Conv.
3
4
5
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
CH
3
CN
7.1
5.2
7.7
5.7
8.1
6.7
47.0
3.3
6.3
6.6
6.8
6.5
7.3
4.4
9.4
3.3
10.0
5.8
10.0
4.7
3.2
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.17
1.04
1.35
0.75
1.35
1.01
0.23
1.73
0.66
0.71
0.66
0.63
14.4
9.6
17.1
9.0
18.0
12.5
57.0
8.0
2
3
4
6
4.5
3
4.5
2
3
3
93
75
88
91
94
95
100
97
100
100
100
100
Acetone
Acetone
Acetone
THF
CH
CH
CHCl
Acetone
THF
2
Cl
Cl
2
2
2
3
9.5
10
11
12
3.7
3.5
3.1
10.3
10.6
9.6
CH
CH
2
Cl
Cl
2
2
3
4
2
a
b
c
All experiments were carried out at rt, under 13 kbar pressure.
Determined by integration of the pertinent peaks in the 1H NMR spectra.
Facial diastereoselectivity: (2R,3S)- and (2S,3R)-adducts arise, respectively, from cycloadditions at the C1-re and C1-si faces of the nitroalkene 1a or 1b.
As observed for cycloadditions between the same nitroalkenes
and (E)-1,1,1-trichloro-3-nitro-2-propene;17 an increase toward
those adducts was observed with increasing substitution at the
terminal positions of the furan diene.
and furan4 or 2-methylfuran, it is noteworthy that none of these
reactions occurred under atmospheric pressure, both at room
temperature and at reflux, even for prolonged periods. In addition,
no reaction was observed when these processes were carried out in
a
4c
4
a,c
In previous publications,
and following a rule stated by
18
Franck, we reported that the facial selectivity in cycloadditions
with 1a or 1b, using dichloromethane as solvent, was dependent
on the configuration of the chiral center adjacent to the dien-
ophilic double bond. Thus, the major adducts were those resulting
of the attack by the diene at the C1-si face of 1a and at the C1-re
face of 1b. Now, when the same solvent and reaction time were
used (Table 1, entries 7 and 11), we found that the attack by 2,5-
dimethylfuran on both sugar nitroolefins occurred predominantly
at the C1-si face, thus leading to (2S,3R)-cycloadducts; i.e., the
facial stereoselectivity in these reactions did not show dependence
on the configuration of chiral center adjacent to the dienophilic
double bond.
1
:1 CH
under mechanical stirring.
Since solubility of nitroalkene 1a in CH
.15 g/mL), we tested other solvents for cycloadditions between this
2 2
Cl –water, or with the same solvent mixture and 5 M LiCl
15
2 2
Cl was rather low (ca.
0
dienophile and 2,5-dimethylfuran. Thus, we observed that some
parameters as reaction time, diastereoselectivity, or endo/exo ratio
were dependent on the solvent. As shown in Table 1, the exo-nitro 3a
was the major adduct in those reactions with acetone (3 or 6 days) or
CH
with acetonitrile, acetone (4 days), tetrahydrofuran or chloroform
entries 1, 3, 5, and 8). It is noticeable the change that occurs in dia-
stereoselectivity with acetone (entries 2–4), as well as the high per-
centage of 3a with CH Cl (entry 7). The diastereoselectivity changed
from 0.23, after 4.5 days in CH Cl (entry 7), being the 2S,3R adduct 3a
predominant, to 1.73 in CHCl after 2 days (entry 8), with 2R,3S
2 2
Cl (entries 2, 4, 6, and 7), whereas the exo-nitro 4a preponderate
(
Structures for 3–5 were supported by spectroscopic data, as well
4
a
2
2
as on their comparison with those for similar adducts from furan
4
c
2
2
and 2-methylfuran. Absolute configuration at the new chiral
centers at C-2 and C-3 were based on X-ray powder diffractome-
try for 3a and chemical correlations (see below).
Treatment of 3a with aqueous methanolic K CO , followed by
3
3
4
b
adduct 4a as the major product. Fluctuation of diastereoselectivity
with reaction time has been previously observed for the reaction
2
16
þ
between methyl nitroacrylate and 2-methylfuran. Regarding time
needed for each one of the cycloadditions, it is noticeable that after 2
acidification to ca. pH 6 with Amberlite IR-120 (H ) resin, led to
a mixture, from which undecul-2-ose 8b and oxocine 9c were
obtained. Conventional reacetylation of the crude mixture and
separation by column chromatography afforded 7d, 8a, and 9e
(Fig. 1). Although bicycle 7f was not isolated, it was characterized as
the corresponding acetyl derivative 7d and the O-methylglycoside
7g. The formation of compounds 7–9 from cycloadduct 3a, under
the deacetylation conditions could be justified through a ring
opening reaction leading to a proposed 1-nitro-1,3-cyclohexadiene
intermediate, followed by intramolecular nucleophilic additions
from hydroxy groups of the sugar side-chain on the diene system
and, finally, carbon–carbon bond heterolytic rupture.4
3
days with CHCl or acetonitrile, were achieved reaction completion
percentages (% conv.) that in acetone required 6 days. From a syn-
thetic point of view, data indicate that the best reaction conditions to
prepare the adduct 3a would be those indicated in entry 7, whereas
those specified in entry 8 would give a better yield of 4a.
4
b
Unlikely to what was observed for 1a, the cycloaddition of 1b and
2
1
,5-dimethylfuran with solvents or reaction times indicated in Table
(entries 9–12) did not show significative changes of the results.
The preference for the exo-nitro adducts in both cycloadditions
b
agrees with previous findings in similar processes between furans

2666
N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
hypothetical carbanion because of steric hindrance. As described,20
removal of the H-3 proton would be at the origin of the opening of
the bicyclic system to the corresponding 1-nitro-1,3-cyclo-
hexadiene intermediate 12 (Scheme 2).
2 3
The reaction with K CO and acid resin, either from 3b or
a mixture 3b–5b led to an oily residue, from which crystallized the
2
e,20c
oxepine 14 (Scheme 3). Similarly to described,
the formation of
this compound can be justified considering that besides depro-
tection of the sugar chain, the intermediate 13 should be formed;
21a,b
then, a tandem process involving nucleophilic attacks
from
hydroxy groups of the sugar chain (Scheme 3, path a), followed by
the marked carbon–carbon heterolytic bond rupture would lead to
1
4. Through this mechanism, that is analogous to that described by
4
b
us for 3a, the oxepine 14 (with the nitromethyl group and the
sugar fragment in a trans-relationship), could only be derived from
1
cycloadduct 3b. The H NMR spectrum of 14 showed four D
2
O ex-
changeable signals (three doublets and a triplet) for hydroxy
groups; on the contrary, a triplet assigned to H-2 did not change, as
would have happened if it were the H-3 of the possible alternative
isomer 17 (Scheme 3). The structure of the oxepine 14 was also
confirmed through its corresponding tetraacetate 19 (Fig. 2); for
both compounds, the coupling constant values between H-2 and H-
3 (8.8 and 9.2 Hz, respectively) support a trans-relationship for
nitromethyl group and the sugar side-chain.
Figure 1. Structures of compounds 7–9.
2 3
The reaction of cycloadduct 4a with K CO and resin, under
identical conditions to those used for 3a, led to different results.
Thus the H NMR spectrum of the crude mixture from 4a showed
1
two doublet signals for a major product (at 6.24 and 6.42 ppm) that
were assigned to olefinic H-5 and H-6; also, a doublet at 4.67 ppm,
and a double doublet at 2.80 ppm suggest the deacetylated struc-
ture 10 (Scheme 2). This compound could not be isolated due to its
transformation, complete after 3 days in the NMR tube, into 2,5-
dimethylfuran and the diastereomeric sugars 11 (R¼H); conven-
tional acetylation of this crude product led to a mixture of two
From the mother liquor of crystallization of 14, 2,5:4,7-dianhy-
droundecul-2-ose 15 (Scheme 3) was obtained as a solid anomeric
mixture of methylglycosides, probably as a result of the presence of
1
13
methanol under the acid conditions. Besides H and C NMR sig-
nals supporting the methoxy group (at 3.08 and 48.8 ppm, re-
spectively), the major anomer of 15 showed three doublets and one
1
13
tetraacetates 11 (R¼Ac) whose H and C NMR spectra were dif-
ferent to those described for 3,4,5,7-tetra-O-acetyl-2,6-anhydro-1-
2
triplet that disappeared by D O exchange; noticeably, this exchange
19a
1
desoxi-1-nitro-
trum of the mixture 11 (R¼Ac) showed that by irradiation at
.36 ppm (H-6), collapsed six signals between 4.39 and 4.06 ppm
D
-glycero-
L
-manno-heptitol.
The H NMR spec-
did not alter the triplet H-7, as it should be expected for its isomer
16 (Scheme 3). Conventional acetylation of 15 led to tetraacetate 18,
also isolated as the major product from 3b, after treatment with
5
that were assigned to protons H-7a, H-7b, and H-5 of both anomers.
These data, and the 1 C NMR shift for C-5 (82.1 ppm), typical for
furanoside derivatives,1 agree with structures of 2,5-anhydro-1-
deoxy-1-nitroalditols 11, formed through retro Diels–Alder
reaction, by cyclization between C-2 and C-5 from deacetylated
derivative of the nitroalkene 1a.
2 3
methanolic K CO /resin and reacetylation. Therefore, both 14 and
3
15 arise from 3b, probably through the 1-nitro-1,3-cyclohexadiene
13, following mechanisms indicated in Scheme 3, paths a and b.
Deacetylation of 3b led to an oil from which methyl glycoside 16
was isolated by PTLC. Formation of 16 could be justified as indicated
in Scheme 3 (path d), by a mechanism involving intramolecular
9b
Scheme 2.
0
The difference in behavior of cycloadducts 3a and 4a could be
justified by (a), difficulty of access by the base to the endo H-3
proton in 4a, located between the sugar side-chain and methyl
group on C-4 and/or (b), the difficulty of stabilizing as nitronate the
nucleophilic addition from OH-2 on the terminal carbon of the
intermediate 13, followed by the marked carbon–carbon bond
rupture and glycosidation with methanol and the acid resin. Con-
ventional acetylation of the crude mixture from 3b yielded the

N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
2667
Scheme 3.
system of 1-nitro-1,3-cyclohexadiene 22, then followed by the
marked carbon–carbon bond ruptures. Path a would lead to 23
where, in contrast to its analogue 14, the nitromethyl group and the
acyclic sugar fragment showed a cis-relationship (J2,3 5.7 Hz). In
a similar way, path b would lead to 4,7:2,8-dianhydroundecul-2-
ulo-2,5-furanoside 24; in this case, after the heterolytic rupture, the
first hydroxy group of the sugar fragment would be very close to the
carbocationic center, thus facilitating the subsequent cyclization.
Compounds 25–28 were obtained by K
2 3
CO deacetylation and
subsequent Ac O/Py reacetylation from 4b. Also, conventional
2
acetylation of an analytical sample of 23 led to tetraacetyl de-
rivative 25 (J2,3 6.0 Hz), whereas tricyclic 24 yielded a mixture of
1
triacetate 26 and diacetate 27 (Fig. 3). The H NMR spectrum of
tricyclic oxime 28 did not show the characteristic AB system for
CH NO group, but a singlet (11.24 ppm) that was assigned to
2 2
CH]N oxyminic proton; also, at 2.25 ppm appeared a singlet at-
tributable to the methyl acetate group on the nitrogen, whereas
those at 2.11, 2.07, and 2.04 ppm were assigned to methyl acetate
groups on the sugar side-chain. Because of their structural analogy,
the formation of 28 could be justified from 26 through conversion
Figure 2. Structures of compounds 18–21.
21
methyl and ethyl glycoside tetraacetates 20 and 21, being the for-
mation of the latter due to the presence of absolute ethanol, used to
remove residual water by coevaporation before the reacetylation.
The 1H NMR spectra of compounds 7–9, 14–16, and 18–21
showed typical AB systems for both protons of their respective
nitromethyl groups; in all cases, the protons that appear at lower
field underwent a more rapid D O exchange than those at higher
2
field. The signals for the sugar side-chain protons of 18 and 19 were
almost superimposable, thus supporting identity between these
of its nitro group into oxime, probably due to silica gel of the
chromatographic plate.
