IJCB 40B(11) 1114

Indian Journal of Chemistry
Vol. 40B, November 2001. pp. 1114-1120
Synthesis of mono- and di-azido-hexopyranoses with N-alkyl and N,N-dialkyl
amino groups at C-2 position: Intermediates for accessing new polyaminosugars t
Bindu Ravindran~ & Tanmaya Pathak*'1
Organic Chemistry Division (Synthesis), National Chemical Laboratory, Pune 411 008, India
Received 31 January 2001 .. accepted 19 June 200 I
Michael addition reactions of morpholine and benzylamine to methyl 2,3-dideoxy-4,6-0-(phenylmethylene)-3-Cphenylsulfonyl-a-D-erythro-hex-2-enopyranoside 9 furnish gluco- derivatives 10 and 11. Desulfonation at C-3 followed by
synthetic manipulation produces intermediates for generating various new modified monosaccharides carry ing N-alkyl and
N,N-dialkyl amino groups at the C-2 position of hexopyranosides. This route also has the potential to furn ish naturally occurring diaminosugars such as tobrosamine.
The amino groups present in the aminoglycoside antibiotics and polysaccharides play an important role in
their biological activities l . 3 • The most important
mechanism of resistance to aminoglycoside antibiotics among resi stant bacteria arises from enzymatic Nacetylation ,O-phosphorylation,and O-nucleotidylation
of specific sites in the antibiotics. To avoid such deactivation processes, several semisynthetic aminoglycoside antibiotics have been designed where either the
hydroxyl groups undergoing enzymatic phosphorylation have been removed and/or the amino groups susceptible to acetylation have been masked by acyl ation
or alkyl ati on3 . The interest in this class of compounds
has been renewed with the di scoveries that aminoglycoside antibiotics interact with a variety of RNA
4
molecules • Studies on structure-activity relationship
have revealed the following important points: (i)
changing an amino group to a hydroxyl group of certain aminoglycoside antibi otics eliminates the inhibitory activity. (ii) The overall charge density presented
by the aminoglycosides toward the RNA host is likely
to be important as aminoglycosides containing four
amino groups show very little RNA binding capability while the most active derivatives contain five or
six amino groups . (iii) When a hydroxyl group
proximal to an amine is removed, higher inhibitory
activity is observed, which could be attributed to the
IDedicated to Prof. U. R. Ghatak on his 70 th birthday
t Present address: Department of Chemistry, The University of
Iowa, Iowa City, IA 52242, USA.
1 Presentaddress:Department of Chemistry, Indian Institute of
Technoogy, Kharagpur 721302, India; e.mail :tpathak@chem.iitkgp.
emet.in
increased basicity of an amino group in a deoxygen4
ated analogue .
Tobrosamine (2,6-diamino-2, 3, 6-trideoxy-D-ribohexose)1 ,5 purpurosamineA(2-amino-2, 3, 4 ,6, 7 pentadeoxy-6-methylamino-D-ribo-heptose) 2,6 purpurosamineB 2, 6-diamino-2, 3, 4, 6, 7-pentadeoxy- D-riboheptose) 3,6 purpurosamine C (2, 6-diamino-2, 3, 4, 6tetradeoxy- D-erythro-hexose) 4,6 sisosamine (2, 6diamino-2, 3, 4, 6-tetradeoxy-D-glycero-hex-4-enose) 57
represent a class of 2, 6-diaminosugars which is part of
variolls aminoglycoside antibiotics. Amongst various
naturally occurring 2,4-diaminosugars, kasugamine
(2, 4-diamino-2, 3 ,4, 6-tetradeoxy-D-arabinohexose) 6 8
has been isolated from the antibiotic kasugamycin. 3Deoxy-prumycin,4- (D-alanylamino) -2-amino-2, 3, 4
dideoxy -L-arabinose 7 is highly potent against a wide
spectrum of phytopathogenic strains retaining the original antileukemic activity of prumycin9. Several other
diaminosugars have been used in different studies. For
example, 2,6-diamino-2,4-dideoxy - ~-D xylopyranoside
unit has been used in chelation-induced ring flip of a
hinge-like monosaccharide unit; 10 a glycophospholipid
consisting in a derivative of N, N- acylated and
bisphosphorylated 2,3-dideoxy-2,3-diamino- D-glucose
has been synthesized and its effect on murine macrophages evaluated 11. Although both mono- and diaminosugars are naturally occurring, sugars containin¥: more
than two amino groups are not known in nature 2. Irrespective of this fact, several triaminosugarsI 3 and
tetraaminosugarsI 4 have been synthesized to study their
biological properties.
