Vinylsulfone-modified carbohydrates: First general route to D-lividosamine (2-amino-2,3-dideoxy-D-glucose) and its new analogues

Article abstract of DOI:10.1016/S0040-4020(00)01081-4

A general route to D-lividosamine and its new analogues has been devised for the first time. The essence of the present synthetic route lies in the diastereoselective introduction of N-monoalkylated and N-dialkylated amines to C-2 carbons of methyl 2,3-di

Full text of DOI:10.1016/S0040-4020(00)01081-4

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1093±1098
Vinylsulfone-modi®ed carbohydrates: ®rst general route
to d-lividosamine (2-amino-2,3-dideoxy-d-glucose) and its
new analogues
²
Bindu Ravindran, Sachin G. Deshpande and Tanmaya Pathakp
Organic Chemistry Division (Synthesis), National Chemical Laboratory, Pune 411 008, India
Received 31 July 2000; revised 26 October 2000; accepted 9 November 2000
AbstractÐA general route to d-lividosamine and its new analogues has been devised for the ®rst time. The essence of the present synthetic
route lies in the diastereoselective introduction of N-monoalkylated and N-dialkylated amines to C-2 carbons of methyl 2,3-dideoxy-3-C-
phenylsulfonyl-a-d-hex-2-enopyranoside and methyl 2,3-dideoxy-3-C-phenylsulfonyl-b-d-hex-2-enopyranoside in equatorial con®gura-
tions. The 2-amino-2,3-dideoxysugrs thus generated, are desulfonated reductively at C-3 sites to produce a known intermediate for the
synthesis of d-lividosamine and several new 2-N-alkylamino- and 2-N,N-dialkylamino-2,3-dideoxy analogues. q 2001 Elsevier Science Ltd.
All rights reserved.
1. Introduction
synthesis will be the designing of methodologies for the
generation of several new modi®ed aminosugars having
one or more deoxygenated centers and mono- or dialkylated
amino groups at speci®c sites.
The most important mechanism of resistance to amino-
glycoside antibiotics among resistant bacteria arises from
enzymatic N-acetylation, O-phosphorylation, and O-nucleo-
tidylation of speci®c sites in the antibiotics. To avoid such
deactivation processes, several semisynthetic aminoglyco-
side 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 acylation or alkylation.1
The interest in this class of compounds has been renewed
with the discoveries that aminoglycoside antibiotics interact
with a variety of RNA molecules.2a±d Other studies on
aminoglycoside antibiotics have shown that: (a) the amines
in these molecules play an important role in relation to their
toxicities, either because of their basic characters or their
interactions with phospholipid bilayers of the inner cortex
tissue; and (b) regiochemical preferences of aminoglyco-
sides are caused by steric reasons and/or the varying
basicity of amino groups present in aminoglycosides.2e
Interestingly, a study addressing the contribution of ring
IV in the properties of neomycin B concluded that gross
changes were tolerated in the structure of aminoglycoside
antibiotics without signi®cant effect on biological activity.2f
It would, therefore, be appropriate to synthesize new anti-
biotics carrying various amino groups with varying basici-
ties and steric bulks. However, the ®rst step of such a
2. Results and discussion
d-Lividosamine (2-amino-2,3-dideoxy-d-glucose) (Fig. 1),
isolated from Streptomyces Lividus,3 is present in amino-
glycoside antibiotics such as lividomycin-A, lividomycin±
B and 30-deoxykanamycin C.4a Several other aminosugars,
structurally related to d-lividosamine are present in tobra-
mycin, dibekacin and gentamicins.4b±d The essence of the
synthetic strategy leading to the preparation of d-lividos-
amine and its alkylated analogues lies in the introduction
of amino and N-alkyl amino groups. These must be intro-
duced at the C-2 carbon of the pyranoses in equatorial
con®gurations followed by (or prior to) deoxygenation at
the C-3 site. Several methods of synthesis of d-lividosamine
starting from d-glucose,5 d-glucosamine,6 ethyl 2,3-
dideoxy-a-d-glycero-hex-2-enopyranoside-4-ulose,7 tri-O-
acetyl glucal,8 1,6-anhydro-b-d-glucose9and even from
non-carbohydrate sources like `naked sugars' have been
Keywords: d-lividosamine; carbohydrates; vinyl sulfone; Michael addition.
