Synthesis and properties of selected 4-substituted anhydro sugars

Article abstract of DOI:10.1515/znb-2000-0714

A new class of 4-deoxy-4-([4-substituted-1-piperazinyl], [4-morpholinyl] and [4-(perhydro1,4-thiazin-4-y])])-2,3-anhydrolyxopyranosides (3a-g and 6a-g) were synthesized from epoxy triflate moities 2 and 5 and 4-substituted piperazines, morpholines and perhydro-1,4-thiazines, respectively, to test their antibacterial activity. The characterized series of new compounds was tested in vitro against E. coli ATCC11229, S. aureus ATCC6538 and C. albicans SATCC10231.

Full text of DOI:10.1515/znb-2000-0714

Synthesis and Properties of Selected 4-Substituted Anhydro Sugars
Raid J. Abdel-Jalil3, Muhammad Saeeda, Peter Heegb, and Wolfgang Voelter3*
a Abteilung für Physikalische Biochemie des Physiologisch-chemischen Instituts der
Universität Tübingen, Hoppe-Seyler-Strasse 4, D-72076 Tübingen, Germany
b Universitäts-Kliniken-Klinikhygiene, Calwer Strasse 7, D-72076 Tübingen, Germany
*
Reprint request to Prof. Dr. Dr. h. c. Wolfgang Voelter.
E-mail: wolfgang.voelter@uni-tuebingen.de
Z. Naturforsch. 55b, 661-666 (2000); received February 15, 2000
Anhydro Sugars, Piperazine Derivatives
A new class of 4-deoxy-4-([4-substituted-l-piperazinyl], [4-morpholinyl] and [4-(perhydro-
l,4-thiazin-4-yl)])-2,3-anhydrolyxopyranosides (3a-g and 6a-g) were synthesized from ep­
oxy triflate moities 2 and 5and 4-substituted piperazines, morpholines and perhydro-1,4-
thiazines, respectively, to test their antibacterial activity. The characterized series of new
compounds was tested in vitro against E. coli ATCC11229, S. aureus ATCC6538 and C.
albicans SATCC10231.
Piperazine and its derivatives belong to a class
of structures exhibiting a broad spectrum of bio­
logical activities [1-4]. Some of the 1,4-disubsti-
tuted piperazine derivatives show anticonvulsant
and perhydro-l,4-thiazine derivatives. The reac­
tion lead to the formation of lyxo products accord­
ing to the inversion of configuration at C-4.
Vicinal coupling constants in the 'H NMR
spectra are indicative, determining the predomi­
nant conformation in pyranoside rings. For com­
pounds 3a-e and 3g, the signals of 5-H appear as
broad triplets (accidentally 7(4,5) is equal to the
geminal coupling constant 7(5A,5B) with coupling
constants in the range of 10-11 Hz, indicating a
diaxial releationship for 4-H and 5-H and the con­
formation is therefore predominantly °H5. For
compound 3f it is not possible to assign 5-H be­
cause its signal overlaps with 3'-H and 5'-H sig­
nals, but the same conformation is assumed, ac­
[5], bronchospasmolytic [6], antipsychotic [7] and
H r antagonist activity [8], On the other hand, car­
bohydrate derivatives, containing on oxirane ring,
are of current interest due to their enzyme inhibit­
ing effect [9-12]. We therefore considered it to
be of interest to extend our ongoing research and
introduce some 4-substituted piperazines, morpho­
lines and perhydro-l,4-thiazines into position 4 of
the cis-oriented epoxy triflates 2 and 5.
In a recent communication [13], we described a
new methodology for construction of chiral piper­
azines on carbohydrate templates and in continua­ cording to the disappearance of the coupling
tion of our research in the field, we describe herein
an easy access to 4-desoxy-4-[4-substituted-l-piper-
between 1-H and 2-H (1-H appears as a singlet).
