New and Easy Access to C-Glycosides of Glucosamine and Mannosamine

Full text of DOI:10.1021/jo970127f

6678
J . Org. Chem. 1997, 62, 6678-6681
Notes
Sch em e 1
New a n d Ea sy Access to C-Glycosid es of
Glu cosa m in e a n d Ma n n osa m in e†
Laura Cipolla, Luigi Lay, and Francesco Nicotra*
Dipartimento di Chimica Organica e Industriale, Universita`
degli Studi di Milano, CNR Centro di Studio sulle Sostanze
Organiche Naturali, Via Venezian 21, 20133 Milano, Italy
Received J anuary 24, 1997
In tr od u ction
The significant roles that cell surface-associated car-
bohydrates exert in most cell-cell and cell-pathogen
recognition phenomena have recently stimulated the
interest in molecules that could interfere in these pro-
cesses. Analogues of cell surface-associated carbohy-
drates, which compete in the adhesion processes, or
inhibitors of carbohydrate-processing enzymes, which
interfere in the biosynthesis of specific cell surface
carbohydrates, are of great pharmaceutical interest.
Therefore many synthetic efforts have been devoted to
this class of molecules,1 and in particular to C-glyco-
sides,1,2 where the glycosidic oxygen is substituted by a
carbon atom.
During the last decade many C-glycosylation proce-
dures have been reported, and ambitious syntheses of
C-glycosidically linked oligosaccharides and glycoconju-
gates have been performed. However, despite these
successes, only few examples of C-glycosylations of ami-
nosugars have been proposed,3 although these com-
pounds, particularly glucosamine and mannosamine, are
involved in important biological processes such as the
biosynthesis of the bacterial cell wall. As far as we know,
no examples of C-glycosylation of mannosamino deriva-
tives have been reported until now.
In our studies devoted to glycomimetics of glucosamino
derivatives, we experienced that the amino group strongly
interferes in the manipulation of the C-glycosidic ap-
pendage, in particular when the C-glycosidic carbon must
be transformed into an electrophile. For example, in the
synthesis of the phosphono analogue of R-D-glucosamine
1-phosphate,4 any attempt to convert the C-glycosidic
carbon of a glucosamino or N-acetylglucosamino deriva-
tive in an electrophile failed. These observations con-
vinced us that a general procedure to synthesize C-glu-
cosaminosides requires the easy introduction of the
amino function at the end of the synthesis. This can be
done by proper manipulation of the selectively depro-
tected C-2 hydroxyl group of a C-glucosidic intermediate,
a procedure that can afford also C-mannosaminosides.
We have previously described an easy method to
synthesize C-glucosides with a free hydroxyl group at
C-2.5 Now, we describe a new and easy method to
deprotect regioselectively the hydroxyl group at C-2 of
R- and â-C-glucosyl-2-propenes, and its application in the
synthesis of R- and â-C-glycosides of glucosamine and
mannosamine.
Resu lts a n d Discu ssion
In our opinion, one of the best methods for the
synthesis of C-glucosides is the Lewis acid catalyzed
allylation of methyl 2,3,4,6-tetra-O-benzyl-R-D-glucopy-
ranoside with allyltrimethylsilane,6 which affords
1-(2′,3′,4′,6′-tetra-O-benzyl-R-D-glucopyranosyl)-2-pro-
pene (1)7 in excellent yield and stereoselection. To obtain
R-C-glucosides with the hydroxyl group at C-2 selectively
deprotected, the possibility to exploit the double bond of
the allylic appendage of 1 was explored. The idea is
based on the observation that the oxygen of a benzyl
ether can act as a nucleophile on a iodonium ion, with
subsequent loss of the benzyl cation, in a intramolecular
process.8 The reaction affords a cyclic iodoether which
on reductive elimination restores the double bond and a
free hydroxyl group, the entire process resulting in a
debenzylation. In the case of 1, the benzyloxy group at
C-2 is the only one that can undergo this intramolecular
reaction. It reacted with the iodonium ion, in a 5-exo type
cyclization, affording the cyclic iodoether 2 (Scheme 1).
Treatment of 2 with Zn and AcOH resulted in the
formation of 1-(3′,4′,6′-tri-O-benzyl-R-D-glucopyranosyl)-
† Dedicated to Professor Dr. Hans Paulsen on the occasion of his
75th birthday.
(1) Topics in Current Chemistry; Driguez, H., Thiem, J ., Eds.,
Springer: Berlin, 1997, Vol 187.
(2) For a comprehensive description of C-glycosides see: (a) Postema,
M. H. D. C-Glycoside Synthesis; CRC Press: Boca Raton, 1995. (b) Levy
D. E.; Tang, C. The Chemistry of C-Glycosides, Tetrahedron Organic
Chemistry Series Volume 13, Pergamon: New York, 1995.
(3) (a) Nicotra, F.; Russo, G.; Ronchetti, F.; Toma, L. Carbohydr.
