Studies on the chemistry of sodium nitronates and nitronic esters derived from 5-glyco-4-nitro-1-cyclohexenes

Article abstract of DOI:10.1016/S0040-4020(02)00082-0

Reactions of sodium nitronates derived from 5-glyco-4-nitro-1-cyclohexenes with D-galacto or D-manno sugar side-chains have been investigated. With acetic anhydride/pyridine, these salts suffered an intramolecular cyclization affording high yields of tetraacetylated isoxazoline N-oxides. Treatment of the latter compounds with sodium methoxide yielded, either the corresponding deacetylated derivative or a bicyclic oxime, depending on the configuration of the sugar side-chain. Furthermore, unstable nitronic acid 13 has been isolated by recrystallization of nitronate 10 in dimethylsulfoxide, as well as by reaction of this substance with cold aqueous sulfuric acid. By refluxing with trimethyl phosphite, the N-oxides 14 and 16 led to isoxazolines which, like their precursors, could be considered as acyclic C-nucleosides.

Full text of DOI:10.1016/S0040-4020(02)00082-0

TETRAHEDRON
Pergamon
Tetrahedron 58 <2002) 2167±2173
Studies on the chemistry of sodium nitronates and nitronic esters
derived from 5-glyco-4-nitro-1-cyclohexenes
p
M. V. Gil, E. Roman and J. A. Serrano
Â
 Â
Departamento de Quõmica Organica, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain
Received 7 December 2001; revised 17 January2002; accepted 22 January2002
AbstractÐReactions of sodium nitronates derived from 5-glyco-4-nitro-1-cyclohexenes with d-galacto or d-manno sugar side-chains have
been investigated. With acetic anhydride/pyridine, these salts suffered an intramolecular cyclization affording high yields of tetraacetylated
isoxazoline N-oxides. Treatment of the latter compounds with sodium methoxide yielded, either the corresponding deacetylated derivative or
a bicyclic oxime, depending on the con®guration of the sugar side-chain. Furthermore, unstable nitronic acid 13 has been isolated by
recrystallization of nitronate 10 in dimethylsulfoxide, as well as by reaction of this substance with cold aqueous sulfuric acid. By re¯uxing
with trimethyl phosphite, the N-oxides 14 and 16 led to isoxazolines which, like their precursors, could be considered as acyclic C-nucleo-
sides. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
The purpose of this paper is to present in full details the
preparation and reactivityof sodium nitronates derived from
5-glyco-4-nitro-1-cyclohexenes, as well as
a further
The diverse reactions of nitro compounds, nitronate salts
and nitronic esters with acids have been under studyfor
over a century.1 In particular, in the past two decades, the
synthetic use of aliphatic nitro compounds has rapidly
expanded.2 In spite of this extensive background, nitronic
acid derivatives have seldom been employed in organic
synthesis, and this situation is in sharp contrast to that of
carboxylic acid derivatives which are highly important
substances. This lack of application of nitronic acids
themselves and some of their derivatives could mainlybe
extension of our work to the synthesis of 2-isoxazolines,
an important class of heterocycles with various synthetically
useful functionalities masked in the ring.7 The new
isoxazolines and their N-oxides could be considered as
C-nucleoside analogs,8 a class of compounds that have
generated considerable interest in view of their anticancer,9a
antiviral9b,c and/or antibiotic9d properties.
1
attributed to the labilityof these compounds. Moreover,
2. Results and discussion
reactions using the somewhat more stable nitronate salts
have been conducted under aqueous acidic media, which
are the typical conditions of Nef reactions.3 However, little
attention has been paid to other nonaqueous protocols.
As the starting materials, we used pentaacetylated trans-5-
glyco-4-nitro-1-cyclohexenes 1, 2, and 5; their preparation
being accomplished by asymmetric Diels±Alder cyclo-
additions between sugar-derived 1-nitroalkenes and
isoprene10 or 2,3-dimethyl-1,3-butadiene.11 Then, following
the same methodologyas for related trans-6-glyco-5-nitro-
2-norbornene derivatives,12 we intended deacetylation of
the above cited adducts, bytreatment of methanolic
solutions of these with a catalytic amount of 2 M sodium
methoxide in methanol. In contrast with those results,13 we
observed here that after addition of one drop of the base, the
pH values in the solutions changed in a few minutes from
clearlyalkaline to slightlyalkaline <pH 8±9). Monitoring of
these processes byTLC <1:1 hexane/AcOEt) showed that
spots corresponding to the respective starting materials
were progressivelyreplaced byothers with lower mobility
in such a waythat, after 3 h at room temperature, stabiliza-
tion of the reaction mixtures was achieved. In this point,
1H NMR spectra revealed the complete absence of each
one of the pentaacetates and the presence of their respective
On the other hand, assuming the need for ef®cient and
speci®c methods for the preparation of alkyl nitronates,
several authors have reported on the use of these derivatives,
both chiral and achiral, for the stereo- and regioselective
In this
1d,4
construction of highlyfunctionalized molecules.
sense, we have previouslyreported a simple procedure in
which chiral nitro sugar derivatives, via their corresponding
nitronate salts, are used in stereoselective Michael addition
reactions,5 as well as for the synthesis of chiral cyclic
nitronic esters <2-isoxazoline-N-oxides).6
Keywords: sugars; nitro compounds; nitronate salts; nitronic acid; isoxazo-
lines; oximes.
p
Corresponding author. Tel.: 134-924-289-381; fax: 134-924-271-149;
e-mail: roman@unex.es
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020<02)00082-0

2168
M. V. Gil et al. / Tetrahedron 58 12002) 2167±2173
deacetylated derivatives and their C-4 epimers <ratio ca.
1:1), together with small quantities <less than 10%) of
other partiallydeacetylated products. These results indicate
that, on treatment with a catalytic amount of sodium
methoxide, compounds 1, 2 and 5 suffer two competitive
processes, i.e. deacetylation of their sugar side-chains and
formation of carbanions at C-4, in a comparable extent;
then, reprotonation of both diastereomeric faces of these
carbanions in the almost neutral reaction media would led
to cis- and trans-mixtures of epimers.14 Concerning the 1:1
ratios of these, we have observed no changes after
prolonged periods of time, thus indicating that the composi-
tion of the mixtures should re¯ect the relative stabilities of
the products; in this sense, we have performed PM3 semi-
empirical calculations15 for epimeric deacetylated 3 and 7,
®nding that the former resulted more stable byonly
1H NMR spectra of the salts and those of their deacetylated
precursors, were the down®eld shifts that exhibited some of
the corresponding protons in the former; as expected, the
major displacements were observed for protons close to the
carbanionic center at C-4; also, the unsaturated character of
this carbon was evident from its chemical shift <130.3±
127.4 ppm), which was in the same region where the
ole®nic C-1 and C-2 <125.5±115.2 ppm) appeared.