2 3
Treatment of 5b with K CO and resin yielded oxepine 30
(Scheme 5). The structure of this compound was supported on its
1
13
H and C NMR spectra, which were very similar to those of 14 and
23. Formation of 30 could be explained through the intermediate
29 (Scheme 5), with subsequent attack from the first hydroxy group
to the nitroalkenic double bond and rupture of the marked carbon–
carbon bond. The value for the coupling constant J2,3 (4.8 Hz) agrees
with a cis-relationship between substituents at C-2 and C-3. Con-
ventional acetylation of 30 led to tetraacetate 31 (Fig. 4) with
fragments.
þ
Treatment of 4b with K
2
CO
3
and Amberlite IR-120 (H ) yielded
oxepine 23 and tricycle 24. As it is showed in Scheme 4, the for-
J
2,3¼4.2 Hz, thus supporting the proposed structures.
1
mation of these both compounds could be justified through intra-
For compounds 23–27 and 30,31 we observed H NMR signals
0
molecular nucleophilic attacks from OH-1 on the unsaturated
for protons corresponding to AB systems in their respective

2668
N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
Scheme 4.
acid–base properties of its geminal protons and the inductive and
resonance effects of this group. As far as we are aware, there is no
antecedent about these new opening reactions of 7-oxani-
tronorbornenic systems under very mild and ecofriendly
conditions.
3. Conclusions
In summary, by using high-pressure asymmetric cycloaddition
between
and 2,5-dimethylfuran, we have obtained new optically pure
-glyco-1,4-dimethyl-3-nitro-7-oxabicyclo[2.2.1]hept-5-enes.
a-nitroalkenes derived from D-galactose or D-mannose
2
Their structures are based on spectroscopic data, including X-ray
powder diffractometry, as well as on chemical correlations. In
addition, we describe a new mild procedure for the ring opening
reaction of the cycloadducts, proposing mechanisms to justify the
spontaneous formation of new chiral mono-, bi-, and tricyclic
ethers.
Figure 3. Structures of compounds 25–28.
Scheme 5.
4. Experimental
4.1. General
All chemicals were purchased from commercial sources and were
used directly, without further purification. Preparative TLC was
performed using silica gel (Merck 60 GF254). TLC was performed on
precoated Merck Kieselgel 60 GF254 aluminum backed plates; bands
were visualized by UV light, iodine vapor or p-anisaldehyde. NMR
1
Figure 4. Structure of oxepine–epoxyde 31.
spectra were taken on a Bruker AC/PC (400 MHz for H and 100 MHz
13
for C) instruments. All chemical shifts were expressed in parts per
million on the respect of the residual solvent signal. Coupling con-
stant values are recorded in hertz. Optical rotations were measured
with a Perkin–Elmer 241 polarimeter in a 1 dm tube. HRMS were
recorded on an AutoSpec spectrometer. High-pressure reactions
were carried out by using a high-pressure apparatus U-101 (Unipress
Equipment Division, High Pressure Research Center, Polish Academy
of Sciences). HPLC separation was carried out using Zorbax RX-Sil
–
CH
2
NO
2
groups; as cited above, these protons were exchange-
able with D
2
O, being this faster for those appearing at lower field.
It is noteworthy that tandem reactions here described involve
up to seven processes (in the case of the formation of 24) of rupture
and formation of bonds in a single synthetic step. Once the sugar
side-chain has been deacetylated, the driving force for the reactions
is the activating effect of the nitro group, which affects both the

N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
2669
2
0
0
USHL001118 column (9.4ꢀ250 mm ), following by UV-detection
J
2
0
0
,3
0
¼9.6 Hz, H-2 ), 5.23 (dd, 1H, H-3 ), 5.17 (m, 1H, J
3
0
,4
0
¼2.0 Hz, H-
0
(
Diode-Array G1315B detector).
4 ), 4.79 (d, 1H, J2,3¼3.2 Hz, H-3), 4.28 (dd, 1H, J
4
0
,5
0
a
¼4.8 Hz, H-5 a),
0
3
.80 (dd, J
4
0
,5
0
b
¼7.2 Hz, J
5
0
a,5
0
b
¼11.6 Hz, H-5 b), 2.51 (dd,1H, H-2), 2.13
0
0
0
0
0
0
4
.2. (2S,3R)-1 ,2 ,3 ,4 ,5 -Penta-O-acetyl-1 -C-(1,4-dimethyl-
-exo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl)- -galacto-
pentitol (3a), (2R,3S)-1 ,2 ,3 ,4 ,5 -penta-O-acetyl-1 -C-(1,4-
dimethyl-3-exo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl)-
-galacto-pentitol (4a), and (2R,3S)-1 ,2 ,3 ,4 ,5 -penta-
O-acetyl-1 -C-(1,4-dimethyl-3-endo-nitro-7-
(s, 3H, OAc), 2.08 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.00
3
D
(s, 3H, OAc), 1.73 (s, 3H, CH
3
3
-1), 1.69 (s, 3H, CH -4).
0
0
0
0
0
0
0
0
0
0
0
0
4.3. (2S,3R)-1 ,2 ,3 ,4 ,5 -Penta-O-acetyl-1 -C-(1,4-dimethyl-
0
0
0
0
0
D
3-exo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl)-D-manno-
pentitol (3b), (2R,3S)-1 ,2 ,3 ,4 ,5 -penta-O-acetyl-1 -C-
(1,4-dimethyl-3-exo-nitro-7-oxabicyclo[2.2.1]hept-5-en-2-
-manno-pentitol (4b), and (2R,3S)-1 ,2 ,3 ,4 ,5 -penta-
O-acetyl-1 -C-(1,4-dimethyl-3-endo-nitro-7-
0
0
0
0
0
0
0
oxabicyclo[2.2.1]hept-5-en-2-exo-yl)-D-galacto-pentitol (5a)
0
0
0
0
0
endo-yl)-
D
0
Method (A). To a solution of (E)-3,4,5,6,7-penta-O-acetyl-
acto-1-nitrohept-1-enitol 1a (1.0 g, 2.3 mmol) in CH
D-gal-
13
2
Cl
2
(7.5 mL)
oxabicyclo[2.2.1]hept-5-en-2-exo-yl)-
D-manno-pentitol (5b)
was added 2,5-dimethylfuran 2 (1.12 mL, 11.6 mmol). After 4.5 days
at room temperature under 13 kbar pressure, the solvent was
evaporated, leading to an oil that consisted of a 47:10:1 mixture of
cycloadducts 3a, 4a, and 5a, respectively. This mixture was dis-
solved in the minimum quantity of ethyl acetate at room temper-
ature and, after standing in the refrigerator, the pure adduct 3a
crystallized as a white powder (two crops; 0.43 g, 43%).
To a solution of (E)-3,4,5,6,7-penta-O-acetyl-
D
-manno-1-nitro-
14
hept-1-enitol 1b (1.56 g, 3.5 mmol) in CH Cl (2.5 mL) was added
2 2
2,5-dimethylfuran 2 (1.49 mL, 14 mmol). After 3 days at room tem-
perature under 13 kbar pressure, the solvent was evaporated to an
oily 6.8:3.5:1.0 mixture of cycloadducts 3b, 4b, and 5b, respectively,
from which pure 5b (0.11 g, 7%) was isolated by column chroma-
13
Method (B). To a solution of 1a, (0.75 g, 1.7 mmol) in CHCl
8.0 mL) was added 2,5-dimethylfuran 2 (0.80 mL, 8.3 mmol). After
days at room temperature under 13 kbar pressure, the solvent
3
tography (Et
crude product was subjected to semipreparative HPLC (EtOAc–
hexane 1:1, 3 mL/min,
¼270 nm), affording cycloadducts 3b
(t ¼10.7 min, 75 mg). Compound 3b:
¼11.6 min, 35 mg) and 4b (t
oil; [ ); IR (NaCl): max 2923 (C–H),1749 (C]O),
þ99.5 (c 0.5, CHCl
1553,1371 (NO ), 1217, 1046 (C–O) cm ; H NMR (CDCl
2
O–light petroleum 1.5:1). A fraction (0.15 g) of the
(
2
l
was evaporated, leading to an oil that consisted of a 3.3:4.7:1.0
mixture of 3a, 4a, and 5a, respectively. Working-up as described in
method A yielded two crops of pure 3a (0.21 g, 30%), together with
a third crop (32 mg) containing this same cycloadduct slightly
contaminated with nitroalkene 1a. Then, the mother liquor was
evaporated and the resulting residue was crystallized from meth-
anol, yielding 0.17 g (24%) of pure 4a and then 0.10 g of a 1:1
R
R
a]
D
3
n
ꢂ1
1
2
3
)
d: 6.24 (d,
1H, J5,6¼5.6 Hz, H-6), 6.23 (d, 1H, H-5), 5.41 (dd, 1H, J
2 ,3
0 0
¼1.6 Hz,
0
0
J
3
0
0
,4
0
¼9.2 Hz, H-3 ), 5.05 (dd, 1H, J
1
0
,2
0
¼4.8 Hz, H-2 ), 5.00 (m, 1H, H-
0
4 ), 4.88 (dd,1H, J
1
0
,2¼9.9 Hz, H-1 ), 4.51 (d,1H, J2,3¼4.0 Hz, H-3), 4.20
0
(dd, J
4
0
,5
0
a
¼2.4 Hz, J
5
0
a,5
0
b
¼12.4 Hz, H-5 a), 4.11 (dd, 1H, J
4
0
,5
0
b
¼4.0 Hz,
0
mixture of 4a and 5a.
