Selective reductions of C-(4,6-O-benzylidene-β-D-glucopyranosyl) nitromethane

Article abstract of DOI:10.1081/SCC-200061554

The nitromethyl group of C-(4,6-O-benzylidene-β-D-glucopyranosyl) nitromethane was manipulated by various reduction and oxidation methods and further functionalizations into -CH₂NHOH, -CH=NOH, -CN, -CH=O, and -CH_2- NHCONH₂

Full text of DOI:10.1081/SCC-200061554

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Selective Reductions of
C‐(4,6‐O‐Benzylidene‐β‐d‐glucopyra
Nitromethane
Ondrej Simo a , Katja Michael b , Wesley Yoshida b ,
Vyacheslav A. Chertkov a & Paul H. Gross a
a Department of Chemistry, University of the Pacific,
Stockton, California, USA
b Department of Chemistry, University of Hawaii,
Honolulu, Hawaii, USA
Published online: 16 Aug 2006.
To cite this article: Ondrej Simo , Katja Michael , Wesley Yoshida ,
Vyacheslav A. Chertkov & Paul H. Gross (2005) Selective Reductions of
C‐(4,6‐O‐Benzylidene‐β‐d‐glucopyranosyl) Nitromethane, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
35:12, 1589-1599, DOI: 10.1081/SCC-200061554
To link to this article: http://dx.doi.org/10.1081/SCC-200061554
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Synthetic Communicationsw, 35: 1589–1599, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200061554
Selective Reductions of
C-(4,6-O-Benzylidene-b-D-glucopyranosyl)
Nitromethane
Ondrej Simo
Department of Chemistry, University of the Pacific, Stockton,
California, USA
Katja Michael and Wesley Yoshida
Department of Chemistry, University of Hawaii, Honolulu, Hawaii, USA
Vyacheslav A. Chertkov and Paul H. Gross
Department of Chemistry, University of the Pacific, Stockton,
California, USA
Abstract: The nitromethyl group of C-(4,6-O-benzylidene-b-D-glucopyranosyl)
nitromethane was manipulated by various reduction and oxidation methods and
further functionalizations into –CH2NHOH, –CH55NOH, –CN, –CH55O, and –CH2-
NHCONH2, all with retention of the 4,6-O-benzylidene group. Certain reduction
methods gave rise to a novel secondary amine via an unusual dimeric aminal.
Keywords: C-glycosides, dimerization, nitro methyl, protective groups, reduction
INTRODUCTION
C-Glycosides are compounds in which the anomeric carbon atom of
carbohydrates is attached to the aglycone by a carbon–carbon bond. They
are cyclic ethers, not cyclic acetals as are O-glycosides. Therefore, they are
much more acid stable than acetals, which are easily hydrolyzed by acids.
Received in the USA February 11, 2005
Address correspondence to Paul H. Gross, Department of Chemistry, University of
the Pacific, Stockton, CA 95211, USA. Fax: (209) 946-2607
1589

1590
O. Simo et al.
C-glycosyl compounds are derivatives of tetrahydrofuran and tetrahydro-
pyran. Many C-glycosides were isolated from natural sources, such as
plants and bacteria. A variety of naturally occurring C-glycosides have been
found to have various important and useful biological properties, such as anti-
mycoplasmal,[1] or antitumor[2] activities with applications in biochemistry
and medicine.[3,4]
Recently, C-glycosides were actively studied as stable pharmacophores
and are used in a variety of applications, e.g., as components of nucleic
acid and cell surface glycoconjugates.[5,6] C-saccharides with structures that
may be difficult to construct by standard procedures of carbohydrate
chemistry[7,8] can serve as metabolically stable enzyme inhibitors. The
synthesis of such C-glycosides would benefit from the kinetic products
observed in our present work. Their synthesis was planned on the basis of
postulating their insolubility in certain solvents and their crystallinity
promoted by the benzene ring and the conformational restriction imposed
by the trans-diequatorial 4,6-acetal structure, which allowed successful
isolation of the product. The principle of Dimroth has been invoked by us
before in the synthesis of the minor component of an anomeric glycoside
product mixture.[9,10] Recently, the starting material 1 in our present investi-
gation was demonstrated to be a kinetic product.[11] To date, there is no
substitute for the experience of the synthetic chemist to bring about such selec-
tivities for kinetic products, which still play an important role in synthetic
carbohydrate chemistry.
