Synthesis of enantiopure pyranoisoxazole and oxepanoisoxazole derivatives from O-alkynyl carbohydrate ethers by the application of intramolecular nitrile oxide cycloaddition

Article abstract of DOI:10.1055/s-1999-3579

A useful synthesis of enantiomerically pure pyrano- and oxepanoisoxazole derivatives by the application of intramolecular cycloaddition of 3-O-alkynyl carbohydrate nitrile oxides is described. One of the isoxazole derivatives was transformed to a furylpyran system having the lasalocid A skeleton using 2-O-allyl carbohydrate nitrone cycloaddition.

Full text of DOI:10.1055/s-1999-3579

PAPER
1569
Synthesis of Enantiopure Pyranoisoxazole and Oxepanoisoxazole Derivatives
from O-Alkynyl Carbohydrate Ethers by the Application of Intramolecular
Nitrile Oxide Cycloaddition
Arani Pal, Ashoke Bhattacharjee, Anup Bhattacharjya*
Indian Institue of Chemical Biology, 4, Raja S. C. Mullick Road, Calcutta- 700032, India
Fax+91(33)4730284; E-mail: iichbio@giascl01.vsnl.net.in
Received 1 April 1999; revised 19 May 1999
formation of the nitrile oxides 8 and 9, which underwent
Abstract: A useful synthesis of enantiomerically pure pyrano- and
cycloaddition in situ.
oxepanoisoxazole derivatives by the application of intramolecular
cycloaddition of 3-O-alkynyl carbohydrate nitrile oxides is de- The formation of the isoxazole 10 was evident from the
scribed. One of the isoxazole derivatives was transformed to a fu-
rylpyran system having the lasalocid A skeleton using 2-O-allyl
carbohydrate nitrone cycloaddition.
appearance of a one-proton singlet at δ = 8.28 due to the
proton attached to the isoxazole nucleus in the H NMR
1
spectrum as well as a quaternary carbon at δ = 154.3 and
Key words: cycloaddition, 3-O-alkynyl carbohydrate nitrile oxides,
chiral isoxazoles, lasalocid A
13
a methine carbon at δ = 150.9 in the C NMR spectrum
of 10. Similarly appearance of singlets at δ = 155.3 and
13
1
61.8 in the C NMR spectrun of 11 was consistent with
the presence of the isoxazole nucleus. Inspite of the pres-
ence of four chiral centres in 10 and 11, due to the pres-
ence of the isoxazole nucleus and the rigidly
Utilization of naturally occurring chiral compounds as
starting materials in the synthesis of enatiomerically pure
compounds is well established. Recently application of
1
1
functionalized cyclic ether moiety, the H NMR spectra of
intramolecular 1,3-dipolar cycloaddition of nitrones and
nitrile oxides derived from O-alkenyl carbohydrate deriv-
atives has proved to be an important strategy for the syn-
thesis of chiral cyclic ether fused isoxazolidines and
1
0 and 11 exhibited first order spectral behaviour even in
the 100 MHz field strength.
The presence of the diisopropylidene ring in the above
isoxazole derivatives makes these compounds amenable
to modifications giving rise to important structural skele-
tons. As a demonstration, the pyranoisoxazole 10 was
treated with methanol in the presence of p-toluenesulfonic
acid to give 12 as a mixture of diastereomers. A sequence
of allylation with allyl bromide afforded 13 and deglyco-
sylation by treatment with aqueous trifluoroacetic acid af-
forded 14. As 14 is a hemiacetal, its reaction with N-
methylhydroxylamine led to the formation of 16 incorpo-
2
, 3
isoxazolines. The particular importance of isoxazole
derivatives as medicinally important compounds has led
us to investigate the possibility of preparing the aforemen-
tioned compounds in enatiomerically pure forms through
cycloaddition of nitrile oxides derived from O-alkynyl
carbohydrate derivatives, and we describe herein the ap-
plication of such a methodology to the synthesis of enan-
tiopure pyranoisoxazoles, oxepanoisoxazoles and a
compound having the furylpyran skeleton characteristic
of lasalocid A and its congeners.