H-5 b), 3.25 (dd, 1H, J2,3¼3.8 Hz, H-2), 2.12 (s, 3H, OAc), 2.10 (s, 3H,
ꢁ
Compound 3a: white solid; mp 189–190 C; [
a
]
D
ꢂ37.4 (c 0.5,
),
OAc), 2.09 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.05 (s, 3H, OAc),1.64 (s, 3H,
13
CHCl
3
); IR (KBr):
n
max 2969 (C–H), 1741 (C]O), 1552, 1379 (NO
2
CH
169.4,169.1 (O–CO–CH
(C-1,4), 72.2, 69.4, 67.8, 66.5 (C-1 ,2 ,3 ,4 ), 61.0 (C-5 ), 51.2 (C-2), 20.9,
3
-1), 1.53 (s, 3H, CH
3
-4); C NMR (CDCl
3
) d: 170.7, 170.1, 169.8,
),141.8 (C-6),137.3 (C-5), 94.0(C-3), 88.7, 87.9
ꢂ1
1
1
6
5
211,1046 (C–O) cm ; H NMR (CDCl
), 6.25 (d, 1H, H-5), 5.23 (dd, 1H, J
.12 (dd, 1H, J
3
0
)
d
: 6.40 (d,1H, J5,6¼5.5 Hz, H-
3
0
0
0
0
0
0
0
¼9.5 Hz, J
0
0
¼1.4 Hz, H-2 ),
2
,3
1
,2
0
0
22
0
0
¼1.8 Hz, H-3 ), 5.09 (m, 1H, H-4 ), 4.78 (dd, 1H,
20.8, 20.6, 20.3 (O–CO–CH
(rel int.): 530 (MþH, 1), 375 (M
100), 187 (48), 97 (35), 96 (43), 61 (42); HRMS (CI) calcd for
31NO13þH 530.1874. Found 530.1847. Compound 4b: oil; [
ꢂ24.8 (c 0.5, CHCl ); IR (NaCl): max 2922 (C–H), 1748 (C]O), 1554,
1371 (NO ), 1216, 1046 (C–O) cm ; H NMR (CDCl
), 18.6 (CH
-1), 14.6 (CH
-4); CIMS m/z
3
,4
3
3
3
0
J
J
5
3
1
0
,2¼11.3 Hz, H-1 ), 4.35 (d, 1H, J2,3¼3.4 Hz, H-3), 4.27 (dd, 1H,
*
þHꢂOAc, 25), 374 (M
*
þHꢂOAc,
0
0
0
¼4.8 Hz, J
0
0
¼11.6 Hz, H-5 a), 3.75 (dd, 1H, J
0
0
¼7.2 Hz, H-
4
,5
a
5
a,5
b
4
,5
b
0
b), 2.97 (dd,1H, H-2), 2.15 (s, 3H, OAc), 2.08 (s, 6H, 2ꢀOAc), 2.05 (s,
C
23
H
a]
D
13
H, OAc), 2.00 (s, 3H, OAc),1.57 (s, 3H, CH
3
-1),1.49 (s, 3H, CH
3
-4);
), 143.1
C-6), 136.6 (C-5), 92.8 (C-3), 88.5, 87.9 (C-1,4), 71.3, 68.3, 67.8, 67.5
C
3
n
ꢂ1
1
NMR (CDCl
3
)
d
: 170.4, 170.2, 169.9, 169.8, 169.4 (O–CO–CH
3
2
3
) d: 6.18 (d, 1H,
(
(
J
J
J
5,6¼5.5 Hz, H-6), 6.13 (d, 1H, H-5), 5.41 (dd, 1H, J
2
0
,3
,2
0
¼3.0 Hz,
0
0
0
0
0
0
0
C-1 ,2 ,3 ,4 ), 62.1 (C-5 ), 51.3 (C-2), 21.0, 20.8, 20.7, 20.6, 20.2 (O–
), 18.7 (CH -1), 14.9 (CH -4); FABMS m/z (rel int.): 552
OAc, 28), 311 (MꢂC ꢂH, 13), 239
ꢂH, 21), 237 (32), 221 (MꢂC12 ꢂOH, 23), 153
3
1
0
0
,4
0
¼8.4 Hz, H-3 ), 5.26 (dd, 1H, H-2 ), 5.14 (dd, 1H, J
1
0
0
¼4.4 Hz,
0
0
CO–CH
3
3
3
,2¼1.8 Hz, H-1 ), 4.99 (m, 1H, H-4 ), 4.64 (d, 1H, J2,3¼4.1 Hz, H-3),
0
(
(
(
MþNa, 7), 456 (MꢂCH
2
9
H
H
13
17
21
O
6
4.23 (dd, 1H, J
4
0
,5
0
0
a
¼2.8 Hz, J
5
0
a,5
0
b
¼12.7 Hz, H-5 a), 4.09 (dd, 1H,
MꢂC12
H
17
O
8
O
8
J
4
0
,5
0
b
¼5.0 Hz, H-5 b), 2.98 (dd,1H, H-2), 2.15 (s, 3H, OAc), 2.07 (s, 6H,
MꢂC15
H
21
O10ꢂCH
3
,13),131 (100), 91 (MꢂC15
H
O
10ꢂNO
2
Hꢂ2CH
3
,
2ꢀOAc), 2.06 (s, 3H, OAc),1.98 (s, 3H, OAc),1.67 (s, 3H, CH
3
-1),1.52 (s,
: 170.6, 169.9, 169.8, 169.7 (O–CO–
3
), 140.8 (C-6), 136.9 (C-5), 91.5 (C-3), 89.2, 87.1 (C-1,4), 70.1, 68.3,
13
4
2), 73 (21); HRMS (FAB) calcd for C23
H
31NO13þNa 552.1693. Found
3H, CH
CH
67.8, 67.6 (C-1 ,2 ,3 ,4 ), 61.2 (C-5 ), 50.9 (C-2), 20.9, 20.8, 20.7, 20.6,
3 3
-4); C NMR (CDCl ) d
þ
ꢁ
(
[
1
MþNa) 552.1689. Compound 4a: white solid; mp: 181–183 C;
0
0
0
0
0
a
]
D
¼þ101.9 (c 0.5, CHCl
3
); IR (KBr): nmax 2986 (C–H), 1748 (C]O),
ꢂ1
1
22
553, 1371 (NO ), 1217, 1041 (C–O) cm ; H NMR (CDCl
2
3
)
d
: 6.19 (d,
20.3 (O–CO–CH
3
), 17.0 (CH
3
–1), 14.6 (CH
þHꢂOAc, 15), 374 (M
O, 25), 219 (25),187 (25), 95 (17), 61 (30); HRMS
31NO13þH 530.1874. Found 530.1867. Compound
); IR (NaCl): max 2917 (C–H), 1748
3
-4); CIMS m/z (rel int.):
1
H, J5,6¼5.6 Hz, H-6), 6.16 (d, 1H, H-5), 5.36 (dd, 1H, J
1
0
,2
0
¼2.4 Hz,
530 (MþH, 10), 375 (M
*
*
þHꢂHOAc, 100), 332
0
0
J
J
2
0
0
,3
,4
0
0
¼9.6 Hz, H-2 ), 5.23 (dd, 1H, J
1
0
,2¼2.4 Hz, H-1 ), 5.13 (dd, 1H,
(M
(CI) calcd for C23
5b: oil; [
(C]O),1544,1368 (NO
*
þHꢂHOAcꢂC
2
H
2
0
0
3
¼2.0 Hz, H-3 ), 5.06 (ddd,1H, H-4 ), 4.70 (d,1H, J2,3¼4.0 Hz, H-3),
H
0
4
.25 (dd, 1H, J
4
0
,5
0
0
a
¼5.2 Hz, J
5
0
a,5
0
b
¼12.0 Hz, H-5 a), 3.76 (dd, 1H,
a
]
D
¼þ20.8 (c 0.24, CHCl
3
n
ꢂ1
1
J
4
0
,5
0
b
¼7.2 Hz, H-5 b), 2.80 (dd,1H, H-2), 2.10 (s, 3H, OAc), 2.09 (s, 3H,
2
),1218,1033 (C–O) cm ; H NMR (CDCl
3
)
d
:
1
3
0
OAc), 2.01 (s, 9H, 3ꢀOAc), 1.70 (s, 3H, CH
NMR (CDCl : 170.8,170.6,170.3,170.2,169.8 (O–CO–CH
), 136.8 (C-5), 90.8 (C-3), 88.9, 87.2 (C-1,4), 70.4, 67.3, 66.7, 64.8 (C-
3
-1), 1.48 (s, 3H, CH
3
-4);
C
6.38 (d, 1H, J5,6¼5.6 Hz, H-6), 6.07 (d, 1H, H-5), 5.50 (dd, 1H, H-3 ),
0
0
)
d
3
),140.6 (C-
5.50 (dd,1H, H-1 ), 5.28 (dd,1H, J
2
0
,3
0
¼2.4 Hz, J
1
0
,2
0
¼9.6 Hz, H-2 ), 5.06
3
0
6
1
CH
3
(m,1H, J
3
0
,4
0
¼9.2 Hz, H-4 ), 4.92 (d,1H, J2,3¼3.6 Hz, H-3), 4.20 (dd,1H,
0
0
0
0
0
0
,2 ,3 ,4 ), 62.0 (C-5 ), 51.8 (C-2), 21.1, 21.0, 20.9, 20.8, 20.4 (O-CO-
J
4
0
0
,5
0
a
¼2.8 Hz, J
5 b), 2.61 (dd,1H, J
2.08 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.06 (s, 3H, OAc),1.75 (s, 3H, CH
5
0
a,5
0
b
¼12.8 Hz, H-5 a), 4.07 (dd, 1H, J
4
0
,5
0
b
¼4.8 Hz, H-
2
2
3
), 17.2 (CH
3
-1), 14.6 (CH
OAc, 20), 456 (MꢂCH
þHꢂHOAc, 40), 261 (10), 201 (22), 95 (57), 96 (75); HRMS (FAB)
calcd for C23
3
-4); FABMS m/z (rel int.): 552 (MþNa,
1
0
,2¼2.8 Hz, H-2), 2.11 (s, 3H, OAc),2.09(s, 3H, OAc),
), 457 (MþHꢂCH
2
2
OAc, 100), 374
3
-
13
(
M
*
1), 1.73 (s, 3H, CH
(O–CO–CH ), 143.8 (C-6), 135.9 (C-5), 91.0 (C-3), 88.1, 86.6 (C-1,4),
69.0, 68.4, 67.7, 67.3 (C-1 ,2 ,3 ,4 ), 61.8 (C-5 ), 48.8 (C-2), 21.0, 20.9,
3 3
-4); C NMR (CDCl ) d: 170.6, 170.5, 169.9, 169.6
H
31NO13þNa 552.1693. Found 552.1698. Compound 5a:
3
1
0
0
0
0
0
oil; H NMR (CDCl
.50 (dd, 1H,
3
)
d
: 6.38 (d,1H, J5,6¼5.6 Hz, H-6), 6.04 (d,1H, H-5),
0
22
5
J
1
0
,2¼4.8 Hz,
J
1
0
,2
0
¼2.4 Hz, H-1 ), 5.41 (dd, 1H,
3 3 3
20.8, 20.7, 20.6 (O–CO–CH ), 17.4 (CH -1), 16.3 (CH -4). CIMS m/z

2670
N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
0
(
5
C
rel int.): 530 (MþH, 1), 375 (M
*
þHꢂOAc, 10), 374 (M
0), 201 (17),187 (30), 97 (50), 96 (100), 61 (37); HRMS (CI) calcd for
31NO13þH 530.1874. Found 530.1885.
*
þHꢂHOAc,
4.76 (dd, 1H, J
1
0
a,6¼6.8 Hz, H-1 a), 4.49 (dd, 1H, J
1
0
a,1
0
b
¼13.6 Hz,
0
J
J
J
1
0
b,6¼6.0 Hz, H-1 b), 4.41 (dd, 1H, J3b,4¼4.4 Hz, H-4), 4.29 (dd, 1H,
23
H
10,11a¼5.6 Hz, H-11a), 4.27 (dd, 1H, J6,7¼8.8 Hz, H-7), 3.93 (dd, 1H,
10,11b¼7.2 Hz, J11a,11b¼11.2 Hz, H-11b), 2.58 (ddd, 1H, H-6), 2.29 (br
4
.4. 4,7:2,8-Dianhydro-1,3,6-trideoxy-5-C-methyl-6-C-
-lyxo- -galacto-undec-2-ulo-2,5-furanoside
8b) and (2R,3S,4S,5S,6R)-5,6-epoxy-3-hydroxy-5,8-dimethyl-
d, 1H, J3a,3b¼14.8 Hz, H-3a), 2.09 (dd, 1H, H-3b), 2.16 (s, 3H, OAc),
nitromethyl-
(
4
a-
D
D
2.13 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.05 (s, 3H, OAc), 1.50 (s, 3H, H-
13
1a,1b,1c), 1.27 (s, 3H, CH
169.8 (O–CO–CH , C-7–O–CO–CH
4), 79.0 (C-8), 72.7 (CH NO ), 68.9, 68.6, 67.9 (C-7,9,10), 62.0 (C-11),
7.3 (C-6), 44.1 (C-3), 28.2 (C-1), 22.8 (CH -5), 20.7, 20.6 (O–CO–
CH , C-7–O–CO–CH
); FABMS m/z (rel int.): 528 (MþNa, 19), 489
(MꢂO, 24), 488 (MꢂOH, 100), 446 (MꢂOHꢂC O, 35), 428
(MꢂOHꢂHOAc, 68), 370 (MꢂOH-2ꢀOAc, 34), 221 (28), 219 (37),
198 (MꢂC ꢂNOꢂHOAc, 44), 151 (97), 123 (19), 123 (68), 109
(50), 97 (58), 96 (74), 95 (63), 81 (43), 73 (95); HRMS (FAB) calcd for
31NO13þNa 528.1693. Found 528.1706. Compound 8a: oil; [
þ68.0 (c 0.50, CHCl ); IR (NaCl): max 3455, 2936 (C–H),1744 (C]O),
1554, 1375 (NO ), 1223, 1049 (C–O) cm ; H NMR (CDCl
3
-5); C NMR (CDCl
3
) d: 170.5, 170.4, 170.1,
), 106.8 (C-2), 91.7 (C-5), 88.7 (C-
0
-nitromethyl-2-(
D
-threo-triitol-1 -yl)-3,4-dihydro-2H-
3
3
oxocine (9c)
2
2
4
3
To a solution of 3a (0.40 g, 0.76 mmol) in 90% methanol (10.2 mL)
3
3
ꢁ
was added K
CO
2 3
(0.46 g) and the mixture was stirred at 0 C for 2 h.