RESULTS AND DISCUSSION
C-(4,6-O-Benzylidene-b-D-glucopyranosyl) nitromethane (1) was found to
be a useful starting material in the synthesis of aminomethyl-C-glycosides.
The benzylidene group influences the solubilities and crystallization of
these compounds. This influence plays an important role in their preparation,
workup, isolation, and selective derivatization. The nitrogroup had been
reduced by Fe/Ni in H2O and THF under a CO2 atmosphere to the amino
group in compound (2) under very mild, neutral conditions.[12,13] We
wanted to improve the yield of the reduction procedure and found a better
method by reduction in methanol under hydrogen with Raney nickel as the
catalyst. The reaction was fast and the product separated from the reaction
mixture in good yield. The benzylidene group remained in place under
these and other reduction conditions that we tried (Scheme 1).
Hydrogenation with Pd as a catalyst in MeOH was found to be a good
method for the preparation of the hydroxylamino derivative (3), which preci-
pitated from the reaction mixture under certain conditions. Quality and yield
of the reaction depended crucially on the activity of the catalyst. If the
palladium catalyst was freshly prepared and too active, aminomethyl
glucose (2) was formed as a by-product, which lowered the yield of the

Selective Reductions of C-Glycoside Derivatives
1591
Scheme 1.
hydroxylamine (3) as the major product and made its isolation difficult. With
deactivated Lindlar catalyst, formation of by-products, including (2), was
minimized. Crude hydroxylamine (3) was pure enough to be directly
oxidized with air under basic conditions (NH4OH). The product of this
reaction was a cis-trans mixture of oximes (4). The mixture could be used
directly, without the difficult separation of isomers, for further reactions.
Oximes (4) did not undergo Pd-catalyzed hydrogenation under the same
conditions as nitromethyl glucose. Only a small amount of a polar product,
presumably (2), was detected in the reaction mixture after a long reaction
time (20 h), but most oxime remained unreacted. Nitrile derivative (6) was
obtained after per-O-acetylation of the oxime mixture to give (5), followed
by selective elimination of AcOH from the acetylated oxime with DBU

1592
O. Simo et al.
(1,8-diazabicyclo[5.4.0]undec-7-ene). The oximes (4) also reacted with H2 in
the presence of Raney nickel catalyst, presumably followed by a solvolytic
step, affording the dimeric aminal (7), in pyridine–water (2:1), in good
yield. MeOH–H2O could also be used, but more aminomethyl glucose (2)
was formed as a by-product. The pH was basic in both solvents after the
reaction (Scheme 1).
The secondary amine (12) was obtained after the reduction of (7) with
NaBH4, in a good solvent system (pyridine, AcOH, MeOH). For workup,
a crude hydrochloride was precipitated with NH4Cl, from which a free base
(12) could be prepared with NaOH. Compound (7) is also important as
a source of 1 mol of aldehyde, detected by TLC and trapped by 1,2-dianilino-
ethane (Wanzlick base), leading to imidazolidine (8). Aminomethyl glucose
(2) was easily separated as the other half of dimeric (7) when the imidazolidine
(8) was prepared (Scheme 1). It (2) was converted to a urea derivative (11) by
reaction with KNCO and NH4Cl in DMF.
A standard and mild method for releasing aldehydes from imidazolidine
derivatives employs p-toluenesulfonic acid monohydrate in CH2Cl2 and
acetone.[14] Reaction of the imidazolidine (8) under these conditions gave
a mixture of products with cleavage of the benzylidene group. Therefore,
the imidazolidine (8) was converted into the 2,3 di-O-acetyl derivative (9),
which was much less polar, and could be selectively hydrolyzed by
p-toluenesulfonic acid monohydrate in absolute THF to give the 2,3-di-O-
acetylated aldehyde (10) after neutralization with Et3N.