It is, therefore, of interest to devise strategies for the
synthesis of common intermediates leading to aminosugars in which most if not all the hydroxyl groups
RA VINDRAN et at.: SYNTHESIS OF MONO-& D1-AZIDO-HEXOPYRANOSES
1115
HO
OH
1 tobrosamine
OH
OH
2 purpurosamine A
3 purpurosamine B
H~
OH
OH
4 purpurosamine C
5 sisosamine
6 kasugamine
7 3-deoxy-prumycin
Figure 1
have been replaced by amino groups to see whether
they alter activities of the parent antibiotics or any
polysaccharide macromolecules.
Results and Discussion
Aminosugars are normally synthesized by reacting
sugar derived epoxides, tosylates, halides or ketones
with azides, pthalimides or amines although several
other minor methods are al so reported 12. Nucleophilic
addition (Michael) to double bonds activated by electron withdrawing groups as part of carbohydrates
could, in theory , serve as a useful methodology for the
functionalisation of monosaccharides. Several examples of Michael addition of nitrogen nucleophiles including amines to hex-2-enose 1s and 3-nitro-hex-2enopyranosides 16,17 have been reported. 2,3-Dideoxyhex-2-en-4-ulopyranosides, for example have been reacted with azide 1sa, partially protected amiu acids and
. ISb
benzy Iam1l1e to generate several new classes of aminosugars. The major drawbacks of usi ng 4-uloses as
starti ng materi als are that a) the products will always be
2, 3-dideoxy derivatives and b) the stereochemical outcome of the reduction of the carbonyl group (C-4) is
dependent on the orientation of the C-2 substituent IS.
Such limitations made this route less attractive for synthetic work. The studies on the addition of nitrogen
nucleophiles to 3-nitro-hex-2-enopyranosides, however, have remained limited mostly to gluco- and gaIacto-pyranoses 16 and have been used for the preparation of few diamino- and triaminosugars 13a.c,17.
Aminosugars 1-7 (Figure 1) represent a class of deoxysugars where C-3 positions are devoid of any hy-
droxyl groups. We have recently reported that methyl
2,3-dideoxy-3-C-phenylsulfonyl-a.-D-hex-2
enopyranoside 9, synthesized from the epoxide 8, reacted
with primary and secondary amines in a diastereoselective fashion IS. Such C-N bond formation in Michael
fashion at C-2 of the vinyl sulfone-modified carbohydrates exclusively produced the thermodynamically
more stable C-N equatorial aminosugars with primary
amines. Secondary amines, on the other hand afforded
a mixture of gluco- (major) and manno-(minor) products with 9. The major isomers were separated by crys' . IS. The products 10 (X = morpholinyl) ls and
ta II IzatlOn
11 (X
benzylamino)19 obtained from the addition
reactions of morpholine and benzyl amine respectively
to 9, can be desulfonated 19 easily to generate compounds 12 (X = morpholinyl) and 13 (X = benzylamino) with methylene groups at C-3 positions
(Scheme I). Thus the core structure present in aminosugars 1-7 (CHrCH-N) can be generated using the
sequence of reactions mentioned above. This methodology has been used in the synthesis of DIi vidosami ne (2-ami no-2,3-dideox y -D-gl ucose) and
.