After treatment with Amberlite IR-120 (H ) resin until ca. pH 6, the
mixture was filtered, and the solvent evaporated to an oily residue
from which compound 8b (15 mg, 8%) was isolated by PTLC (CH
MeOH 7:1, three elutions). The oxocine 9c (37 mg,15%) was obtained
2 2
H
þ
9 13 6
H O
2 2
Cl –
C
21
H
a]
D
1
by extraction of the residue with CDCl
3
. Compound 8b: oil; H NMR
3
n
0
ꢂ1
1
(
(
1
J
1
DMSO-d
6
)
d
: 4.94 (dd, 1H, J
1
0
a,1
0
b
¼14.5 Hz, J
1
0
a,6¼4.8 Hz, H-1 a), 4.62
2
3
) d: 5.45
dd, 1H, J6,7¼6.6 Hz, J7,8¼1.9 Hz, H-7), 4.61 (dd, 1H, J
1
0
b,6¼9.2 Hz, H-
(ddd, 1H, H-10), 5.23 (dd, 1H, J9,10¼1.6 Hz, H-9), 4.74 (dd, 1H,
0
0
b), 4.36 (d,1H, J3a,4¼5.6 Hz, J3b,4<1 Hz, H-4), 3.71 (dd,1H, J9,10<1 Hz,
J
1
0
0
a,1
0
b
¼13.6 Hz, J
1
0
a,6¼4.8 Hz, H-1 a), 4.56 (dd, 1H, J
1
0
b,6¼9.6 Hz, H-
8,9¼10.0 Hz, H-9), 3.64 (t, 1H, J10,11a¼J10,11b¼6.8 Hz, H-10), 3.63 (dd,
1 b), 4.48 (dd, 1H, J3b,4¼4.0 Hz, J3a,4<1.0 Hz, H-4), 4.23 (dd, 1H,
H, H-8), 3.38 (dd, 1H, H-11a), 3.32 (dd, 1H, J11a,11b¼10.3 Hz, H-11b),
.82 (ddd, 1H, J6,7¼6.6 Hz, H-6), 2.04 (dd, 1H, H-3a), 1.92 (br d, 1H,
J
J
J
11a,11b¼12.0 Hz, J10,11a¼4.8 Hz, H-11a), 4.09 (br d, 1H, J6,7¼6.4 Hz,
7,8z0 Hz, H-7), 4.06 (dd, 1H, J10,11b¼8.0 Hz, H-11b), 3.36 (d, 1H,
8,9¼9.2 Hz, H-8), 3.05 (ddd, 1H, H-6), 2.29 (br d, 1H, J3a,3b¼14.4 Hz,
2
J
1
3
3a,3b¼14.0 Hz, H-3b),1.37,1.35 (s, 3H, H-1a,1b,1cand s, 3H, CH
3
-5); C
NMR(DMSO-d
6
)
d
:108.4(C-2),89.4(C-5), 85.5(C-8), 77.2, 76.4(C-7,4),
H-3a), 2.18 (s, 3H, OAc), 2.12 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.04 (dd,
13
7
2.9 (CH
5.8 (C-1), 21.2 (CH
s,1H, H-7), 4.68 (dd,1H, J
2
NO
2
), 69.3, 68.2 (C-9,10), 62.9 (C-11), 49.8 (C-6), 44.7 (C-3),
1H, H-3b), 1.46 (s, 3H, H-1a,1b,1c), 1.33 (s, 3H, CH
(CDCl : 172.3, 170.5, 170.1 (O–CO–CH ), 106.7 (C-2), 92.3 (C-5),
89.4 (C-4), 81.1 (C-7), 74.8 (CH NO ), 70.8, 70.2, 69.6 (C-8,9,10), 62.6
(C-11), 47.9 (C-6), 43.8 (C-3), 27.4 (C-1), 22.4 (CH -5), 20.7, 20.6 (O–
CO–CH O, 25),
); CIMS m/z (rel int.): 446 (MþH, 35), 428 (MþHꢂH
3
-5); C NMR
1
2
3
-5). Compound 9c: oil; H NMR (CDCl
3
)
d: 4.94 (br
3
)
d
3
0
0
00a,100
¼13.6 Hz, J
00a,4¼6.0 Hz, H-1 a), 4.67(br
1
b
1
2
2
s, 1H, J6,7 1.0 Hz, J6,CH3-8¼1.2 Hz, H-6), 4.38 (dd, 1H, J
1
00b,4¼6.4 Hz, H-
3
0
0
0
1
3
b), 3.99 (ddd,1H, H-2 ), 3.95 (dd,1H, J2,3¼1.2 Hz, J3,4¼10.4 Hz, H-3),
3
2
0
.82 (d, 1H, H-2), 3.82 (d, 1H, J
1
0
,2
0
¼4.8 Hz, H-1 ), 3.70 (dd, 1H,
386 (MþHꢂHOAc, 58), 331 (22), 326 (MþHꢂ2HOAc, 20), 228
0
0
J
2
0
,3
0
a
¼2.4 Hz, J
3
0
a,3
0
b
¼7.6 Hz, H-3 a), 3.63 (dd,1H, J
2
0
,3
0
b
¼1.2 Hz, H-3 b),
(MꢂC
9
H
13
O
6
,11), 219 (13),198 (MꢂC
H
9 13
O
6
ꢂNO,100),187 (25),169
ꢂHNO ꢂCO, 30), 151
, 27), 96 (42), 95 (63), 61
27NO11þH 446.1662. Found 446.1642.
); IR (NaCl): max 3024
(]C–H), 2972 (C–H), 1747 (C]O), 1668 (C]C), 1559, 1373 (NO ),
2
(
2
.98 (ddd, 1H, H-4), 1.84 (s, 3H, CH
3
-8), 1.49 (s, 3H, CH
3
-5); CIMS m/z
H, 15),
H, 21), 228
O, 18), 198
(MꢂC
9
H
13
O
6
ꢂNOꢂCOH, 13), 153 (MꢂC
H
9 13
O
6
2
rel int.): 320 (MþH, 62), 302 (MꢂOH, 18), 255 (MꢂOHꢂNO
NO
18),
ꢂNO, 30), 197 (23), 188 (26), 183 (MꢂC
ꢂNOꢂOH, 18), 153 (MꢂC
2
(21), 123 (MꢂC
9
H
13
O
6
ꢂHNO
2
ꢂCOꢂ2CH
3
42 (MꢂOHꢂCH
2
2
, 23), 237 (MꢂOHꢂH
2
OꢂNO
2
(26); HRMS (CI) calcd for C19
Compound 9e: oil; [
H
(
(
2
4
MꢂC
3
H
H
7
O
O
3
,
224 NO
(MꢂOHꢂCH
2
2
ꢂH
2
a
]
D
þ24.5 (c 0.51, CHCl
3
n
MꢂC
3
7
3
H
3 7
O
3
ꢂNOꢂCH
3
,
,
2
ꢂ1
1
3), 181 (MꢂC H O
3 7 3
H O
3 7 3
ꢂCH
2
NO
2
ꢂCH
3
1216, 1032 (C–O) cm
;
H
NMR (CDCl
3
)
d
:
5.54 (dd, 1H,
0
0
5), 123 (43), 113 (100), 103 (58), 97 (30), 91 (37), 87 (67), 85 (37), 84
J
1
0
,2
0
¼2.4 Hz, H-1 ), 5.35 (m,1H, H-2 ), 5.19 (dd,1H, J
1
0
,2¼9.6 Hz, H-2),
0
0
(
C
25), 73 (50), 69 (25), 57 (29), 48 (41); HRMS (CI) calcd for
4.84 (br s, 1H, H-7), 4.61 (dd, 1H, J
1
00a,4¼7.6 Hz, H-1 a), 4.57 (br s, 1H,
21NO
8
þH 320.1345. Found (MþH)þ 320.1354.
J
6, CH3-8¼1.2 Hz, J6,7<1.0 Hz, H-6), 4.43 (dd, 1H, J
1
0
00b,4¼4.4 Hz,
13
H
0
0
J
1
00a,100
b
¼14.4 Hz, H-1 b), 4.24 (dd, 1H, J
2
0
0
,3
0
a
¼5.6 Hz, H-3 a), 3.94 (dd,
4
.5. (9,10,11-Tri-O-acetyl)-7-acetoxy-4,8-anhydro-1,3,6-
-lyxo- -galacto-undec-
-ulo-2,5-furanose (7d), (9,10,11-tri-O-acetyl)-4,7:2,8-
dianhydro-1,3,6-trideoxy-5-C-methyl-6-C-nitromethyl-
-lyxo- -galacto-undec-2-ulo-2,5-furanoside (8a), and
2R,3S,4S,5S,6R)-2-(1 ,2 ,3 -tri-O-acetyl-
1H, J
3,4¼10.8 Hz, H-3), 2.58 (ddd, 1H, H-4), 2.12 (s, 3H, OAc), 2.09 (s, 3H,
OAc), 2.06 (s, 3H, OAc), 2.03 (s, 3H, OAc), 1.81 (s, 3H, CH -8), 1.41
: 170.4, 170.3, 170.1 (OꢂCOꢂCH ),
), 160.5 (C-8), 95.1 (C-7), 91.7 (C-5), 90.4 (C-
3
0
a,3
0
b
¼11.6 Hz, J
2
0
,3
0
b
¼7.2 Hz, H-3 b), 3.64 (dd, 1H, J2,3¼2.4 Hz,
trideoxy-5-C-methyl-6-C-nitromethyl-
D
D
J
2
3
1
3
(s, 3H, CH
3
-5); C NMR (CDCl
3
)
d
3
a
-D
D
169.2 (C-3ꢂOꢂCOꢂCH
3
0
0
0
0
0
0
(
3
4
D
-threo-triitol-1 -yl)-
6), 75.1 (C-2), 71.4 (CH
2
NO
2
), 68.7, 68.0 (C-1 ,2 ), 66.3 (C-3), 61.9 (C-
-8), 20.6, 20.5 (OꢂCOꢂCH C-
-5); CIMS m/z (rel int.): 488 (MþH, 19),
29 (MþHꢂOAc, 20), 428 (MꢂHOAc, 100), 386 (MꢂHOAcꢂC O,
0
-acetoxy-5,6-epoxy-5,8-dimethyl-4-nitromethyl-3,
3 ), 47.1 (C-4), 22.0 (CH
3
3
,
-dihydro-2H-oxocine (9e)
3ꢂOꢂCOꢂCH
3 3
), 13.5 (CH
4
2 2
H
Following the procedure described in Section 4.4, a solution of
a (0.30 g, 0.57 mmol) in 90% methanol (16 mL) was treated with
(0.34 g), affording 0.15 g of an oily residue that was dissolved
in pyridine (1.2 mL) and acetic anhydride (1.2 mL). After 12 h at
14), 383 (MþHꢂOAcꢂNO
2
,
14), 370 (MþH-2OAc, 26), 326
3
K
(MþHꢂ2HOAcꢂC
2
H
H
2
O, 10), 325 (Mꢂ2HOAcꢂC
2
H
2
O, 18), 266
2
CO
3
(MþHꢂ3HOAcꢂC
2
2
O, 13), 265 (Mꢂ3HOAcꢂC
2 2
H O, 40), 263
(MþHꢂOAcꢂ2HOAcꢂNO
2
, 18), 257 (39), 243 (18), 229 (MþHꢂ
O, 14), 221 (13), 203 (13), 198 (MꢂC
NO , 36), 123
29NO12þH 488.1768. Found
ꢁ
ꢂ15 C and 1 h at room temperature, the mixture was poured onto
C
C
9
H
H
13
O ꢂC H
6 2 2
9 13 6
H O ꢂ
ice-cold water (30 mL), extracted with CH
2
Cl
2
(3ꢀ30 mL) and
2
2
OꢂNO, 37), 153 (MꢂC
H
9 13
O
6
ꢂC
2
H
H
2
OꢂCH
2
2
ꢂCH
3
washed successively with 1 M HCl (1ꢀ30 mL), saturated aqueous
NaHCO
(1ꢀ30 mL), and water (1ꢀ30 mL). The organic layer was
dried (MgSO ) and the solvent evaporated to an oil (0.21 g) that was
(15), 96 (15); HRMS (CI) calcd for C21
3
488.1754.