Reduction of (7) with NaBH4 gave 28amine (12), which was used for the
synthesis of the selectively cyclic urethane derivative (13) and for coupling
with photoreactive amino acids reported in a related paper.[15,16] Similar 28
difucopyranosylamines were recently prepared by reduction of acetylated
L-fucononitrile.[17] Related work from our group is cited in several review
papers.[18–20]
EXPERIMENTAL
Melting points were determined in a Thomas Hoover melting point apparatus
model No. 6404H and are uncorrected. Optical rotations were measured with
an O. C. Rudolph & Sons, Inc., model No. 956 polarimeter. The homogenity
of the compounds synthesized was determined by silica-gel thin layer chrom-
atography. The compounds were visualized by extinction of UV-fluorescence
and by spraying with 10–15% H2SO4–MeOH followed by heating for about
15 min at 1208C.
Deuterated solvents (CDCl3, D2O, pyridine-d5, acetone-d6, Me2SO-d6)
were purchased from Aldrich (Milwaukee, WI) and were dried over
˚
molecular sieves (5 A). Traces of acid were removed by storing CDCl3 over
K2CO3. NMR spectra were recorded on 300-MHz Varian Mercury and
500-MHz Varian Unity Inova spectrometers. Chemical shift values are

Selective Reductions of C-Glycoside Derivatives
1593
given in ppm relative to tetramethylsilane (Me4Si) or one of the standard
solvent peaks. Coupling constants J are given in Hz. Flash chromatography
was performed using 40 mm J. T. Baker Chemical Co. silica gel with the
solvents indicated.
C-(4,6-O-Benzylidene-b-D-glucopyranosyl) Methylamine (2)
Raney nickel (slurry, 3 g) was added to a suspension of nitro derivative 1
(3.11 g, 10 mmol) in MeOH (40 mL). The reaction mixture was degassed by
evacuating the flask and filling with H2 three times, and was stirred under H2
until TLC (SiO2, CHCl3–EtOH 6:1) indicated the disappearance of (1)
(ꢀ15 h). The white product was dissolved in boiling MeOH, the catalyst was
filtered off, and the methanolic filtrate was concentrated in vacuo to a small
volume. The amine (2) was filtered off after cooling, washed with a minimal
amount of MeOH, and dried (2.34 g, 83%). Melting point: 230–2328C
(dec.). All analytical data concurred with the data published earlier.[12]
N-(4,6-O-Benzylidene-b-D-glucopyranosylomethyl)
Hydroxylamine (3)
A suspension of (1) (934 mg, 3 mmol) and Lindlar catalyst (70 mg) in MeOH
(15 mL) was flushed with H2 three times, and was stirred under hydrogen at rt,
until TLC indicated the consumption of the fast-moving spot (8–10 h).
The product was then filtered off as a grey mixture with the catalyst,
washed with MeOH, and dried (846 mg of the crude product, 87%). TLC
(SiO2, CHCl3–EtOH 6:1, Rf 0.32) showed the product as a streak from the
origin. The crude product was used in other reactions without further purifi-
cation. Pure product for analysis was prepared by dissolving the crude in
DMF at 458C, filtering off the catalyst, concentrating the solution, and preci-
pitating with Et2O, mp: 225–2278C (dec.), [a]2D2 258.4 (DMF), MS m/z
[M þ H]þ 298.7 (APCIþ) (MeOH). MW 297.30, C14H19NO6, calc.:
1
C: 56.56, H: 6.44, N: 4.71; found: C: 56.70, H: 6.56, N: 4.69. H NMR
(300 MHz, DMSO-d6): 7.39 (m, 5H, C6H5), 5.56 (s, 1H, CHPh), 5.46 (br. s,
1H, NH), 5.28 (br. s, 2H, C2–OH), 4.18 (dd, 1H, J ¼ 4.5, 3.9, H6), 3.63
(t, 1H, J ¼ 9.6, 9.9, H6), 3.39 (m, H1, H2, H3, H5), 3.16 (dd, 1H, J ¼ 2.1,
12.3, CH2N), 3.08 (t, 1H, J ¼ 8.7, H4), 2.73 (dd, 1H, J ¼ 7.8, 8.1, CH2N);
13C NMR (300 MHz, DMSO-d6): 137.58 (aromatic C-subst.), 128.31
(aromatic Cp-), 127.74, 126.10 (aromatic Co-, m-), 100.29 (HCPh), 80.89
(C2), 76.67 (C5), 73.10 (C4), 73.20 (C1), 69.86 (C3), 67.72 (C6), 55.90 (CH2N).