Res. 1983, 124, C5. (b) Giannis, A.; Munster, P.; Sandhoff, K.; Steglich,
W. Tetrahedron 1988, 44, 7177. (c) Petrusova, M.; Fedoronko, M.;
Petrus, L. Chem. Pap. 1990, 44, 267. (d) Vyplel, H.; Scholz, D.; Macher,
I.; Schindlmaier, K.; Schutze, E. J . Med. Chem. 1991, 34, 2759. (e)
Hoffmann, M.; Kessler, H. Tetrahedron Lett. 1994, 35, 6067. (f) Kim,
K.-I.; Holligsworth, R. I. Tetrahedron Lett. 1994, 35, 1031. (g) Roe, B.
A.; Boojamra, C. G.; Griggs, J . L.; Bertozzi C. R. J . Org. Chem. 1996,
61, 6442. (h) Urban, D.; Skrydstrup, T.; Riche, C.; Chiaroni, A.; Beau,
J .-M. J . Chem. Soc., Chem. Commun. 1996, 1883.
(5) Boschetti, A.; Nicotra, F.; Panza, L.; Russo, G. J . Org. Chem.
1988, 53, 4181.
(6) Lewis, M. D.; Kun Cha, J .; Kishi, Y. J . Am. Chem. Soc. 1982,
104, 4976.
(7) We named C-glycosides by semisistematic names generally
accepted for this class of compounds; this allows an easier comparison
with the parent sugar.
(8) (a) Rychnovsky, S. D.; Bartlett, P. A. J . Am. Chem. Soc. 1981,
103, 3963. (b) Nicotra, F.; Panza, L.; Russo, G. J . Org. Chem. 1987,
52, 5627.
(4) Casero, F.; Cipolla, L.; Lay, L.; Panza, L.; Russo, G. J . Org. Chem.
1996, 61, 3428.
S0022-3263(97)00127-8 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 19, 1997 6679
Sch em e 2
Sch em e 4
Sch em e 3
Ch a r t 1
2-propene (3),9 the regioselective deprotection process
occurring in 81% yield.
The process can also be applied to 1-(2′,3′,4′,6′-tetra-
O-benzyl-â-D-glucopyranosyl)-2-propene (4)6 (Scheme 2),
although more controlled experimental conditions are
required to obtain the cyclic iodoether 5 in good yields.
The reductive elimination of 5 with Zn and AcOH
afforded 1-(3′,4′,6′-tri-O-benzyl-â-D-glucopyranosyl)-2-pro-
pene (6) in 72% overall yield (from 4).
The conversion of the free hydroxyl group of 3 and 6
into an amino function was accomplished alternatively
with retention and with inversion of the configuration,
so affording all the possible R and â, gluco and manno
2-amino-2-deoxy-C-glycopyranosides (Schemes 3 and 4).
The R-manno isomer, 1-(2′-amino-3′,4′,6′-tri-O-benzyl-
2′-deoxy-R-D-mannopyranosyl)-2-propene (8), was ob-
tained by converting 3 into the triflate, treating the
triflate with Bu4NN3, and reducing the obtained 1-(2′-
azido-3′,4′,6′-tri-O-benzyl-2′-deoxy-R-D-mannopyranosyl)-
2-propene (7) with LiAlH4. The triflate intermediate was
very labile, undergoing spontaneous elimination at room
temperature with formation of the glucal 18. Direct
treatment of the crude triflate with the azide was then
required. The manno configuration of 8 was confirmed
by a 3.2 Hz coupling constant between H-2′ and H-3′ (see
Experimental Section).
ing from the less hindered â-face of the R-glycoside.10 The
gluco isomer 11 was easily separated from the manno
isomer 8 by flash chromatography.
To obtain the â-gluco isomer, 1-(2′-amino-3′,4′,6′-tri-
O-benzyl-2′-deoxy-â-D-glucopyranosyl)-2-propene (17), 6
was oxidized with DMSO-Ac2O to afford the ketone 12,
which was stereoselectively10 reduced with LiAlH4 in
THF at -40 °C affording only the manno isomer 13
(according with the J 2,3 ) 3.4 Hz). Finally, the hydroxyl
group of 13 was converted into an amino group, with
inversion of the configuration, by treatment with Tf2O
in Py and reaction of the obtained triflate with Bu4NN3.
The obtained 1-(2′-azido-3′,4′,6′-tri-O-benzyl-2′-deoxy-â-
D-glucopyranosyl)-2-propene (15) underwent a spontane-
ous cycloaddition, as reported for its R-epimer,11 to afford
19; so immediate reduction with LiAlH4 to 1-(2′-amino-
3′,4′,6′-tri-O-benzyl-2’-deoxy-â-D-glucopyranosyl)-2-pro-
pene (17) was required.
The synthesis of â-mannosides is in general disfavored.
