Synthesis and biological activity of a novel pentacyclic heterocycle

Article abstract of DOI:10.1002/jhet.982

A novel pentacyclic heterocycle has been synthesized starting from D-glucose involving two crucial conversions: the intramolecular cycloaddition of O-allyloxy furanaldoxime derived from D-glucose to furanopyran-2-isoxazoline and its diastereoselective red

Full text of DOI:10.1002/jhet.982

430
Synthesis and Biological Activity of a Novel Pentacyclic
Heterocycle [1]
Vol 50
a
a
a
*
Biswanath Das, Avula Satyakumar, Bommena Ravikanth,
Bommena Vittal Rao,b Tuniki Venugopal Raju,c Busi Siddhardhad and
Upadyayula Suryanaryana Murtyd
aOrganic Chemistry Division‐I, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
bOrganic Chemistry Division‐I, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
cNMR Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
dBiology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
*
E-mail: biswanathdas@yahoo.com
Received February 25, 2011
DOI 10.1002/jhet.982
Published online 29 March 2013 in Wiley Online Library (wileyonlinelibrary.com).
A novel pentacyclic heterocycle has been synthesized starting from D‐glucose involving two crucial
conversions: the intramolecular cycloaddition of O‐allyloxy furanaldoxime derived from D‐glucose to
furanopyran‐2‐isoxazoline and its diastereoselective reductive cleavage to the corresponding cis‐1,3‐amino
alcohol. The antibacterial and antifungal activities of the synthesized heterocycle have been examined.
J. Heterocyclic Chem., 50, 430 (2013).
INTRODUCTION
deprotection of the C‐5, C‐6 acetonide of this compound was
carried out with 0.8% aqueous H2SO4 in MeOH for 2 h at
room temperature to furnish a diol 9. The cleavage of the diol
with NaIO4 in the presence of saturated aqueous NaHCO3 at
room temperature for 4 h yielded the aldehyde 10, which
was readily condensed with NH2OH·HCl in aqueous NaOH
at 0°C to room temperature for 1 h to form the corresponding
oxime 5. Compound 5 was treated with diacetoxy iodoben-
zene at 0°C to room temperature for 1 h to form furanpyranoi-
soxazoline 4. The hypervalent iodine generated nitrile oxide
from oxime 5 [7,9], and then cycloaddition took place involv-
ing the nitrile oxide and the double bond of the allyl group
[7,10]. In the next step, isoxazoline 4 was reductively cleaved
to form the corresponding 1,3‐amino alcohol and the amine
group was in situ Boc protected in one‐pot. To achieve this
coversion, 4 was first treated with NiCl2·6H2O at 0°C
followed by addition of NaBH4 in portions to the reaction
mixture [8,11]. After 2 h (Boc)2O was added along with cata-
lytic amount of Et3N in the same pot to obtain 1,3‐amino alco-
hol 3 exclusively. The stereochemistry of 3 was settled from
NOESY experiment which clearly showed that H‐5 (δ 4.01,
1H, td, J = 9.5, 4.0 Hz) was related to H‐6 (δ 1.74, 1H, m)
and H‐6 with H‐4 (δ 4.30, 1H, m) indicating that H‐5 and
H‐6 are in cis‐configuration and all the H‐4, H‐5 and H‐6 are
α‐oriented.
Polycyclic heterocycles have gained much importance in
recent years as potentially bioactive molecules [2]. Several
fused tricyclic and pentacyclic heterocycles are known to
exhibit various pharmacological properties including
anxiolytic, antigastric, and antiallergic activities [3–6]. In
continuation of our work [7,8] on the development and
applications of useful synthetic methodologies, we envi-
sioned on the basis of earlier reports [2–6] the construction
of a pentacyclic heterocycle 1 to explore its biological
properties. Herein we report the synthesis and antibacterial
and antifungal activities of this compound.