C-(4,6-O-Benzylidene-b-D-glucopyranosyl) Formaldoximes (4)
Air was bubbled through a stirred suspension of crude (3) (3 g) in MeOH
(120 mL) and NH4OHc (50 mL) until TLC indicated the consumption of (3)

1594
O. Simo et al.
as the slow spot (10–16 h). The reaction mixture was filtered and was concen-
trated in vacuo. The white precipitation (mixture of both isomers) was filtered
off and was recrystallized from H2O (2.2 g), mp 227–2308C (dec.), Rf 0.34,
0.39 (CHCl3–EtOH 10 : 1), MS m/z [M þ H]þ 296.7 (APCIþ) (MeOH),
MW 295.29, C14H17NO6, calc.: C: 56.94, H: 5.80, N: 4.74; found: C: 57.24,
1
H: 6.01, N: 4.69. H NMR of the major isomer (500 MHz, THF-d8): 10.07
(s, 1H, NOH), 7.50–7.45 (m, 2H, aromatic), 7.33–7.26 (m, 3H, aromatic),
3
7.21 (d, 1H, JHC55N1 ¼ 7.0, HC55N), 5.51 (s, 1H, CH-Ph), 4.77 (d, 1H,
3
3JOH3 ¼ 3.6, OH-3), 4.20 (m, 1H, H5), 3.83 (dd, 1H, J1,2 ¼ 9.5, H1), 3.63
(m, 1H, H4), 3.54 (m, 1H, H6), 3.44–3.34 (m, 3H, H2, H3, H6); 13C NMR
of the major isomer (125.8 MHz, THF-d8): 148.3 (C55N), 129.2, 128.5,
127.3 (aromatic), 102.4 (C–Ph), 82.6 (C2), 79.2 (C1), 75.7 (C3), 73.9, 71.5
(C4, C5), 69.5 (C6).
Tri-O-acetyl Derivative (5) of (4)
A solution of Ac2O (0.76 mL, 8 mmol) in pyridine (1 mL) was added to a
solution of oximes 4 (590 mg, 2 mmol) and a catalytical amount of DMAP
(4-dimethylaminopyridine) in pyridine (4 mL) at 08C. The reaction mixture
was allowed to warm to room temperature and was stirred for 5 h. Pyridine
was removed in vacuo and the product was precipitated with ice-cold H2O
(12 mL). The suspension was stirred for 2 h. The white product was filtered
off, washed with water, and dried; (778 mg, 92 %), mp: 182–1848C, [a]D22
223.7 (CHCl3), MW 421.41, C20H23NO9, calc.: C: 57.00, H: 5.50, N: 3.32;
found: C: 56.94, H: 5.69, N: 3.36. 1H NMR (300 MHz, CDCl3): 7.56
(d, 1H, J ¼ 7.2, HC55N), 7.40 (m, 5H, C6H5), 5.51 (s, 1H, CHPh), 5.43
(t, 1H, J ¼ 9.0, 9.3, H3), 5.10 (t, 1H, J ¼ 9.6, H2), 4.38–4.28 (m, 2H, H1,
H6), 3.78–3.61 (m, 3H, H4, H5, H6), 2.15, 2.07, 2.05 (s, s, s, 9H, three
CH3CO); 13C NMR (300 MHz, CDCl3): 169.98, 169.51, 167.43 (three
CH3CO), 153.56 (CH55N), 136.38 (aromatic C-subst.), 128.97 (aromatic
Cp-), 128.04, 125.89 (aromatic Co-, m-), 101.42 (CHPh), 78.35, 75.77,
71.67, 70.81, 69.75, 68.17 (C1–C6), 20.72, 20.64, 19.21 (three CH3CO).