Corresponding author. Tel./fax: 191-20-5893153
p
²
Present address: Department of Chemistry, The University of Iowa, Iowa
City, IA 52242, USA.
Figure 1.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01081-4

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B. Ravindran et al. / Tetrahedron 57 (2001) 1093±1098
Scheme 1. Reagents: (i) Ref. 13, 88% (in 4 steps); (ii) PhCH2NH2, MeOH, re¯ux, 15 h, 90%; (iii) Mg, MeOH, re¯ux, 11 h, 90%; (iv) a. Pd(OH)2, C, H2, EtOH,
rt, 22 h, b. Ac2O, Py, rt, 4 h, 79%.
reported.10 Nevertheless, no method11,12 reported so far had
the potential to be exploited as a general route for the syn-
thesis of 2-amino-2,3-dideoxy-d-glucose and its analogues
carrying various N-monoalkyl- and N-dialkylamino groups.
the phenylsulfonyl group is very suitably located in all these
products to generate methylene groups at C-3 via reductive
desulfonation leading to the synthesis of a reported5,6 inter-
mediate 6 of d-lividosamine. Several partially and fully
protected analogues of d-lividosamine could be synthesized
using a similar approach.
We have recently reported that amines, both primary and
secondary, react in a diastereoselective fashion with methyl
2,3-dideoxy-3-C-phenylsulfonyl-a-d-hex-2-enopyranoside
2 and methyl 2,3-dideoxy-3-C-phenylsulfonyl-b-d-hex-2-
enopyranoside 13.13 Such a C±N bond formation in Michael
fashion at C-2 of the vinylsulfone-modi®ed carbohydrates
exclusively produced the thermodynamically more stable
C±N equatorial aminosugars with primary amines. Second-
ary amines, on the other hand produced a mixture of gluco-
(major) and manno-(minor) products with a-anomer 2. The
major isomers were separated by crystallization. Primary as
well as secondary amines produced only the gluco-deriva-
tive with b-anomer 13.13 We envisaged that benzylamine
would react with 2 and 13 to generate exclusively the gluco-
isomer, from which the benzyl group could be removed
reductively to generate the free amino function. In addition,
Compound 213 was reacted with benzylamine in anhydrous
methanol to produce 314 exclusively in 90% yield.
Compound 3 was desulfonated on treatment with mag-
nesium in methanol in 90% yield to generate the 2-N-
benzylamino-2,3-dideoxy product 4. Compound 4 was
debenzylated to 5 on treatment with palladium hydroxide
on charcoal. Crude 5 was isolated as the acetyl derivative 6
(Scheme 1).5,6 However, to reduce the number of steps
involved in the synthesis of 6, compound 2 was reacted
directly with conc. aq. ammonia in dioxane. The reaction
produced a mixture of products although the desired
deoxyaminosugar 7 was present in a major amount
(1H-NMR). No attempt was made to establish the identity
Scheme 2. Reagents: (i) 30%, aq. NH3, dioxane, rt, 24 h; (ii) MeOH, Mg,
re¯ux, 3.5 h; (iii) Ac2O, Py, rt, 16 h, 65% (in three steps).
Scheme 3. Reagents: (i) Mg/MeOH, re¯ux.

B. Ravindran et al. / Tetrahedron 57 (2001) 1093±1098
1095
Scheme 4. Reagents: (i) Ref. 13, 75% (in 4 steps); (ii) for 13: neat PhCH2NH2, 90±1008C, 3 h, 75%; for 14 and 15: Ref. 13; (iii) MeOh, Mg, re¯ux.
of the impurity. The mixture was desulfonated as above and
the free amino compound 5 was acylated. Pure 6 was
crystallized out from benzene-pet. ether mixture in 65%
overall yield (Scheme 2). Similarly, the pyrrolidino and
morpholino derivatives 813 and 913 were desulfonated to
10 and 11 in 91 and 85% yields, respectively (Scheme 3).
ethyl 2-acetamido-2,3-dideoxy-a-d-ribo-hexapyranoside
via 23 (Fig. 2); the overall yield from glucal was less than
45%.8 Synthesis of N-protected d-lividosamine starting
from compound 24 (Fig. 2) had an overall yield of 29%.9
Our methodology (Scheme 1) afforded 6 in overall 40%
starting from methyl-a-d-glucopyranoside or in 56% from
the manno epoxide 1.