In our case the attempts to convert the hydroxyl group
of 6 into an azide with inversion of configuration failed,
the triflate intermediate undergoing spontaneous elimi-
nation to glucal 18. In the light of the excellent stereo-
selection in favor of the â-manno isomer, obtained in the
The R-gluco isomer, 1-(2′-amino-3′,4′,6′-tri-O-benzyl-2′-
deoxy-R-D-glucopyranosyl)-2-propene (11), was obtained
by oxidation of 3 to the corresponding ketone 9, conver-
sion of the ketone into the methyloxime 10, and reduction
of the methyloxime with LiAlH4. This reduction was
stereoselective (5:1, gluco/ manno), the hydride approach-
(10) Lichtentaler, F. W.; Kaji, E. Liebigs Ann. Chem. 1985, 1659
and refs cited therein.
(11) Bertozzi, C. R.; Bednarski, M. D. Tetrahedron Lett. 1992, 33,
3109.
(9) Cipolla, L.; Lay, L.; Nicotra, F. Carbohydr. Lett. 1996, 2, 131.

6680 J . Org. Chem., Vol. 62, No. 19, 1997
Notes
1 H, J ) 9.3 Hz), 3.79 (t, 1 H, J ) 9.3 Hz), 3.76-3.62 (m, 3 H),
2.93 (d, 1 H, J ) 8.0 Hz), 2.53-2.35 (m, 2 H); 13C NMR (75.43
MHz, CDCl3) δ 135.4 (d), 117.5 (t), 78.2 (d), 75.47 (d), 74.2 (d),
73.9 (2t), 73.4 (t), 71.7 (d), 69.7 (d), 68.8 (t), 33.9 (t). Anal. Calcd
for C30H34O5: C, 75.92%; H, 7.22%. Found: C, 76.08%; H, 7.08%.
1-(3′,4′,6′-Tr i-O-ben zyl-â-D-glu copyr an osyl)-2-pr open e (6).
To a solution of 4 (1.00 g, 1.77 mmol) in dry CH2Cl2 (50 mL)
was added iodine (4.5 g, 17.7 mmol) at 0 °C under N2 atmo-
sphere. The reaction mixture was allowed to warm to room
temperature and stirred for 5 h. The reaction was then
quenched with aqueous Na2S2O3 till the organic phase became
colorless. Usual workup and chromatography (85:15, hexane-
EtOAc) afforded 5 (765 mg, 72%) as a colorless oil (mixture of
diastereomers). 13C NMR (75.43 MHz, CDCl3) of the major
isomer: δ 83.9 (d), 83.8 (d), 80.9 (d), 78.0 (d), 77.6 (d), 77.5 (d),
75.3 (t), 73.5 (t), 73.0 (t), 69.3 (t), 34.3 (t), 11.2 (t). The cyclic
iodoether 5 (600 mg), treated with Zn and AcOH as described
for the preparation of 3, afforded 6 as a white solid (473 mg,
quantitative yield) which crystallizes from Et2O-hexane. [R]D
+37.5° (c 0.9, CHCl3); mp 63-65 °C; 1H NMR (300 MHz, CDCl3)
δ 7.45-7.25 (m, 15 H), 6.05-5.88 (m, 1 H), 5.14 (broad dd, 1 H,
J ) 16.0, 2.0 Hz), 5.08 (broad d, 1 H, J ) 10.0 Hz), 4.97, 4.63
(Abq, 2 H, J ) 11.4 Hz), 4.83, 4.75 (Abq, 2 H, J ) 10.4 Hz),
4.65, 4.58 (Abq, 2 H, J ) 11.8 Hz), 3.79-3.67 (m, 2 H), 3.64 (t,
1 H, J ) 9.0 Hz), 3.51 (t, 1 H, J ) 9.0 Hz), 3.47-3.43 (m, 1H),
3.38 (t, 1 H, J ) 9.0 Hz), 3.27 (ddd, 1 H, J ) 9.0, 6.4, 2.4 Hz),
2.59 (ddd, 1 H, J ) 15.0, 6.4, 2.4 Hz), 2.32 (dt, 1 H, J ) 15.0, 6.4
Hz), 2.05 (s, 1 H); 13C NMR (75.43 MHz, CDCl3) δ 134.6 (d), 117.1
(t), 86.8 (d), 79.2 (d), 78.8 (d), 78.5 (d), 75.2 (t), 74.9 (t), 74.8 (t),
73.5 (t), 69.0 (t), 36.2 (t). Anal. Calcd for C30H34O5: C, 75.92%;
H, 7.22%. Found: C, 75.80%; H, 7.31%.
reduction of the ketone 12 at -40 °C with LiAlH4, to
prepare the â-C-mannosamino derivative 16 the reduc-
tion of the methyloxime 14 was tested. The reduction
does not occur at temperatures lower than 20 °C, and at
20 °C the stereoselection in favor of the â-manno isomer
16 was very low (50% de). Different reducing agents,
such as LiEt3BH or catalytic hydrogenation with Raney-
Ni, gave worst results. Surprisingly, increasing the
temperature to 40 °C the reduction of 14 with LiAlH4
became more stereoselective, affording the â-manno
isomer 16 in 83% de, which was isolated in pure form by
flash chromatography. The manno configuration of 16
was confirmed by the 3.8 Hz coupling constant between
H-2′ and H-3′.