19
Its analogues . The same strategy can be utilised for
the synthesis of 6-azido, 4-azido, and 4,6-diazido intermediates with 2-N-benzylamino and 2-Nmorpholino at C-2 position in equatorial configuration
to afford a series of new deoxypolyaminosugars.
=
Synthesis of methyl 4-0-acetyl-6-azido-2-Nmorpholino-2,3,6-trideoxy-a.-D-ribohexopyranoside
18a and methyI2-N-(acetyl benzylamino)-4-0-acetyl6-azido-2,3,6-trideoxya.-D-ribo-hexopyranoside 18b.
INDIAN J CHEM ., SEC. B, NOVEMBER, 2001
1116
Ph
/'\:'-\O~)(\I
( /\ °
0
o
_
(i)
OMe
8
~Ph\;;~ ~
Ph\'~q
o~
OMe
Ac-7 oMe
bn
12, 13
14
Reaction conditions: (i) ref. 18; (ii) ref. 19; (iii) Ac2 0, py
Scheme I
MethyI2,3-dideoxy2-N-morpholino-4, 6-0(phenylmethylene)-a-D-ribo -hexopyranoside 12 (X = morpholinyl) obtained through known sequence of reactions l8. 19 was debenzylidenated with 0.1 N HCl in
methanol. The resulting 4,6-diol 15a was selectively
tosylated at 6-position by treatment with tosy\Choride in
pyridine to afford 16a. The 6-tosylate of 16a was then
displaced by azido group using LiN3 in DMF at 11020°C to produce 17a. The 4-hydroxyl group of 17a was
acetylated to afford methyl 4-0-acetyl-6-azido-2-Nmorpholino-2,3,6-trideoxy-a-D-ribo-hexopyranoside
18a (Scheme II). In order to mask the NH function of
13 (X = benzylamino) from electrophilic reagents, 13
was reacted with acetic anhydride in pyridine to obtain
2-N-(acetylbenzylarnino)-2,3-dideoxy-4,6-0 (phenylmethylene)-a-D-ribo-hexopyranoside 14 (Scheme I).
The same reaction sequence discussed for morpholino
derivative was then repeated with 14 to afford 18b
(Scheme II).
Synthesis of methyl 4-azido-2-N-morpholino-6-0trityl-2,3,4-trideoxy-a-D-xylo-hexopyranoside 21a
and methyl 2-N-(acetyl benzylarnino)-4-azido-6-0trityl-2, 3, 4-trideoxy-a-D-xylo-hexopyranoside 21b.
The 4,6-diol 15a was selectively protected at the 6hydroxy position with trityl chloride in anhyd. pyridine
to afford 6-0-trityl derivative 19a. The 4-hydroxy was
then mesylated using methansulfonyl choride at O°c.
The mesylated derivative 20a on treatment with LiN3 in
DMF at 1l0-200C, afforded methyl 4- azido-2-Nmorpholino-6-0-tri ty 1-2, 3, 4-trideox y-a-D-xylohexopyrano-side 21a, with inversion of configuration at
C-4 (Scheme III). Synthesis of methyl 2-N(acetylbenzylarnino)-4-azido-6-0-trityl-2,3,4-trideoxy-
H~O\
HO
TS~O\
~~HO
~
OMe
-
(ii)
OMe
15a,15b
16a,16b
N~O\
AoO'
~
OMe
17a,17b
1Sa,1Sb
/\
X=a: 0
N
"---I
X=b: ~
"=I'NAc
Reaction conditions: (i) TsCl , py; (ii) LiN.), DMF; (iii) Ac,o, py
Scheme II
a-D-xylo-hexopyranoside 21b was attempted following the same reaction sequences as reported for
21a. Although the intermediate 20b was synthesized
with reasonable purity, the final product 21b could
not be obtained in pure form.