In the other series, 6a-g, 7(4,5A) or 7(4,5B) are
azinyl]-pyranosides (3a-e and 6a-e) as well as 4- small (0-4 Hz and 0 Hz, respectively) indicating
desoxy-4-[4-morpholinyl] (3f, 6f) and [4-(perhy-
dro-l,4-thiazin-4-yl)] pyranosides (3 g, 6g).
axial-equatorial, equatorial-equatorial relation­
ships and the adopted conformation is therefore
again predominantly °H5. In a preliminary report
[17], we have described the displacement of the
triflate group with a variety of amino acids leading
to products with conformations in full agreement
with the structures presented here.
The ds-oriented epoxy triflates 2 and 5 were
synthesized from the partially blocked sugars, ben­
zyl 2,3-anhydro-/3-L-ribopyranoside (1) and benzyl
2
,3-anhydro-a-D-ribopyranoside (4), respectively,
by reaction with triflic anhydride in the presence
of pyridine at 0 °C [14], The latter anhydro sugars
were prepared by standard methods [15,16] from
L-arabinose and D-arabinose, respectively. The
facile nucleophilic substitution is due to the pow­
erful triflate leaving group and the strong nucleo-
philicity of the substituted piperazine, morpholine
Bioassay
All the newly synthesized compounds 3a-g and
6a-g were tested in vitro, as hydrochloride salts
in aqueous solutions against E. coli ATCC11229,
0932-0776/2000/0700-0661 $06.00 © 2000 Verlag der Zeitschrift für Naturforschung, Tübingen •www.znaturforsch.com
D
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662
R. J. Abdel-Jalil et al. ■Synthesis and Properties of Selected 4-Substituted Anhydro Sugars
/
6
r °
y — x
N
.....
\
V 7 OCHjPh
o
s
e
3a-g
3'
2'
TfO"
Y - X
N
-----
V3 2 /
“
-
O
O
.
a
V 7 OCH2Ph
O
^
7
OCH2Ph
5
6
T 7 OCH2Ph
Ö
6a-g
No.
a
b
c
d
e
f
g
X
Y
N
N
N
N
N
O
S
CH3
CH2CH3
;
© 'OL,
S. aureus ATCC6538 and C. albicans SATCC10231.
The in vitro antibacterial activity was evaluated by
the minimal inhibitory concentration (MIC) tech­
nique according to the macrodilution method [17].
As positive control, the commercial antibiotic
Ciprofloxacine was used. However, none of the
above compounds showed any significant activity
at concentrations = 500 //g/ml.
elution system and by thin-layer chromatography
TLC) on precoated 0.25 mm silica gel glass plates
60 F254, Merck), employing the elution system
(
(
dichloromethane/ ethyl acetate (70:30). Melting
points of the compounds were recorded with a dig­
ital apparatus of Bachofer and optical rotations
were measured at room temperature with a Zeiss
digital polarimeter, Model LEP A2. !H NMR
spectra were performed with a Bruker AC 250
spectrometer and 13C NMR spectra were recorded
with GASPE (Gated Spin-Echo) on the same in­
strument in deuteriochloroform and TMS was
used as reference standard. All chemical shifts are
given in parts per million and the coupling con­
In conclusion, introduction of 2,3-anhydro-
pyranosides at position 4 of the piperazine moiety
decreases the biological activity against selected
types of bacteria and fungi, compared to piper­
azine derivatives containing aryl or alkyl substi­
tuents. Therefore, it is worth to test these new
compounds after hydrogenation of the benzyl
group not only against bacteria or fungi, but also
as its CNS depressant activity, since a large
number of piperazine derivatives are CNS depres­
sant compounds. This study is now under investi­
gation and will be published separately.
stants (J ) are given in Hertz. Mass spectra were
recorded on a Varian MAT 711 spectrometer.
Tetrahydrofuran was distilled from sodium-benzo-
phenone under an argon atmosphere. Other rea­
gents and chemicals were used as received (from
Aldrich).