0.5 kcal mol21
.
The different behaviour between cyclohexenes and nitro-
norbornenes against the base, that is, their different acidities,
could be attributed to the greater geometrical limitations in
angles of the carbanions that would be formed from the
more strained [2.2.1] systems.
After several days at room temperature, NMR spectra of
deuterium oxide solutions of nitronates 10, 11 and 12 did
not show anychanges, therebyindicating that no deuterium
addition had occurred under these conditions. On the
contrary, as it is depicted in Scheme 1 for 10, NMR spectra
in DMSO-d6 solutions were time-dependent and, after ca.
1.5 h at room temperature theyshowed, almost exclusively,
signals that could be assigned to deacetylated trans <3) and
Bytreatment with a small excess of 2 M sodium methoxide,
solutions in either acetone or methanol of trans-5-<penta-O-
acetyl-pentitol-1-yl)-4-nitro-1-cyclohexenes 1, 2 or 5 led, in
each case, to a white precipitate <91% to quantitative yields)
that was identi®ed as the corresponding deacetylated
sodium nitronate 10, 11 or 12. On the other hand, by
using an identical procedure, these same products were
obtained in similar yields from methanolic solutions of
deacetylated derivatives <3, 4 and 6) of the above cited
nitrocyclohexenes, or from their epimers at C-4 <7, 8 and
9).10,11 The new nitronates appeared to be stable compounds
that could be recrystallized from methanol/water, and did
not decompose after long time of storage in desiccator.
Their structures were in agreement with their elemental
analyses, showing the typical yellowish colouration indicat-
ing the presence of sodium in the combustion test with
platinum wire; IR spectra showed, as characteristic bands,
those at ca. 3500±3000 cm21 <OH), 1600±1570 cm21
<CvN) and 1140±1120 cm21 <C±O).
16
cis <7) nitro compounds, without anyfurther evolution.
Moreover, compound 10 could be recrystallized from
1
DMSO, affording a crystalline material whose H NMR
spectrum was identical to the product isolated bydirect
treatment of 10 with dilute H2SO4 at 2108C <Scheme 1).
The latter appears to be consistent with the formation of the
corresponding nitronic acid 13 from which 3 and 7 arise.
Compound 13 appeared to be a rather unstable1 substance
that even in solid state darkened in a few minutes; also, by
polarimetric measurements in water, we could observe that,
in a period of 90 min at room temperature, the initial value
of 2208 was changing to 08. Spectroscopic data of 13 were
clearlydistinct from those of their nitro tautomers; 10,11 thus,
an IR absorption at 1655 cm21 was indicative of the
With deuterium oxide as solvent we found that, besides the
absence of the signals of H-4, the main differences between
1
presence of the CvN group; the H NMR spectrum of a
Scheme 1.

M. V. Gil et al. / Tetrahedron 58 12002) 2167±2173
2169
Scheme 2.
freshlyprepared solution of this substance in DMSO- d6
exhibited a D2O-exchangeable broad singlet <6.33 ppm),
being assigned to CvN±OH proton;17 in addition, the
allylic character of H-5 and H-3a,3b was evident from
their chemical shifts, that were at lower ®elds than for the
corresponding protons in trans and cis nitro compounds 3
and 7 <Ddˆ1.15±0.23 ppm).
could be deduced from 13C NMR spectra, where C-3 signals
on isoxazoline N-oxides appeared at clearlylower ®eld than
the signals of C-10 in their corresponding precursors.
As it was discussed previously,6 transformation of the
sodium salts 10±12 into the isoxazoline-N-oxides 14±16
could be explained bysupposing the formation of an inter-
mediate acetic nitronic anhydride 17 <Scheme 2), in which
the acetate group on the nitrogen would suffer an intra-
molecular nucleophilic displacement from the hydroxyl
group at C-1. Although verylittle is known about nitronic
anhydrides, mainly as a result of their instability,1a some of
them have been either isolated21±23 or postulated as inter-
mediates24 in various types of reactions; thus, in a related
precedent with the processes here described, Miyashita et
al.22 have reported that in the boron tri¯uoride-promoted
hydrolysis of a series of acetic nitronic anhydrides, the
acetoxygroup on the nitrogen is intramolecularlydisplaced
bya d-carbonyl oxygen.
It is noteworthythat, on recrystallization of d-galacto nitro-
nate 10 from 0.1 M HCl, the product that crystallized <28%
yield) was the pure cis-4-nitro-5-<d-galacto-pentitol-1-yl)-
1-cyclohexene 718 remaining, almost exclusively, unaltered
salt in dissolution <Scheme 1). Similarly, d-manno nitronate
12 afforded a small quantity<5%) of a solid that consisted in
a 1:1.6 mixture of 6 <trans) and 9 <cis); these compounds
were also present in the mother liquor <ca. 1:1 ratio),
together with unchanged salt as major component. These
facts, indicating a partial protonation of the carbanions,
should not be related with its stereochemical course;
instead, from the equilibrium between the cis- and trans-
nitro compounds, the solid product we isolated in each case
should depend on its relative solubilityin the aqueous
media.
In order to obtain their respective deacetylated derivatives,
compounds 14 and 16 were treated with a catalytic amount
of sodium methoxide in methanol; however, although the
latter led quantitavelyto the expected deacetylated isoxazo-
line N-oxide 18 <see Section 3.1.10), this was not parallel
with what occurred when starting from 14; instead, the only
product in this case <90% yield) was a bicyclic oxime 19
<Scheme 3) that was additionallycharacterized through its
penta-O-acetyl derivative 20 <see Section 3.1.9). Explana-
tions about the formation of 19, as well as a justi®cation for
the different behaviour of 14 and 16 against sodium
methoxide have been provided.6
Byusing increased concentrations of the acid, we could
observe <1H NMR) a progressive complication in the
reaction media and, with 2 M HCl, we obtained a mixture
of products arising from a Nef reaction, followed byintra-
molecular cyclization of the intermediate glycocyclo-
hexenones <Scheme 1).19
On the other hand, when nitronates 10, 11 or 12 were
dissolved in pyridine and treated with acetic anhydride for
1.5 h at room temperature theygave, after pouring on ice-
water, 80±90% yields of tetraacetylated isoxazoline
N-oxides 14, 15 or 16, respectively<Scheme 2). These
compounds, that maybe considered as cyclic nitronic esters,
were stable solids with elemental analyses and spectro-
scopic data in agreement with their proposed structures;
thus, there was absence of IR bands for hydroxyl or nitro
groups, whereas those for nitronic esters <nCvN, 1650±
Scheme 3.