The described regioselective debenzylation procedure
is limited to the propenyl derivatives. In fact 1-(2′,3′,4′,6′-
tetra-O-benzyl-â-D-glucopyranosyl)-3-butene (20), treated
with iodine in different experimental conditions, gave
unsatisfactory results even if the 6-exo-type cyclization
is allowed as well.
In conclusion, the “late amination” of C-glucosides with
the hydroxyl group at C-2 selectively deprotected is a
useful procedure to obtain different R- and â-C-glycosides
of glucosamine and mannosamine. We have previously
reported a C-glycosylation procedure that affords R-C-
glucosides with a free hydroxyl group at C-2.5 Now we
have described a procedure that allows the regioselective
deprotection at C-2 of the easily available R- and â-
1-(2′,3′,4′,6′-tetra-O-benzyl-D-glucopyranosyl)-2-prope-
nes (1 and 4) and their conversion into R- and â-C-
glycosides of glucosamine and mannosamine. It is wor-
thy of note that the procedure can be exploited in general
to obtain R- and â-C-glycosides differently functionalized
at C-2.
1-(2′-Azid o-3′,4′,6′-tr i-O-ben zyl-2′-d eoxy-r-D-m a n n op yr a -
n osyl)-2-p r op en e (7). To a solution of 3 (100 mg, 0.21 mmol)
in dry CH2Cl2 (2 mL) were added dry pyridine (68 µL, 0.84 mmol)
and Tf2O (69 µL, 0.42 mmol) at 0 °C under N2. After 1 h the
reaction was complete. Usual workup afforded the crude triflate
(150 mg), which was dissolved in dry toluene (2 mL), under N2
atmosphere, and stirred overnight with a solution of Bu4NN3
(120 mg) in dry toluene (2 mL). Evaporation of the solvent to
dryness, and chromatographic purification (9.5:0.5, hexane-
EtOAc) afforded 7 (32 mg, 31%) as a white amorphous solid.
[R]D +13.0° (c 0.8, CHCl3); IR (film) ν 2096 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.38-7.28 (m, 15 H), 5.85-5.71 (m, 1 H), 5.08
(d, 1 H, J ) 9.5 Hz), 5.06 (d, 1 H, J ) 17.9 Hz), 4.72, 4.55 (ABq,
2 H, J ) 11.4 Hz), 4.66 (broad s, 2 H), 4.57, 4.48 (ABq, 2 H, J )
12.4 Hz), 3.97 (broad dt, 1 H), 3.89 (dd, 1 H, J ) 7.0, 3.7 Hz),
3.87-3.66 (m, 4 H), 3.63 (t, 1 H, J ) 3.7 Hz), 2.48-2.26 (m, 2
H); 13C NMR (75.43 MHz, CDCl3) δ 133.4 (d), 117.9 (t), 78.26
(d), 74.1 (t), 74.1 (d), 73.5 (d), 73.4 (t), 72.9 (d), 72.7 (t), 68.8 (t),
60.5 (d), 35.0 (t). Anal. Calcd for C30H33N3O4: C, 72.12%; H,
6.66%; N, 8.41%. Found: C, 71.97%; H, 6.50%; N, 8.55%.
1-(2′-Am in o-3′,4′,6′-tr i-O-ben zyl-2′-d eoxy-r-D-m a n n op yr a -
n osyl)-2-p r op en e (8). Product 7 (25 mg, 0.05 mmol) was
dissolved in dry THF (2 mL) under N2 atmosphere, and a 1 M
solution of LiAlH4 in THF (125 µL) was added; the reaction
mixture was stirred for 20 min and then quenched with EtOAc.
Usual workup and chromatography (9.5:0.5, CH2Cl2-MeOH)
afforded 8 (23 mg, quantitative yield) as a colorless oil. [R]D
Exp er im en ta l Section
Gen er a l. 1H NMR and 13C NMR spectra were recorded with
TMS as internal reference. The signals of the aromatic carbons
in the 13C NMR spectra are not reported. [R]D values were
measured at 20 °C and are given in units of 10-1 deg cm2 g-1
.
Chromatographic purifications were performed with the flash
procedure using silica gel 60 (230-400 mesh). TLC were
performed on silica gel 60 F254 plates and visualized by spraying
with a solution containing H2SO4 (31 mL), ammonium molybdate
(21 g), and Ce(SO4)2 (1 g) in water (500 mL) and then heating
at 110 °C for 5 min. Usual workup refers to dilution with an
organic solvent, washing with water to neutrality (pH test
paper), drying with Na2SO4, filtration, and evaporation under
reduced pressure.
1-(3′,4′,6′-Tr i-O-ben zyl-r-D-glu copyr an osyl)-2-pr open e (3).