In the b-series, compound 13, which was obtained from
epoxide 12,13 was reacted with neat benzylamine to produce
exclusively the 2-N-benzylamino-2,3-dideoxy product 1414
in 90% yield. Compound 14 and previously synthesized 1513
and 1613 were desulfonated to 17, 18 and 19 in 76, 42 and
47% yields, respectively (Scheme 4).
A comparison of the ef®ciency of the present method for the
synthesis of intermediate 6 over the earlier reported routes
from carbohydrates would be pertinent here. The major
dif®culty encountered, in the synthesis of d-lividosamine
from d-glucose5 was the reduction of acetylimino-glycoside
20 (Fig. 2) to the corresponding amine which afforded a
mixture of ribo and arabino isomers.5c The reduction of
20 with LiAlH4, followed by acetylation, gave only 38%
pure ribo isomer. In the case of synthesis from d-glucos-
amine, the deoxygenation of the secondary hydroxyl group,
C-3, was problematic because of the stereoelectronic
2
hindrance of an SN process at this carbon. Moreover, the
presence of the amino group, ironically, required an
additional step for the protection of the amino group to
get 21 (Fig. 2) as the starting material. These factors
contributed to the lower overall yield of the ®nal product;6
in any case, this method could not have been used for the
generation of analogues. The addition of NaN3 to 227(Fig. 2)
always afforded a mixture at C-2 (ribo:lyxo). Further, the
reduction of the carbonyl group again produced a mixture of
isomers (erythro and threo). Thus, the overall yield was
reduced to 7%.7 Tri-O-acetyl glucal was converted to
Figure 2.

1096
B. Ravindran et al. / Tetrahedron 57 (2001) 1093±1098
3. Conclusion
benzylamine (2 mL) was heated for 3 h at 90±1008C. The
reaction mixture was taken in EtOAc (40 mL), washed with
water (3£15 mL), dried over anhydrous Na2SO4, and evapo-
rated under reduced pressure. The resulting syrup was puri-
®ed on silica gel (eluent 65% EtOAc±petroleum ether) to
yield the title compound 14 (0.23 g, 75%) as a white solid,
m.p. 143±1448C; [Found: C, 65.00; H, 6.70; N, 2.85.
Although the C±N bonds at the C-2 positions of naturally
occurring aminosugars, d-glucosamine,15 d-galactos-
amine,15 d-lividosamine3,15are present in equatorial con®g-
urations, there are only a few reports on the synthesis of
equatorially located N-alkyl and N,N-dialkyl-d-glucos-
amine derivatives via N-alkylation or N,N-dialkylation of
glucosamine.16 The other most commonly used methods
for the synthesis of aminosugars, involved opening of
epoxides 1 or 12 by amines that always produced the C-3
deoxy C-3 aminosugars and not the C-2 deoxy C-2 amino-
sugars.17 Reactions of primary and secondary amines with
C27H29NO6S requires C, 65.43; H, 5.90; N, 2.83%]; ‰aŠ24 2
D
66:6 (cˆ 1.016, CHCl3); nmax(CHCl3) 3427, 1635, 1384,
1320, 1145, 1105 cm21; dH 7.76 (2 H, m, aromatic),
7.50±7.25 (11 H, m, aromatic), 7.03 (2 H, m, aromatic),
5.30 (1 H, s, PhCH), 4.49 (1 H, d, Jˆ6.6 Hz, H-1), 4.29
(1 H, dd, Jˆ4.8, 10.6 Hz), 4.13±3.91 (3 H, m), 3.73 (1 H,
t, Jˆ10.3 Hz), 3.62±3.36 (3 H, m), 3.58 (3 H, s, OMe). dC
140.3, 136.3, 133.4, 129.0, 128.8, 128.6, 128.4, 127.9, 127.0,
126.1, 106.5, 101.3, 75.8, 69.0 (CH2), 66.9 (2 peaks), 57.2,
56.9, 53.0 (CH2); m/z (EI) 355 (17, M1-SO2Ph1H), 354 (7,
M1-SO2Ph).
methyl
2,3
anhydro-4,6-O-(phenylmethylene)-d-allo-
pyranoside, on the other hand, produced exclusively the
C-2 deoxy, C-2 amino products with the C±N bond in the
axial con®guration.18 None of the above methods could
have been used as a general route11,12 for the synthesis of
d-lividosamine and its analogues either because of the
undesired con®guration or position of the C±N bond and/
or the additional functionalization of the C-3 hydroxyl
groups required for the deoxygenation of the C-3 center.