General procedure for the preparation of
compounds 3a-g and 6a-g
Experimental
To a stirred solution of epoxy triflate 2 or 5
(1 mmol) in 10 ml dry THF 3 mmol of the corre­
sponding substituted piperazine, morpholine or
perhydro-l,4-thiazine was added. The reaction
The compounds were purified by column chro­
matography (Silica gel, 70-230 mesh ASTM,
Merck) using an ethyl acetate/ dichloromethane
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R. J. Abdel-Jalil et al. • Synthesis and Properties of Selected 4-Substituted Anhydro Sugars
Table I. Physical and analytical data for compounds (3a-g and 6a-g).
663
Compd
Yield
%)
m.p. [°C]
Molecular
formula
Molecular
weight
Analysis [%]
(Calcd/Found)
H
(
C
N
3
a
85
81
8 6
oil
oil
C
C
1 7
H
24
N
2
O
3
304.2
318.2
366.2
384.2
384.2
291.2
307.1
304.2
318.2
366.2
384.2
384.2
291.2
307.1
67.08
7.95
7.93
8.23
8 . 2 0
9.20
9.19
8.80
8.83
7.64
7.59
7.29
7.28
7.29
7.28
4.81
4.80
4.56
4.53
9.20
9.20
8.80
8.78
7.64
7.63
7.29
7.27
7.29
7.23
4.81
4.80
4.56
4.55
6
7.00
67.90
7.87
72.11
2.10
68.73
8.70
68.73
8.71
65.96
5.93
62.52
2.51
67.08
7.03
67.90
7.88
72.11
2.10
68.73
8.72
68.73
8.71
65.96
5.90
62.52
2.50
3b
18 H26 N203
6
3
c
118-119
oil
C22H26N203
7.15
7.13
6.55
6.51
6.55
6.54
7.27
7.29
6.89
6 . 8 8
7
3d
83
83
89
C22H2 5 FN203
6
C2 2 H 25 FN2 0 3
3e
94-95
oil
6
3
f
c
16
h
2 1 n o
4
6
8
6
oil
c 1 6 h 2 1 n o 3s
3
g
6
6a
85
8 6
oil
C17H24N203
7.95
7.94
8.23
8 . 2 0
6
6b
oil
C18 H26 N2 0 3
6
6
c
8 6
oil
C22H26N203
C22H25FN203
C22H25FN203
C16H21N04
7.15
7.15
6.55
6.53
6.55
6.53
7.27
7.24
6.89
6 . 8 8
7
6d
80
82
90
94-95
6
6
e
1 1 1 - 1 1 2
6
6
f
oil
99-100
6
8
6
c 1 6 h 2 1 n o 3s
6
g
6
mixture was then stirred untill the TLC analysis
showed no more starting material. The aqueous
workup yields the 4- substituted lyxopyranoside
derivatives.
Benzyl-2,3-anhydro-4-deoxy-4-(4-ethyl-
l-piperazinyl)-a-D-lyxopyranoside (3b)
XH NMR (250 MHz, CDC13); (3 = 1.27-7.70 (m
H, C H5), 4.99 (s, 1H, 1-H), 4.79 (d, J = 11.6 Hz,
H, OC//HPh), 4.56 (d, 11.9 Hz, 1H,
= 10.7, 11.0 Hz, 1H, 5A-H),
= 0.9, 6.4, 11.0 Hz, 1H, 5B-H), 3.36 (d,
= 3.7 Hz, 1H, 2-H), 3.10 (d, = 4.0 Hz, 1H,
= 6.1, 10.4 Hz, 1H, 4-H), 2.39-
2.86 (m, 10H, H-2', H-3', 5B-H, H- ', N-
CH2CH3), 1.09 (t, J = 7.2 Hz, 3H, N-CH CH3).