6
rating a furylpyran system via the cycloaddition of the ni-
trone 15. The structure of 16 was secured from H and C
NMR spectral analyses. The appearance of a three proton
singlet due to the NCH at δ = 2.73 in the H NMR spec-
1
13
The well known 1,2:5,6-diisopropylidene-α-D-glucofura-
noside (1) was converted to the corresponding O-propar-
1
3
4
13
gyl ether 2 in 90% yield by alkylation with propargyl
trum and a peak due to the NCH at δ = 43.3 in the
C
3
bromide in the presence of tetrabutylammonium bromide
in a biphasic medium consisting of dichloromethane and
spectrum of 16 as well as absence of peaks due to the allyl
moiety was indicative of the occurrence of cycloaddition.
The stereochemistry of the ring juncture of the furoisox-
azolidene system in 16 was assigned on the basis of anal-
ogy with related systems obtained from similar
cycloadditions. It is worthy of mention that the furylpyr-
an skeleton present in 16 constitutes the structural frame-
work of lasalocid A and its congeners, and 16 thus
represents a potentially useful molecule for developing
structural analogs of the aforementioned compounds.
5
0% aqueous NaOH solution (Scheme). Reaction of 2
with butyllithium followed by treatment with methyl io-
dide afforded the 3-O-butynyl ether 3 in 50% yield
6
(
4
Scheme). Both 2 and 3 were converted to the aldehydes
and 5 following standard procedures involving selec-
5
7
tive deprotection by treatment with 75% aqueous acetic
acid and subsequent oxidation with sodium metaperiodate
(
Scheme). Oximation of 4 and 5 with hydroxylammonium
chloride in pyridine/methanol gave the corresponding
oximes 6 and 7. In contrast to the purification of oxime 6,
that of 7 proved to be difficult, and 7 was used without pu-
rification in the next step. Oxidation of the oxime 6 and 7
with chloramine-T in refluxing alcohol gave the isoxazole
derivatives 10 (84%) and 11 (53%) respectively, via the
In a separate route, the aldehyde 4 was converted to the ni-
tro derivative 17 according to a known protocol
8
(
Scheme). Treatment of 17 with phenyl isocyanate at
2
5 °C resulted in the formation of the oxepanoisoxazole
derivative 19 in 28% yield via the cycloaddition of the ni-
1
trile oxide 18. A one-proton singlet at δ = 8.16 in the H
Synthesis 1999, No. 9, 1569–1572 ISSN 0039-7881 © Thieme Stuttgart · New York

1
570
A. Pal et al.
PAPER
trum of 19 is the appearance of a set of two doublets of
doublets due to the 4-CH , which is fully consistent with
2
the assigned structure.
In conclusion, although the work described here involved
alkynyl nitrile oxides generated from isopropylidene-
dioxy carbohydrate derivatives, the strategy is expected to
be general and bears significant potential for further appli-
cations related to the synthesis of chiral isoxazoles.
Melting points were determined in open capillaries and are uncor-
1
13
rected. Unless otherwise mentioned all H and C NMR spectra
were recorded at 100 and 25 MHz, respectively, using CDCl as sol-
3
vent and TMS as the internal standard. Mass spectra were run on EI
mode at 70 ev. Elemental analysis was performed at Indian Associ-
ation for the Cultivation of Science, Calcutta, India. Organic ex-
tracts were dried over anhyd Na SO and concentrated under
2
4
reduced pressure using a rotary evaporater. Unless otherwise men-
tioned, silica gel (60–120 mesh) was used for column chromatogra-
phy. Petroleum ether refers to the fraction having bp 60–80 °C.
1
,2:5.6-Diisopropylidene-3-O-propargyl-α-D-glucose (2)
To a solution of 1 (5g, 19 mmol) and propargyl bromide (80% in tol-
uene, 2.5 mL) in CH Cl (40 mL) was added 50% aq NaOH solution
2
2
(
40 mL) and the mixture was stirred vigorously. Bu NBr (0.6g, 1.9
4
mmol) was then added to this mixture and stirring was continued for
further 15 h at 25 °C. The organic layer was separated and the aque-
ous layer was extracted with CH Cl . The combined organic ex-
2
2
tracts were washed with H O, dried and evaporated to give an oil,
2
which was chromatographed over neutral alumina using EtOAc/pe-
troleum ether (1:9) as eluent to give 2 (90%) as a pale yellow oil;
2
8
[
α]D −18.6 (c = 0.84, CHCl3).