To a solution of 1 (1.00 g, 1.77 mmol) in dry THF (4 mL) was
added iodine (2.3 g, 9 mmol) at 0 °C, under N2 atmosphere. After
1 h 30 min, the reaction mixture was diluted with EtOAc,
aqueous Na2S2O3 was added, and the mixture was stirred till
the organic layer became colorless. Usual workup and chroma-
tography (9:1, hexane-EtOAc) afforded 2 (876 mg, 81%) as a
colorless oil (mixture of diastereomers). 13C NMR (50.29 MHz,
CDCl3) of the major isomer: δ 85.2 (d), 83.8 (d), 82.4 (d), 76.1
(d), 75.9 (d), 75.6 (d), 75.0 (t), 74.0 (t), 73.5 (t), 70.4 (t), 38.8 (t),
10.8 (t). Product 2 (870 mg, 1.45 mmol) was dissolved in a 1:1
mixture of Et2O-MeOH (15 mL), and powdered zinc (872 mg,
13.2 mmol) and glacial acetic acid (152 µL, 2.72 mmol) were
sequentially added. The suspension was stirred overnight and
then filtered over a Celite pad. The filtrate was evaporated, and
the residue was submitted to usual workup and filtration over
a short column of silica gel (8:2, hexane-EtOAc), affording 3
(687 mg, quantitative yield) as a white solid. [R]D +33.3° (c 1,
CHCl3); mp 69-71 °C; 1H NMR (300 MHz, CDCl3) δ 7.42-7.28
(m, 15 H), 5.95-5.78 (m, 1 H), 5.15 (broad dd, 1 H, J ) 16.0, 3.2
Hz), 5.07 (broad dd, 1 H, J ) 9.6, 3.2 Hz), 4.68-4.46 (m, 6 H),
4.11-4.04 (m, 1 H), 3.93 (ddd, 1 H, J ) 8.0, 5.8, 3.5 Hz), 3.82 (t,
1
+25.6° (c 0.9, CHCl3); H NMR (300 MHz, CDCl3) δ 7.35-7.24
(m, 15 H), 5.88-5.72 (m, 1 H), 5.08 (d, 1 H, J ) 16.2 Hz), 5.05
(d, 1 H, J ) 11.0 Hz), 4.76, 4.53 (ABq, 2 H, J ) 11.3 Hz), 4.59
(broad s, 2 H), 4.57, 4.50 (ABq, 2 H, J ) 12.2 Hz), 3.88 (dt, 1H,
J ) 7.2, 3.3 Hz), 3.83-3.69 (m, 4H), 3.65 (dd, 1H, J ) 9.5, 3.2
Hz), 3.10 (t, 1 H, J ) 3.2 Hz), 2.47 (dt, 1 H, J ) 14.5, 7.2 Hz),
2.33 (dt, 1 H, J ) 14.5, 7.2 Hz), 1.71 (broad s, 2 H); 13C NMR
(75.43 MHz, CDCl3) δ 134.42 (d), 117.2 (t), 79.8 (d), 76.1 (d), 74.3
(t), 74.0 (d), 73.4 (t), 73.0 (d), 71.9 (t), 69.2 (t), 50.8 (d), 29.7 (t).
Anal. Calcd for C30H35NO4: C, 76.08%; H, 7.45%; N, 2.96%.
Found: C, 75.97%; H, 7.53%; N, 3.04%.
1-(3′,4′,6′-Tr i-O-ben zyl-r-D-a r a bin o-h exu lop yr a n osyl)-2-
p r op en e (9). In a double-necked flask, under N2 atmosphere,
containing 1 g of 4 Å activated powdered molecular sieves and
PCC (457 mg, 2.12 mmol), was added a solution of 3 (503 mg,
1.06 mmol) in dry CH2Cl2 (20 mL) by a double ended needle.
After 2 h, the reaction was complete; the reaction mixture was
filtered over a Celite pad and the filtrate concentrated. The
residue was purified on a short chromatographic column of 70-
230 mesh silica gel (9:1, hexane-EtOAc), affording 9 (372 mg,

Notes
J . Org. Chem., Vol. 62, No. 19, 1997 6681
1
74%) as a colorless oil. [R]D +50.0° (c 1, CHCl3); H NMR (300
MHz, CDCl3) δ 7.50-7.15 (m, 15 H), 5.80-5.71 (m, 1 H), 5.10
(d, 1 H, J ) 17.8 Hz), 5.08 (d, 1 H, J ) 11.7 Hz), 4.95, 4.51 (Abq,
2 H, J ) 11.6 Hz), 4.80, 4.60 (Abq, 2 H, J ) 11.5 Hz), 4.50, 4.42
(Abq, 2 H, J ) 12.0 Hz), 4.39 (d, 1 H, J ) 8.0 Hz), 4.26 (t, 1 H,
J ) 8.0 Hz), 4.04 (dt, 1 H, J ) 8.0, 3.5 Hz), 3.89 (dd, 1 H, J )
8.8, 7.5 Hz), 3.65-3.56 (m, 2 H), 2.50 (broad t, 2 H, J ) 8.0 Hz);
13C NMR (75.43 MHz, CDCl3) δ 208.4 (s), 133.0 (d), 119.0 (t),
85.1 (d), 80.5 (d), 79.0 (d), 76.1 (d), 75.0 (t), 74.5 (t), 74.1 (t),
70.3 (t), 35.5 (t). Anal. Calcd for C30H32O5: C, 76.25%; H, 6.83%.