Synthesis of methyl 4, 6-diazido -2-N-morpholino2, 3, 4, 6-tetradeoxy-a- D-xylohexopyranoside 23a
and methyI2-N- (acetyl benzylarnino) -4, 6-diazido-2,
3,4, 6-tetradeoxy-a-D-xylo-hexopyranoside 23b. The
4,6-diol 15a was mesylated using methansulfonyl chloride at O°c. The dimesylated derivative 22a was treated
with LiN3 in DMF at 11O-20°C to afford methyl 4,6diazido-2-N-morpholino-2, 3, 4, 6-tetradeoxy-a-D-xylohexopyranoside 23a (Scheme IV). Merhyl 2-N-(acetyl
benzylarnino)-4,6-diazido-2,3,4,6-tetradeoxy-a-D-xylo-
RA VINDRAN et al.: SYNTHESIS OF MONO-& D1-AZIDO-HEXOPYRANOSES
15a,15b
0
Tr~
(i)
(ii)
HO
..
15a, 15b
MS~
0
_(i)
MsO
X
_
(")
II
N_N~3
3
X
X
22a,22b
Tr~o\
M,O
~
N3
(III
"')
0
OMe
OMe
19a,19b
1117
.. Tro-~
0
x = a:
1\
0
N
"--!
OMe
23a,23b
X=b:~
~NAc
Reaction conditions: (i) MsCl, py; (ii) LiN3' DMF
OMe
Scheme IV
20a,20b
X=b: ~
~NAc
Reaction conditions: (i) TrCl, py; (ii) MsCl, py; (iii) LiN3' DMF
Scheme III
hexopyranoside 23b was synthesized following the
same reaction sequence from 15b (Scheme IV).
The H-l protons of compounds 16a, 18a, 20a, 21a,
and 22a appeared in the 'H spectra as doublets (h2 =
3.0-4.0 Hz) in the region of 4.75-4.88 ppm as expected 's. Similarly in I3C NMR spectra of these compounds C-l appeared in the region 96.8-98.1 ppm. In
the mass spectra, compounds 16a, 18a, 20a, 21a, 22a,
and 23a showed peaks corresponding to M+, M+-OCH3,
or M+- N3 fragments . The presence of IR band in the
region of 2102-2100 cm'l in compounds 18a, 21a, and
23a indicates the presence of azido groups in these
compounds. The H-l peaks of N-acetyl benzylamino
compounds 18b and 23b could not be assigned because
they always overlapped with the peaks arising of other
ring protons. It should be noted that in this series most
of the compounds were always contaminated with minor unknown impurities. Compound 23b, however gave
the correct elemental analysis. In the mass spectra, 18b
and 23b showed peaks corresponding to M+, M+-OCH3,
or M+- N3 fragments. The presence of IR band at 2120
cm'l in compounds 18b and 23b indicated the presence
of azido groups in these compounds.
Conclusion
We have, for the first time synthesized intermediates
for generating various new synthetic polyaminosugars
with N-alkyl and N,N-dialkyl amino groups at the C-2
position of the hexopyranosides. It will also be possible
to access the naturally occurring diaminosugars through
this route because we have already established '9 the protocols for debenzylations of benzylamino derivatives
closely related to 18b, 21b or 23b; direct reaction of
ammonia with vinyl sulfone-modified carbohydrates 19,
such as 9 followed by the synthetic manipulations presented here should also generate naturally occurring
aminosugars. The stability of the acetylated benzylamino derivatives to the reaction conditions described here should be studied in detail before embarking on the synthesis of aminosugars containing secondary amino groups. Work is currently in progress to
synthesize aminosugars 1-7 and their analogues using
this powerful strategy of addition of amines to vinyl
sulfone-modified carbohydrates.