Our method circumvents both the problem of the intro-
duction of N-monoalkylated and N-dialkylated amines to
the C-2 carbon of pyranoses in equatorial con®gurations
as well as the deoxygenation of the C-3 position. It also
compares well with the reported5±10 synthesis starting
from d-glucosamine or d-glucose and could be used as a
general route for the synthesis of d-lividosmaine and its
analogues. Work is currently in progress to synthesize
unnatural aminoglycoside antibiotics using some of these
analogues of d-lividosamine.
4.1.3. General procedure for the desulfonation of (3), (7),
(8), (9), (14), (15) and (16). To a solution of substrate
(1 mmol) in anhydrous methanol (35 mL), was added
magnesium turnings (15 mmol). The reaction mixture was
heated under re¯ux for 1±12 h. Solvent was evaporated to
dryness under reduced pressure. The resulting residue was
dissolved in EtOAc (50 mL), and ®ltered. The ®ltrate was
washed with water (3£20 mL), dried over anhydrous
Na2SO4, and evaporated to dryness under reduced pressure.
The resulting syrup was puri®ed by column chromatography
on silica gel (eluents mentioned against each experimental
procedure in brackets) to give pure desulfonated products.
4.1.4.
Methyl
2-N-benzylamino-2,3-dideoxy-4,6-O-
(phenylmethylene)-a-d-ribo-hexopyranoside (4). Com-
pound 3 (0.68 g, 1.37 mmol) was desulfonated (eluent
65% EtOAc±petroleum ether) in 11 h to yield a white
solid 4 (0.41 g, 90%), m.p. 97±988C; [Found: C, 70.62; H,
7.62; N, 3.67. C21H25NO4 requires C, 70.96; H, 7.09; N,
4. Experimental
4.1. General
3.94%]; ‰aŠ24 1 2:3 (cˆ0.103, CHCl3); nmax(Nujol) 3460,
For general methods see Ref. 13.
D
1633, 1365, 1097 cm21; dH 7.35±7.20 (10 H, m, aromatic),
5.25 (1 H, s, PhCH), 4.69 (1 H, d, Jˆ3.3 Hz, H-1), 4.26 (1 H,
dd, Jˆ3.3, 8.7 Hz), 3.80±3.47 (5 H, m), 3.42 (3 H, s, OMe),
2.92 (1 H, m), 2.33 (1 H, dt, Jˆ4.2, 11.4 Hz), 1.74 (1 H, q,
Jˆ11.7 Hz); dC 140.1, 137.7, 128.9, 128.4, 128.2, 128.1,
127.1, 126.2, 101.6, 98.9, 77.2, 69.4 (CH2), 64.3, 55.2,
55.0, 50.2 (CH2), 31.0 (CH2); m/z (EI) 355 (3 M1), 324
(3, M1-OCH3).
4.1.1. Methyl 2-N-benzylamino±2,3-dideoxy-4,6-O-
(phenylmethylene)-3-C-phenylsulfonyl-a-d-glucopyrano-
side (3). Benzylamine (1.01 mL, 9.29 mmol) was added to a
solution of 2 (0.72 g, 1.86 mmol) in anhydrous methanol
(25 mL). The solution was heated under re¯ux for 15 h.
The product which crystallized out on cooling of the reac-
tion mixture was ®ltered and washed with petroleum ether
to yield 3 (0.83 g, 90%) as a white solid. It was recrystal-
lized from methanol, m.p. 176±1788C; [Found: C, 65.51; H,
6.14; N, 2.87. C27H29NO6S requires C, 65.43; H, 5.90; N,
4.1.5.
Methyl
2-(acetylamino)-2,3-dideoxy-4,6-O-
(phenylmethylene)-a-d-ribo-hexopyranoside (6). To a
solution of 4 (0.44 g, 1.24 mmol) in ethanol (25 mL), was
added palladium hydroxide on carbon (40 mg). The reaction
mixture was shaken at ambient temperature for 22 h under
hydrogen (35 lbs). The reaction mixture was then ®ltered
through celite, washed with ethanol (3£15 mL), and the
combined extract was concentrated under reduced pressure
to a syrup. Ac2O (1.17 mL, 1.26 mmol) was added to a
solution of the crude syrup in anhyd. pyridine (20 mL).