Found: C, 76.03%; H, 6.74%.
Hz), 3.46-3.42 (m, 1 H), 3.38 (t, 1 H, J ) 7.2 Hz), 2.58 (dt, 1 H,
J ) 14.1, 7.2 Hz), 2.47 (dt, 1 H, J ) 14.1, 7.2 Hz), 2.25 (broad s,
1 H); 13C NMR (75.43 MHz, CDCl3) δ 134.5 (d), 117.5 (t), 83.6
(d), 79.4 (d), 77.7 (d), 75.2 (t), 74.8 (d), 73.5 (t), 71.6 (t), 69.5 (t),
67.6 (d), 35.4 (t). Anal. Calcd for C30H34O5: C, 75.92%; H,
7.22%. Found: C, 75.78%; H, 7.11%.
1-(2′-Azid o-3′,4′,6′-tr i-O-ben zyl-2′-d eoxy-â-D-glu cop yr a n o-
syl)-2-p r op en e (15). Reaction of 13 (100 mg, 0.21 mmol) as
described for the preparation of 7, afforded the crude azide 15
which was directly submitted to the next reaction. An analytical
sample of 15 was purified by flash chromatography, eluting with
1-(3′,4′,6′-Tr i-O-ben zyl-r-D-a r a bin o-h exu lop yr a n osyl)-2-
p r op en e m eth yloxim e (10). The ketone 9 (97 mg, 0.20 mmol)
dissolved in a 1/1 mixture of THF-MeOH (1 mL) was stirred
overnight with a buffer solution (1.7 mL) prepared dissolving
NH2OH‚HCl (500 mg) and AcONa‚3HCl (1.00 g) in water (the
pH was adjusted to 4.5 with AcOH). Usual workup and
chromatography (9:1, hexane-EtOAc) afforded 10 (96 mg, 96%)
as a colorless oil. [R]D +17.2° (c 1.2, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 7.45-7.20 (m, 15 H), 5.92-5.74 (m, 1 H), 5.18-5.08
(m, 3H), 4.95, 4.53 (ABq, 2H, J ) 12.2 Hz), 4.82, 4.61 (ABq, 2
H, J ) 12.2 Hz), 4.66, 4.51 (ABq, 2 H, J ) 12.9 Hz), 4.36 (d, 1
H, J ) 7.9 Hz), 3.95-3.88 (m, 4 H), 3.77 (t, 1 H, J ) 7.9 Hz),
3.67 (dd, 1 H, J ) 10.5, 8.0 Hz), 3.58 (dd, 1 H, J ) 10.5, 3.8 Hz),
2.60 (dt, 1 H, J ) 14.7, 8.7 Hz), 2.47 (dd, 1 H, J ) 14.7, 7.0 Hz);
13C NMR (75.43 MHz, CDCl3) δ 156.1 (s), 134.2 (d), 118.2 (t),
79.6 (d), 78.9 (d), 74.7 (d), 74.7 (t), 74.4 (d), 74.1 (t), 73.7 (t),
70.4 (t), 62.9 (q), 34.5 (t). Anal. Calcd for C31H35NO5: C, 74.23%;
H, 7.03%; N, 2.79%. Found: C, 74.07%; H, 7.10%; N, 2.85%.
1-(2′-Am in o-3′,4′,6′-tr i-O-ben zyl-2′-d eoxy-r-D-glu cop yr a -
n osyl)-2-p r op en e (11). To a solution of the methyloxime 10
(350 mg, 0.70 mmol) in dry THF (7 mL) was added a 1 M solution
of LiAlH4 in THF (4.2 mL, 4.2 mmol) under N2 atmosphere. After
4 days the reaction was quenched with EtOAc. Usual workup
and chromatography (9:1, hexane-EtOAc) afforded the gluco
isomer 11 (169 mg, 51%) as a colorless oil (and 34 mg of the
manno isomer, 10%). [R]D +59.7° (c 1, CHCl3); 1H NMR (300
MHz, CDCl3) δ 7.40-7.25 (m, 15 H), 5.90-5.76 (m, 1 H), 5.11
(d, 1 H, J ) 17.0 Hz), 5.06 (d, 1 H, J ) 10.0 Hz), 4.82, 4.50 (ABq,
2 H, J ) 12.4 Hz), 4.70, 4.64 (ABq, 2 H, J ) 11.2 Hz), 4.61, 4.54
(ABq, 2 H, J ) 11.3), 4.00 (dt, 1 H, J ) 9.9, 4.7 Hz), 3.84-3.75
(m, 2 H), 3.66 (dd, 1 H, J ) 9.7, 3.1 Hz), 3.63 (t, 1 H, J ) 7.6
Hz), 3.57 (t, 1 H, J ) 7.6 Hz), 3.03 (dd, 1 H, J ) 7.6, 4.7 Hz),
2.47-2.28 (m, 2 H), 1.50 (broad s, 2 H); 13C NMR (50.29 MHz,
CDCl3) δ 135.70 (d), 117.4 (t), 82.5 (d), 78.4 (d), 78.0 (d), 77.7
(d), 74.8 (t), 74.3 (t), 74.1 (t), 69.9 (t), 54.2 (d), 32.8 (t). Anal.