25
Following the procedure described byFoucaud et al., the
1670 cm21
) and for carbonyl esters <nCvO, 1740±
1750 cm21) were evident. H NMR spectra showed four
singlets <ca. 2.1 ppm) attributable to methyl acetates.
When compared with their respective <deacetylated) nitro-
nates, we observed the characteristic down®eld acylation
shifts20 that exhibited protons on the sugar backbones,
with the sole exception of H-3 <H-10 in 10, 11 and 12)
which underwent a lesser down®eld shift; the latter suggests
that the ®rst hydroxyl group in the sugar side-chain remains
deacetylated and it is therefore involved in the cyclization
step leading to 14±16; an additional support to this fact
1
reaction of isoxazoline N-oxides 14 and 16 with trimethyl
phosphite in dioxane yielded the corresponding isoxazolines
1
21 and 22 <Scheme 4). After re¯uxing for 14 h, H NMR
spectra of the crude reaction mixtures revealed about 90%
conversion into the reduced products, also appearing a small
quantityof the starting materials together with unidenti®ed
by-products.26 Isolation of 21 and 22 was performed by
preparative TLC, their structures being demonstrated by
IR, NMR and high resolution mass spectra. Thus, whereas
strong IR bands were observed for carbonyl acetate groups

2170
M. V. Gil et al. / Tetrahedron 58 12002) 2167±2173
white crystalline product and the reaction mixture was
cooled at 08C for 6 h. Then, the solid was ®ltered, washed
on the ®lter with cold methanol and recrystallized from
methanol/water; yield: 0.62 g <98%); mp 228±2308C; Rf
0.70 <3:1 AcOEt/EtOH); [a]Dˆ15.48 <c 0.55, H2O);nmax
<KBr) 3090, 2870, 1585, 1420, 1300, 1130, 1070, 1040,
1020 cm21
;
1H NMR <D2O)
d
4.01 <t, 1H,
0
Scheme 4.
0
0
0
0
0
00
J3 ,4 ,J4 ,5 ˆ6.3 Hz, J4 ,5 ˆ1.0 Hz, H-4 ), 3.90 <d, 1H,
J1 ,5ˆ9.7 Hz, H-10), 3.80±3.70 <m, 2H, H-20, H-30), 3.73
0
<1740±1750 cm21), those for CvN <1640±1670 cm21
)
<dd, 1H, H-50), 3.69 <dd, J5 ,5 ˆ9.5 Hz, H-5 ), 3.61 <dd,
1H, J5,6aˆ5.2 Hz, J5,6b,1 Hz, H-5), 3.18 <d, 1H, H-3a),
2.91 <d, 1H J3a,3bˆ22.2 Hz, H-3b), 2.39 <br d, 1H, H-6a),
2.07 <d, 1H, J6a,6bˆ17.2 Hz, H-6b), 1.75 <s, 3H, Me), 1.72 <s,
3H, Me); 13C NMR <D2O) d 129.3 <C-4), 124.4, 123.8 <C-1,
C-2), 72.3, 71.1, 70.2 <C-10, C-20, C-30, C-40), 64.1 <C-50),
38.3 <C-5), 33.1, 32.5 <C-3, C-6), 19.1, 18.4 <Me-1, Me-2).
Anal. calcd for C13H22NO7Na´H2O: C, 45.21; H, 7.00; N,
4.05. Found: C, 45.43; H, 6.89; N, 4.01.
00
0
00
appeared much more weaker than the same for their
precursors. Although proton resonances of 21 and 22 differ
verylittle from those of 14 and 16, signi®cative divergences
were found between 13C NMR spectra; as could be
expected, the larger differences were encountered for
carbons bonded to nitrogen <C-7a), which appeared more
deshielded in isoxazolines than in the respective N-oxides
byabout 44 ppm.
Summarizing the above results, ef®cient and easysyntheses
of opticallypure heteroccylic compounds have been
achieved from stable nitronate salts of 5-glyco-4-nitro-1-
cyclohexenes. The major advantage of the methods
described in this paper relies on the simple reaction condi-
tions which have been used; furthermore, the syntheses
demonstrate the versatilityof these sodium nitronates,
readilyavailable in opticallypure form, for the preparation
of molecules with potential pharmacological activity.
3.1.2. Sodium salt of 1-C-[)4S,5S)-1-methyl-4-nitro-1-
cyclohexen-5-yl]-d-galacto-pentitol )11). Following the
same procedure described above for the preparation of 10,
treatment of a solution of 210 <0.38 g, 0.76 mmol) in metha-
nol <6 mL) with 2 M sodium methoxide in methanol
<0.8 mL, 0.40 mmol) led to the title compound as a white
solid <0.24 g, quantitative): mp 166±1688C <from methanol/
water); Rf 0.68 <3:1 AcOEt/EtOH); [a]Dˆ124.78 <c 0.90,
H2O); nmax <KBr) 3300, 2950, 1580, 1440, 1275, 1140,
1
1015, 1080 cm21; H NMR <D2O) d 5.51 <br s, 1H, H-2),
0
0
0
0
0
00 00
4.01 <t, 1H, J3 ,4 ,J4 ,5 ˆ6.3 Hz, J4 ,5 ˆ1.0 Hz, H-4 ), 3.93
<d, 1H, J1 ,5ˆ10.0 Hz, H-10), 3.80±3.65 <m, 4H, H-20, H-30,
0
3. Experimental
3.1. General
H-50, H-500), 3.66 <dd, 1H, J5,6aˆ5.8 Hz, J5,6b,1 Hz, H-5),
3.22 <dd, 1H, H-3a), 2.94 <d, 1H, J3a,3bˆ22.7 Hz, H-3b),
2.37 <br d, 1H, H-6a), 2.07 <d, 1H, J6a,6bˆ17.4 Hz, H-6b),
1.74 <s, 3H, Me-1); 13C NMR <D2O) d 130.3 <C-4), 125.5
<C-1), 115.2 <C-2), 69.3, 68.3, 67.4 <C-10, C-20, C-30, C-40),
61.2 <C-50), 35.2 <C-5), 28.1, 24.7 <C-3, C-6), 20.5 <Me-1).
Anal. calcd for C12H20NO7Na: C, 46.00; H, 6.43; N, 4.47.
Found: C, 45.77; H, 6.64; N, 4.22.
Solvents were evaporated under reduced pressure below
408C bath temperature. Melting points were determined
with an Electrothermal 8100 apparatus and are uncorrected.