GASPE NMR (63 MHz, CDC13): <3 = 11.9 (N-
CH CH3), 49.4, 53.0 (C-2', C-3', C-5', C- '), 50.1,
52.3 (C-2. C-3), 52.7 (N-C// CH3), 55.7 (C-5),
56.0 (C-4), 69.8 (OCH Ph), 94.0 (C-l), 128.0-
128.5, 137.3, (C H 5). FAB-MS: m/z = 319; [a]D =
+71.1° (c = 0.37, CH C12).
5
1
6
J
=
OCH//Ph), 3.75 (dd,
J
Benzyl-2,3-anhydro-4-deoxy-4-(4-methyl-
1-piperazinyl)-a-D-lyxopyranoside (3a)
3.50 (ddd, J
J
J
*
H NM R (250 MHz, CDC13): <3 = 7.28-7.38 (m,
H, C6H 5), 4.99 (s, 1H, 1-H), 4.80 (d, J = 11.9 Hz,
H, OC/ZHPh), 4.56 (d, 11.6 Hz, 1H,
3-H), 2.91 (dd, J
5
1
6
J
=
2
OCH//Ph), 3.74 (dd, J = 10.7, 11.0 Hz, 1H, 5A-H),
.52 (ddd, = 0.9, 6.4, 11.0 Hz, 1H, 5B-H) 3.35 (d,
J = 3.7 Hz, 1H, 2-H), 3.09 (d, = 4.0 Hz, 1H,
-H), 2.91 (dd, = 6.4, 10.7 Hz, 1H, 4-H), 2.61-
.85 (m, 8H, H-2\ H-3', H-5', H-6'), 2.28 (s, 3H,
N-CH3). GASPE NMR (63 MHz, CDC13): (3 =
4.5 (N-CH3), 47.9, 53.8 (C-2', C-3', C-5', C-6'),
8.6, 51.1 (C-2, C-3), 54.1 (C-5), 54.4 (C-4), 68.3
OCH2Ph), 92.5 (C-l), 126.4-127.0, 137.0 (C6H5).
3
J
2
6
J
2
3
J
2
2
6
2
4
4
(
Benzyl-2,3-anhydro-4-deoxy-4-(4-phenyl-
l-piperazinyl)-a-D-lyxopyranoside (3c)
FAB-MS: m/z = 305; [a]D = +77.3° (c = 0.35,
CH2C12).
’H NM R (250 MHz, CDC13): (3= 6.85-7.39 (m,
10H, C6 H5, C6 H5'), 5.28 (s, 1H, 1-H), 5.10 (d, J =
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664
R. J. Abdel-Jalil et al. • Synthesis and Properties of Selected 4-Substituted Anhydro Sugars
1
1.6 Hz, 1H, OC//HPh), 4.58 (d,
OCHT/Ph), 4.09 (dd, = 10.6, 10.7 Hz, 1H, 5A-H),
.85 (dd, J = 6.1, 11.0 Hz, 1H, 5B-H), 3.70 (b.d, J =
J
= 11.7 Hz, 1H,
4H,
C
2
-H,
C6 -H). GASPE NMR(63 MHz,
J
CDCI3 ): d: 50.2 (C2S Ce-), 67.1 (C3S C5-), 50.0, 52.3
(C-2, C-3), 55.6 (C-5), 56.4 (C-4), 69.9 (OCH
94.1 (C-l), 128.1-128.6, 137.0, 157.7, (C
3
2
6
Ph),
H5).
3
C
.4 Hz, 1H, 2-H), 3.50 (bt,
J
= 4.6 Hz, 4H, C
= 4.0 Hz, 1H, 3-H), 3.07-3.30 (m,
'-H, C -H). GASPE NMR (63 MHz,
= 49.5, 49.7 (C-2', C-3', C-5', C- '), 50.3,
2.1 (C-2, C-3), 55.7 (C-5), 56.1 (C-4), 70.0
OCH Ph), 94.1 (C-l), 116.3, 120.1, 128.1-129.2,
37.1, 158.2 (C H5, C H s'). FAB-MS: m/z= 305;
a]D = +67.6° (c = 0.11, CH C12).