After 4 h at ambient temperature, the reaction mixture was
poured into sat. aq. NaHCO3 solution (50 mL) and extracted
with chloroform (3£15 mL). The combined organic layer
was dried over anhyd. Na2SO4, and concentrated under
reduced pressure. The crude product was puri®ed over silica
2.83%]; ‰aŠ28:5 1 27:9 (cˆ0.708, CHCl3); nmax(Nujol)
D
3463, 1645, 1380, 1363, 1284, 1112 cm21; dH 7.80 (2 H,
m, aromatic), 7.39±7.05 (13 H, m, aromatic), 5.29 (1 H, s,
PhCH), 4.60 (1 H, d, Jˆ3.6 Hz, H-1), 4.19 (1 H, dd, Jˆ3.5,
9.6 Hz), 3.92±3.68 (6 H, m), 3.53 (1 H, dd, Jˆ3.6, 10.2 Hz),
3.36 (3 H, s, OMe); dC 141.8, 140.2, 136.5, 133.0, 129.0,
128.5, 128.2, 128.1, 127.9, 127.1, 126.2, 101.6, 98.2, 76.2,
69.2 (CH2), 65.1, 62.2, 56.4, 55.3, 51.6 (CH2); m/z (EI) 495
(2 M1), 464 (10 M1-OCH3), 354 (67 M1-SO2Ph).
4.1.2. Methyl 2-N-benzylamino±2,3-dideoxy-4,6-O-
(phenylmethylene)-3-C-phenylsulfonyl-b-d-glucopyrano-
side (14). A solution of 13 (0.24 g, 0.618 mmol) in neat

B. Ravindran et al. / Tetrahedron 57 (2001) 1093±1098
1097
gel (eluent 40% EtOAc±petroleum ether) to afford a white
solid 6 (0.30 g, 79% in 2 steps from 4), m.p. 2368C (sublim);
lit5 2458C (sublim) [Found: C, 62.62; H, 7.08; N, 4.37.
m, aromatic), 5.55 (1 H, s, PhCH), 4.80 (1 H, d,
Jˆ3.1 Hz, H-1), 4.27 (1 H, dd, Jˆ3.3, 8.8 Hz), 3.80±3.54
(7 H, m), 3.43 (3 H, s, OMe), 2.85±2.65 (3 H, m), 2.45 (2 H,
m), 2.10 (1 H, dt, Jˆ11.3, 4.0 Hz), 2.00 (1 H, q, Jˆ11.2 Hz);
dC 137.4, 128.8, 128.0, 126.0, 101.5, 99.0, 77.4, 69.2 (CH2),
66.9 (CH2), 64.2, 63.2, 54.4, 50.4 (CH2), 26.3 (CH2); m/z
(EI) 335 (5 M1), 320 (12 M1-CH3), 304 (10 M1-OCH3).
C16H21NO5 requires C, 62.52; H, 6.89; N, 4.56%]; ‰aŠ28 1
D
55:0 (cˆ2.208, CHCl3); lit5 1 55.5 (cˆ0.95); nmax(CHCl3)
3333, 1733, 1650, 1550, 1358, 1116 cm21; dH 7.50±7.36 (5
H, m, aromatic), 5.74 (1 H, d, Jˆ9.2 Hz), 5.55 (1 H, s,
PhCH), 4.61 (1 H, d, Jˆ3.5 Hz, H-1), 4.39±4.26 (2 H, m),
3.73 (3 H, m), 3.43 (3 H, s, OMe), 2.20 (1 H, dt, Jˆ11.5 Hz),
2.01 (3 H, s, OCOMe), 1.82 (1 H, q, Jˆ11.4 Hz); dC 169.5,
137.6, 129.2, 128.4, 126.3, 101.9, 98.0, 76.6, 69.4 (CH2),
64.2, 55.1, 47.6, 30.9 (CH2), 23.4. m/z (EI) 276 (3 M1-
OCH3), 248 (28 M1-NHAcH1).