−1
IR (neat): ν = 3274, 2120 cm .
1H NMR: δ = 1.24 (s, 3H), 1.28 (s, 3 H), 1.36 (s, 3 H), 1.44 (s, 3 H),
2
.40 (br s, 1 H), 3.84–4.12 (m, 5 H), 4.22 (d, J = 3 Hz, 2 H), 4.58 (d,
J = 4Hz, 1 H), 5.82 (d, J = 4 Hz, 1 H)
MS: m/z = 297 (M+−1), 283 (M+−15).
1
,2:5.6-Diisopropylidene-3-O-(buty-2-nyl) -α-D-glucose (3)
To a solution of 2 (2.3 g, 8 mmol) in THF (35 mL), cooled to −40 °C
was added BuLi (15% in hexane, 10 mL), and the mixture was al-
lowed to stir at −40 °C for 1.5 h, after which MeI (1 mL) was added
and stirred for further 2 h. The mixture was then poured into H O
2
and concentrated. The residual solution was extracted with Et O
2
and dried. The residue obtained after removal of solvent was chro-
Reagents and conditions: a) propargyl bromide/CH Cl /50% aq
matographed using EtOAc/petroleum ether (1:9 to 2:8) affording 3
2
2
2
8
NaOH/Bu NBr, 25 °C, 15 h, 90%; b) MeI/BuLi/THF, –40 °C, 1.5 h,
(1.2g, 50%) as a pale yellow syrupy liquid; [α]D +2.1 (c = 0.38,
4
5
2
7
0%; c) 75% aq AcOH, 25 °C, 15 h; d) NaIO /MeOH/H O, 0 to
4 2
CHCl3).
IR (neat): ν = 2230 cm−1.
1H NMR: δ = 1.32 (s, 3 H), 1.36 (s, 3 H), 1.44 (s, 3 H), 1.52 (s, 3 H),
1.88 (br s, 3 H), 4.00–4.42 (m, 7 H), 4.64 (d, J = 4 Hz, 1 H), 5.92 (d,
J = 4 Hz, 1 H).
5 °C, 2 h; e) NH OH•HCl/pyridine/MeOH, reflux, 5 h, 6:68%,
2
:60%; f) chloramine-T/MeOH, reflux, 7 h, 10:84%, 11:53%; g)
TsOH/MeOH, reflux, 6 h, 90%; h) allyl bromide/NaH/THF, 0 to
5 °C, 15 h, 66%; i)50% aq CF CO H, 25 °C, 24 h; j) MeNHOH•HCl/
2
3
2
NaHCO /80% aq EtOH, reflux, 20 h, 39%; k) nitromethane/KF/pro-
3
pan-2-ol, 25 °C, 15 h; l) Ac O/CH Cl /DMAP, 25 °C, 15 h; m)
2
2
2
NaBH /EtOH, 0 to 25 °C, 15 h, 48%; n) PhNCO/Et N/benzene,
4
3
Oximes 6 and 7; General Procedure
2
5 °C, 48 h, 28%
Aldehydes 4 and 5: A solution of 2 or 3 (27 mmol) in 75% aq HOAc
(40 mL) was stirred for 15 h at 25 °C. The mixture was then concen-
trated and the residue was coevaporated with toluene (3 ´ 50 mL)
in order to remove AcOH. The residue was chromatographed over
silica gel using EtOAc as eluent to give a colourless syrup. To a
Scheme
NMR spectrum and quaternary carbon peaks at δ = 117.0 methanolic solution of the above material cooled to 0 °C was added
and 158.7 and a methine carbon at δ = 153.5 in the 13
C
dropwise a solution of NaIO (19 mmol) in H O (50 mL) with stir-
ring, which was continued at 0 °C for 30 min and at 25 °C for 2 h.
The mixture was filtered and the filtrate was concentrated under re-
4
2
NMR spectrum of 19 clearly indicated the presence of the
1
isoxazole nucleus. Another feature of the H NMR spec-
Synthesis 1999, No. 9, 1569–1572 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Enantiopure Pyranoisoxazole and Oxepanoisoxazole Derivatives
1571
duced pressure. The residue was extracted with CHCl and dried.