Optical rotations were obtained at 20^28C with a Perkin±
Elmer 241 polarimeter. Infrared spectra were recorded in
the range 4000±600 cm21 with Perkin±Elmer 399 or
Midac FT-IR spectrophotometers. NMR spectra were
recorded at 208C on a Bruker spectrometer AM 400
3.1.3. Sodium salt of 1-C-[)4R,5R)-1,2-dimethyl-4-nitro-
1-cyclohexen-5-yl]-d-manno-pentitol )12). Following the
same procedure described above for the preparation of 10,
compound 511 <1.00 g, 1.94 mmol) led to the title compound
as a white solid <0.58 g, 91%): mp 173±1758C <from metha-
nol/water); Rf 0.70 <3:1 AcOEt/EtOH); [a]Dˆ15.48 <c 0.84,
1
<400.13 MHz for H, 100.62 MHz for 13C) with TMS or
residual CHCl3/DMSO as internal standards. NMR assign-
ments were con®rmed byhomonuclear double-resonance
experiments, and DEPT. Chemical shifts are reported in
ppm and coupling constants are reported in Hz. Mass
spectra were recorded on a VG Autospec spectrometer.
TLC was performed on precoated plates of silica gel 60
GF254 <Merck), with visualisation of spots byUV light or
iodine vapour, and the solvent systems speci®ed. Prepara-
tive thin layer chromatography <p.TLC) was carried out on
0.20 mm Merck silica gel 60F254 plates. Elemental analyses
H2O); nmax <KBr) 3400, 2900, 1585, 1430, 1150, 1120,
1
1010 cm21; H NMR <D2O) d 3.93 <d, 1H, J1 ,5ˆ3.1 Hz,
0
J1 ,2 ˆ9.0 Hz, H-10), 3.88 <dd, 1H, J4 ,5 ˆ1.9 Hz,
0
0
0
0
0
0 0
0
00
J5 ,5 ˆ11.8 Hz, H-5 ), 3.79 <m, 2H, H-3 , H-4 ), 3.66 <dd,
00
0
0
00
1H, J4 ,5 ˆ5.1 Hz, H-5 ), 3.56 <m, 2H, H-2 , H-5), 3.15 <d,
1H, H-3a), 3.00 <d, 1H, J3a,3bˆ22.5 Hz, H-3b), 2.59 <dd, 1H,
J5,6aˆ5.5 Hz, H-6a), 2.15 <d, 1H, J5,6b,1 Hz, J6a,6b
ˆ
17.6 Hz, H-6b), 1.71 <s, 3H, Me), 1.69 <s, 3H, Me); 13C
NMR <D2O) d 127.4 <C-4), 124.4, 122.4 <C-1, C-2), 76.3
<C-10), 71.2, 70.3, 69.2 <C-20, C-30, C-40), 63.3 <C-50), 36.1
<C-5), 34.2, 33.7 <C-3, C-6), 18.2, 17.9 <Me-1, Me-2). Anal.
calcd for C13H22NO7Na: C, 47.70; H, 6.77; N, 4.28. Found:
C, 47.85; H, 6.70; N, 4.04.
Â
were determined bythe Servicio de Microana lisis of our
department.
3.1.1. Sodium salt of 1-C-[)4S,5S)-1,2-dimethyl-4-nitro-
1-cyclohexen-5-yl]-d-galacto-pentitol )10). To a solution
of 1,2,3,4,5-penta-O-acetyl-1-C-[<4S,5S)-1,2-dimethyl-4-
nitro-1-cyclohexen-5-yl]-d-galacto-pentitol 111 <1.00 g,
1.94 mmol) in methanol <15 mL) was added dropwise a
solution of 2 M sodium methoxide in methanol <1 mL,
2.00 mmol). In a few moments, there was apparition of a
3.1.4. 1-C-[)5S)-1,2-Dimethyl-4-acinitro-1-cyclohexen-5-
yl]-d-galacto-pentitol )13). To a solution of compound 10
<0.12 g, 0.35 mmol) in water <1 mL) was added dropwise a

M. V. Gil et al. / Tetrahedron 58 12002) 2167±2173
2171
3:1 mixture of H2SO4/H2O at 2108C until the apparition of a
crystalline product. This solid was rapidly ®ltered and dried
<0.05 g, 45%), showing mp 99±1018C <decomp.); Rf 0.48
<AcOEt); [a]546 varied from 2208 to 08 in 90 min <c 0.37,
H2O); nmax <KBr) 3400, 3300, 3220, 3150, 2960, 2920,
J3a,4aˆ7.0 Hz, J4a,4bˆ16.2 Hz, H-4a), 2.18 <m, 1H, H-4b),
2.16 <s, 3H, OAc), 2.12 <s, 3H, OAc), 2.08 <s, 3H, OAc),
2.04 <s, 3H, OAc), 1.73 <s, 3H, Me-5); 13C NMR <CDCl3) d
170.4, 170.3, 170.1, 169.2 <O±CO±CH3), 132.7 <C-5),
117.2 <C-6), 114.5 <C-7a), 79.2 <C-3), 68.5, 68.1, 67.9
<C-10, C-20, C-30), 61.8 <C-40), 41.8 <C-3a), 34.8 <C-4),
23.9 <C-7), 23.4 <Me-5), 20.7, 20.6 <O±CO±CH3). Anal.
calcd for C20H27NO10: C, 54.41; H, 6.16; N, 3.17. Found:
C, 54.32; H, 6.15; N, 3.20.
1
2850, 1655, 1100, 1040 cm21; H NMR <freshlyprepared
solution in DMSO-d6) d 6.33 <br s, 1H, N±OH), 4.70±4.10
<m, 5H, 5OH), 3.75±3.20 <m, 7H, H-5, H-10, H-20, H-30,
H-40, H-50, H-500), 2.94 <d, 1H, J3a,3bˆ22.5 Hz, H-3a), 2.75
<d, 1H, H-3b), 2.07 <br d, 1H, H-6a), 1.89 <d, 1H,
J6a,6bˆ8.2 Hz, H-6b), 1.62 <s, 3H, Me), 1.60 <s, 3H, Me).
A progressive change in this spectrum could be observed;
3.1.7. )3R,3aR)-3-)10,20,30,40-Tetra-O-acetyl-d-arabino-
tetritol-1-yl)-5,6-dimethyl-)3,3a,4,7)-tetrahydrobenzisoxa-
zoline N-oxide )16). Following the same procedure
described above for the preparation of 14, compound 12
<0.12 g, 0.37 mmol) led to the title compound as a white
solid <0.09 g, 54%): mp 146±1488C <from 96% EtOH); Rf
0.40 <1:1 hexane/AcOEt); [a]Dˆ2119.28 <c 0.49, CHCl3);
nmax <KBr) 2990, 2920, 2860, 1740, 1660, 1365, 1250, 1210,
thus, after 90 min at room temperature, those signals
11
corresponding to previouslydescribed trans- and cis-5-
glyco-4-nitro-1-cyclohexenes <3 and 7, respectively) were
preponderant.