Experimental Section
MethyI4-0-acetyl-6-azido -2-N-morpholino-2,3, 6trideoxy--a-D-ribo- hexopyranoside 18a. A solution
of 12 (0.31 g, 0.94 mmole) in O.lN HCl (18 mL), and
methanol (9 mL), was heated under reflux for 3 hr. The
reaction mixture was concentrated to dryness under reduced pressure to afford a syrup 15a. The residual moisture was co-evaporated with anhyd. methanol. pToulenesulfonyl chloride (0.18 g, 0.94 mmole) in anhyd. pyridine (5 mL) was added to a solution of 15a in
anhyd. pyridine (10 mL) at O°C and the mixture was
stirred at ambient temperature for 12 hr. The reaction
mixture was poured into satd. aq. NaHC03 (60 mL)
and the solution was extracted with dichloromethane
(3 x 20 mL). Organic layers were pooled together,
dried over anhyd. Na2S04, filtered and the filtrate was
concentrated under reduced pressure to a syrupy residue. The syrup was purified over silica gel (75% ethyl
acetate-pet. ether) to afford a white solid of methyl
2,3-dideoxy-2-N-morpholino-6-0-tosyl-a-D-ribohexopyranoside 16a, yield 0.35 g (93%); m.p. 15657°C; [afsD: +33.4° (c 0.415, MeOH); 'H NMR:
8 1.79 (m, IH), 2.11 (m, IH), 2.37-2.96 (m, 5H), 2.45
(s, 3H), 3.35 (s, 3H), 3.63-3.76 (m, 6H), 4.20 (m, IH),
4.39 (dd, J =3 .9, 11.3 Hz, IH), 4.75 (d, J =3.4 Hz,
IH), 7.37 (m, 2H), 7.82 (m, 2H); I3C NMR (DMSO-
1118
INDIAN J CHEM., SEC. B, NOVEMBER , 2001
d6 ): <520.9, 29.3 (CH 2), 49.8 (CH 2), 53.7, 61.7, 64.7,
66.4 (CH 2), 70.1 (CH 2), 70.8, 97.7, 127,4, 129.9,
132.6, 144.6; MS: EI mlz (%) 401 (M+, 3), 386 (M+CH 3, 5), 370 (M+-OCH 3, 10). To a solution of 16a
(0.25 g, 0.62 mmole) in anhyd. DMF (5 mL), was
added LiN3 (0.30 g, 6.23 mmole). After heating the
mixture at 110°C for 10 hr it was concentrated to dryness under reduced pressure. Acetic anhydride (0.29
mL, 3.11 mmole) was added to a solution of crude
17a in anhyd. pyridine (15 mL) and the solution was
stirred overnight at ambient temperature. The reaction
mixture was poured into satd. ag. NaHC0 3 solution
(40 mL) and the solution was extracted with dichloromethane (3 x 15 mL). Organic layers were
pooled together, dried over anhyd. Na2S04, filtered
and concentrated to dryness. The crude residue was
purified over silica gel (60% ethyl acetate-pet. ether)
to afford a yellowish syrupy residue 18a, yield, 0.11g
(56% in 3 steps from 15a); IR (CHCI 3):2102 em-I;
[af30 : +133S (c 0.620, CHCh); IH NMR: <51.81 (m,
IH), 2.06 (s, 3H), 2.21 (m, 1H), 2.43-2.76 (m, 5H),
3.31 (d, J =4.0 Hz, 2H), 3.45 (s, 3H), 3.71 (m, 4H),
3_86 (m, IH), 4.72 (m, IH), 4.79 (d, J =3.4 Hz, 1H);
IJC NMR: <520.3,25.8 (CH 2), 50.1 (CH 2), 5l.1 (CH 2),
54.2,61.9,66.6 (CH 2), 68.4, 69.1, 98.0, 169.1. MS:
FAB+ mlz (%) 314 (M+, 28), 299 (M+ -CH3, 6), 283
(M+-OCH 3, 9), 272 (M+-N 3, 6).