4.1.9. Methyl 2-N-benzylamino±2,3-dideoxy-4,6-O-
(phenylmethylene)-b-d-ribo-hexopyranoside (17). Com-
pound 14 (0.51 g, 1.03 mmol) was desulfonated (eluent
70% EtOAc±petroleum ether) in 2 h to yield a white solid
17 (0.28 g, 76%), m.p. 123±1248C; [Found: C, 70.51; H,
6.98; N, 3.85. C21H25NO4 requires: C, 70.96; H, 7.09; N,
4.1.6. Compound 6 via ammonia addition route. To a
mixture of 30% aqueous ammonia (10 mL) in dioxane
(15 mL), 2 (0.39 g, 1 mmol) was added and the solution
was stirred at rt for 24 h. The reaction mixture was evapo-
rated to dryness and the residual dioxane was co-evaporated
with anhyd. methanol. The crude reaction mixture was
desulfonated using Mg in MeOH (see general procedure).
Methanol was evaporated to dryness. The resulting residue
was taken in EtOAc (50 mL) and the insoluble matters were
®ltered. The ®ltrate was washed with water (3£20 mL),
dried over Na2SO4, ®ltered and the ®ltrate was evaporated
under reduced pressure. The residue was dried further by
coevaporating with dry pyridine and dissolved in dry
pyridine (10 mL). Acetic anhydride (5 eq.) was added to
this solution and the reaction mixture was stirred at rt for
16 h. The reaction mixture was partitioned between
NaHCO3 solution (30 mL) and dichloromethane (25 mL£
3). The organic layer was dried over Na2SO4, ®ltered and the
®ltrate was evaporated to dryness. Residual pyridine was co-
evaporated with toluene. Flash silica column afforded a
mixture of products (eluent 55% EtOAc±petroleum ether)
from which the desired product was obtained in pure form
by crystallization from benzene±petroleum ether (0.2 g, 65%).
3.94%]; ‰aŠ24 2 97:0 (cˆ0.470, CHCl3); nmax(CHCl3) 3416,
D
1508, 1475, 1316, 1150 cm21; dH 7.57±7.21 (5 H, m,
aromatic), 5.54 (1 H, s, PhCH), 4.34 (2 H, m), 3.95±3.42
(5 H, m), 3.55 (3 H, s, OMe), 2.78 (1 H, m), 2.44 (1 H, dt,
Jˆ4.3, 11.9 Hz), 1.64 (1 H, q, Jˆ11.6 Hz); dC 139.8, 137.5,
129.0, 128.5, 128.3, 128.1, 127.1, 126.2, 106.4, 101.7, 76.6,
70.4, 69.1 (CH2), 57.0, 56.8, 50.7 (CH2), 33.5 (CH2); m/z
(EI) 355 (6 M1), 340 (11, M1-OCH3).
4.1.10. Methyl 2,3-dideoxy-4,6-O-(phenylmethylene)-2-
N-pyrrolidino-b-d-ribo-hexopyranoside (18). Compound
15 (0.61 g, 1.33 mmol) was desulfonated (eluent 60%
EtOAc±petroleum ether) in 3 h to yield a pale brown
solid 18 (0.18 g, 42%), m.p. 141±1428C; [Found: C,
67.47; H, 8.07; N, 4.26. C18H25NO4 requires C, 67.68; H,
7.89; N, 4.38%]; ‰aŠ24 2 69:6 (cˆ0.376, CHCl3); nmax(Nu-
D
jol) 3450, 1379, 1103 cm21; dH 7.52±7.27 (5 H, m,
aromatic), 5.55 (1 H, s, PhCH), 4.45 (1 H, d, Jˆ7.8 Hz,
H-1), 4.33 (1 H, dd, Jˆ4.9, 10.5 Hz), 3.78 (1 H, t,
Jˆ9.5 Hz), 3.67±3.40 (2 H, m), 3.55 (3 H, s, OMe),
2.79±2.56 (m, 5 H), 2.40 (1 H, m), 1.78 (5 H, m); dC
137.4, 128.9, 128.1, 126.0, 105.2, 101.5, 76.5, 69.8, 69.0
(CH2), 61.9, 56.4, 51.1 (CH2), 31.5 (CH2), 23.1 (CH2); m/z
(EI) 319 (5 M1), 304 (12 M1-CH3).