3 -H,
5
-H), 3.41 (d,
J
FAB-MS: m/z= 292; [a]D = +81.3° (c = 0.51,
CH C12).
5
H, 4-H, C
2
6
2
CDC13):
5
ö
6
Benzyl-2,3-anhydro-4-deoxy-4-(perhydro-l,4-
thiazin-4-yl)-a-D-lyxopyranoside (3g)
(
2
1
[
6
6
lH NMR (250 MHz, CDC13): 7.21-7.34 (m, 5H,
2
C
6
H5), 4.90 (s, 1H, 1-H), 4.73 (d,
OCtfHPh), 4.49 (d, / = 11.9 Hz, 1H, OCH//Ph),
.70 (dd, = 10.4, 11.0 Hz, 1H, 5A-H), 3.43 (dd,
= 6.4,11.6 Hz, 1H, 5B-H), 3.31 (b.s, 1H, 2-H),
3.06-2.62 (m, 10H, 3-H, 4-H, Cr -H, C3-H C -H,
.-H). GASPE NMR (63 MHz, CDCI ): (3: 28.3,
29.7 (C3-, Cv), 52.3 (C2S C6-), 50.1, 52.0 (C-
C-3), 55.0 (C-5), 57.4 (C-4), 70.0 (OCH Ph), 94.0
(C-l), 128.1-128.6, 137.0, (C H5). FAB-MS: m/z=
308; [a]D = +72.2° (c = 0.17, CH C12).
J = 11.9 Hz,
Benzyl-2,3-anhydro-4-deoxy-4-[4-(2-fluoro-
phenyl)-l-piperazinyl]-a-D-lyxopyranoside (3d)
3
J
J
XH NMR (250 MHz, CDCI
H, C H5), 6.91-7.07 (m, 4H, C
-H), 4.83 (d, = 11.9 Hz, 1H, OC//HPh), 4.59 (d,
J = 11.9 Hz, 1H, OCH//Ph), 3.86 (dd, = 10.1,
0.7 Hz, 1H, 5A-H), 3.60 (dd, = 5.6, 11.3 Hz, IH,
B-H), 3.47 (bs, 1H, 2-H), 2.92-3.17 (10H, m, 3-H,
-H, Cr -H, C -H C -H, C -H). GASPE NMR
63 MHz, C D C I3): = 49.8, 50.6 (C-2', C-3', C-5',
C- '), 50.3, 52.1 (C-2, C-3), 55.5 (C-5), 56.2
C-4), 70.0 (OCH Ph), 94.1 (C-l), 116.0, 116.3,
19.2, 123.0, 124.5, 128.1-128.6, 137.1, 155.2
H5, C H4). FAB-MS: m/z = 376; [a]D = +58.5°
c = 0.13, CH C12).
3
): (3 - 7.25-7.38 (m,
5
5
1
6
6
H4), 5.00 (s, 1H,
C
6
3
J
2 ,
J
2
1
J
6
5
4
2
3
5
6
(
ö
Benzyl-2,3-anhydro-4-deoxy-4-(4-methyl-
l-piperazinyl)-ß~L-lyxopyranoside a)
6
(
6
(
1
2
!