4
subjected to flash column chromatography (EtOAc–hexane 1:1),
4.6. Methyl (9,10,11-tri-O-acetyl)-7-acetoxy-4,8-anhydro-
affording compounds 7d (0.12 g, 60%), 8a (40 mg, 20%), and 9e
1,3,6-trideoxy-5-C-methyl-6-C-nitromethyl-D-lyxo-D-galacto-
(
(
1
9
30 mg, 15%). Compound 7d: oil; [
a
]
D
þ29.4 (c 0.54, CHCl
), 1217,
: 5.57 (dd, 1H, J9,10¼2.4 Hz, H-
), 5.37 (ddd, 1H, H-10), 5.11 (dd, 1H, J7,8¼1.6 Hz, J8,9¼9.6 Hz, H-8),
3
); IR
undec-2-ulo-2,5-furanoside (7g)
NaCl): max 3479, 2977 (C–H), 1746 (C]O), 1556, 1373 (NO
n
2
ꢂ1
1
037 (C–O) cm ; H NMR (CDCl
3
)
d
To a solution of 7d (60 mg, 0.12 mmol) in methanol (3 mL) was
þ
ꢁ
added Dowex 50Wx8-100 (H ) resin (0.3 g) and kept at 3 C for 5

N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
2671
days. Then, filtration of the resin and evaporation of the solvent led
to a chromatographically pure oil (52 mg, 87%) consisting of com-
yielded 0.2 g (8%) of the oxepine 14 as a white solid. Concentration
of the solvent afforded two crops of compound 15 (0.17 g, 7%). By
the same method, an analytical sample of 14 was obtained from 3b,
pound 7g as a 1:1 mixture of the
these anomers could be isolated pure by PTLC (Et
:1); oil; IR (NaCl):
max 2920 (CꢂH), 1747 (C]O), 1556, 1375 (NO
a
and
b
anomers; 8.2 mg of one of
O–light petroleum
),
: 5.55 (dd,1H, J9,10¼2.4 Hz,
2
2
after PTLC (Et O–hexane 1:1) of the crude product. Compound 14:
1
1
n
2
[
a
]
D
þ1.2 (c 0.5, CH
3
OH); IR (KBr):
n
max 3349, 3235 (O–H), 2936,
ꢂ1
1
ꢂ1
218,1057 (CꢂO) cm ; H NMR (CDCl
3
)
d
2849 (C–H), 1671 (C]C), 1549, 1376 (NO
2
), 1077, 1034 (C–O) cm
;
1
H-9), 5.35 (ddd, 1H, H-10), 5.11 (dd, 1H, J7,8¼2.0 Hz, J8,9¼9.6 Hz, H-8),
H NMR (DMSO-d
00a,100
6
)
d
: 4.82 (br s, 1H, H-6), 4.75 (dd, 1H,
0
00
4
.71 (dd, 1H, J
0
1
0
a,6¼8.0 Hz, H-1 a), 4.41 (dd, 1H, J
1
0
a,1
0
b
¼13.6 Hz,
J
1
b
¼14.5 Hz, J
1
00a,3¼5.0 Hz, H-1 a), 4.66 (br s, 1H, H-5), 4.57 (dd,
0
00
J
J
J
1
b,6¼4.0 Hz, H-1 b), 4.35 (dd, 1H, J3b,4¼5.6 Hz, H-4), 4.27 (dd, 1H,
1H, J
1
00b,3¼7.7 Hz, H-1 b), 4.46 (d, 1H, JH,OH¼7.6 Hz, OH), 4.45 (d, 1H,
0
10,11a¼4.8 Hz, H-11a), 4.15 (dd, 1H, J6,7¼10.8 Hz, H-7), 3.92 (dd, 1H,
), 2.47 (ddd,
H, H-6), 2.23 (br d, 1H, J3a,3b¼14.8 Hz, H-3a), 2.05 (dd, 1H, H-3b),
.13 (s, 3H, OAc), 2.12 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.03 (s, 3H, OAc),
J
H,OH¼4.4 Hz, OH), 4.35 (t, 1H, JH-4
0
,OH¼5.6 Hz, OH-4 ), 4.32 (d, 1H,
0
10,11b¼7.2 Hz, J11a,11b¼11.6 Hz, H-11b), 3.24 (s, 3H, OCH
3
J
H,OH¼7.2 Hz, OH), 3.69 (t, 1H, J
¼2.6 Hz,
1
0
,2¼8.4 Hz, J
1
0
,2
0
z1 Hz, H-1 ), 3.56
0
1
2
1
1
(
(ddd, 1H,
J
3
0
,4
0
a
J
4
0
a,4
0
b
¼10.6 Hz, H-4 a), 3.49 (t, 1H,
0
0
0
J
2,3¼8.8 Hz, H-2), 3.34 (m, 3H, H-2 ,3 ,4 b), 2.75 (ddd, 1H, H-3), 1.78
13
13
.43 (s, 3H, H-1a,1b,1c), 1.29 (s, 3H, CH
70.4, 170.2 (O–CO–CH ), 169.3 (C-7–O–CO–CH
C-5), 87.7 (C-4), 77.5 (C-8), 71.4 (CH NO ), 68.7, 68.2, 66.9 (C-7,9,10),
), 46.1 (C-3), 23.7, 23.5 (C-1, CH
), 20.7, 20.6, 20.5, 20.3 (O–CO–CH , C-7–O–CO–CH ); FABMS m/z
3
-5); C NMR (CDCl
3
)
d: 170.5,
(s, 3H, CH
3
-7), 1.36 (s, 3H, CH
3
-4). C NMR (DMSO-d
6
)
d
: 159.0 (C-
NO ), 71.7,
-7), 13.6 (CH
4); CIMS m/z (rel int.): 320 (MþH, 100), 304 (MþHꢂO, 12), 302
(MþHꢂH O, 28), 284 (MþHꢂ2H O, 9), 237 (Mꢂ2H OꢂNO , 5), 198
(MꢂC , 19), 28 (11). HRMS (CI) calcd for C13 þHꢂO
304.1396. Found 304.1381. Compound 15 (major anomer): white
3
3
), 109.8 (C-2), 92.4
7), 96.5 (C-6), 92.7 (C-4), 90.1 (C-5), 77.2 (C-2), 73.7 (CH
2
2
0
0
0
0
2
2
70.9, 70.4 (C-1 ,2 ,3 ), 63.8 (C-4 ), 51.2 (C-3), 22.8 (CH
3
3
-
6
5
2.2 (C-11), 49.6 (C-6), 46.8 (O–CH
3
3
-
3
3
2
2
2
2
(
(
(
2
(
rel int.): 542 (MþNa, 13), 413 (MꢂHOAcꢂNO
2
,
35), 385
2
, 18), 357
H
4 9
O
4
H21NO
8
MꢂHOAcꢂOAcꢂCH
Mꢂ2HOAcꢂC O, 14), 281 (Mꢂ2HOAcꢂC
21 (Mꢂ3HOAcꢂC Oꢂ2CH ꢂNO
57), 133 (13), 105 (19), 95 (23), 91 (29); HRMS (FAB) calcd for
3
, 20), 371 (MꢂHOAcꢂC
H
2 2
OꢂNO
1
H
2 2
2 2
H Oꢂ2CH
3
2
ꢂNO , 13),
solid;
H
NMR (DMSO-d
6
)
d:
4.68 (d, 1H,
b,6¼7.6 Hz, H-1 b), 4.48 (d, 1H,
J
1
0
a,6¼5.6 Hz,
0
0
H
2 2
3
2
, 11), 207 (18), 149 (100), 147
J
J
1
0
a,1
0
b
¼15.2 Hz, H-1 a), 4.67 (d, 1H, J
0
1
H,OH¼6.8 Hz, OH), 4.42 (dd, 1H, H-4), 4.40 (d, 1H, JH,OH¼7.2 Hz, OH),
22
C H33NO13þNa 542.1849. Found 542.1853.
4.34 (t, 1H, JH-11,OH¼5.2 Hz, OH-11), 4.32 (d, 1H, OH), 3.69 (t, 1H,
6,7¼8.0 Hz, J7,8¼9.2 Hz, H-7), 3.68 (m, 1H, H-8), 3.57 (m, 1H, H-11a),
3.37 (m, 3H, H-9,10,11b), 3.08 (s, 3H, OCH ), 2.69 (ddd, 1H, H-6),
2.26 (dd, 1H, J3a,4¼6.8 Hz, J3a,3b¼14.0 Hz, H-3a), 1.93 (dd, 1H,
J
0
4
.7. (2R,3S)-1 -C-(1,4-dimethyl-3-exo-nitro-
3
7
-oxabicyclo[2.2.1]hept-5-en-2-endo-yl)-
D
-galacto-pentitol
-manno- or
13
(
10) and 2,5-anhydro-1-deoxy-1-nitro-
D
-glycero-
L
J
3b,4¼4.0 Hz, H-3b), 1.36 (s, 3H, CH
NMR (DMSO-d : 110.0 (C-2), 91.6 (C-5), 88.2 (C-4), 79.5 (C-7),
4.3 (CH NO ), 71.7, 71.1, 70.4 (C-8,9,10), 64.0 (C-11), 51.2 (C-6), 48.8
(OCH ), 45.0 (C-3), 24.7 (C-1), 22.5 (CH -5).
3
-5), 1.35 (s, 3H, H-1a,1b,1c).
C
D
-glycero-
L
-gluco-heptitol (11)
6
) d
7
2
2
Following the procedure described in Section 4.4, a solution of
3
3
4
a (0.30 g, 0.57 mmol) in 90% methanol (8.4 mL) was treated with
K
2
CO
3
(0.33 g), affording 0.16 g (88%) of an oil with deacetylated
4.9. Methyl 4,8-anhydro-1,3,6-trideoxy-5-C-methyl-6-C-
nitromethyl- -arabino- -altro-undec-2-ulo-2,5-furanoside (16)
cycloadduct 10 as the major product. After 5 days at room tem-
perature, the H NMR spectrum of the reaction crude showed the
D
L
1
absence of 10, and the formation of deacetylated anhydro 11 (R¼H)
and 2,5-dimethylfuran. Then, evaporation of the solvent and con-
ventional acetylation of the resulting residue (0.15 g), led to an oil
Following the procedure described in Section 4.4, a solution of 3b
(0.11 g, 0.21 mmol) in 90% methanol (2.8 mL) was treated with
K
2
3
CO (0.12 g), affording 53 mg of an oily mixture containing com-
from which 91 mg (51%) of a 1.0:0.8 diastereoisomeric mixture of 11
pounds 14, 15, and 16. Pure 16 (6.6 mg, 12%) was isolated by PTLC
1
1
(
R¼Ac) was isolated by PTLC (Et
2
O–hexane 1:1). Compound 10: H
(EtOAc–EtOH 16:1). Compound 16: oil; H NMR (DMSO-d
6
)
d
: 4.81
0
NMR (DMSO-d
4
3
steroisomer: H NMR (CDCl ) d
3
5
4
OAc), 2.13 (s, 3H, OAc), 2.12 (s, 3H, OAc); C NMR (CDCl
1
7
6
)
d
: 6.42 (d, 1H, J5,6¼5.2 Hz, H-6), 6.24 (d, 1H, H-5),
.67 (d, 1H, J2,3¼4.0 Hz, H-3), 2.80 (dd, 1H, J ,2¼6.8 Hz, H-2), 1.55 (s,
H, CH -1), 1.34 (s, 3H, CH
-4). Compound 11 (R¼Ac). Major dia-
: 5.36 (m, 1H, H-6), 5.24 (t, 1H, H-4),
.11 (dd, 1H, H-3), 4.77–4.65 (m, 3H, H-1a,1b,2), 4.34 (dd, 1H, H-7a),
.23 (dd, 1H, H-5), 4.19 (dd, 1H, H-7b), 2.16 (s, 3H, OAc), 2.15 (s, 3H,
(dd, J
1
0
a,1
0
b
¼14.8 Hz, J
1
0
a,6¼6.4 Hz, H-1 a), 4.56 (dd, 1H, J
1
0
b,6¼10.0 Hz,
0
0
H-1 b), 4.25 (dd, 1H, H-4), 4.06 (dd, 1H, J6,7¼6.8 Hz, H-7), 3.74 (br d,
1H, J7,8¼10.0 Hz, H-8), 3.58 (ddd, J10,11a¼2.4 Hz, J11a,11b¼10.8 Hz,
H-11a), 3.40 (m, 1H, H-10), 3.35 (d, 1H, J9,10¼8.4 Hz, J8,9z0 Hz, H-9),
1
3
3
1
3.35 (dd, 1H, J10,11b¼3.6 Hz, H-11b), 3.03 (s, 3H, OCH
3
), 2.86 (ddd, 1H,
H-6), 2.31 (dd, 1H, J3a,3b¼14.0 Hz, J3a,4¼7.6 Hz, H-3a), 1.92 (dd, 1H,
3b,4¼3.6 Hz, H-3b), 1.40 (s, 3H, H-1a,1b,1c), 1.32 (s, 3H, CH -5).