3.1.5. )3S,3aS)-3-)10,20,30,40-Tetra-O-acetyl-d-lyxo-tetritol-
1-yl)-5,6-dimethyl-)3,3a,4,7)-tetrahydrobenzisoxazoline N-
oxide )14). A suspension of the sodium salt of 1-C-
[<4S,5S)-1,2-dimethyl-4-nitro-1-cyclohexen-5-yl]-d-galacto-
pentitol 10 <0.50 g, 1.53 mmol) in pyridine <5 mL) and
acetic anhydride <3 mL) was stirred at room temperature
until dissolution <ca. 1.5 h). Then, the mixture was poured
onto ice cold water <200 mL), yielding the title compound
<0.53 g, 81%) as a white solid which was ®ltered and
washed on the ®lter with cold water: mp 152±1548C
<from 96% EtOH); Rf 0.40 <1:1 hexane/AcOEt);
[a]Dˆ188.08 <c 0.54, CHCl3); nmax <KBr) 2980, 2960,
2920, 2860, 1745, 1670, 1660, 1365, 1200, 1055,
1
1060, 1040, 1020 cm21; H NMR <CDCl3) d 5.51 <dd, 1H,
0
0
0
0
0
0
J1 ,2 ˆ2.4 Hz, J2 ,3 ˆ8.7 Hz, H-2 ), 5.39 <dd, 1H, H-1 ), 5.09
<ddd, 1H, H-30), 4.29 <t, 1H, J3,3a,J3,1 ˆ7.6 Hz, H-3), 4.25
0
0
0
0
0
00
<dd, 1H, J3 ,4 ˆ2.8 Hz, H-4 ), 4.09 <dd, 1H, J3 ,4 ˆ5.0 Hz,
00
0
00
J4 ,4 ˆ12.5 Hz, H-4 ), 3.32 <m, 1H, J3a,4a,J3a,4bˆ7.0 Hz,
H-3a), 2.98 <br d, 1H, J7a,7bˆ21.5 Hz, H-7a), 2.90 <br d,
1H, H-7b), 2.25 <m, 2H, H-4a, H-4b), 2.14 <s, 3H, OAc),
2.13 <s, 3H, OAc), 2.08 <s, 3H, OAc), 2.07 <s, 3H, OAc),
1.71 <s, 3H, Me), 1.66 <s, 3H, Me); 13C NMR <CDCl3) d
170.7, 170.0, 169.2 <O±CO±CH3), 124.3, 122.7 <C-5, C-6),
115.4 <C-7a), 78.5 <C-3), 70.0, 68.1 <C-10, C-20, C-30), 61.7
<C-40), 43.0 <C-3a), 37.3 <C-4), 29.4 <C-7), 20.8, 20.7
<O±CO±CH3), 19.3, 18.8 <Me-5, Me-6). Anal. calcd for
C21H29NO10: C, 55.38; H, 6.42; N, 3.07. Found: C, 55.42;
H, 6.42; N, 3.07.
1025 cm21
;