H, C H5), 5.01 (d,
H NMR (250 MHz, CDC13): (3= 7.29-7.40 (m,
= 2.4 Hz, 1H, 1-H), 4.79 (d,
5
J
6
J
(
(
C
6
6
= 12.2 Hz, 1H, OC//HPh), 4.60 (d, J = 12.6 Hz,
H, OCH//Ph), 3.86 (dd, / = 3.4, 12.5 Hz, 1H,
2
1
5
2
8
A-H), 3.66 (d, J = 12.8 Hz, 1H, 5B-H) 3.34 (m,
H, 2-H, 3-H), 2.92 (bs, 1H, 4-H), 2.46-2.82 (m,
Benzyl-2,3-anhydro-4-deoxy-4-[4-(4-fluoro-
phenyl)-l-piperazinyl]-a-D-lyxopyranoside (3e)
H, C2 -H, C3 -H, Cv-H, C6 -H ), 2.29 (s, 3H,
>
H NMR (250 MHz, CDC13): <5 =: 7.31-7.39 (m,
H, C H5), 6.90-7.00 (m, 4H, C H4), 5.03 (s, 1H,
-H), 4.82 (d, = 11.9 Hz, 1H, OC//HPh), 4.57 (d,
= 11.9 Hz, 1H, OCH//Ph), 3.80 (dd, / = 10.5,
0.7 Hz, 1H, 5-H), 3.57 (ddd, J = 0.91, 6.4,11.3 Hz,
H, 5A-H), 3.41 (d, J = 3.7 Hz, 1H, 2-H), 2.74-
.13 (m, 10H, 3-H, 4-H, Cr -H, C3-H C -H, C6-
H). GASPE NMR (63 MHz, CDC13):
= 49.8,
0.9 (C-2', C-3', C-5', C- '), 50.3, 52.7 (C-2, C-3),
5.7 (C-5), 56.1 (C-4), 69.9 (OCH Ph), 94.1 (C-l),
16.0, 116.4, 119.2, 122.5, 122.8, 124.5, 124.6,
N-CH3). GASPE NMR (63 MHz, CDC13):
46.1 (N-CH3), 50.3, 55.5 (C-2', C-3', C-5', C-
ö
=
'),
5
1
6
6
6
J
51.1, 51.8 (C-2, C-3), 57.0 (C-5), 56.95 (C-4), 69.1
(OCH Ph), 92.4 (C-l), 127.8-128.5, 137.6 (C H5).
FAB-MS: m/z= 305; [a]D = +46.9° (c = 0.10,
CH C12).
J
1
1
2
6
2
3
5
ö
Benzyl-2,3-anhydro-4-deoxy-4-(4-ethyl-
l-piperazinyl)-ß-L-lyxopyranoside (6b)
5
6
5
1
1
2
'
H NMR (250 MHz, CDC13):
H, C H5), 4.93 (d, J = 3.1 Hz, 1H, 1-H), 4.73 (d,
= 12.5 Hz, 1H, OC//HPh), 4.53 (d, = 12.5 Hz,
H, OCH//Ph), 3.79 (dd, = 3.4, 12.5 Hz, 1H,
= 12.5 Hz, 1H 5B-H), 3.27 (m,
H, 2-H, 3-H), 2.84 (dd, - 1.5, 2.2 Hz, 4-H),
.34-2.78 (m, 10H, C -H, C -H, C -H, C -H,
CH3), 1.03 (t,/= 7.2 Hz, 3H, N-CH
d = 7.19-7.33 (m,
5
J
6
28.0-128.5, 137.3, 153.2 157.7 (C6 H5, C6 H4).
J
FAB-MS: m/z= 385; [a]D = +67.3° (c = 0.11,
CH C12).
1
J
2
5
2
2
A-H), 3.59 (bd, J
J
Benzyl-2,3-anhydro-4-deoxy-4-(4-morpholino)-
a-D-lyxopyranoside (3f)
2
3
5
6
N-C//
GASPE NMR (63 MHz, CDC13):
(N-CH
51.0, 51.8 (C-
4), 57.5 (C-5), 69.1 (OCH
128.5, 137.6 (C H5). FAB-MS: m/z = 319; [a]D =
+49.0° (c = 0.24, CH C12).
2
2
CH3).