RESULTS AND DISCUSSION
The retrosynthetic analysis (Scheme 1) reveals that 1 can
be synthesized from D‐glucose involving two important
conversions: (1) the intramolecular cycloaddition of O‐
allyloxy furanaldoxime 5 prepared from D‐glucose (6) to
furanopyran‐2‐isoxazoline 4 and (2) the diastereoselective
reductive cleavage of 4 to cis‐1,3‐amino alcohol 3.
We initiated the synthesis of 1 starting from D‐glucose (6)
(Scheme 2) by converting it into diacetone‐D‐glucose (7) by
reacting with acetone in the presence of anhydrous CuSO4
using a catalytic amount of conc. H2SO4 at room temperature
for 18 h. O‐Allylation of 7 was achieved by treatment with
allyl bromide utilizing K2CO3 in acetone under reflux for 4
h to obtain O‐allyl diacetone‐D‐glucose (8). The regioselective
N‐Boc protected 1,3‐amino alcohol 3 was subsequently
reacted with TsCl in the presence of Et3N at −5°C to room
temperature for 2 h to form the O‐tosyl derivative 11,
© 2013 HeteroCorporation

March 2013
Synthesis and Biological Activity of a Novel Pentacyclic Heterocycle
431
Scheme 2
which on treatment with NaN3 at 70°C for 2 h afforded the
N‐Boc protected 1,3‐amino azide 12. This azide derivative
underwent 1,3‐dipolar cycloaddition with DMAD at room
temperature producing the triazole compound 2. Finally
the treatment of 2 with TFA at 0°C for 0.5 h led to the
removal of the protecting group (Boc), and subsequent
addition of the excess amount of Et3N afforded the target
heterocycle 1 by intramolecular cycloaddition between free
amine and an ester group to generate a new lactam ring.
Reagents and conditions. (i). Acetone, conc. H2SO4,
anhydrous CuSO4, rt, 18 h, 90%; (ii) allyl bromide, warm
K2CO3, acetone, reflux, 4 h, 95%; (iii) 0.8% aq. H2SO4,
MeOH, rt, 2 h, 94%; (iv) NaIO4, DCM, sat. NaHCO3, rt,
4 h, 79%; (v) NH2OH·HCl, NaOH in H2O, 0°C, 1 h, 9%;
(vi) PhI(OAc)2, CH2Cl2, 0°C to rt, 1 h, 68%; (vii)
NaBH4 NiCl2·6H2O (4:1), MeOH, 0°C to rt, 2 h, (Boc)
2O, Et3N, 0°C to rt, 4 h, 73%; (viii) TsCl, Et3N, dry
DCM, −5°C to rt, 2 h, 81%; (ix) NaN3, DMF, 70°C, 2 h,
74%; (x) DMAD, CHCl2, rt, 2 h, 89%; (xi) TFA, DCM,
0°C to rt, 0.5 h, excess of Et3N up to pH = 9, 62%.
The structures of all the products were settled from their
1
spectral (IR, H and 13C‐NMR, and MS) and analytical
data. The one‐ and two‐dimensional NMR (1H‐1H COSY,
NOESY, HSQC, and HMBC) spectra of the final product 1
were thoroughly studied to assign correctly all the protons
and carbons present in the molecule. The stereo configura-
tion of 1 (H‐1 and H‐2: β and H‐3, H‐4, H‐5, and H‐6: α)
was confirmed from NOESY experiment.
The antibacterial and antifungal activities of 1 were
examined following the agar cup bioassay method [12]
earlier adopted by us [13]. The compound showed moder-
ate antibacterial activity against both Gram‐positive and
Gram‐negative organisms (Table 1). Streptomycin was
used as a positive control. However, the compound showed
significant activity against some fungi using clotrimazole
as a positive control (Table 2).
CONCLUSION
Scheme 1
In conclusion, we have synthesized a novel pentacyclic
heterocycle starting from D‐glucose applying simple and
convenient protocols. The antibacterial and antifungal ac-
tivities of the compounds were also evaluated.