(5aS,6R,7R,8aR)-3-Methyl-5a,6,7,8a-tetrahydro-6,7-isopropy-
lidenedioxy-4H-furo[2’,3’:5,6]pyrano[4,3-c]isoxazole (11)
Yield:53%; white needles; mp 134–135 °C; [α]D +30.9 (c = 0.7,
3
Removal of solvent afforded the aldehyde 4 or 5 as a colourless syr-
upy liquid, which was used immediately for the next step without
any purification.
2
8
CHCl3).
Aldehyde 4
IR (neat): n = 2120, 1738 cm .
1H NMR: δ = 1.36 (s, 3 H), 1.56 (s, 3 H), 2.36 (s, 3 H), 4.08 (d, J = <
2 Hz, 1 H), 4.46 (d, J = 14 Hz, 1 H), 4.68 (d, J = 4 Hz, 1 H), 4.82
-
1
(
d, J = 14 Hz, 1 H), 5.16 (d, J = < 2 Hz, 1 H), 6.00 (d, J = 4 Hz, 1 H).
Aldehyde 5
IR (neat): n = 2236, 1739 cm .
-
1
13C NMR: δ = 11.1 (quartet), 26.2 (quartet), 26.7 (quartet), 60.6 (t),
6
1
8.8 (d), 80.2 (d), 83.4 (d), 105.9 (d), 108.3 (s), 112.2 (s), 155.3 (s),
61.8 (s).
Oximes 6 and 7: A solution of the aldehyde 4 or 5, NH OH•HCl (10
mmol) and pyridine (5 mL) in MeOH (25 mL) was refluxed for 5 h.
Solvent was removed and the residue was extracted with CHCl3.
2
MS: m/z = 253 (M+).
The organic layer was washed with H O, dried and concentrated to
give the oxime 6 or 7 as a syrup which was used directly for the next
step.
2
Anal. Calcd. for C H NO : C, 56.90; H, 5.97; N, 5.53. Found C,
1
2
5
5
5
6.83; H, 5.88; N, 5.12.
Oxime 6
Yield: 68%; pale yellow syrup.
IR (neat): ν = 3400, 3286, 2120 cm .
1H NMR (mixture of syn and anti isomers): δ = 1.32 (s, 3 H), 1.48
(5aS,6R,7R/S,8aR)-5a,6,7,8a-Tetrahydro-6-hydroxy-7-meth-
oxy-4H-furo[2’,3’:5,6]pyrano[4,3-c]isoxazole (12)
A solution of 10 (1.7 g, 7.1 mmol) and TsOH (0.15g) in MeOH (25
mL) was refluxed for 6 h. The mixture was cooled to 0 °C and neu-
−1
tralized with aq satd NaHCO solution and then concentrated. The
(
4
s, 3 H), 2.48 (m, 1 H), 4.20 (m, 2.5 H), 4.48 (d, J = 2 Hz, 0.5 H),
.68 (d, J = 4 Hz, 1 H), 4.72–4.84 (m, 0.5 H, partly overlapped with
3
residue was extracted with EtOAc (5 x 20 mL) and the combined or-
ganic extracts were dried. Removal of solvent yielded a colourless
oil which was chromatographed over silica gel using EtOAc as elu-
the doublet at 4.68), 5.24 (t, J = 4 Hz, 0.5 H), 5.98 (d, J = 4 Hz, 1
H), 6.92 (d, J = 4 Hz, 0.5 H), 7.48 (d, J = 6 Hz, 0.5 H).
2
8
ent giving 12 (90%) as white granules; mp 82–83 °C; [α]D −14.5
c = 1.59, CHCl3).
1
3
C NMR (75 MHz):d = 26.10, 26.62, 26.67, 57.46, 57.55, 75.20,
5.44, 75.60, 77.54, 78.53, 81.06, 81.87, 82.01, 82.31, 83.09,
04.53, 105.00, 105.39, 111.93, 112.085, 112.19, 146.91, 148.73,
51.43.