'
H NMR (250 MHz, CDC13): 7.27-7.41 (5H, m,
H5), 4.99 (s, 1H, 1-H), 4.80 (d, = 11.9 Hz, 1H,
OC/THPh), 4.57 (d, = 11.9 Hz, 1H, OCH//Ph),
.73 (m, 5H, 5A-H, C -H, Cv-H), 3.54 (ddd,
.2, 6.4, 11.3 Hz, 5B-H), 3.37 (d, J = 3.7 Hz, 1H,
-H), 3.11 (d, J = 3.7 Hz, 1H,. 3-H), 2.59-2.92 (m.
ö
=
11.8
C
6
J
2
CH3), 50.2, 53.2 (C-2', C-3', C-5', C-
. C-3), 52.3 (N-CH CH,), 57.0 (C-
Ph), 92.4 (C-l), 127.8-
6 '),
J
2
2
3
3
J
=
2
1
2
6
2
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R. J. Abdel-Jalil et al. • Synthesis and Properties of Selected 4-Substituted Anhydro Sugars
665
Benzyl-2,3-anhydro-4-deoxy-4-(4-phenyl-
OC//HPh), 4.61 (d, J = 12.2 Hz, 1H, OCH//Ph),
3.92 (bd, = 11.3 Hz, 1H, 5-H), 3.74 (bd, J = 11.3
Hz, 1H, 5B-H), 3.38 (m, 2H, 2-H, 3-H), 2.94-3.15
m, 9H, 4-H, Cr -H, C3-H C <-H, C -H). GASPE
NMR (63 MHz, CDC13): ö = 50.6 (C-2', C-3',
C-5', C- '), 54.5 (C-2, C-3), 55.7 (C-5), 56.1
C-4), 69.2 (OCH Ph), 92.1(C-1), 116.0-128.5,
37.3, 157.7, 155.1 (C H5, C H4). FAB-MS: m/z=
85; [a]D = +33.9° (c = 0.36, CH C12).
1
-piperazinyl)-ß-L-lyxopyranoside
(
6
c)
H NMR (250 MHz, CDC13): (3 = 6.84-7.41 (m,
0H, C H5, C H 5'), 4.98 (d, = 2.7 Hz, 1H, 1-H),
J
!
(
5
6
1
6
6
J
4
1
.74 (d, J = 12.2 Hz, 1H, OC//HPh), 4.54 (d, J =
2.2 Hz, 1H, OCH//Ph), 3.84 (dd, = 3.4, 12.6 Hz,
H, 5A-H), 3.67 (d, = 12.5 Hz, 1H, 5B-H), 3.34
m, 2H, 2-H, 3-H), 3.34 (bs, 4H, C -H, C -H), 2.92
-H). GASPE NMR (63
= 49.6, 50.6 (C-2', C-3', C-5',
6
J
(
1
3
2
1
J
6
6
(
(
3
5
2
m, 5H, 4-H, C
2
-H, C
6
MHz, CDC13):
C-
OCH
37.2 (C
22.1° (c = 0.11, CH
ö
Benzyl-2,3-anhydro-4-deoxy-4-(4-morpholino)-
ß-L-lyxopyranoside (6f)
6
'), 51.8 (C-2, C-3), 56.7 (C-5), 57.3 (C-4), 69.2
Ph), 92.3 (C-l), 116.3, 120.0, 127.0-129.2,
H 5, C H5'). FAB-MS: m/z= 367; [a]D =
C12).