2,3-Di-O-acetyl-4,6-O-benzylidene-b-D-glucopyranosyl Cyanide (6)
DBU (0.36 mL, 2.4 mmol) was added to a stirred solution of 5 (842.8 mg,
2 mmol) in CHCl3 (12 mL) at 08C. The reaction mixture was stirred
overnight, concentrated in vacuo, purified on a short column (5 g SiO2,
CHCl3–hexane 2:1), and recrystallized from EtOH: (535 mg, 74 %), mp:
208–2108C, [a]D22 283.6 (CHCl3), MW 361.36, C18H19NO7, calc.:
1
C: 59.83, H: 5.30, N: 3.88; found: C: 59.48, H: 5.48, N: 3.86. H NMR
(300 MHz, CDCl3): 7.40 (m, 5H, C6H5), 5.51 (s, 1H, CHPh), 5.30 (m, 2H,
H2, H3), 4.38 (m, 2H, H1, H6), 3.75 (m, 2H, H4, H6), 3.55 (ddd, 1H,

Selective Reductions of C-Glycoside Derivatives
1595
J ¼ 4.5, 4.8, H5), 2.12, 2.06 (s, s, 6H, two COCH3); 13C NMR (300 MHz,
CDCl3): 169.79, 168.77 (two CH3CO), 136.19 (aromatic C-subst.), 129.23
(aromatic Cp-), 128.20, 125.99 (aromatic Co-, m-), 114.27 (CN), 101.66
(CHPh), 77.56, 71.71, 71.56, 69.68, 67.91, 66.89 (C1–C6), 20.75, 20.50
(two CH3CO).
Cyclic Aminal between Compound 2 and C-(4,6-O-benzylidene-b-D-
glucopyranosyl) Formaldehyde (7)
Raney nickel (slurry, 2 g) was added to a suspension of oximes 4 (5.91 g,
20 mmol) in pyridine (30 mL) and H2O (60 mL), and the reaction flask was
evacuated and filled with H2 three times and stirred under H2 at ambient temp-
erature for 50–60 h. The catalyst was filtered off, and the product was
dissolved in pyridine (100 mL) at 40–458C. The catalyst was filtered off.
Pyridine was evaporated in vacuo. From the resulting syrup, product was
precipitated by adding MeOH. Upon refrigeration, white crystals were
filtered off, washed with MeOH, and dried (4.3 g, 79 %); mp: 223–2258C
(dec.), [a]2D2 255.2 (pyridine), Rf 0.41 (SiO2, CHCl3–EtOH 10 : 1) MS m/z
[M þ H]þ 544.2 (ESIþ) (MeOH). MW 543.58, C28H33NO10, calc.:
C: 61.87, H: 6.12, N: 2.58; found: C: 61.21, H: 6.31, N: 2.52. Because the
molecule is asymmetrical, the sugar ring with the two free hydroxyl groups
is designated “A,” the other one “B” for NMR assignments. 1H NMR
(500 MHz, DMSO-d6): 7.47–7.42 (m, 4H, aromatic), 7.39–7.35 (m, 6H,
aromatic), 5.58 (s, 1H, CH–Ph), 5.57 (s, 1H, CH–Ph), 5.25 [d, 1H, OH-3
3
3
(A), J3,OH-3 ¼ 4.7], 5.18 [d, 1H, OH-3 (B), J3,OH-3 ¼ 4.6], 5.16 [d,
3
3
1H, OH-2 (A), J2,OH-2 ¼ 5.5], 4.29 (d, 1H, O–CH–N, JCH,NH ¼ 11.4 Hz),
0
4.20–4.14 [m, 2H, H6(A), H6(B)], 3.70 [dd, 1H, H6 (A),
3
2
0
0
J5,6 ¼ J6,6 ¼ 10.1], 3.69–3.58 [m, 2H, H6 (B), H3(B)], 3.53 [m, 1H,
H2(A)], 3.48–3.40 [m, 3H, H4(B), H5(B), H3(A)], 3.37 [dd, 1H, H4(A),