EXPERIMENTAL
General methods. IR spectra recorded on a Perkin Elmer RX
1 FT‐IR spectrometer, NMR spectra on Gemini 200 MHz
spectrometer, and mass spectra on LC‐MSD‐Trap‐SL
instrument. Optical rotations were measured with JASCO DIP
300 digital polarimeter. Column chromatography was carried
out using silica gel 60–120 mesh (Quingdao Marine Chemicals,
China) and thin layer chromatography (TLC) on merck silica
gel 60 F254 plates.
Experimental procedure. Diacetone‐D‐glucose 7. D‐Glucose
(5.00 g, 27 mmol) and anhydrous copper sulfate (8.83 g, 54 mmol)
was taken in a three neck round bottomed flask. Acetone (100 mL)
was added to it. Conc. H2SO4 (catalytic amount) was added and
stirred for 18 h at room temperature. After completion of the
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

432
B. Das, A. Satyakumar, B. Ravikanth, B. V. Rao, T. V. Raju, B. Siddhardha, and U. S. Murty
Vol 50
Table 1
Antibacterial activity of compound 1 compared to that of streptomycin against various organisms.a
Compound 1
50 μg/μL
Streptomycin
Organism
25 μg/μL
MICb
25 μg/μL
50 μg/μL
MICb
Staphylococcus aureus
Staphylococcus epidermidis
Pseudomonas aeruginosa
Escherichia coli
14 mm
16 mm
14 mm
24 mm
20 mm
22 mm
20 mm
28 mm
100 μg/μL
50 μg/μL
100 μg/μL
25 μg/μL
8 mm
8 mm
8 mm
8 mm
10 mm
10 mm
10 mm
10 mm
18 μg/μL
18 μg/μL
18 μg/μL
18 μg/μL
aInhibitory zone diameters are in mm.
bMinimum inhibitory concentration.
reaction (monitored by TLC), reaction mixture was filtered and 2 g of
NaHCO3 was added to the filtrate and stirred for another 4 h. Then the
compound was extracted with CH2Cl2 (3 × 100 mL) and subjected to
column chromatography using hexane and ethyl acetate as eluent to
obtain pure diacetone‐D‐glucose 7 as white crystalline solid (6.31 g,
90%, mp: 109–110°C). ½αꢀD = −11.0 (c = 5.0, EtOH). H‐NMR
(200 MHz, CDCl3): δ 5.87 (1H, d, J = 3.7 Hz), 4.48 (1H, d, J = 3.7
Hz), 4.32–4.10 (3H, m), 4.02–3.90 (2H, m), 2.39 (1H, brs), 1.50
(3H, s), 1.42 (3H, s), 1.34 (3H, s), 1.31 (3H, s). ESIMS: m/z 261
[M+H]+
Diol 9. A solution of O‐allyl diacetone‐D‐glucose 8 (6.00 g, 20
mmol) in methanol (50 mL) and 0.8% aq. H2SO4 (15 mL) was
stirred for 3 h. After completion of reaction, solid Ba2CO3 was
added to the reaction mass to adjust the pH to neutral. It was
filtered and filtrate concentrated to a syrupy residue and
chromatographed over silica gel using hexane, EtOAc as eluent
25
1
25
to obtain diol 9 as a yellowish viscous mass (4.88 g, 94%).½αꢀD
= −21.9 (c = 0.8, CHCl3). IR (neat): 3435, 2933, 1531 cm−1
.