Methyl 4-azido-2-N-morpholino-2,3,4,-trideoxy6-0-trityl-a-D-xylo-hexopyranoside 21a. Compound 12 (0.40 g, 1.194 mmole) was deprotected to
syrupy 15a following the procedure for the sy nthesi s
of 18a. A solution of 15a and trityl chloride (0.66 g,
2.39 mmole) in anhyd. pyridine (20 mL) was stirred
overn ight at ambient temperature_ The reaction mixture was poured into satd. aq. NaHC0 3 solution (50
mL) and the aq. layer was extracted with dichloromethane (3 x 20 mL). Organic layers were pooled
together, dried over anhyd. Na2S04, filtered and the
filtrate was concentrated under reduced pressure to a
syrupy mass. The syrup was purified over silica gel
(80% ethyl acetate-pet. ether) to afford 19a (0.51 g,
87 %)_ Methanesulfonyl chloride (0.38 mL, 4.91
mmole) in anhyd. pyridine (10 mL) was added dropwise to a solution of 19a (0.48 g, 0.981 mmole) in
anhyd. pyridine (25 mL) at O°C and the reaction mixture was left at +4°C overnight. After usual work-up
as described for the synthesis of 19a the crude solid
was purified over silica gel (65% ethyl acetate-pet.
ether) to afford a colourless solid of methyl 2,3dideoxy-4-0-mesyl-2-N-morpholino-6-0-trityl-a-D-
ribo-hexopyranoside 20a, yield 0.46 g (76% in 3 steps
from 12); m.p. 188°C (decomp); [a]30 o::+72.6° (c
0.173, CHCI 3); IH NMR: <52.06 (m, IH), 2.41-2.79
(m, 6H), 2.59 (s, 3H), 3.19 (dd, J = 4.9,10.2 Hz, IH),
3.41 (d, J = 2 Hz, IH), 3.47 (s, 3H), 3.74 (m, 5H),
4.70 (m, IH), 4.88 (d, J =3.0 Hz, IH), 7.25-7.49 (m,
15H); I3C NMR: <528.7 (CH 2), 37.9, 50.5 (CH 2), 54.6,
62.1 (CH 2), 62.5, 67.0 (CH 2), 68.8, 74.8, 86.6, 97.8 ,
127.1, 127.7, 128.7, 143.4; MS: EI mJz (%) 567 (M+,
7),552 (M+-CH 3, 4),536 (M+-OCH3, 1). LiN3 (0_23 g,
4.76 mmole) was added to a solution of 20a (0.27 g,
0.476 mmole) in DMF (10 mL) and the mixture was
heated at l20°C for 12 hI'. The reacti on mixture was
worked-up as described for the synthesis of 18a and
the crude product was purified over silica gel (45 %
ethyl acetate-pet. ether) to afford a brownish syrupy
21a, yield 0.20 g (82%); IR (CHCI 3) : 2100 cm-I (N 3);
[af8 o : +17.5° (c 1.005, CHCI 3); IH NMR: <52.08 (m,
2H), 2.52 (m, 2H), 2.70 (m, 3H), 3.18 (m, 1H), 3.353.55 (m, IH), 3.38 (s, 3H), 3_71-3.94 (m, 6H), 4.77 (d,
J =3.0 Hz, 1H), 7.21-7.49 (m, ISH); 13C NMR: <524.5
(CH 2), 49.9 (CH 2), 54.7, 57.6, 59.2, 62.8 (CH 2) , 64.6
(CH 2), 68.1, 87.2, 95.6, 127.0, 127.7, 128.4, 143.6;
MS: EI mlz (%) 514 (M+, 1),472 (M+-N 3, 5).