Calcd for C30H35NO4: C, 76.08%; H, 7.45%; N, 2.96%. Found:
C, 76.13%; H, 7.37%; N, 2.89%.
(3′,4′,6′-Tr i-O-b en zyl-â-D-a r a bin o-h exu lop yr a n osyl)-2-
p r op en e (12). A mixture of 6 (2.00 g, 4.2 mmol) and 2:1
DMSO-Ac2O (100 mL) was stirred for 5 h under N2 atmosphere.
The reaction was quenched with ice-cold water. Usual workup
and chromatography (9:1, hexane-EtOAc) afforded 12 (1.76 g,
88% yield), a white solid which crystallizes from EtOAc by
addition of hexane: mp 64-66 °C, [R]D -42.7° (c 1.1, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.48-7.20 (m, 15H), 5.93-5.82
(m, 1H), 5.14 (broad dd, 1H, J ) 17.9, 1.4 Hz), 5.09 (broad d,
1H, J ) 10.5 Hz), 4.99, 4.61 (Abq, 2H, J ) 11.3 Hz), 4.84, 4.55
(Abq, 2H, J ) 10.8 Hz), 4.62-4.57 (m, 2H), 4.18 (d, 1H, J ) 8.9
Hz), 3.87 (t, 1H, J ) 8.9 Hz) 3.83-3.68 (m, 4H), 2.63 (dt, 1H, J
) 14.8, 5.8 Hz), 2.41 (dt, 1H, J ) 14.8, 7.2 Hz); 13C NMR (75.43
MHz, CDCl3) δ 201.9 (s), 133.7 (d), 117.5 (t), 86.6 (d), 80.5 (d),
80.3 (d), 79.4 (d), 75.0 (t), 73.8 (t), 73.5 (t), 68.9 (t), 32.9 (t). Anal.
Calcd for C30H32O5: C, 76.25%; H, 6.83%. Found: C, 75.97%;
H, 6.68%.
a gradient of 95:5 f 9:1 of hexane-EtOAc. IR (film) 2100 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.40-7.20 (m, 15 H), 6.00-5.83
(m, 1 H), 5.18 (dd, 1 H, J ) 19.0, 1.5 Hz), 5.15 (d, 1 H, J ) 9.9
Hz), 4.89 (broad s, 2H), 4.82, 4.60 (ABq, 2H, J ) 10.7 Hz), 4.64,
4.55 (ABq, 2H, J ) 12.7 Hz), 3.72-3.68 (m, 2 H), 3.64 (t, 1 H, J
) 9.4 Hz), 3.60 (t, 1 H, J ) 9.4 Hz), 3.40 (dt, 1 H, J ) 9.4, 3.0
Hz), 3.32 (t, 1 H, J ) 9.4 Hz), 3.19 (ddd, 1 H, J ) 9.8, 6.3, 3.7
Hz), 2.66-2.54 (m, 1 H), 2.38 (dt, 1 H, J ) 13.6, 6.3 Hz); 13C
NMR (75.43 MHz, CDCl3) δ 133.6 (d), 117.8 (t), 85.4 (d), 81.0
(d), 79.2 (d), 77.9(d), 75.5 (t), 73.5 (t), 73.1 (t), 69.2 (t), 55.2 (d),
36.7 (t). Anal. Calcd for C30H33N3O4: C, 72.12%; H, 6.66%; N,
8.41%. Found: C, 71.88%; H, 6.45%; N, 8.62%.
1-(2′-Am in o-3′,4′,6′-tr i-O-ben zyl-2′-d eoxy-â-D-glu cop yr a -
n osyl)-2-p r op en e (17). The crude azide 15 obtained in the
previous preparation was reduced following the same procedure
described for the preparation of 8. Chromatographic purification
(6:4, hexane-EtOAc + 0.1% Et3N) afforded 17 (57 mg, 57% yield
from 13), as a pale yellow oil. [R]D +49.0° (c 1.1, CHCl3); 1H
NMR (300 MHz, CDCl3) δ 7.49-7.10 (m, 15 H), 5.96-5.90 (m, 1
H), 5.11 (d, 1 H, J ) 18.0 Hz), 5.07 (d, 1 H, J ) 10.1 Hz), 4.98,
4.57 (ABq, 2 H, J ) 12.0 Hz), 4.79-4.50 (m, 4 H), 3.72-3.70 (m,
2 H), 3.62 (t, 1H, J ) 9.5 Hz), 3.45 (dt, 1H, J ) 9.5, 2.9 Hz), 3.35
(t, 1H, J ) 9.5 Hz) 3.21-3.15 (m, 1H), 2.69 (t, 1 H, J ) 9.5 Hz)
2.55-2.50 (m, 1 H), 2.29 (dt, 1 H, J ) 14.5, 7.0 Hz), 2.16 (broad
s, 2H); 13C NMR (75.43 MHz, CDCl3) δ 134.6 (d), 116.9 (t), 86.8
(d), 80.0 (d), 79.4 (d), 79.2 (d), 75.3 (t), 74.7 (t), 73.5 (t), 69.1 (t),
56.3 (d), 36.6 (t). Anal. Calcd for C30H35NO4: C, 76.08%; H,
7.45%; N, 2.96%. Found: C, 76.11%; H, 7.30%; N, 2.72%.