(
1
+
2
]
H NMR (250 MHz, CDC13): 7.27-7.40 (m, 5H,
H5), 5.02 (d, J = 3.1 Hz, 1H, 1-H), 4.80 (d, J =
2.2 Hz, 1H, OC//HPh), 4.60 (d, = 12.2 Hz, 1H,
OCH//Ph), 3.89 (dd, = 3.4, 12.8 Hz, 1H, 5A-H),
.68-3.74 (m, 5H, 5B-H, C -H, C -H), 3.36-3.43
m, 2H, 2-H, 3-H), 2.77-2.40 (m, 5H, 4-H, C -H,
Q-H). GASPE NMR (63 MHz, CDC13): (3: 51.0
6
6
C
6
2
1
J
J
Benzyl-2,3-anhydro-4-deoxy-4-[4-(2-fluoro-
phenyl)-l-piperazinyl]-ß-L-lyxopyranoside (6d)
3
3
5
(
2
lH NMR (250 MHz, CDC13): (5= 7.28-7.41 (m,
5
2
H, C
.7 Hz, 1H, 1-H), 4.81 (d,
= 12.2 Hz, 1H, OCH//Ph),
= 3.1, 12.5 Hz, 1H, 5A-H), 3.77 (d, J =
3.1 Hz, IH, 5B-H), 3.48 (bs, 1H, 3-H), 3.39 (dd,
= 2.9, 3.1 Hz, 2-H), 3.00-3.17 (9H, m, 4-H,
-H, C3-H Cv-H, -H). GASPE NMR
63 MHz, CDCI ): (3 = 50.7 (C-2', C-3', C-5',
C- '), 51.9, 55.1 (C-2, C-3), 56.2 (C-5), 57.1
C-4), 69.9 (OCH Ph), 92.3 (C-l), 116.0, 119.2,
24.5, 127.9-128.5, 137.1 (C H5, C H4). FAB-MS:
m/z= 385; [a]D = +36.8° (c = C12).
6
H5), 6.99-7.10 (m, 4H, C
6
H4), 5.05 (d, / =
(
(
C2-, QO, 67.1 (C3S C5-), 50.9, 51.8 (C-2, C-3), 56.8
C-5), 57.6 (C-4), 69.1 (OCH Ph), 92.2 (C-l),
27.9-128.5, 137.5 (C H5). FAB-MS: m/z= 292;
a]D = +47.2° (c = 0.28, CH C12).
J
= 12.2 Hz, 1H,
2
OC//HPh), 4.62 (d,
.92 (dd,
J
1
[
6
3
J
2
1
J
C
(
Benzyl-2,3-anhydro-4-deoxy-4-(perhydro-
l,4-thiazin-4-yl)-ß-L-lyxopyranoside
g)
H NMR (250 MHz, CDC13): 7.27-7.39 (m, 5H,
2
C6
(
6
3
’
6
C
6
H5), 5.00 (d, J = 2.7 Hz, 1H, 1-H), 4.80 (d, J =
(
2
1
2.5 Hz, 1H, OCH//Ph), 4.61 (d, J = 12.2 Hz, 1H,
OCH//Ph), 3.87 (d, J = 11.90 Hz, 1H, 5A-H), 3.71
d, J = 12.5 Hz, 1H, 5B-H), 3.34 (b.s, 2H, 2-H,
1
6
6
0 .1 0 , CH2
(
3
4
-H), 3.00 (b.s, 5H, 4-H, Cr -H, C
H, C -H, C -H). GASPE NMR (63 MHz,
): (3: 27.6 29.2 (C3S C5S C2, C6-), 51.8(C-2,
C-3), 53.00 (C-5), 58.7 (C-4), 69.2 (OCH Ph), 92.2
(C-l), 127.9-128.5 (C H5). FAB-MS: m/z= 308;
[a]D = +46.7° (c = 0.10, CH C12).
3 <-H), 2.67 (b.s,
Benzyl-2,3-anhydro-4-deoxy-4-[4-(4-fluoro-
phenyl)-l-piperazinyl]-ß-L-lyxopyranoside (6 e)
5
6
CDCI
3
NMR (250 MHz, CDC13): ö =: 7.28-7.41 (m,
H, C H5), 6.84-7.00 (m, 4H, C H4), 5.05 (d,
.1 Hz, 1H, 1-H), 4.81 (d, = 12.2 Hz, 1H,
2
5
6
6
J
=
6
3
J
2
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66
R. J. Abdel-Jalil et al. • Synthesis and Properties of Selected 4-Substituted Anhydro Sugars
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