Methyl 4, 6-diazido-2-N-morpholino-2, 3, 4, 6tetradeoxy -a-D-xylo- hexopyranoside 23a. Compound 12 (0.54 g, 1.61 mmole) was deprotected to a
syrupy compound 15a following the procedure for
the synthesis of 18a. Methanesulfonyl chloride (1.24
mL, 16.11 mmole) in anhyd. pyridine (15 mL) was
added dropwi se to a solution of 15a in anhyd. pyridine (30 mL) at O°C and the solution was left at +4°C
overnight. The reaction mixture was worked-up as
described for the synthesis of 21a and the crude res idue was purified over si lica gel (ethyl acetate) to afford a colourless syrupy methyl 2,3-dideoxy-4,6-0dimesyl-2-N-morpholino-a-D-ribo-hexopyranoside
22a, yield 0.37 g (57% in 2 steps from 12); [a]29.So:
+103.7 (c 0.644, CHCh); IH NMR: 82 .1 2 (g, J =12.0
Hz, 1H), 2.32-2.77 (m, 6H), 3.09 (s, 3H), 3.10 (s, 3H),
3.44 (s, 3H), 3.71 (m, 4H), 3.93 (m, IH), 4.40 (m,
2H), 4.69 (m, IH), 4.80 (d, J =2.0 Hz, 1H); 13C NMR:
<527.4 (CH 2), 37.6, 39.0, 50.5 (CH 2) , 55.2, 62.2, 66 .6
(CH 2), 67.8, 69.2 (CH 2), 73 .2, 98.1; MS: EI mlz (%)
403 (M+, 14), 388 (M+ -CH 3, 8), 372 (M+-OCH 3, 11),
308
(M+-S0 2CH 3, 40) ; AnaL:
Calcd.
for
CI3H2SNOgS2: C, 38.01; H, 6.42; N, 3.83_ Found: C,
38.69; H, 6.24; N, 3.47 %. LiN3 (0.16 g, 3.22 mmole)
was added to a solution of 22 (0.37 g, 0.918 mmole)
in DMF (10 mL) and the mixture was heated over-
RA VINDRAN et al.: SYNTHESIS OF MONO-& DI-AZIDO-HEXOPYRANOSES
1119
night at l20°e. The mixture was worked-up as described for the synthesis of 18a and the crude residue
was purified over silica gel (40% ethyl acetate-pet.
ether) to afford yellowish syrupy 23a, yield 0.17 g
(62%) . IR (CHCI 3): 2120 cm" (N 3); [af4 o: -7.2° (c
0.202, CHCI 3); 'H NMR: 02.10 (m, 2H), 2.51 (m,
2H), 2.66-2.84 (m, 3H), 3.21 (dd, J =6.0, 14.0 Hz,
IH), 3.43 (s, 3H), 3.46-3.56 (m, IH), 3.71 (m, 4H),
3.81 (m, IH), 3.92 (m, IH), 4.83 (d, J =2.9 Hz, IH);
l3C NMR: 024.8 (CH 2), 50.1 (CH 2), 51.5 (CH 2), 54.7,
57.7,58.0,66.5 (CH 2), 67.9, 98.0. MS: FAB+ LR mlz
(%) 297 (M+, 38), 282 (M+ -CH 3, 8), 266 (M+-OCH 3,
16),255 (M+- N3, 13).
MethyI2-N-(acetyl benzylamino) 2,3-dideoxy 4,6O-(phenylmethylene)-a-D-ribo hexopyranoside 14.
To a solution of methyI2-N-benzylamino-2, 3-dideoxy4, 6-0-(phenylmethylene)-a-D-ribo hexopyranoside 13
(0.25 g, 0.704 mmole) in anhyd. pyridine (10 mL), was
added acetic anhydride (0.306 mL, 3.52 mmole) and
the reaction mixture was stirred at ambient temperature
for 8 hr. The reaction mixture was poured into satd. aq.
NaHC03 (40 mL) and the aq. solution was extracted
with dichloromethane (3 x5 mL). Organic layers were
pooled together, dried over anhyd. Na2S04, filtered and
the filtrate was concentrated under reduced pressure to
afford a syrup. The syrup was purified over silica gel
(50% ethyl acetate-pet. ether) to a colourless solid 14,
yield 0.26 g (93%); m.p. 56-7°C; 'H NMR: 01.94 (m,
2H), 2.08 (s, 3H), 3.33 (m, 3H), 3.73 (m, 3H), 4.25 (m,
IH), 4.60-4.87 (m, 3H), 5.04 (m, IH), 5.52 (s, IH),
7.15-7.74 (m, 1OH); l3C NMR: 022.0,28.3 (CH2), 48.7
(CH 2), 51.5, 54.7, 63.9, 69.2 (CH 2), 77.2, 98.3, 101.6,
125.1, 126.0, 126.5, 128.1, 128.6, 128.9, 137.2, 138.4,
172.4; MS: EI mlz (%) 397 (M+, 40), 366 (M+-OCH 3,
18).