1H‐NMR (200 MHz, CDCl3): δ 5.90 (1H, m), 5.85 (1H, d, J =
3.7 Hz), 5.32 (1H, dd, J = 1.5, 15.8 Hz), 5.21 (1H, dd, J = 1.5,
15.8 Hz), 4.51 (1H, dd, J = 3.7 Hz), 4.19 (1H, dd, J = 5.5, 7.4
Hz), 4.12–3.87 (4H, m), 3.80 (1H, dd, J = 2.9, 8.5 Hz), 3.71
(1H, dd, J = 2.9, 8.5 Hz), 2.83 (1H, brs), 2.52 (1H, brs), 1.48
(3H, s), 1.31 (3H, s). 13C‐NMR (50 MHz, CHCl3): δ 113.8,
117.4, 111.4, 104.8, 81.9, 81.3, 79.5, 70.9, 68.6, 64.0, 26.4,
25.9. ESIMS: m/z 543 [2M+Na]+, 261 [M+H]+.
O‐Allyl diacetone‐D‐glucose 8.
A stirred solution of
diacetone‐D‐glucose 7 (6.00 g, 23 mmol), allyl bromide (3.10
mL, 40 mmol), and potassium carbonate (9.10 g, 66 mmol) in
distilled acetone (100 mL) was refluxed for 4 h. After the
reaction was completed (monitored by TLC), solvent was
evaporated under reduced pressure. The reaction mixture was
then extracted with ethyl acetate (3 × 30 mL) and water. The
organic layer was separated, and the aqueous layer was further
washed with EtOAc (2 × 20 mL). The combined organic
portion was washed with NaHCO3 solution (30 mL) and dried
over Na2SO4 and concentrated under reduced pressure. The
residue was subjected to column chromatography over silica gel
using hexane, EtOAc as eluent to afford O‐allyl diacetone‐D‐
Aldehyde 10. To diol 9 (4.50 g, 17 mmol) in CH2Cl2, NaIO4
(7.40 g, 34 mmol) and saturated NaHCO3 (10 mL) were added.
The reaction mixture was stirred for 4 h at room temperature.
After completion of the reaction indicated by TLC, reaction
mixture was further diluted with water (50 mL), and the mixture
was extracted with CH2Cl2 (3 × 20 mL). The organic layer was
dried on anhydrous Na2SO4 and concentrated at low
temperature (below 35°C), and the thick syrupy material
aldehyde 10 (3.11 g, 79%) was subjected to perform the next
reaction immediately.
glucose 8 as a viscous mass (6.57 g, 95%).½αꢀ2D5 = −41.0 (c =
1
0.2, CHCl3). H‐NMR (200 MHz, CDCl3): δ 5.87 (1H, m), 5.82
(1H, d, J = 3.7 Hz), 5.30 (1H, dd, J = 1.5, 15.8 Hz), 5.18 (1H,
dd, J = 1.5, 15.8 Hz), 4.49 (1H, d, J = 3.7 Hz), 4.25 (1H, dd, J
= 6.0, 7.5 Hz), 4.12–3.86 (6H, m), 1.49 (3H, s), 1.42 (3H, s),
1.32 (3H, s), 1.28 (3H, s). 13C‐NMR (50 MHz, CHCl3): δ
133.9, 116.9, 111.4, 108.7, 105.0, 82.6, 81.2, 80.1, 72.2, 71.0,
67.0, 26.6, 26.6, 26.0, 25.1. ESIMS: m/z 323 [M+Na]+.
Oxime 5. A solution of sodium hydroxide (1.56 g, 39 mmol)
in water (20 mL) was cooled to 0°C, and aldehyde 10 (3.00 g, 13
mmol) was slowly added under stirring. Hydroxylamine
hydrochloride (1.80 g, 26 mmol) was slowly added to the
stirred mixture. After the addition, the mixture was allowed to
warm to room temperature. After standing for 1 h, it was cooled
on ice bath. Then the reaction mixture was extracted with
EtOAc (3 × 100 mL), and the organic layer was subjected to
column chromatography over silica gel using hexane and
EtOAc as eluent to yield oxime 5 as an yellowish viscous mass
Table 2
Antifungal activity of compound 1 compared to that of clotrimazole
(2.90 g, 91%).½αꢀ2D5 = −211.0 (c = 2.0, CHCl3). IR (neat): 3435,
against various fungi.a
2933, 1531 cm−1 1H‐NMR (200 MHz, CDCl3): δ 8.70 (1H,
.