3J3,4 ¼ 3J4,5 ¼ 9.1], 3.33 [m, 1H, H5(A), overlapped with H2O signal], 3.28
3
3
[dd, 1H, H1(A), J1,2 ¼ 9.8; J1,O–CH–N ¼ 1.7], 3.20 [m, 1H, H1(B)],
3.16–3.10 [m, 2H, H2(B), CH of anomeric CH2], 2.64–2.53 (m, 2H, NH,
CH0 of anomeric CH2); 13C NMR: (125.8 MHz, DMSO-d6): 137.8, 137.7
(aromatic, quarternary), 128.8, 128.7, 128.0, 126.4, 126.3 (aromatic), 100.9,
100.5 (CH–Ph), 84.9 (O–CH–N), 82.0, 81.9 [C2(B), C4(B)], 80.7 [C4(A)],
80.6 [C1(A)], 74.2 [C3(A)], 73.6 [C1(B)], 70.8 [C3(B)], 70.5 [C5(A), C5(B)],
69.9 [C2(A)], 67.9 [C6(A)], 67.8 [C6(B)], 46.9 (anomeric CH2).
Diphenylimidazolidine Derivative of C-(4,6-O-Benzylidene-b-D-
glucopyranosyl) Formaldehyde (8)
Aminal (7) (1.087 g, 2 mmol) was suspended in a solution of dianilinoethane
(445.8 mg, 2.1 mmol) in THF (20 mL). 1 N HCl (2.4 mL) was added at 08C,

1596
O. Simo et al.
the reaction mixture was allowed to warm to rt and was stirred for 2 h. Et3N
(0.42 mL, 3 mmol) was added and volatiles were removed in vacuo. CHCl3
(30 mL) was added, the mixture was stirred for 1 h, and most of (2) was
filtered off. The concentrated CHCl3 solution was subjected to column chrom-
atography (20 g SiO2, CH2Cl2, Rf ¼ 0.24), which removed remnants of (2) and
Wanzlick base to give 855 mg (90%) of 8.
2,3-Di-O-acetyl Derivative (9)
A solution of Ac2O (0.21 mL, 2.22 mmol) in anhyd. pyridine (0.5 mL) was
added to a solution of 8 (190 mg, 0.4 mmol) and a catalytical amount of
DMAP in anhyd. pyridine (0.5 mL) at 08C. The reaction mixture was then
allowed to come to rt and was stirred for 3 h. Ice-cold H2O (5 mL) was
added, and the resulting suspension was stirred for 2 h and was filtered. The
white product was washed twice with H2O and was dried (206 mg, 92%).
MW 558.64, C32H34N2O7. 1H NMR (300 MHz, CDCl3): 7.33 (m, 10H,
N-C6H5), 6.77 (m, 5H, C–C6H5), 5.47 (s, 1H, Ph–CH), 5.45 (s, 1H, HC–
N), 5.19 (t, 1H, J ¼ 8.7, 9.3, H3), 5.09 (t, 1H, J ¼ 9.6, 9.0, H2), 4.42 (dd,
1H, J ¼ 4.8, H6), 4.06 (dd, 1H, J ¼ 0.9, 9.6, H1), 3.77 (t, 1H, J ¼ 9.9, 10.2,
H6), 3.55 (m, 2H, H4, H5), 2.04, 1.95 (s, s, two CH3CO); 13C NMR
(300 MHz, CDCl3): 170.31, 168.86 (two COCH3), 146.24, 145.56 (two
aromatic C–N), 136.63 (aromatic C-subst.), 129.25, 129.06, 128.89, 127.98,
125.96 (aromatic C-subst., o-, m-, p-), 118.32, 117.69, 113.72, 112.74
(aromatic Co-, m-, p-N), 78.94, 77.82, 75.33, 73.95, 70.35, 68.65 (C1–C6,
CH–N), 47.18, 46.62 (two H2C–N), 20.88, 20,77 (s, s, 6H, two COCH3).