1H NMR <CDCl3) d 5.51 <dd, 1H,0 J1 ,2
ˆ
0
0
0
0
0
9.2 Hz, J2 ,3 ˆ2.0 Hz, H-2 ), 5.34 <ddd, 1H, H-3 ), 5.25
<dd, 1H, H-10), 4.36 <dd, 1H, J3,3aˆ7.7 Hz, J3,1 ˆ2.3 Hz,
0
0
0
0
0
00
H-3), 4.25 <dd, 1H, J3 ,4 ˆ5.6 Hz, J4 ,4 ˆ11.6 Hz, H-4 ),
00
3.91 <dd, 1H, J3 ,4 ˆ7.1 Hz, H-4 ), 3.17 <m, 1H, H-3a),
2.97 <br d, 1H, J7a,7bˆ21.4 Hz, H-7a), 2.86 <br d, 1H,
H-7b), 2.35 <dd, 1H, J3a,4aˆ7.1 Hz, J4a,4bˆ15.8 Hz, H-
4a), 2.17 <m, 1H, J3a,4bˆ7.1 Hz, H-4b), 2.16 <s, 3H,
OAc), 2.11 <s, 3H, OAc), 2.08 <s, 3H, OAc), 2.04 <s, 3H,
OAc), 1.71 <s, 3H, Me), 1.67 <s, 3H, Me); 13C NMR
<CDCl3) d 170.4, 170.3, 170.1, 169.2 <O±CO±CH3),
124.4, 122.7 <C-5, C-6), 115.3 <C-7a), 79.0 <C-3), 68.5,
68.1 <C-10, C-20, C-30), 61.8 <C-40), 41.8 <C-3a), 36.5 <C-
4), 29.4 <C-7), 20.7, 20.6 <O±CO±CH3), 19.3, 18.8 <Me-5,
Me-6). Anal. calcd for C21H29NO10: C, 55.38; H, 6.42; N,
3.07. Found: C, 55.03; H, 6.40; N, 3.04.
3.1.8. 7-En-)4S)-4-hydroxy-)3R)-3-[)10S,20R)-10,20,30-tri-
hydroxypropyl]-1,8-dimethyl-2-oxabicyclo[3.3.1]nonan-
6-one oxime )19). To a solution of compound 14 <1.00 g,
2.19 mmol) in methanol <12.5 mL) was added dropwise 2 M
sodium methoxide in methanol <0.8 mL). The reaction
mixture was stirred for 1.5 h at room temperature and the
solvent evaporated, yielding the title compound as a white
solid that was recrystallized from methanol <0.57 g, 90%):
mp 137±1398C; Rf 0.50 <5:1 AcOEt/EtOH); [a]Dˆ1158.98
<c 0.48, H2O); nmax <KBr) 3400, 3300, 2970, 2940, 2900,
2860, 1630, 1340, 1030 cm21; 1H NMR <DMSO-d6) d 10.85
0
00
<s, 1H, vN±OH), 6.07 <br s, 1H, H-7), 4.64 <d, 1H, J4,OH
4.9 Hz, OH-4), 4.35 <t, 1H, J3 ,OHˆ4.8 Hz, OH-30), 3.99 <d,
ˆ
0
3.1.6. )3S,3aS)-3-)10,20,30,40-Tetra-O-acetyl-d-lyxo-tetri-
tol-1-yl)-5-methyl-)3,3a,4,7)-tetrahydrobenzisoxazoline-
N-oxide )15). Following the same procedure described
above for the preparation of tetrahydrobenzisoxazoline
N-oxide 14, compound 11 <0.14 g, 0.44 mmol) led to the
title compound as a white solid <0.11 g, 57%): mp 143±
1458C <from 96% EtOH); Rf 0.35 <1:1 hexane/AcOEt);
[a]Dˆ1110.98 <c 0.65, CHCl3); nmax <KBr) 2960, 2920,
2860, 1745, 1670, 1660, 1365, 1240, 1200, 1060, 1040,
1H, J1 ,OHˆ7.6 Hz, OH-10), 3.83 <d, 1H, J2 ,OHˆ7.0 Hz,
0
0
OH-20), 3.65 <m, 1H, J3,1 ˆ8.1 Hz, J1 ,2 ˆ1.5 Hz, H-1 ),
3.61 <m, 1H, J4,5ˆ2.3 Hz, J3,4ˆ1.5 Hz, H-4), 3.55 <m, 1H,
H-20), 3.45±3.25 <m, 4H, H-3, H-30, H-300, H-5), 2.05 <dd,
1H, J9syn,9antiˆ12.5 Hz, J9syn,5ˆ2.4 Hz, H-9syn), 1.36 <dd,
1H, J9anti,5ˆ3.3 Hz, H-9anti), 1.73 <s, 3H, Me-8), 1.20 <s,
3H, Me-1); 13C NMR <DMSO-d6) d 155.5 <C-6), 139.8
<C-8), 124.7 <C-7), 70.7, 70.6, 69.6, 67.6 <C-1, C-4, C-10,
C-20), 63.0 <C-30), 62.2 <C-3), 34.1 <C-5), 31.7 <C-9), 25.0
<Me-1), 18.1 <Me-8). Anal. calcd for C13H21NO6: C, 54.34;
H, 7.37; N, 4.87. Found: C, 53.88; H, 7.49; N, 4.72. CI MS
m/z <rel. int.): 288 <MH1, 44), 272 <M2CH3, 20), 270
<M1H±H2O, 5), 253 <M22OH, 3), 238 <M22OH±CH3,
6), 167 <37), 150 <19), 137 <83), 120 <100). HRMS <CI)
calcd for C13H21NO61H: 288.1447. Found <M1H)1
288.1439.
0
0
0
0
1020 cm21
;
1H NMR <CDCl3) d 5.52 <dd, 1H, J1 ,2
ˆ
0
0
0
0
0
9.3 Hz, J2 ,3 ˆ2.1 Hz, H-2 ), 5.42 <br s, 1H, H-6), 5.34
<ddd, 1H, H-30), 5.25 <dd, 1H, H-10), 4.37 <dd, 1H, J3,3a
ˆ
0
0
0
8.2 Hz, J3,1 ˆ2.0 Hz, H-3), 4.25 <dd, 1H, J3 ,4 ˆ5.5 Hz,
0
00
0
00
0
00
J4 ,4 ˆ11.5 Hz, H-4 ), 3.92 <dd, 1H, J3 ,4 ˆ7.1 Hz, H-4 ),
3.23 <m, 1H, J3a,4bˆ7.0 Hz, H-3a), 3.04 <br d, 1H, J7a,7b
21.9 Hz, H-7a), 2.93 <br d, 1H, H-7b), 2.34 <dd, 1H,
ˆ

2172
M. V. Gil et al. / Tetrahedron 58 12002) 2167±2173
3.1.9.
)4S)-4-O-Acetyl-)3R)-3-[)10S,20R)-10,20,30-tri-O-
<0.08 mL, 0.66 mmol). After the reaction mixture had
been re¯uxed for 14 h, its 1H NMR spectrum showed
about 90% conversion of the starting N-oxide into the title
compound. Then, the crude mixture was evaporated and the
resulting oil was subjected to p.TLC <1:3 hexane/AcOEt),
affording a pure analytical sample of compound 21 <0.05 g):
oil; Rf 0.60 <1:1 hexane/AcOEt);[a]Dˆ1102.58 <c 0.48,
CHCl3); nmax <®lm) 2900, 2840, 1740, 1640, 1360, 1200,
acetylpropyl]-7-en-1,8-dimethyl-2-oxabicyclo[3.3.1]-
nonan-6-one oxime acetate )20). A suspension of
compound 19 <0.10 g, 0.35 mmol) in pyridine <1 mL) and
acetic anhydride <0.5 mL) was stirred at room temperature
until dissolution <ca. 2 h). Then, the mixture was poured
onto ice cold water <100 mL), extracted with methylene
dichloride <3£25 mL) and washed successivelywith 1 M
hydrochloric acid <2£25 mL), saturated aqueous sodium
hydrogencarbonate <2£25 mL) and water <2£25 mL). The
organic layer was dried <MgSO4) and the solvent evapo-
rated, yielding the title compound as a white solid residue
which was recrystallized from 96% ethanol <0.14 g, 78%):
mp 142±1448C; Rf 0.43 <1:1 hexane/AcOEt); [a]Dˆ133.98
<c 0.61, CHCl3); nmax <KBr) 3020, 2970, 2920, 2845, 1740,
1040, 1020 cm21
;
1H NMR <C0DCl3) d 5.56 <dd, 1H,
0
0
0
0
0
J1 ,2 ˆ9.2 Hz, J2 ,3 ˆ1.8 Hz, H-2 ), 5.35 <m, 1H, H-3 ),
0
0
0
0
5.22 <dd, 1H, J3,1 ˆ2.5 Hz, H-1 ), 4.26 <dd, 1H, J3 ,4
ˆ
ˆ
5.3 Hz, H-40), 4.23 <dd, 1H, H-3), 3.92 <dd, 1H, J4 ,4
0
00
00
0
00
11.5 Hz, J3 ,4 ˆ7.2 Hz, H-4 ), 3.07 <dd, 1H, J3,3aˆ17.8 Hz,
J3a,4aˆ7.9 Hz, H-3a), 2.97 <br d, 1H, H-7a), 2.85 <br d, 1H,
J7a,7bˆ19.6 Hz, H-7b), 2.38 <dd, 1H, J4a,4bˆ16.0 Hz, H-4a),
2.19 <m, 1H, H-4b), 2.15 <s, 3H, OAc), 2.07 <s, 6H, 2£OAc),
2.03 <s, 3H, OAc), 1.69 <s, 3H, Me), 1.64 <s, 3H, Me); 13C
NMR <CDCl3) d 170.4, 170.2, 169.3 <O±CO±CH3), 159.1
<C-7a), 124.5, 123.9 <C-5, C-6), 82.4 <C-3), 69.1, 68.8, 68.2
<C-10, C-20, C-30), 61.9 <C-40), 47.2 <C-3a), 37.6 <C-4), 29.6
<C-7), 20.7 <O±CO±CH3), 18.9 <Me-5, Me-6). CI MS m/z
<rel. int.): 440 <MH1, 6), 398 <M1H±C2H2O, 8), 380
<M2OAc, 16), 338 <M2C2H2O±OAc, 13), 320
<M2OAc±HOAc, 4), 259 <M23£HOAc, 8), 192 <21),
150 <M2C12H17O8, 100), 122 <18). HRMS <CI) calcd for
C21H29NO91H: 440.1920. Found <M1H)1 440.1948.