brd, J = 12.5 Hz), 6.89 (1H, d, J = 4.2 Hz), 5.91 (1H, d, J = 3.5
Hz), 5.78 (1H, m), 5.18 (1H, dd, J = 4.9 Hz), 5.14 (1H, dd, J =
3.5 Hz), 4.52 (1H, dd, J = 3.5 Hz), 4.23 (1H, dd, J = 2.8 Hz),
4.05–3.98 (2H, dd, J = 1.4, 4.2 Hz), 1.49 (3H, s), 1.30 (3H, s).
13C‐NMR (50 MHz, CHCl3): δ 149.2, 133.7, 117.6, 111.9,
104.7, 82.9, 82.1, 75.5, 71.3, 26.7, 26.1. ESIMS: m/z 266 [M
+Na]+, 244 [M+H]+.
Compound 1
Clotrimazole
Fungi
25 μg/μL 50 μg/μL
25 μg/μL 50 μg/μL
Candida albicans 12 mm
18 mm
18 mm
8 mm
8 mm
10 mm
10 mm
Saccharomyces
cerevisiae
10 mm
Aspergillus niger 14 mm
16 mm
8 mm
10 mm
Isoxazoline 4. Oxime 5 (2.50 g, 10.2 mmol) dissolved in
CH2Cl2 (50 mL) was kept on ice bath and stirred, while
aInhibitory zone diameters are in mm.
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Synthesis and Biological Activity of a Novel Pentacyclic Heterocycle
433
diacetoxy iodobenzene (3.96 g, 12.2 mol) was added in three
portions. The mixture was stirred for 1 h. Completion of the
reaction was indicated by TLC. Water (20 mL) was added to
the reaction mixture, and the mixture was extracted with
CH2Cl2 (3 × 20 mL). The organic layer was separated and
further washed with saturated solution of NaHCO3 (2 × 20 mL)
and dried over Na2SO4. The organic layer was concentrated
under reduced pressure, and the residue was subjected to
column chromatography over silica gel using hexane–EtOAc as
eluent to yield the product isoxazoline 4 as white crystals in
(1H, t, J = 11.3 Hz), 2.48 (3H, s), 1.48 (3H, s), 1.42 (9H, s),
1.29 (3H, s). 13C‐NMR (50 MHz, CHCl3): δ 155.4, 144.8,
132.5, 129.8, 127.9, 112.0, 104.8, 83.7, 79.8 79.5, 75.7, 68.3,
67.6, 47.7, 37.8, 28.2, 26.6, 26.0, 21.6. ESIMS: m/z 500 [M+H]+.
N‐Boc azido chromane 12. Sodium azide (0.30 g, 5 mmol)
was added under magnetic stirring to a solution of O‐tosyl N‐
Boc protected 1,3‐amino alcohol 11 (1.00 g, 2.0 mmol) in
dimethylformamide (15 mL). The mixture was heated to 70°C
on a water bath for 2 h. Completion of the reaction was
indicated by TLC. The mixture was filtered, and water (5 mL)
was added to the filtrate. A white precipitate appeared. It was
recovered by filtration and recrystallized from ethanol to yield
0.54 g, 74% of N‐Boc azido chromane 12 as a viscous mass.
½αꢀD = +22.3 (c = 0.3, CHCl3). H‐NMR (200 MHz, CDCl3): δ
5.89 (1H, d, J = 3.0 Hz), 5.06 (1H, d, J = 9.0 Hz), 4.50 (1H, d,
J = 3.7 Hz), 4.22 (1H, m), 3.99–3.90 (2H, m), 3.80 (1H, td, J =
3.0, 10.0 Hz), 3.53 (1H, dd, J = 3.7, 9.0 Hz), 3.23–3.12 (2H,
m), 2.01 (1H, m), 1.52 (3H, s), 1.49 (9H, s), 1.32 (3H, s).