13
3
)
d
: 170.6–
, eight signals), 82.1 (C-5), 80.2 (C-2), 78.8 (C-3),
8.1 (C-4), 76.2 (C-1), 69.5 (C-6), 62.4 (C-7), 20.9, 20.8, 20.7 (O–CO–
J
3
69.4 (O–CO–CH
3
4.10. Methyl (8,9,10,11-tetra-O-acetyl)-4,7-anhydro-1,3,6-
trideoxy-5-C-methyl-6-C-nitromethyl-D-arabino-L-altro-
undec-2-ulo-2,5-furanoside (18)
1
CH
: 5.39 (dd, 1H, H-3), 5.3 (m, 1H, H-6), 5.13 (t, 1H, H-4), 4.87 (m, 1H,
H-2), 4.58 (m, 2H, H-1a,1b), 4.39 (dd, 1H, H-7a), 4.12 (dd, 1H, H-7b),
.06 (dd, 1H, H-5), 2.17 (s, 3H, OAc), 2.15 (s, 3H, OAc), 2.07 (s, 3H,
3
). Compound 11 (R¼Ac). Minor diasteroisomer: H NMR (CDCl
3
)
d
4
Conventional acetylation of 15 (48 mg, 0.15 mmol) with 1:1
O–pyridine (0.8 mL) led to an oil from which oily compound 18
(27 mg, 38%) was isolated by PTLC (EtOAc–hexane 2:1); [
ꢂ22.5
(c 0.4, CDCl ); IR (NaCl): max 2964 m, 2926 m (C–H), 1748 f (C]O),
556 m, 1374 m (NO ), 1219 f, 1048 m (C–O) cm ; H NMR (CDCl
13
OAc), 2.06 (s, 3H, OAc); C NMR (CDCl
CH , eight signals), 82.2 (C-5), 77.4 (C-4), 76.4 (C-3), 76.1 (C-2), 73.8
C-1), 69.5 (C-6), 62.6 (C-7), 20.9, 20.8, 20.7 (O–CO–CH ).
3
):
d: 170.6–169.4 (O–CO–
Ac
2
3
a]
D
(
3
3
n
ꢂ1
1
1
2
3
)
4
2
4
.8. (2R,3S,4S,5R)-4,5-Epoxy-4,7-dimethyl-3-nitromethyl-
d
: 5.50 (dd, 1H, J9,10¼8.8 Hz, H-9), 5.16 (dd, 1H, J8,9¼2.4 Hz, H-8),
0
0
-(
,7-anhydro-1,3,6-trideoxy-5-C-methyl-6-C-nitromethyl-
-arabino- -altro-undec-2-ulo-2,5-furanoside (15)
D-arabino-tetritol-1 -yl)-2,3-dihydrooxepine (14) and methyl
5.10 (ddd, 1H, H-10), 4.71 (dd, J
4.48 (dd, 1H, H-4), 4.37 (dd, 1H, J
1
0
a,1
0
b
¼14.0 Hz, J
1
0
a,6¼5.2 Hz, H-1 a),
0
0
b,6¼7.2 Hz, H-1 b), 4.26 (dd,
1
D
L
J
10,11a¼2.8 Hz, H-11a), 4.11 (dd, 1H, J10,11b¼5.2 Hz, J11a,11b¼12.0 Hz,
H-11b), 3.86 (dd, 1H, J6,7¼8.0 Hz, J7,8¼6.8, H-7), 3.19 (s, 3H, OCH
3
),
Following the procedure described in Section 4.4, a solution of
a mixture of 3b, 4b, and 5b (3.0 g, 5.6 mmol; 6.8:3.5:1.0 ratio) in
9
2.72 (ddd, 1H, H-6), 2.40 (dd, 1H, J3a,3b¼14.4 Hz, J3a,4¼6.4 Hz, H-3a),
2.02 (dd, 1H, J3b,4¼2.0 Hz, H-3b), 2.11 (s, 3H, OAc), 2.10 (s, 3H, OAc),
2.07 (s, 3H, OAc), 2.06 (s, 3H, OAc), 1.47 (s, 3H, H-1a,1b,1c), 1.39 (s,
0% methanol (75 mL) was treated with K
2 3
CO (3.3 g), affording
13
2
.5 g of an oily residue which, by crystallization from methanol,
3 3
3H, CH -5). C NMR (CDCl ) d: 170.7, 170.4, 170.0, 169.6 (O–CO–

2672
N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
þ
CH
0.2, 68.2, 68.1 (C-8,9,10), 61.7 (C-11), 50.3 (C-6), 48.8 (OCH
C-3), 22.9, 22.3 (C-1, CH -5), 20.8, 20.7, 20.6 (O–CO–CH ). ESI MS
m/z (rel int.): 504 (MꢂCH , 10), 488 (MꢂOCH , 100), 489 (MꢂNO,
1), 473 (MꢂNO 29), 472 (MꢂHNO 47), 461 (28), 460
MþHꢂHOAc, 80), 446 (MꢂOCH ꢂC O, 36), 429 (MꢂNOꢂHOAc,
8), 428 (MꢂOCH ꢂHOAc, 68), 370 (MꢂOCH ꢂHOAcꢂNOꢂCO, 14),
69 (11), 355 (MꢂOCH ꢂHOAcꢂNOꢂCOꢂCH , 14), 329 (12), 289
11), 198 (MꢂHOCH , 20), 183 (MꢂC12 ꢂNO H, 22),
51 (MꢂHOCH ꢂHNO , 11), 127 (19), 123 (11); HRMS
ESI) calcd for C21 30NO12 488.1763. Found 488.1765.
3
), 109.8 (C-2), 91.5 (C-5), 88.3 (C-4), 79.4 (C-7), 73.4 (CH
2
NO
), 46.1
2
),
for (MꢂOCH
3
)
C
21
H
30NO12 488.1763. Found 488.1753. Compound
1
7
(
3
3
21: oil; H NMR (CDCl ) d
: 5.48 (dd, 1H, J9,10¼8.8 Hz, H-9), 5.45 (dd,
1H, J8,9¼2.4 Hz, H-8), 5.00 (ddd, 1H, H-10), 4.64 (dd, J
1
0
a,1
0
b
¼15.2 Hz,
3
3
0
0
J
1
0
a,6¼6.4 Hz, H-1 a), 4.47 (dd, 1H, J
0
1
b,6¼8.8 Hz, H-1 b), 4.34 (dd, 1H,
3
3
4
(
1
3
(
1
(
2
,
2
,
H-4), 4.24 (dd, J10,11a¼2.8 Hz, H-11a), 4.10 (dd, 1H, J6,7¼6.4 Hz,
3
2
H
2
J
7,8¼8.4 Hz, H-7), 4.05 (dd, 1H, J10,11b¼5.6 Hz, J11a,11b¼12.4 Hz, H-
11b), 3.48 (dt,1H, Jgem¼9.2 Hz, JH,CH3¼7.2 Hz, OCH CH ), 3.40 (dt,1H,
OCH CH
), 2.88 (ddd, 1H, H-6), 2.48 (dd, 1H, J3a,3b¼14.8 Hz,
3a,4¼7.2 Hz, H-3a),1.99 (dd,1H, J3b,4¼3.6 Hz, H-3b), 2.13 (s, 3H, OAc),
2.09 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.05 (s, 3H, OAc), 1.48 (s, 6H, H-
1a,1b,1c, CH -5), 1.10 (t, 3H, OCH CH ).
3
3
2
3
3
3
2
3
3
ꢂC12
ꢂC12
H
17
O
8
H
17
O
8
2
J
3
H
17
O
8
2
H
3
2
3
0
0
0
0
4
.11. (2R,3S,4S,5R)-(1 ,2 ,3 ,4 -Tetra-O-acetyl-
D
-arabino-
0
4.13. (2R,3R,4R,5S)-4,5-Epoxy-4,7-dimethyl-3-nitromethyl-
tetritol-1 -yl)-4,5-epoxy-4,7-dimethyl-3-nitromethyl-
,3-dihydrooxepine (19)
0
2-(D-arabino-tetritol-1 -yl)-2,3-dihydrooxepine (23) and 4,7:
2
2
b
,8-dianhydro-1,3,6-trideoxy-5-C-methyl-6-C-nitro-methyl-
-arabino- -galacto-undec-2-ulo-2,5-furanoside (24)
-D
L
Conventional acetylation of 14 (40 mg, 0.13 mmol) with 1:1
2
O–pyridine (0.6 mL) led to an oil from which oily compound 19
34 mg, 63%) was isolated by PTLC (EtOAc–hexane 2:1); IR (NaCl):
Ac
(
n
Following the procedure described in Section 4.4, treatment of
b (0.10 g, 0.19 mmol) in 90% methanol (2.8 mL) with K CO
4
2
3
max 2919 (C–H), 1747 (C]O), 1661 (C]C), 1557, 1373 (NO
2
), 1219,
¼2.0 Hz,
ꢂ1
0
1
(0.11 g), afforded 0.049 g of an oily residue from which the pure
1043 (C–O) cm
;
H NMR (CDCl
3
0
)
d
: 5.51 (dd, 1H, J
1
0
,2
0
0
compounds 23 (5.2 mg, 10%) and 24 (3.2 mg, 7%) were isolated by
J
2
0
,3
0
¼8.8 Hz, H-2 ), 5.16 (dd, 1H, J
1
,2¼5.7 Hz, H-1 ), 5.11 (m, 1H, H-
1
0
PTLC (EtOAc–EtOH 16:1). Compound 23: oil; H NMR (DMSO-d
6
)
d
:
3
), 4.82 (br s, 1H, H-6), 4.66 (br s, 1H, H-5), 4.65 (dd, 1H,
4.83 (br s, 1H, H-6), 4.82 (dd, 1H, J1 a,1 b
00 ¼14.8 Hz, J 00 ¼5.4 Hz, H-
0
0
0
0
1 a,3
J
1
00a,100
b
¼14.3 Hz, J
1
00a,3¼5.3 Hz, H-1 a), 4.33 (dd, 1H, J
1
0
00b,3¼6.8 Hz, H-
00
00
1 a), 4.54 (br s, 1H, H-5), 4.36 (dd, 1H, J1 b,3
00
¼10.0 Hz, H-1 b), 3.93
0
0
1
b), 4.26 (dd,1H, J
3
0
,4
0
a
¼2.5 Hz, J
4
0
a,4
0
b
¼12.4 Hz, H-4 a), 4.11 (dd,1H,
(dd, 1H, J2,3¼5.7 Hz, H-2), 3.67 (br d, 1H, J1 ,2
0
¼9.6 Hz, J
0
0
z1 Hz, H-
1 ,2
0
J
3
0
,4
0
b
¼5.1 Hz, H-4 b), 3.71 (dd, 1H, J2,3¼9.2 Hz, H-2), 2.92 (m, 1H, H-
0
0
1
), 3.57 (dd, 1H, J
3
0
,4
0
a
¼2.9 Hz, J
4
0
a,4
0
b
¼11.2 Hz, H-4 a), 3.35 (m, 3H,
3
), 2.11 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.05 (s, 3H,
0
0
0
1
3
H-2 ,3 ,4 b), 3.05 (ddd, 1H, H-3), 1.70 (s, 3H, CH
). Compound 24: oil; H NMR (DMSO-d ) d
6
3
-7), 1.38 (s, 3H, CH
: 5.13 (dd, 1H,
b,6¼3.6 Hz, H-
3
-
OAc), 1.80 (s, 3H, CH
1
(
1
3
-7), 1.26 (s, 3H, CH
), 160.1 (C-7), 95.8 (C-6), 92.3
C-4), 91.1 (C-5), 78.2 (C-2), 73.1 (CH NO ), 69.9, 68.1, 67.7 (C-
-7), 20.8, 20.7 (O–CO–CH ),
-4); FABMS m/z (rel int.): 470 (MꢂOH,1), 468 (MꢂOHꢂH
5), 355 (MꢂHOAcꢂC OꢂNO, 1), 300 (MꢂOHꢂH ꢂ2HOAcꢂNO
5), 281 (5), 221 (MꢂOHꢂH ꢂ3HOAcꢂNO
47 (15), 133 (100), 108 (2); HRMS (FAB) calcd for C21
3 3
-4); C NMR (CDCl ) d:
1
4
70.7, 170.4, 170.0, 169.7 (O–CO–CH
3
0
J
1
0
0
a,1
0
b
¼16.4 Hz, J
1
0
a,6¼10.0 Hz, H-1 a), 4.71 (dd, 1H, J
0
1
2
2
0
0
0
0
1 b), 4.70 (d, 1H, JH-9,OH¼6.8 Hz, OH-9), 4.48 (d, 1H, JH-10,OH¼5.6 Hz,
OH-10), 4.38 (d, 1H, J3b,4¼6.8 Hz, H-4), 4.31 (t, 1H, JH-11,OH¼3.2 Hz,
OH-11), 4.30 (d,1H, J6,7¼6.4 Hz, J7,8z0 Hz, H-7), 4.29 (d, 1H, H-8),
,2 ,3 ), 61.8 (C-4 ), 49.5 (C-3), 22.6 (CH
3
3
13.7 (CH
3
2
,
,
1
1
1
4
2
H
2
2
2
3
.50 (dd, 1H, J10,11a¼3.2 Hz, H-11a), 3.39 (m, 1H, H-10), 3.33 (dd, 1H,
2
2
, 5), 207 (61), 193 (2),
29NO12ꢂOH
J
J
J
11a,11b¼11.2 Hz, J10,11b¼2.0 Hz, H-11b), 3.27 (dd, 1H, J9,10¼8.8 Hz,
8,9¼2.4 Hz, H-9), 2.62 (ddd, 1H, H-6), 2.28 (d, 1H, J3a,3b¼14.8 Hz,
3a,4z0 Hz, H-3a), 1.98 (dd, 1H, H-3b), 1.40 (s, 3H, H-1a,1b,1c), 1.37
H
70.1662. Found 470.1674.
(
3
(
2
(
8
3
s, 3H, CH
3
-5); CIMS m/z (rel int.): 322 (Mþ3, 36), 321 (Mþ2, 100),
4
.12. Methyl (9,10,11-tri-O-acetyl)-7-acetoxy-4,8-anhydro-1,3,6-
-arabino- -altro-undec-
-ulo-2,5-furanoside (20) and ethyl (9,10,11-tri-O-acetyl)-
-acetoxy-4,8-anhydro-1,3,6-trideoxy-5-C-methyl-6-C-
-arabino- -altro-undec-2-ulo-2,5-furanoside (21)
þ
20 (Mþ1, 93), 319 (M , 9), 303 (MꢂO, 24), 302 (MꢂOH, 19), 279
trideoxy-5-C-methyl-6-C-nitromethyl-
2
7
D
L
18), 259 (19), 258 (18), 229 (MþHꢂC
3), 199 (MþHꢂC ꢂNO, 20), 198 (MꢂC
20), 151 (21), 139 (24), 124 (55), 123 (76), 113 (27), 97 (40), 96 (33),
3
H
7
O
3
, 19), 228 (MꢂC
3 7 3
H O ,
ꢂNO, 22), 153
3
H
7
O
3
3 7 3
H O
nitromethyl-
D
L
5 (34); HRMS (CI) calcd for C13
20.1346.
H21NO
8
þH 320.1345. Found
Following the procedure described in Section 4.5, treatment of
the mixture 3b–5b (0.15 g, 0.28 mmol) led to an oil from which the
pure compounds 20 (14.1 mg, 13%) and 21(11.7 mg, 10%) were iso-
0
0
0
0
4.14. (2R,3R,4R,5S)-(1 ,2 ,3 ,4 -Tetra-O-acetyl-
tetritol-1 -yl)-4,5-epoxy-4,7-dimethyl-3-nitromethyl-2,3-
dihydrooxepine (25), (9,10,11-tri-O-acetyl)-4,7:2,8-dianhydro-
D
-arabino-
0
lated by PTLC (EtOAc–hexane 2:1). Compound 20: oil; [
.56, CDCl ); IR (NaCl): max 2964, 2926 (C–H), 1747 (C]O), 1557,
372 (NO ), 1215, 1057 (C–O) cm ; H NMR (CDCl
a
]
D
þ46.4 (c
0
1
3
n
ꢂ1
1
2
3
)
d
: 5.48 (dd, 1H,
1,3,6-trideoxy-5-C-methyl-6-C-nitromethyl-
-galacto-undec-2-ulo-2,5-furanoside (26), (10,11-di-O-acetyl)-
4,7:2,8-dianhydro-1,3,6-trideoxy-5-C-methyl-6-C-nitromethyl-
-arabino- -galacto-undec-2-ulo-2,5-furanoside (27), and
(9,10,11-tri-O-acetyl)-4,7:2,8-dianhydro-1,3,6-trideoxy-5-C-
b-D-arabino-
J
1
9,10¼8.8 Hz, H-9), 5.45 (dd, 1H, J8,9¼2.4 Hz, H-8), 5.00 (ddd, 1H, H-
L
0
0), 4.65 (dd, J
1
0
a,1
0
0
b
¼15.2 Hz, J
1
0
a,6¼6.4 Hz, H-1 a), 4.47 (dd, 1H,
J
1
0
b,6¼9.2 Hz, H-1 b), 4.34 (dd, 1H, H-4), 4.24 (dd, J10,11a¼2.8 Hz, H-
b
-D
L
1
1a), 4.09 (dd, 1H, J6,7¼6.0 Hz, J7,8¼7.6, H-7), 4.05 (dd, 1H,
J
1
10,11b¼5.6 Hz, J11a,11b¼12.4 Hz, H-11b), 3.15 (s, 3H, OCH
3
), 2.82 (ddd,
methyl-6-C-(N-acetoxy-oxime)-b-D-arabino-L-galacto-undec-
2-ulo-2,5-furanoside (28)
H, H-6), 2.47 (dd, 1H, J3a,3b¼14.0 Hz, J3a,4¼6.0 Hz, H-3a), 1.99 (dd,
H, J3b,4¼3.6 Hz, H-3b), 2.13 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.06 (s, 3H,
1
OAc), 2.05 (s, 3H, OAc),1.47 and 1.46 (s, 3H, H-1a,1b,1c and s, 3H, CH
3
-
Following the same procedure described in Section 4.5, com-
pound 4b (0.12 g, 0.23 mmol) led to an oily mixture, from which 25
(3.3 mg, 4%), 26 (13 mg, 17%), 27 (5.6 mg, 7%), and 28 (3.6 mg, 5%)
were isolated pure by PTLC (EtOAc–hexane 2:1). Compound 25: oil;
13
5
2
). C NMR (CDCl
), 92.3 (C-5), 88.5 (C-4), 78.9 (C-8), 71.6 (CH
), 47.1 (C-3), 24.6 (C-1),
); ESI MS m/z (rel int.): 504
, 8), 489 (MꢂNO, 59), 488 (MꢂOCH ,100), 473 (MꢂNO ,17),
72 (MꢂHNO , 24), 460 (MþHꢂHOAc, 33), 446 (MꢂOCH ꢂC O,
), 428 (MꢂOCH ꢂHOAc, 25), 355 (MꢂOCH ꢂHOAcꢂNOꢂCOꢂCH
), 329 (10), 198 (MꢂHOCH ꢂC ꢂHOAcꢂCH , 10), 183
ꢂC ꢂHOAcꢂNO, 12), 127 (26); HRMS (ESI) calcd
3
)
d
: 170.6,170.1,169.9,169.4 (O–CO–CH
3
),111.5 (C-
2
NO ), 69.2, 68.3, 68.0
2
(
2
(
4
8
9
C-7,9,10), 61.8 (C-11), 48.7, 48.6 (C-6, OCH
1.6 (CH -5), 20.9, 20.7 (O–CO–CH
MꢂCH
3
3
3
IR (NaCl):
(NO ), 1217, 1042 (C–O) cm
¼2.0 Hz, J
nmax 2926 (C–H), 1747 (C]O), 1665 (C]C–O), 1557, 1372
ꢂ1
1
3
3
2
2
;
H NMR (CDCl
3
)
d
: 5.49 (dd, 1H,
0
0
0
0
0
0
0
¼8.4 Hz, H-2 ), 5.34 (dd, 1H, J
0
,2¼9.2 Hz, H-1 ),
2
3
2
H
2
J
1
,2
2
,3
1
3
3
3
,
5.01 (m, 1H, H-3 ), 4.91 (br s, 1H, H-6), 4.72 (br s, 1H, J3,5z1 Hz, H-
0
0
00a,100
0
¼15.2 Hz, J
00a,3¼8.0 Hz, H-1 a), 4.44 (dd, 1H,
¼2.8 Hz, J ¼12.4 Hz, H-
3
H
9 13
O
6
3
5), 4.58 (dd, 1H, J
1
0
b
1
(
MꢂHOCH
3
9
H
13
O
6
J
1
00b,3¼6.8 Hz, H-1 b), 4.21 (dd, 1H, J
3
0
,4
0
a
0 0
4 a,4 b

N. Ara u´ jo et al. / Tetrahedron 66 (2010) 2664–2674
2673
0
0
4
4
6
a), 4.10 (dd, 1H, J2,3¼6.0 Hz, H-2), 4.04 (dd, 1H, J
b), 3.08 (ddd, 1H, H-3), 2.11 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.05 (s,
-7), 1.43 (s, 3H, CH -4); FABMS m/z (rel
3
0
,4
0
b
¼6.0 Hz, H-
(15), 109 (11), 97 (23), 96 (49), 95 (23); HRMS (ESI) calcd for
29NO11ꢂH 470.1657. Found 470.1659.