(
7
1
1
−1
IR (KBr): ν = 3984, 3728, 3580,1613 cm .
1H NMR (300 MHz, mixture of diastereomers): δ = 3.22 (d, J = 4.8
MS: m/z = 241 (M+).
Hz, 0.5 H), 3.29 (s, 1.5 H), 3.55 (br m, 0.5 H), 3.59 (s, 1.5 H), 4.13
(
d, J = 2.1 Hz, 0.5 H), 4.17 (d, J = 3.9 Hz, 0.5 H), 4.35 (br m, 1 H),
Anal. calcd. for C H NO : C, 54.76; H, 6.27; N, 5.80. Found C,
1
1
15
5
4
4
.49 (t, J = 14.3, 10.2 Hz, 1 H), 4.92 (dd, J = 14.3, 10.2 Hz, 1 H),
.99 (s, 0.5 H), 5.16 (d, J = 3.1 Hz, 0.5 H), 5.19 (d, J = 4.4 Hz, 0.5
5
4.60; H, 6.18; N, 5.15.
Oxime 7
Yield:60%; dark red oil mixed with unidentifed impurities.
H), 5.26 (d, J = 4.1Hz, 0.5 H), 8.25 (s, 0.5 H), 8.27 (s, 0.5 H).
13
C NMR (75 MHz, mixture of diastereomers): δ = 55.7 (CH ), 56.4
3
−1
IR (neat): ν = 3400, 2230 cm .
(CH ), 59.7 (CH , 59.9 (CH ), 66.8 (CH), 69.4 (CH), 76.2 (CH),
3
2)
2
1H NMR: δ = 1.32 (s, 3 H), 1.50 (s, 3 H), 1.84 (t, J = < 2 Hz, 3 H),
79.4 (CH), 81.9 (CH), 82.5 (CH), 103.2 (CH), 110.9 (CH), 112.8
quartet), 151.2 (CH), 151.4 (CH), 155.3 (quartet), 156.2 (quartet).
(
4
4
5
.16 (m, 2.5 H), 4.46 (d, J = 4 Hz, 0.5 H), 4.68 (d, J = 4 Hz, 1 H),
.72–4.84 (m, 0.5 H, partly overlapped with the doublet at 4.68),
.24 (t, J = 4 Hz, 0.5 H), 5.98 (br d, J = 4 Hz, 1 H), 6.92 (d, J = 4
Anal. Calcd. for C H NO : C, 50.70; H, 5.20; N, 6.57. Found C,
9
11
5
50.70; H, 5.16; N, 6.42.
Hz, 0.5 H), 7.52 (d, J = 6 Hz, 0.5 H).
(
5aS,6R,7R/S,8aR)-6-Allyloxy-5a,6,7,8a-tetrahydro-7-methoxy-
Isoxazoles 10 and 11; General Procedure
4H-furo[2’,3’:5,6]pyrano[4,3-c]isoxazole (13)
A mixture of the oxime 6 or 7 (1.25 mmol), MeOH (10 mL) and
chloramine-T hydrate (98%, 342 mg, 1.5 mmol) was refluxed for 7
h. After removal of solvent, the residue was extracted with CH Cl .
To a suspension of oil-free NaH (74 mg, 3 mmol) in THF (5 mL)
cooled to 0 °C was added a solution of 12 (440 mg, 2 mmol) with
stirring followed by addition of allyl bromide (0.5 mL, 5 mmol) at
0 °C. The mixture was allowed to come to 25 °C and stirring was
continued for 15 h. Excess NaH was destroyed by careful addition
of ice and THF was removed under reduced pressure. The residue
was extracted with CH Cl , washed with H O and dried. Removal
2
2
The organic extract was washed successively with aq 1 N NaOH,
H O, brine and dried. Removal of solvent gave a syrup which was
2
chromatographed over silica gel using EtOAc/petroleum ether (2:8)
as eluent to furnish the pyranoisoxazole derivatives.