1370, 1230, 1200, 1030, 1000 cm21; H NMR <CDCl3) d
1
0
0
0
00
6.40 <br s, 1H, H-7), 5.49 <ddd, 1H, J2 ,3 ˆ6.3 Hz, J2 ,3
ˆ
1.0 Hz, H-20), 5.31 <dd, 1H, J3,1 ˆ9.6 Hz, J1 ,2 ˆ1.8 Hz,
0
0
0
H-10), 4.73 <t, 1H, J4,5,J3,4ˆ2.5 Hz, H-4), 4.25 <dd, 1H,
J2 ,3 ˆ4.8 Hz, J3 ,3 ˆ11.7 Hz, H-30), 3.86 <dd, 1H,
0
0
0
0000
0
00
J2 ,3 ˆ7.5 Hz, H-3 ), 3.68 <dd, 1H, H-3), 3.66 <m, 1H,
H-5), 2.23 <s, 3H, vN±OAc), 2.10 <s, 3H, OAc), 2.05 <s,
3H, OAc), 2.02 <s, 3H, OAc), 2.02 <m, 1H, H-9syn), 2.00 <s,
3H, OAc), 1.82 <d, 3H, JMe-8,H-7ˆ1.2 Hz, Me-8), 1.66 <dd,
1H, J9anti,9synˆ13.3 Hz, J9anti,5ˆ3.2 Hz, H-9anti), 1.37 <s,
3H, Me-1); 13C NMR <CDCl3) d 170.4, 170.1, 169.7,
168.3 <O±CO±CH3, vN±O±CO±CH3), 161.3 <C-6),
147.2 <C-8), 123.4 <C-7), 71.6 <C-1), 68.7, 68.2, 67.3
<C-4, C-10, C-20), 63.8 <C-3), 62.5 <C-30), 33.4 <C-5), 32.0
<C-9), 24.5 <Me-1), 21.0, 20.6, 20.5, 19.3 <O±CO±CH3,
vN±O±CO±CH3), 18.7 <Me-8). Anal. calcd for
C23H31NO11´1/2H2O: C, 54.54; H, 6.36; N, 2.76. Found:
C, 54.26; H, 6.12; N, 2.55.
3.1.12. )3R,3aR)-3-)10,20,30,40-Tetra-O-acetyl-d-arabino-
tetritol-1-yl)-5,6-dimethyl-)3,3a,4,7)-tetrahydrobenzisoxa-
zoline )22). Following the same procedure described above
for the preparation of 21, compound 16 <0.24 g, 0.53 mmol)
afforded 88% 1H NMR yield of the title compound. A pure
analytical sample of 22 <0.03 g) was obtained byp.TLC <1:3
hexane/AcOEt): oil; Rf 0.60 <1:1 hexane/AcOEt); [a]Dˆ
2125.58 <c 0.51, CHCl3); nmax <®lm) 3000, 2900, 2850,
3.1.10. )3R,3aR)-3-)d-arabino-Tetritol-1-yl)-5,6-dimethyl-
)3,3a,4,7)-tetrahydrobenzisoxazoline
1
1745, 1660, 1430, 1360, 1240, 1050, 1020 cm21; H NMR
N-oxide
)18).
0
0
0
0
0
<CDCl3) d 5.55 <dd, 1H, J1 ,2 ˆ2.8 Hz, J2 ,3 ˆ8.5 Hz, H-2 ),
Following the same procedure described above for the
preparation of 19, treatment of a solution of 16 <0.30 g,
0.66 mmol) in methanol <5 mL) with 2 M methanolic
sodium methoxide led to the title compound as a white
solid <0.19 g, quantitative): mp 218±2208C <from metha-
nol/water); Rf 0.50 <2:1 AcOEt/EtOH); [a]Dˆ298.88 <c
0.52, H2O); nmax <KBr) 3300, 2920, 2880, 1670, 1400,
5.30 <dd, 1H, H-10), 5.11 <m, 1H, H-30), 4.26 <dd, 1H,
J3 ,4 ˆ2.8 Hz, J4 ,4 ˆ12.4 Hz, H-40), 4.20 <t, 1H,
0
0
0
00
0
0
00
J3,3a,J3,1 ˆ7.3 Hz, H-3), 4.10 <dd, 1H, J3 ,4 ˆ5.5 Hz,
H-400), 3.21 <m, 1H, J3a,4a,J3a,4bˆ7.6 Hz, H-3a), 2.95 <br
d, 1H, J7a,7bˆ20.8 Hz, H-7a), 2.93 <br d, 1H, H-7b), 2.25
<m, 2H, H-4a, H-4b), 2.17 <s, 3H, OAc), 2.14 <s, 3H, OAc),
2.10 <s, 3H, OAc), 2.06 <s, 3H, OAc), 1.69 <s, 3H, Me), 1.64
<s, 3H, Me); 13C NMR <CDCl3) d 170.6, 170.1, 169.9, 169.3
<O±CO±CH3), 159.3 <C-7a), 124.5, 124.0 <C-5, C-6), 82.4
<C-3), 70.5, 68.7, 68.2 <C-10, C-20, C-30), 61.8 <C-40), 58.5
<C-3a), 38.2 <C-4), 29.9 <C-7), 20.8, 20.7 <O±CO±CH3),
19.0, 18.9 <Me-5, Me-6). CI MS m/z <rel. int.): 440 <MH1,
18), 398 <M1H±C2H2O, 8), 380 <M2OAc, 17), 338
<M2C2H2O±OAc, 8), 320 <M2OAc±HOAc, 8), 259
<M23£HOAc, 8), 192 <23), 150 <M2C12H17O8, 100), 122
<24). HRMS <CI) calcd for C21H29NO91H: 440.1920.
Found <M1H)1 440.1909.