ESIMS: m/z 393 [M+Na]+, 371 [M+H]+.
25
68% yield (1.68 g, mp: 124–125°C). ½αꢀD = +398.0 (c = 0.1,
CHCl3). 1H‐NMR (200 MHz, CDCl3): δ 5.97 (1H, d, J = 3.0
Hz), 4.96 (1H, d, J = 2.3 Hz), 4.55 (1H, d, J = 3.0 Hz), 4.52
(1H, d, J = 2.3 Hz), 4.20 (1H, dd, J = 4.5, 6.0 Hz), 3.98 (1H, d,
J = 2.3 Hz), 3.87 (1H, t, J = 9.1 Hz), 3.64 (1H, m), 3.31 (1H, t,
J = 10.6 Hz), 1.56 (3H, s), 1.34 (3H, s). 13C‐NMR (50 MHz,
CHCl3): δ 154.1, 112.4, 106.1, 83.2, 82.4, 71.2, 70.6, 69.9,
43.9, 26.7, 26.2. ESIMS: m/z 264 [M+Na]+, 242 [M+H]+.
25
1
N‐Boc protected 1,3‐amino alcohol 3. Isoxazoline 4 (1.50 g,
6.2 mmol) was dissolved in 25 mL of distilled MeOH at 0°C on
an ice bath. NiCl2·6H2O (2.90 g, 12.4 mmol) was added, and
the mixture was allowed to stir for 5 min. NaBH4 (1.83 g, 49.6
mmol) was added in four to five portions during 15 min. The
greenish color of the solution turned to bluish black. The
reaction mixture was allowed to stir at room temperature for 2
h. The completion of the reaction was confirmed by TLC. Then,
again the reaction mixture was kept on an ice bath. Catalytic
amount of triethylamine was added to it along with (Boc)2O,
and the reaction mixture was stirred at room temperature for 4
h. The completion of the reaction was indicated by TLC, which
turned pinkish after charring with ninhydrin solution. Solvent
was evaporated from the reaction mixture and 1N HCl solution
(5 mL) was added in it. The mixture was extracted with EtOAc
(4 × 30 mL). The organic layer was separated, dried over
Na2SO4, and concentrated under reduced pressure. The residue
was subjected to column chromatography using hexane and
EtOAc as eluent to obtain pure N‐Boc protected amino alcohol
Triazole 2. A mixture of 0.50 g (1.35 mmol) of N‐Boc azido
chromane 12 and 0.24 mL of DMAD (2.02 mmol) in 10 mL
dry CH2Cl2 was stirred at room temperature for 2 h. Reaction
was monitored by TLC. After completion of the reaction,
CH2Cl2 was evaporated under reduced pressure. The crude
product was subjected to column chromatography to obtain pure
triazole compound 2 as colorless viscous mass (0.61 g, 89%).
½αꢀD = +11.8 (c = 0.8, CHCl3). H‐NMR (200 MHz, CDCl3): δ
5.86 (1H, d, J = 3.7 Hz), 5.25 (1H, d, J = 9.5 Hz), 4.78 (1H,
dd, J = 3.0, 11.0 Hz), 4.48 (1H, d, J = 3.7 Hz), 4.42–4.25 (2H,
m), 4.01 (3H, s), 3.96 (3H, s), 3.94–3.79 (2H, m), 3.68 (1H, dd,
J = 3.7, 8.0 Hz), 3.30 (1H, t, J = 11.7 Hz), 2.41 (1H, m), 1.52
(3H, s), 1.48 (9H, s), 1.30 (3H, s). 13C‐NMR (50 MHz, CHCl3):
δ 160.5, 158.6, 155.8, 139.9, 130.0, 112.0, 104.7, 83.6, 80.1,
79.2, 75.5, 67.7, 53.6, 52.2, 49.1, 48.9, 39.0, 28.3, 26.5, 25.8.
ESIMS: m/z 535 [M+Na]+.