C-(2,3-Di-O-Acetyl-4,6-O-benzylidene-b-D-glucopyranosyl)
Formaldehyde (10)
A solution of p-toluenesulfonic acid monohydrate (59 mg, 0.31 mmol) in THF
(2 mL) was added dropwise to a stirred solution of (9) (70 mg, 0.125 mmol) in
THF (4 mL) at 08C. The reaction mixture was stirred until TLC analysis
showed the starting material to be consumed (CH2Cl2–EtOAc 5:1,
Rf ¼ 0.32). Then, Et3N was added at 08C to pH 8–9. White triethylammonium
salt was filtered off and was washed with THF. The THF solution was concen-
trated in vacuo, and was subjected to column chromatography (SiO2,
CH2Cl2–EtOAc 5:1) to give a colorless oil (26 mg, 57%). MS m/z
[M þ Na]þ 387.1 (ESIþ) (MeOH), MW 364.35, C18H20O8. 1H NMR
(300 MHz, CDCl3): 9.54 (d, 1H, J ¼ 1.8, CH55O), 7.41 (m, 5H,
C6H5), 5.53 (s, 1H, CHPh), 5.34 (t, 1H, J ¼ 9.3, H3), 5.18 (dd, 1H, J¼
10.2, H2), 4.41 (dd, 1H, J ¼ 4.8, 4.2, H6), 3.95 (dd, 1H, J1,2 ¼ 10.2,
J1,CH55O ¼ 1.5, H1), 3.81 (t, 1H, H6), 3.71 (t, 1H, H4), 3.62 (ddd, 1H,
J ¼ 4.2, 4.5, H5), 2.07, 2.06 (s, s, 6H, two COCH3); 13C NMR (300 MHz,

Selective Reductions of C-Glycoside Derivatives
1597
CDCl3): 195.12 (CH55O), 169.77, 169.48 (two CH3–CO), 136.35 (aromatic
C-subst.), 128.99 (aromatic Cp-), 128.05, 125.89 (aromatic Co-, m-), 101.42
(CH-Ph), 80.33 (C1), 78.01 (C5), 72.14 (C2), 70.52 (C4), 68.17, 68.05 (C3,
C6), 20.72, 20.54 (two COCH3).
C-(4,6-O-Benzylidene-b-D-glucopyranosyl)N-methylurea (11)
Aminomethyl glucose 2 (281.3 mg, 1 mmol), was stirred with KNCO
(121.7 mg, 1.5 mmol) and NH4Cl (74.9 mg, 0.14 mmol) in DMF (20 mL) at
rt for 4 h. DMF was evaporated under reduced pressure, H2O (10 mL) was
added to the resulting syrup and the mixture was stirred for 2 h. The
filtered-off white precipitate was washed with H2O. Recrystallization from
H2O gave 2.3 g (69%) of the product; mp: 222–2238C, [a]2D2 238.0 (DMF),
MS m/z [M þ H]þ 324.9 (ESIþ), MW 324.34, C15H20N2O6, calc.: C: 55.55,
1
H: 6.22, N: 8.64; found: C: 55.34, H: 6.41, N: 8.45. H NMR (300 MHz,
DMSO-d6): 7.41 (m, 5H, C6H5), 6.04 (t, 1H, J ¼ 5.7, CH2NH), 5.59 (s, 1H,
NH2), 5.57 (s, 1H, Ph–CH), 5.32, (d, 1H, J ¼ 5.1, C2OH), 5.26 (d, 1H,
J ¼ 4.5, C3OH), 4.19 (dd, 1H, J ¼ 3.3, 4.2, H6), 3.65 (t, 1H, J ¼ 9.9, 9.6,
H6), 3.45 (m, 1H, H3), 3.35 (m, 2H, H1, H5), 3.25 (m, 1H, H4), 3.06
(m, 2H, H2C–NH); 13C NMR (300 MHz, DMSO-d6): 158.83
(C55O), 137.53 (aromatic C-subst.), 128.54 (aromatic Cp-), 127.73, 126.07
(aromatic Co-, m-), 100.48 (HC–Ph), 80.97 (C2), 79.93 (C5), 73.42 (C4),
71.87 (C1), 70.03 (C3), 67.88 (C6), 40.74 (H2C–NH).