4.1.7. Methyl 2,3-dideoxy-4,6-O-(phenylmethylene)-2-N-
pyrrolidino-a-d-ribo-hexopyranoside (10). Compound 8
(0.30 g, 0.65 mmol) was desulfonated (eluent 60% EtOAc±
petroleum ether) in 4 h to yield a pale brown solid 10
(0.14 g, 91%); m.p. 141±1428C; [Found: C, 67.55; H,
7.36; N, 4.18. C18H25NO4 requires C, 67.68; H, 7.89; N,
4.1.11. Methyl 2,3-dideoxy-2-N-morpholino-4,6-O-
(phenylmethylene)-b-d-ribo-hexopyransoide (19). Com-
pound 16 (0.27 g, 0.57 mmol) was desulfonated (eluent
65% EtOAc± petroleum ether) in 1 h to yield a pale
brown solid 19 (0.09 g, 47%); m.p. 138±1398C; [Found:
C, 64.59; H, 8.26; N, 3.71. C18H25NO5 requires C, 64.46;
4.38%]; ‰aŠ24 1 66:9 (cˆ0.539, CHCl3); nmax(CHCl3)
D
2933, 2400, 1450, 1383, 1133, 1100 cm21; dH 7.55±7.25
(5 H, m, aromatic); 5.56 (1 H, s, PhCH), 4.73 (1 H, d,
Jˆ3.1 Hz, H-1), 4.28 (1 H, dd, Jˆ3.5, 9.0 Hz), 3.83±3.56
(3 H, m), 3.45 (3 H, s, OMe), 2.65±2.41 (5 H, m), 2.23 (1 H,
dt, Jˆ 4.0, 11.5 Hz), 2.00 (1 H, q, Jˆ11.6 Hz), 1.81 (m, 4
H); dC 137.5, 129.0, 128.2, 126.2, 101.8, 99.0, 77.2, 69.4
(CH2), 64.1, 63.7, 54.9, 51.6 (CH2), 29.8 (CH2), 23.0 (CH2);
m/z (EI) 319 (20 M1), 304 (40 M1-CH3), 288 (30 M1-
OCH3).
H, 7.51; N, 4.18%]; ‰aŠ28:5 2 36:9 (cˆ0.188, CHCl3); nmax(-
D
Nujol) 3475, 1643, 1382, 1190, 1095 cm21; dH 7.52±7.27 (5
H, m, aromatic), 5.54 (1 H, s, PhCH), 4.48 (1 H, d,
Jˆ8.2 Hz, H-1), 4.32 (1 H, dd, Jˆ4.8, 10.5 Hz) 3.82±3.61
(6 H, m), 3.56 (3 H, s, OMe), 3.38 (1 H, m), 2.87 (2 H, m),
2.65 (3 H, m), 2.26 (1 H, dt, Jˆ4.3, 11.9 Hz), 1.70 (q, 1 H,
Jˆ11.5 Hz); dC 137.4, 129.1, 128.3, 126.2, 103.8, 101.6,
77.0, 70.2, 69.0 (CH2), 66.9 (CH2), 63.6, 56.5, 50.4 (CH2),
30.2 (CH2); m/z (EI) 335 (11 M1), 320 (21 M1-OCH3).
4.1.8.
Methyl
2,3-dideoxy-2-N-morpholino-4,6-O-
(phenylmethylene)-a-d-ribo-hexopyranoside (11). Com-
pound 9 (0.35 g, 0.74 mmol) was desulfonated (eluent 35%
EtOAc±petroleum ether) in 7 h to yield a white solid 11
(0.21 g, 85%), m.p. 118±1208C; [Found: C, 64.85; H,
6.93; N, 4.03. C18H25NO5 requires C, 64.46; H, 7.51; N,
Acknowledgements
B. R. and S. G. D. thank the Council for Scienti®c and
Industrial Research, New Delhi for fellowships. This work
was supported by the Department of Science and Technol-
ogy, New Delhi, India.
4.18%]; ‰aŠ28 1 99:3 (cˆ0.141, CHCl3);
nmax(Nujol)
D
3444, 2358, 1633, 1377, 1108 cm21; dH 7.53±7.27 (5 H,

1098
B. Ravindran et al. / Tetrahedron 57 (2001) 1093±1098
(i) Miyashita, M.; Chida, N.; Yoshikoshi, A. J. Chem. Soc.
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