2
2
2
of solvent yielded a colourless syrup which was chromatographed
(
5aS,6R,7R,8aR)-5a,6,7,8a-Tetrahydro-6,7-isopropylidene-
over silica gel using CHCl /petroleum ether (1:1) as eluent yielding
3
dioxy-4H-furo[2’,3’:5,6]pyrano[4,3-c]isoxazole (10)
2
8
Yield:84%; white needles; mp 152–153 °C; [α]D28+42.0 (c = 0.7,
13 (66%) as white needles; mp 102–103 °C; [α] +34.6 (c = 1.57,
D
CHCl3).
CHCl3).
−1
1H NMR: δ = 1.36 (s, 3 H), 1.56 (s, 3 H), 4.14 (d, J = 2 Hz, 1 H),
4
Hz, 1 H), 5.24 (d, J = 2 Hz, 1 H), 6.02 (d, J = 4 Hz, 1 H), 8.24 (s, 1
H).
IR (KBr): ν = 1648, 1613, 1367 cm .
1H NMR (300 MHz, mixture of diastereomers): δ = 3.56 (s, 3 H),
4.11 (dd, J = 4.4, 2.8 Hz, 1 H), 4.18 (d, J = 5.9 Hz, 2 H), 4.32 (dd,
J = 4.4, 2.7 Hz, 1 H), 4.49 (d, J = 14.2 Hz, 1 H), 4.86 (d, J = 14.1
Hz, 1 H), 5.11 (d, J = 4.7 Hz, 1 H), 5.16 (d, J = 4.5 Hz, 1 H), 5.26
.54 (dd, J = 14, <2 Hz, 1 H), 4.72 (d, J = 4 Hz, 1 H), 4.94(d, J = 14
1
3
C NMR (50 MHz): δ = 26.3 (CH ), 26.9 (CH ), 60.3 (CH ), 68.2
3
3
2
(
8
d, J = 9.0 Hz, 1 H), 5.34 (dd, J = 17.2, 1.2 Hz, 1 H), 5.97 (m, 1 H),
.26 (s, 1 H).
(
CH), 80.4 (CH), 105.9 (CH), 112.1 (quaternary), 112.3 (quaterna-
ry), 150.9 (CH), 154.3 (quaternary).
13C NMR (75 MHz): δ = 55.8 (CH
CH ), 80.9 (CH), 83.7 (CH), 102.5 (CH), 113.1 (quartet), 118.5
), 59.4 (CH ), 65.9 (CH), 72.2
2
+
3
Mass: m/z = 239 (M ), 224 (M+− 15).
(
2
Anal. calcd. for C H NO : C, 55.22; H, 5.48; N, 5.85. Found C,
5
1
1
13
5
(CH ), 133.9 (CH), 151.3 (CH), 155.7 (quartet).
2
5.28; H, 5.49; N, 5.46.
Synthesis 1999, No. 9, 1569–1572 ISSN 0039-7881 © Thieme Stuttgart · New York

1
572
A. Pal et al.
PAPER
1
Anal. Calcd. for C H NO : C, 56.91; H, 5.97; N, 5.53. Found C,
H NMR (300 MHz): d = 1.32 (s, 3 H), 1.49 (s, 3 H), 2.37 (m, 2 H),
1
2
15
5
5
6.91; H, 5.60; N, 5.36.
2.52 (t, J = 2.2 Hz, 1 H), 4.04 (d, J = 3.2 Hz, 1 H), 4.16–4.33 (m, 3
H), 4.54–4.62 (m, 3 H), 5.88 (d, J = 3.8 Hz, 1 H).
Furylpyran Derivative 16
13
C NMR (75 MHz): d = 26.5 (CH ), 26.5 (CH , overlapping), 27.1
3 2 2
3
2
A solution of 13 (530 mg, 2.09 mmol) in 50% aq TFA (5 mL) was
stirred at r.t. for 24 h. After completion of reaction (24 h) as indicat-
ed by TLC, the mixture was neutralized at 0 °C by careful addition
of aq NaHCO solution, and then extracted with CHCl , washed
(CH ), 57.6 (CH ), 72.7 (CH ), 75.9 (CH), 76.9 (CH), 79.1 (quar-
tet), 82.1 (CH), 82.4 (CH), 105.1 (CH), 112.2 (CH).