1-(3′,4′,6′-Tr i-O-ben zyl-â-D-a r a bin o-h exu lop yr a n osyl)-2-
p r op en e Meth yloxim e (14). Following the same procedure
described for the preparation of 10, 12 (200 mg, 0.42 mmol) was
converted into 14 (199 mg, 94%). Oil; 13C NMR (50.29 MHz,
CDCl3) δ 155.9 (s), 134.8 (d), 116.4 (t), 79.4 (d), 77.6 (d), 76.8
(d), 74.7 (d), 73.2 (t), 71.1 (t), 70.3 (t), 69.9 (t), 62.2 (q), 36.8 (t).
Anal. Calcd for C31H35NO5: C, 74.23%; H, 7.03%; N, 2.79%.
Found: C, 74.27%; H, 6.98%; N, 2.73%.
1-(2′-Am in o-3′,4′,6′-tr i-O-ben zyl-2′-d eoxy-â-D-m a n n op yr a -
n osyl)-2-p r op en e (16). The methyloxime 14 (86 mg, 0.17
mmol) in dry THF (4 mL) was treated overnight with LiAlH4
(1.6 mL of a 1 M solution in THF) at 40 °C under N2 atmosphere.
Usual workup and chromatographic purification (6:4, hexane-
EtOAc) afforded 16 (41 mg, 54%) (and 4 mg, 5%, of its C-2 epimer
1
17). [R]D -15.5° (c 1.65, CHCl3); H NMR (300 MHz, CDCl3) δ
7.43-7.10 (m, 15 H), 5.88-5.79 (m, 1 H), 5.15 (broad d, 1 H, J
) 17.5 Hz), 5.07 (broad d, 1 H, J ) 10.7 Hz), 4.86, 4.51 (ABq, 2
H, J ) 10.9 Hz), 4.72, 4.60 (ABq, 2 H, J ) 11.5 Hz), 4.60, 4.53
(ABq, 2 H, 11.7 Hz), 3.80-3.69 (m, 3 H), 3.56 (dd, 1 H, J ) 8.9,
3.8 Hz), 3.43-3.37 (m, 2 H), 3.21 (d, 1 H, J ) 3.8 Hz), 2.52 (dt,
1 H, J ) 13.9, 6.9 Hz), 2.39 (dt, 1 H, J ) 13.9, 6.9 Hz), 2.26
(broad s, 2 H); 13C NMR (75.43 MHz, CDCl3) δ 134.53 (d), 117.3
(t), 84.2 (d), 79.4 (d), 77.9 (d), 75.1 (t), 74.3 (d), 73.5 (t), 71.2 (t),
69.3 (t), 50.4 (d), 35.9 (t). Anal. Calcd for C30H35NO4: C, 76.08%;
H, 7.45%; N, 2.96%. Found: C, 75.90%; H, 7.51%; N, 3.07%.
1-(3′,4′,6′-T r i-O -b e n zy l-â-D -m a n n o p y r a n o s y l)-2-p r o -
p en e (13). To a solution of the ketone 12 (200 mg, 0.42 mmol)
in dry THF (2 mL), cooled to -40 °C and under N2 atmosphere,
was added a 1 M solution of LiAlH4 in THF (200 µL). After 10
min, the reaction was quenched with EtOAc. Usual workup and
chromatography (8:2, hexane-EtOAc) afforded 13 (130 mg,
65%), colorless oil. [R]D -10.9° (c 0.75, CHCl3); 1H NMR (300
MHz, CDCl3) δ 7.45-7.25 (m, 15 H), 5.91-5.80 (m, 1 H), 5.18
(dd, 1 H, J ) 17.1, 1.3 Hz), 5.10 (broad d, 1 H, J ) 10.0 Hz),
4.87, 4.56 (Abq, 2 H, J ) 10.9 Hz), 4.76, 4.67 (Abq, 2 H, J )
11.4 Hz), 4.64, 4.58 (Abq, 2 H, J ) 12.5 Hz), 3.96 (d, 1 H, J )
3.4 Hz), 3.79 (t, 1 H, J ) 9.2 Hz), 3.78 (dd, 1 H, J ) 10.9, 3.2
Hz), 3.70 (dd, 1 H, J ) 10.9, 5.1 Hz), 3.60 (dd, 1 H, J ) 9.2, 3.4
Ack n ow led gm en t. We thank MURST and CNR for
the financial support, and Mr. S. Crippa and E. Caneva
for the NMR spectra.
J O970127F