1240, 1080, 1060, 1020, 1005 cm21; H NMR <DMSO-d6)
1
0
0
0
d 4.27 <t, 1H, J3,3a,J3,1 ˆ6.6 Hz, H-3), 3.83 <d, 1H, J1 ,2
ˆ
1.0 Hz, H-10), 3.60 <dd, 1H, J3 ,4 ˆ2.7 Hz, J4 ,4 ˆ11.1 Hz,
0
0
0
00
H-40), 3.47 <m, 1H0,0 H-30), 3.43 <m, 1H, H-3a), 3.41 <dd, 1H,
0
0
00
0
0
J3 ,4 ˆ6.5 Hz, H-4 ), 3.28 <d, 1H, J2 ,3 ˆ8.7 Hz, H-2 ), 2.88
<br d, 1H, H-7a), 2.74 <br d, 1H, J7a,7bˆ21.3 Hz, H-7b), 2.34
<dd, 1H, J3a,4aˆ7.2 Hz, J4a,4bˆ16.4 Hz, H-4a), 2.15 <dd, 1H,
J3a,4bˆ11.1 Hz, H-4b), 1.62 <s, 3H, Me), 1.58 <s, 3H, Me);
13C NMR <DMSO-d6) d 126.0 <C-7a), 122.7, 120.3 <C-5,
C-6), 82.8 <C-3), 71.4, 71.0, 70.1 <C-10, C-20, C-30), 64.0
<C-40), 43.2 <C-3a), 37.9, 29.6 <C-7, C-4), 19.9, 19.3 <Me-5,
Me-6). Anal. calcd for C13H20NO6: C, 54.54; H, 7.04; N,
4.89. Found: C, 54.78; H, 7.11; N, 5.05.
Acknowledgements
3.1.11. )3S,3aS)-3-)10,20,30,40-Tetra-O-acetyl-d-lyxo-tetri-
tol-1-yl)-5,6-dimethyl-)3,3a,4,7)-tetrahydrobenzisoxazo-
line )21). To a solution of <3S,3aS)-3-<10,20,30,40-tetra-O-
acetyl-d-lyxo-tetritol-1-yl)-5,6-dimethyl-<3,3a,4,7)-tetra-
hydrobenzisoxazoline N-oxide 14 <0.24 g, 0.53 mmol) in
1,4-dioxane <3 mL) was added trimethyl phosphite
This work was supported bythe Spanish Ministerio de
Â
Educacion yCultura <CICYT, PB98-0997) and the Junta
de Extremadura-Fondo Social Europeo through grants
IPR98A066 and IPR00C021. We also thank the Unidad de
 Â
Espectrometrõa de Masas de la Universidad de Cordoba

M. V. Gil et al. / Tetrahedron 58 12002) 2167±2173
2173
14. Similar results <i.e. the same ratios between epimers) were
obtained when the starting materials were deacetylated
derivatives of compounds 1, 2, or 5, or their C-4 epimers
<either deacetylated or pentaacetylated).
<Spain) for mass spectra, and Professor Pedro Cintas
<Universidad de Extremadura) for his help.
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17. Chemical shift for this signal is at somewhat lower ®eld than is
usual for hydroxyl protons in alcohols <0.5±5.5 ppm):
Jackman, L. M.; Sternhell, S. Applications of Nuclear
Magnetic Resonance Spectroscopy in Organic Chemistry;
2nd ed; Pergamon: Oxford, 1969; p 216.
Moreover, a similar D2O-exchangeable signal was encoun-
1
tered at 7.68 ppm in the H NMR spectrum of a DMSO-d6
freshlyprepared solution of nitronate 12.
18. In a similar experiment with 0.1 M DCl as the solvent, the
solid we obtained was the corresponding cis-4-nitro-5-<d-
galacto-pentitol-1-yl)-1-cyclohexene deuterated at C-4. This
compound, as well as its penta-O-acetyl derivative, showed 1H
NMR spectra in which the signal of H-4 was absent.
Â
5. Areces, P.; Gil, M. V.; Higes, F. J.; Roman, E.; Serrano, J. A.
Tetrahedron Lett. 1998, 39, 8557.
Â
6. Gil, M. V.; Roman, E.; Serrano, J. A. Tetrahedron Lett. 2000,
41, 3221.
7. Kanemasa, S.; Tsuge, O. Heterocycles 1990, 30, 719.
Â
19. Gil, M. V.; Roman, E.; Serrano, J. A. Tetrahedron Lett. 2000,
41, 10201.
Â
8. Mancera, M.; Roffe, I.; Galbis, J. A. Tetrahedron 1995, 51,
6349.
20. We found that these down®eld acylation shifts were about
1.5 ppm for protons on secondarycarbons <H-1 0, H-20,
H-30), 0.5 ppm for those on primary<H-4 0, H-400) and
0.4 ppm for H-3. For a discussion on acylation shifts, see
Ref. 17, p 176.
9. <a) Sweeney, M. J.; Davis, F. A.; Gutowski, G. E.; Hamill,
R. L.; Huffman, D. H.; Poore, G. A. Cancer Res. 1973, 33,
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22. Miyashita, M.; Awen, B. Z. E.; Yoshikoshi, A. Tetrahedron
1990, 46, 7569.
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10. Roman, E.; BanÄos, M.; Gutierrez, J. I.; Serrano, J. A.
J. Carbohydr. Chem. 1995, 14, 703.
11. Serrano, J. A.; Moreno, M. Ch.; Roman, E.; Arjona, O.;
Â
23. Gil, M. V.; Roman, E.; Serrano, J. A. Symposium papers,
Second EuroConference on Carbohydrates in Drug Research,
C17, Estoril, Portugal, 2000.
24. McKillop, A.; Kobylecki, R. J. Tetrahedron 1974, 30, 1365.
Â
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Plumet, J.; Jimenez, J. J. Chem. Soc., Perkin Trans. 1 1991,
3207.
12. Serrano, J. A.; Roman, E. J. Org. Chem. 1989, 54, 6114.
Â
25. Melot, J. M.; Texier-Boullet, F.; Foucaud, A. Synthesis 1988,
558.
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13. We did not observe either epimerization or changes in the pH
values during the reactions between a catalytic amount of
sodium methoxide and pentaacetylated trans-6-glyco-5-
nitro-2-norbornenes. The onlyproducts, isolated in quantita-
tive yields, were their respective trans-deacetylated
derivatives.
26. TLC of the reaction mixtures in various solvents always
showed similar Rf values for the products, the starting
materials and for the by-products. Furthermore, changes in
the re¯uxing time or in the concentration of the reactants led
to poorer results.