Anal. Calcd. for C H NO : C, 53.13; H, 6.32; N, 5.17. Found C,
1
2
17
6
3
3
5
3.20; H, 6.24; N, 4.73.
with H O and dried. Removal of solvent yielded 14 as a brown syr-
2
up, which was used without purification for the next step.
(
5aS,6R,7R,8aR)-5a,6,7,8a,9-Pentahydro-6,7-isopropylidene-
Compound 14
dioxy-4H-furo[2’,3’:6,7]oxepano [4,3-c]isoxazole (19)
A solution of 17 (400 mg, 1.47 mmol), PhNCO (1.6 mL, 14.7
mmol) and Et N (2 mL, 14.3 mmol) in benzene (25 mL) was stirred
at 25 °C for 48 h. H O (50 mL) was added to the mixture and srtirred
1
H NMR (300 MHz, mixture of diastereomers, selected peaks):
δ = 5.93 (m, 1 H), 8.24 (s, 0.5 H), 8.26 (s, 0.5 H).
13C NMR (75 MHz, mixture of diastereomers): δ = 66.9 (CH), 69.5
3
2
(
8
CH), 71.0 (CH ), 72.3 (CH ), 79.3 (CH), 79.7 (CH), 81.3 (CH),
5.4 (CH), 97.7 (CH), 102.4 (CH), 112.0 (q), 112.4 (q), 117.9
at 25 °C for 15 h. It was then filtered through a sintered glass funnel
and the residue was washed repeatedly with benzene. The organic
layer of the filtrate was separated and the aqueous layer was extract-
ed with benzene. The combined organic extracts were washed with
2
2
(CH ), 118.6 (CH ), 133.1 (CH), 133.5 (CH), 151.2 (CH), 151.3
2 2
(
CH), 155.1 (quartet), 155.5 (quartet).
H O and dried. Removal of solvent yielded a dark brown oil, which
2
was chromatographed over silica gel (100–200 mesh) using EtOAc/
petroleum ether (1:4) as eluent yielding 19 (28%) as white needles;
mp 98–99 °C; [α]D −15.2 (c = 0.25, CHCl3).
Conversion of 14 to Furylpyran Derivative 16
2
8
A mixture of the above syrupy material (239 mg), NaHCO (106
3
mg, 1.26 mmol) and MeNHOH•HCl (239 mg, 0.84 mmol) in 80%
aq EtOH (20 mL) was refluxed for 20 h, and the mixture was con-
centrated under reduced pressure. The residue was extracted with
1H (300 MHz): δ = 1.31 (s, 3 H), 1.49 (s, 3 H), 3.28 (dd, J = 15.0,
5
.4 Hz, 1 H), 3.36 (dd, J = 15.0, 6.9 Hz, 1 H), 4.06 (d, J = 2.5 Hz, 1
H), 4.49 (m, 1 H), 4.56 (d, J = 13.5 Hz, 1 H), 4.57 (d, J = 3.6 Hz, 1
H), 4.83 (d, J = 13.5 Hz, 1 H), 5.90 (d, J = 3.6 Hz, 1 H), 8.16 (s, 1
H).
CH Cl , washed with H O and dried. Removal of solvent yielded a
2
2
2
reddish brown oil, which was chromatographed over silica gel with
MeOH/EtOAc (1:9) as eluent to give 16 as white needles (39%); mp
13C NMR (75 MHz): δ = 26.0 (CH
CH ), 77.0 (CH), 84.6 (CH), 84.7 (CH), 104.8 (CH), 111.6 (quar-
), 26.2 (CH ), 26.7 (CH ), 62.4
3 3
62–163 °C; [α]D28+5.4 (c = 0.59, CHCl3).
2
1
(
2
1H NMR (300 MHz): δ = 2.73 (s, 3 H), 3.44 (m, 1 H), 3.57 (dd,
J = 7.4, 1.4 Hz, 1 H), 3.65 (d, J = 8.0 Hz, 1 H), 3.7 (d, J = 6.9 Hz, 1
H), 3.82 (dd, J = 9.2, 1.3 Hz, 1 H), 3.91 (t, J = 7.8 Hz, 1 H), 4.19
tet), 117.0 (quartet), 153.5 (CH), 158.7 (quartet).