2.02 (s, 3H), 3.18-3.49 (m, 2H), 3.30 (s, 3H), 3.81 (m,
IH), 4.55-4.80 (m, 4H), 5.01 (m, IH), 7.05-7.48 (m,
5H); l3C NMR: 020.8, 22.1, 27.7 (CH 2), 48.3 (CH 2),
50.5,51.3 (CH 2), 54.8, 68.2, 69.3, 97.6, 125.1, 126.8,
128.7, 138.5, 169.4, 172.4; MS: EI mlz (%) 376 (M+,
5), 345 (M+-OCH3, 10).
Methyl 2-N-(acetyl benzylamino) -4-0-acetyl-6azido-2, 3, 6-trideoxy-a-D-ribo-hexopyranoside 18b.
Compound 14 (0.40 g, 1.01 mmole) was converted to
methyl 2-N-(acetyl benzylamino)-6-0-tosyl-2, 3dideoxy-a-D-ribo-hexopyranoside 16b following the
procedure described for the synthesis of 16a. To a
solution of 16b (0.28 g, 0.603 mmole) in anhyd. DMF
(5 mL), was added LiN3 (0.295 g, 6.02 mmole). The
reaction mixture was heated at 120°C for 12 hr. The
mixture was worked-up and acetylated, as described for
the synthesis of compound 18a to afford yellowish syrupy 18b, yield 0.15 g (59% in 4 steps from 14); IR
(CHCI 3): 2120 cm-' (N3);[af90:+99.8° (c 0.945,
CHCI 3); 'H NMR: 0 1.79-2.14 (m, 2H), 1.97 (s, 3H),
References
Methyl 2-N-(acetyl benzylamino)-4, 6-diazido-2,
3, 4, 6-tetradeoxy-a-D-xylo-hexopyrano side 23b.
Compound 14 (0.26 g, 0.655 mmole) was deprotected
and mesylated as described for the synthesis of 22a to
afford a yellowish syrupy compound methyl 2-N(acetyl benzylamino)-4,6-0-dimesyl-2,3-dideoxy-a-Dribo-hexopyranoside 22b. To a solution of 22b (0.15 g,
0.322 mmole) in DMF (5 mL), was added LiN3 (0.158
g, 3.22 mmole) and the mixture was heated at 100°C
for 6 hr. The reaction mixture was worked-up as described for the synthesis of 23a to afford a colourless
solid 23b, yield 0.06 g (27% in 3 steps from 14); m.p.
90-loC; IR (CHCh): 2120 cm-' (N3); [a]29 0:+26.9° (c
0.753, CHCh); 'H NMR: 0 1.70-1.90 (m, IH), 2.09 (s,
3H), 2.12-2.25 (m, IH), 3.22-3.36 (m, IH), 3.31 (s,
3H), 3.52 (m, IH), 3.75 (m, IH), 3.89 (m, IH), 4.73 (m,
3H), 5.16·5.27 (m, IH), 7.15-7.38 (m, 5H); l3C NMR:
022.1, 26.7 (CH2), 47.5, 48.5 (CH 2), 51.6 (CH 2), 55.1
58.2,67.8,98.3, 125.2, 127.0, 128.8, 138.7, 172.6. MS:
FAB+ mlz (%) 356 (M+, 4), 328 (M+·OCH3, 100), (M+·
N3, 12); Anal.: Calcd. for C'6H2,N703: C, 53.47; H,
5.89; N, 27.28. Found: C, 52.92; H, 6.09; N, 26.66%.
Acknowledgement
BR thanks the Council of Scientific and Industrial
Research, New Delhi for a fellowship. TP is grateful to
the Department of Science and Technology, New Delhi
for financial support.
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