25
1
Compound 1. To the compound 2 (0.50 g, 0.97 mmol) in
CH2Cl2 (50 mL) trifluoro acetic acid (0.096 g, 0.97 mmol) was
added and stirred for 0.5 h at 0°C to room temperature.
Removal of N‐Boc protected group was indicated by TLC.
Then the reaction mixture was basified with excess of triethyl
amine. After completion of the reaction dichloromethane was
evaporated under reduced pressure. The crude product was
subjected to column chromatography to obtain pure product 1
25
3 as white solid in yield of 1.56 g (73%, mp: 158–159°C).½αꢀD
1
= +19.4 (c = 0.1, CHCl3). H‐NMR (200 MHz, CDCl3): δ 5.87
(1H, d, J = 3.8 Hz), 5.21 (1H, d, J = 9.0 Hz), 4.46 (1H, d, J =
3.8 Hz), 4.29 (1H, brs), 4.02–3.93 (2H, m), 3.80 (1H, dd, J =
3.7, 8.3 Hz), 3.71–3.36 (4H, m), 1.73 (1H, m), 1.54 (3H, s),
1.50 (9H, s), 1.33 (3H, s). 13C‐NMR (50 MHz, CHCl3): δ
157.2, 111.9, 105.4, 83.9, 80.4, 79.6, 76.2, 68.5, 59.5, 47.1,
40.0, 28.2, 26.6, 26.0. ESIMS: m/z 368 [M+Na]+.
25
as a white solid (0.23 g, 62%, mp: 269–270°C). ½αꢀD = 0.1,
CHCl3). IR (neat): 3421, 1730, 1689 cm−1 1H‐NMR (200
.
MHz, CDCl3): δ 6.71 (1H, d, J = 6.6 Hz), 5.98 (1H, d, J = 3.7
Hz), 4.70–4.39 (4H, m), 3.98 (3H, s), 3.96–3.82 (2H, m), 2.89
(1H, m), 1.50 (3H, s), 1.31 (3H, s). 13C‐NMR (50 MHz,
CHCl3): δ 159.8, 158.1, 140.0, 133.7, 112.6, 105.8, 83.4, 79.5,
74.2, 67.8, 52.7, 52.5, 49.7, 37.8, 26.7, 26.1. ESIMS: m/z 381
[M+H]+. Anal. calcd. For C16H20N4O7: C, 50.53; H, 5.26; N,
14.74%, Found: C, 50.41; H, 5.32; N, 14.68%.
O‐Tosyl N‐Boc protected 1,3‐amino alcohol 11. A mixture of
N‐Boc protected 1,3‐amino alcohol 3 (1.00 g, 2.8 mmol) and dry
CH2Cl2 (25 mL) was stirred until complete dilution. The mixture
was cooled to −5°C, and catalytic amount of Et3N was added.
Tosyl chloride was slowly added to the mixture and stirred for 2
h at room temperature. After completion of the reaction
(monitored by TLC), the reaction mixture was quenched with
saturated NH4Cl and extracted with CH2Cl2 (3 × 20 mL). The
organic layer was dried on NaSO4, concentrated under reduced
pressure, and subjected to column chromatography using
hexane and EtOAc as eluent to obtain pure O‐tosyl N‐Boc
protected 1,3‐amino alcohol 11 as a colorless viscous mass in
Acknowledgments. The authors thank CSIR and UGC, New Delhi,
for financial assistance.
25
1
yield of 1.17 g, 81%.½αꢀD = +61.0 (c = 0.7, CHCl3). H‐NMR
(200 MHz, CDCl3): δ 7.78 (2H, d, J = 8.0 Hz), 7.32 (2H, d, J =
8.0 Hz), 5.82 (1H, d, J = 3.0 Hz), 5.01 (1H, d, J = 9.8 Hz),
4.43 (1H, d, J = 3.0 Hz), 4.17 (1H, m), 4.10–3.61 (6H, m), 3.13
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Vol 50
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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