Anal. Calcd. for C H NO : C, 56.91; H, 5.97; N, 5.53. Found C,
1
2
15
5
5
7.47; H, 5.77; N, 5.41.
(
dd, J = 9.1, 7.1 Hz, 1 H), 4.42 (t, J = 8.8 Hz, 1 H), 4.64 (d, J = 14.3
Hz, 1 H), 4.85 (br s, 1 H), 4.97 (br s, 1 H), 5.07 (d, J = 14.3 Hz, 1
H), 8.24 (s, 1 H).
Acknowledgement
1
3
C NMR (75 MHz): δ = 43.3 (CH ), 46.9 (CH), 61.2 (CH), 61.4
3
A.P. is grateful to I.I.C.B. for a temporary assignment. As.B. is
thankful to CSIR, India for the award of a Research Associateship.
A.B. acknowledges the financial help from DST, India. Thanks are
due to Dr. R. Mukhopadhyay and Dr. V. S. Giri for help in NMR
analysis.
(
1
CH ), 69.7 (CH , 74.5 (CH ), 75.0 (CH), 79.8 (CH), 82.3 (CH),
12.7 (quartet), 151.3 (CH), 158.0 (quartet).
2 2) 2
Anal. Calcd. for C H N O : C, 53.72; H, 6.01; N, 10.44. Found C,
5
12
16
2
5
3.50; H, 5.85; N, 10.39.
(
2R,3R,4S,5R)-2,3-Isopropylidenedioxy-4-propargyloxy-5-(2-
nitroethyl)-2,3,4,5-tetrahydrofuran (17)
References
A mixture of the aldehyde 4 (3.5 g, 0.02 mol), nitromethane (8.8
mL), anhyd KF (1.24 g, 27 mmol) and propan-2-ol (50 mL) was
stirred at 25 °C for 15 h, after which it was filtered and the filtrate
was concentrated to afford a syrupy liquid. To a solution of this ma-
terial in CH Cl (50 mL) at 0 °C, Ac O (2 mL) and DMAP (90 mg)
were added and the mixture was kept at 25 °C for 15 h. It was then
washed with a cold brine, dried and concentrated to yield a yellow
oil. The latter was dissolved in EtOH (50 mL) and added dropwise
(
1) Hannesian, S. Total Synthesis of Natural Products: The
"Chiron" Approach; Pergamon Press: Oxford 1983.
(
(
(
2) Gothelf, K. V.; Jorgensen, K. A. Chem. Rev. 1998, 98, 863.
3) Frederickson, M. Tetrahedron 1997, 53, 403.
2
2
2
4) Bhattacharjee, A.; Chattopadhyay, P.; Kundu, A. P.;
Mukhopadhyay, R.; Bhattacharjya, A. Ind. J. Chem. 1995,
35B, 69.
(5) Bhattacharjee, A.; Bhattacharjya, A.; Patra, A. Tetrahedron
Lett. 1995, 36, 4677.
to a stirred suspension of NaBH (1.3 g, 35 mmol) in EtOH (50 mL)
4
at 0 °C. The mixture was stirred at 25 °C for 15 h and then treated
carefully with AcOH at 0 °C in order to remove excess of NaBH4.
(6) Mukhopadhyay, R.; Kundu, A. P.; Bhattacharjya, A.
Tetrahedron Lett. 1995, 36, 7729.
After evaporation of solvent from the mixture, H O (50 mL) was
2
(
(
7) Westley, J. W. Adv. Appl. Microbiol. 1977, 22, 177.
8) Kozikowski, A.P.; Li, C.-S. J. Org. Chem. 1985, 50, 778.
added to the residue. It was then extracted with CHCl , washed with
3
H O and dried. Removal of solvent yielded a yellow oil which was
2
chromatographed over neutral alumina using EtOAc/petroleum
ether (1:1) giving 17 (2g, 48%) as a light yellow syrupy liquid;
[
α]D28 −47.6 (c = 0.25, CHCl3).
Article Identifier:
437-210X,E;1999,0,09,1569,1572,ftx,en;Z02999SS.pdf
1
−1
IR (neat): n = 1549, 1375 cm .
Synthesis 1999, No. 9, 1569–1572 ISSN 0039-7881 © Thieme Stuttgart · New York