21
C H
H, 2ꢀOAc), 1.85 (s, 3H, CH
3
3
int.): 489 (Mþ2, 25), 488 (MþH, 100), 428 (MþHꢂHOAc, 39), 383
MþHꢂHOAcꢂNOꢂCH , 22), 368 (MþHꢂ2HOAc, 24), 322 (MþHꢂ
HOAcꢂNO , 17), 308 (MþHꢂ3HOAc, 16), 263 (MþHꢂ2HOAcꢂ
NO , 32), 221 (MꢂOHꢂH
ꢂOAc, 25), 261 (Mꢂ3HOAcꢂNO
HOAcꢂNO 26), 219 (Mꢂ3HOAcꢂNO ꢂC O, 23), 201
Mꢂ4HOAcꢂNO , 10), 198 (MꢂC12 , 77), 151 (MꢂC12
HNO ꢂCOꢂHNO , 35),113
, 15), 149 (39),129 (18), 123 (MꢂC12
21), 109 (26), 97 (32), 96 (86), 95 (48); HRMS (FAB) calcd for
4.15. (2R,3R,4S,5R)-4,5-Epoxy-4,7-dimethyl-3-nitromethyl-
0
(
2
3
2-(
D
-arabino-tetritol-1 -yl)-2,3-dihydrooxepine (30)
2
2
2
2
ꢂ
Following the procedure described in Section 4.4, a solution of
5b (0.10 g, 0.19 mmol) in 90% methanol (2.8 mL) was treated with
CO (0.11 g), affording compound 30 (53 mg, 87%) as a chro-
matographically pure oil; [
þ8.8 (c 0.5, DMSO); IR (NaCl):
3368 (O–H), 2935 (C–H), 1658 (C]C–O), 1554, 1376 (NO ), 1076,
4.92 (dd, 1H,
3
(
2
,
2
2 2
H
2
H
17
O
8
H
17
O
8
ꢂ
K
2
3
2
H
17
O
8
2
a
]
D
n
max
(
2
þ
ꢂ1
1
C
21
H
29NO12þH 488.1768. Found 488.1784. Compound 26: oil; [
a
]
D
1034 (C–O) cm
¼15.2 Hz, J
;
H
NMR (DMSO-d
6
)
d:
0
0
þ18.6 (c 0.36, CHCl
3
); IR (NaCl): max 2964 (C–H), 1745 (C]O), 1552,
n
J
1
00a,100
b
1
00a,3¼4.0 Hz, H-1 a), 4.74 (br s, 1H, H-6), 4.66 (br s,
ꢂ1
1
00
1
J
J
1
J
J
1
3
3
(
8
371 (NO
2
), 1217, 1041 (C–O) cm ; H NMR (CDCl
3
)
d
: 5.38 (t, 1H,
1H, H-5), 4.60 (dd, 1H, J
1
00b,3¼10.0 Hz, H-1 b), 3.98 (dd, 1H,
0
9,10¼J8,9¼5.6 Hz, H-9), 5.21 (ddd, 1H, H-10), 5.07 (dd, 1H,
J
2,3¼4.8 Hz, J
1
0
,2¼9.6 Hz, H-2), 3.68 (br d, 1H, H-1 ), 3.58 (dd, 1H,
0
0
0
0
0
0
0
0
¼16.0 Hz, J
0
a,6¼8.8 Hz, H-1 a), 4.67 (dd, 1H, J
0
b,6¼3.6 Hz, H-
J
3
0
0
¼3.2 Hz, J
0
0
¼10.8 Hz, H-4 a), 3.5–3.2 (m, 3H, H-2 ,3 ,4 b),
1
a,1
b
1
1
,4
a
4
a,4
b
13
b), 4.55 (d, 1H,
J
6,7¼6.0 Hz,
J
7,8z0 Hz, H-7), 4.44 (d, 1H,
3.08 (m, 1H, H-3), 1.80 (s, 3H, CH
(DMSO-d : 159.3 (C-7), 95.3 (C-6), 94.1 (C-4), 88.7 (C-5), 75.9 (C-
2), 72.7 (CH
18.3 (CH -7), 13.5 (CH
(MþHꢂH O, 10), 224 (18), 198 (MꢂC
(MþHꢂC ꢂNO , 46), 151 (MꢂC
127 (26), 123 (MþHꢂC ꢂNO ꢂ2CH
103 (36), 97 (100), 96 (86), 95 (48), 87 (42), 85 (60), 81 (34), 73 (68),
3 3
-7), 1.25 (s, 3H, CH -4); C NMR
3b,4¼6.8 Hz, H-4), 4.43 (dd, 1H, J10,11a¼2.8 Hz, H-11a), 4.33 (d, 1H,
6
) d
0
0
0
0
8,9¼5.6 Hz, H-8), 4.08 (dd, 1H, J11a,11b¼12.4 Hz, J10,11b¼6.8 Hz, H-
2
NO
2
), 70.7, 70.2, 66.8 (C-1 ,2 ,3 ), 63.6 (C-4 ), 47.3 (C-3),
-4); CIMS m/z (rel int.): 320 (MþH, 17), 302
, 44), 188 (18), 153
ꢂNO H, 44), 139 (24),
, 48), 113 (46), 109 (40),
1b), 2.72 (ddd, 1H, H-6), 2.36 (d, 1H, J3a,3b¼15.2 Hz, J3a,4z0 Hz, H-
3
3
a), 2.10 (dd, 1H, H-3b), 2.08 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.03 (s,
2
4 9 4
H O
13
H, OAc), 1.47 (s, 3H, H-1a,1b,1c), 1.46 (s, 3H, CH
: 170.7, 170.0, 169.8 (O–CO–CH ), 108.7 (C-2), 88.8 (C-5),
5.6 (C-4), 80.9, 79.9 (C-7,8), 71.5 (CH NO ), 70.6, 70.5 (C-9,10), 61.8
-5), 20.8, 20.7, 20.3
). ESI MS m/z (rel int.): 447 (Mþ2, 38), 446 (MþH, 100),
28 (MþHꢂH O, 29), 388 (11), 386 (MþHꢂHOAc, 28), 326
MþHꢂ2HOAc, 11), 228 (MꢂC , 6), 198 (MꢂC ꢂNO, 6),
87 (9), 169 (MꢂC ꢂNOꢂCOꢂH, 10), 123 (MꢂC
HNO , 67); HRMS (ESI) calcd for 29NO13þNa
ꢂCOꢂ2CH
68.1476. Found 468.1465. Compound 27: oil; [
¼ꢂ7.8 (c 0.4,
CHCl ); IR (NaCl): max 3473 (O–H), 2967 (C–H), 1745 (C]O), 1554,
376 (NO
3
-5); C NMR
4
H
8
O
4
2
4
H
9
O
4
2
CDCl
3
)
d
3
4
H
9
O
4
2
3
2
2
(
(
4
(
C-11), 51.3 (C-6), 42.3 (C-3), 24.4 (C-1), 21.7 (CH
O–CO–CH
3
69 (76), 61 (96), 57 (67), 55 (36); HRMS (CI) calcd for C13
320.1345. Found 320.1338.
H21NO
8
þH
3
2
0
0
0
0
9
H
13
O
6
9
H
13
O
6
4.16. (2R,3R,4S,5R)-(1 ,2 ,3 ,4 -Tetra-O-acetyl-
D-arabino-
0
1
9
H
13
O
6
9
H
13
O
6
ꢂ
tetritol-1 -yl)-4,5-epoxy-4,7-dimethyl-3-nitromethyl-
2,3-dihydrooxepine (31)
2
3
21
C H
a]
D
4
3
n
Conventional acetylation of 30 (41 mg, 0.13 mmol) with 1:1
ꢂ1
0
1
1
J
1
4
4
2
), 1223, 1048 (C–O) cm ; H NMR (CDCl
3
)
d
: 5.18 (dd, 1H,
Ac O–pyridine (0.6 mL) led to an oil from which oily compound 31
2
1
0
0
¼15.6 Hz, J
0
a,6¼9.6 Hz, H-1 a), 5.06 (dd, 1H, H-10), 4.57 (dd,
(8 mg, 13%) was isolated by PTLC (EtOAc–hexane 2:1); H NMR
(CDCl ):
1
a,1
b
1
0
0
H, J
1
0
b,6¼3.6 Hz, H-1 b), 4.52 (d, 1H, J6,7¼6.0 Hz, J7,8z0 Hz, H-7),
d
5.44 (dd,1H, J
0
0
¼3.5 Hz, J
0 0
¼9.0 Hz, H-2 ), 5.29 (dd,1H,
3
1 ,2
2 ,3
0
0
.45 (d, 1H, J3b,4¼7.2 Hz, H-4), 4.42 (dd, 1H, J10,11a¼2.8 Hz, H-11a),
.36 (dd, 1H, J11a,11b¼13.2 Hz, J10,11b¼3.6 Hz, H-11b), 4.16 (d, 1H,
J
1
0
,2¼8.9 Hz, H-1 ), 5.09 (m, 1H, H-3 ), 4.88 (dd, 1H, J
1
00a,100
b
¼18.5 Hz,
0
0
J100 ¼2.8 Hz, H-1 a), 4.73 (br s, 1H, H-6), 4.60 (br s, 1H, H-5), 4.30
a,3
0
0
J
8,9¼2.4 Hz, H-8), 3.76 (ddd, 1H, J9,10¼8.0 Hz, H-9), 2.87 (d, 1H, JH-
(dd, 1H,
J
1
00b,3¼10.8 Hz, H-1 b), 4.24 (dd, 1H,
J
3
0
,4
0
a
¼2.7 Hz,
0
0
,OH¼6.4 Hz, OH-9), 2.81 (ddd, 1H, H-6), 2.31 (d, 1H, J3a,3b¼15.2 Hz,
3a,4z0 Hz, H-3a), 2.03 (dd, 1H, H-3b), 2.10 (s, 3H, OAc), 2.08 (s, 3H,
J
0
0
¼12.5 Hz, H-4 a), 4.03 (dd, 1H, J
0 0
¼5.3 Hz, H-4 b), 3.87 (dd,
9
4 a,4 b
3 ,4 b
J
1H, J2,3¼4.2 Hz, H-2), 2.98 (dt, 1H, H-3), 2.11 (s, 3H, OAc), 2.08 (s, 3H,
OAc), 2.06 (s, 6H, 2ꢀOAc), 1.90 (s, 3H, CH -7), 1.40 (s, 3H, CH -4).
13
3
OAc), 1.46 and 1.49 (s, 3H, H-1a,1b,1c) and (s, 3H, CH -5); C NMR
3
3
(
8
5
CDCl
), 81.8, 80.8 (C-7,4), 71.9 (CH
1.1 (C-6), 42.6 (C-3), 24.6 (C-1), 21.7 (CH
CO–CH
); ESI MS m/z (rel int.): 405 (Mþ2, 7), 404 (MþH, 38), 386
O, 8), 344 (MþHꢂHOAc, 8), 326 (MþHꢂH OꢂHOAc, 6),
58 (8), 228 (MꢂC , 29), 169 (MꢂC ꢂNOꢂCOꢂH, 8),
ꢂHNO ꢂCOꢂ2CH , 100), 113 (11), 97
10), 81 (12); HRMS (ESI) calcd for C17
25NO11þH 404.1551. Found
04.1545. Compound 28: oil; H NMR (CDCl : 11.24 (s, 1H,
3
)
d
: 171.5, 169.7 (O-CO-CH
3
), 108.8 (C-2), 88.9 (C-5), 85.6 (C-
), 71.5, 70.1 (C-9,10), 62.5 (C-11),
-5), 21.0, 20.9, 20.8 (O–
2
NO
2
Acknowledgements
3
3
The authors are grateful to Ministerio de Educaci o´ n y Ciencia,
Direcci o´ n General de Investigaci o´ n and Junta de Extremadura
through grants CTQ2007-66641/BQU and PRI07A015.
(
2
1
(
MþHꢂH
2
2
7
H
11
O
5
7 11 5
H O
39 (12), 123 (MꢂC
7
11
H O
5
2
3
H
References and notes
1
4
3
) d
1. (a) Just, G.; Martel, A. Tetrahedron Lett. 1973, 1517; (b) Just, G.; Martel, A.;
CH]NOAc), 5.35 (dd, 1H, J9,10¼6.4 Hz, H-9), 5.26 (ddd, 1H, H-10),
Grozinger, K.; Ramjeesingh, M. Can. J. Chem. 1975, 53, 131.
4
J
J
2
2
.54 (d, 1H, H-7), 4.46 (d, 1H, J3b,4¼6.4 Hz, H-4), 4.37 (dd, 1H,
2. (a) Grieco, P. A.; Zelle, R. E.; Lis, R.; Finn, J. J. Am. Chem. Soc. 1983, 105, 1403;
(b) Grieco, P. A.; Zelle, R. E.; Lis, R.; Finn, J. J. Am. Chem. Soc. 1986, 108, 5908;
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11a,11b¼12.4 Hz, J10,11b¼6.4 Hz, H-11b), 3.01 (d, 1H, J6,7¼6.4 Hz, H-6),
(
2
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13
(
g) Just, G.; Lim, M. I. Can. J. Chem. 1977, 55, 2993; (h) Sera, A.; Itoh, K.;
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3
-5); C NMR (CDCl
), 163.0 (CH–N–OAc),
09.1 (C-2), 87.5 (C-5), 86.3 (C-4), 81.2, 80.9 (C-7,8), 70.2, 70.1 (C-
3
) d: 170.7,
Yamaguchi, H. Tetrahedron Lett. 1990, 31, 6547.
1
1
9
3 3
70.4, 169.7 (O–CO–CH ), 167.6 (N–O–CO–CH
3
. Fraile, J. M.; Garc ı´ a, J. I.; Gracia, D.; Mayoral, J. A.;Pires, E. J. Org. Chem.1996, 61, 9479.
4. (a) Ara u´ jo, N.; Gil, M. V.; Rom a´ n, E.; Serrano, J. A. Synthesis 2006, 2503;
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Tetrahedron: Asymmetry 2009, 20, 1999.
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1.1, 20.9, 20.7 (O–CO–CH ), 18.3 (N–O–CO–CH ); ESI MS m/z (rel
int.): 471 (M , 20), 470 (MꢂH, 84), 428 (MꢂC O, 42), 427
, 67), 358 (15),
ꢂO, 10), 210
ꢂOAc, 12), 187 (13),
,15),139 (100),138 (14),123 (14),115
3
-5),
2
3
3
þ
2 3
H
5
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N.; Chattopadhyay, P. Tetrahedron 2005, 61, 9368 and references cited therein.
(
3
(
1
MꢂHꢂC
53 (MꢂC
MꢂC
81 (MꢂC
2
H
3
O, 67), 414 (14), 413 (MꢂC
2
H
3
OꢂCH
ꢂHOAc, 13), 238 (MꢂC
O, 12), 195 (MꢂC
OꢂCH
3
2
H
3
OꢂCH
3
9 13 6
H O
9
H
13
O
6
ꢂHꢂC
2
H
3
9 13 6
H O
9
H
13
O
6
ꢂC
2
H
3
3

2674
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6
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Kishimoto, S. Can. J. Chem. 2006, 84, 392.
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. (a) Nicolaou, K. C.; Reddy, K. R.; Skokotas, G.; Sato, F.; Xiao, X.-Y.; Hwang, C. K.
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. (a) Hirama, M.; Oishi, T.; Uehara, H.; Inoue, M.; Maruyama, M.; Oguri, H.; Sa-
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9
. Jørgensen, M.; Iversen, E. H.; Madsen, R. J. Org. Chem. 2001, 66, 4625.
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8
253; (d) Knapp, S.; Gore, V. K. Org. Lett. 2000, 2, 1391.
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1
1
1
dicated these latter with the symbol M .
*