N,N-Bis-(4,6-O-Benzylidene-b-D-glucopyranosylomethyl) Amine (12)
NaBH4 (powder) (151.3 mg, 4 mmol) was added to a stirred suspension of
aminal (7) (1.087 g, 2 mmol) in pyridine–AcOH (2:1) (10 mL) and MeOH
(8 mL) at rt during 20 min. The resulting solution was stirred for 1 h.
Solvents were evaporated under reduced pressure. The resulting gelatinous
precipitate was solidified by adding Et2O (40 mL) with vigorous stirring.
A white solid was filtered off after 2 h, washed with Et2O, and dissolved in
MeOH (15 mL) under reflux. NH4Cl (428 mg, 8 mmol) in H2O (10 mL) was
added into the refluxed solution. A white solid precipitated after a few
minutes. The suspension was refluxed for 5 min, cooled, and filtered. The
white hydrochloride was washed with H2O and was dried (966 mg, 83%);
mp: 250–2518C (dec). 2N NaOH (0.52 mL, 1.04 mmol) was added to a
stirred suspension of hydrochloride (582.05 mg, 1 mmol) in MeOH (20 mL)
and H2O (7 mL). The resulting solution (pH 9) was stirred for 20 min at rt,
concentrated in vacuo, and treated with H2O (20 mL). The product was
filtered off, washed with H2O, and dried (490 mg, 90%); mp: 233–2348C,
[a]2D2 244.6 (DMF), MS m/z [M þ H]þ 546.3 (APCIþ) (MeOH), MW
545.59, C28H35NO10, calc.: C: 61.64, H: 6.47, N: 2.57; found: C: 61.71,

1598
O. Simo et al.
H: 6.81, N: 2.59. 1H NMR (500 MHz, THF-d8): 7.47–7.46 (m, 4H,
aromatic), 7.31–7.26 (m, 6H, aromatic), 5.50 (s, 2H, 2 ꢀ CHPh), 4.20 (dd,
3
3
0
60
3
2H, 2 ꢀ H6, J6,
¼ 10.3, J5,6 ¼ 4.3), 3.62 (m, 2H, 2 ꢀ H6 ), 3.51
(dd, 2H, 2 ꢀ H3, J2,3 ¼ 3J3,4 ¼ 8.5), 3.40 (m, 2H, 2 ꢀ H1), 3.37–3.30
2
0
(m, 6H, 2 ꢀ H2, 2 ꢀ H4, 2 ꢀ H5), 2.96 (dd, 2H, 2 ꢀ CH–N, JCH-N, CH -
3
3
¼ 12.3, J1, CH–N ¼ 3.7), 2.79 (dd, 2H, 2 ꢀ CH0 –N, J1, CH –N ¼ 6.2).
0
N
Cyclic Urethane (13)
Hexachloroacetone (0.16 mL, 1.05 mmol) and N,N-diisopropylethyl amine
(1.4 mL, 8 mmol) were added to a suspension of (12) (381.7 mg, 0.7 mmol)
in dry CHCl3 (20 mL) and the mixture was refluxed for 12 h.
Hexachloroacetone (0.053 mL, 0.35 mmol) and N,N-diisopropylethyl amine
(0.7 mL, 4 mmol) were added and the reflux continued for 12 h. The same
amounts of hexachloroacetone (0.053 mL) and N,N-diisopropylethyl amine
(0.7 mL) were added and the reaction mixture was refluxed for 6 h. The
product was filtered off after cooling and was recrystallized from EtOH
(192 mg, 48%); mp: 290–2928C, [a]2D2 þ48.4 (DMF), MS m/z [M þ H]þ
572.3 (ESIþ) (MeOH), MW 571.59, C29H33NO11, calc.: C: 60.94, H: 5.82,
N: 2.45; found: C: 60.86, H: 6.11, N: 2.45. Because the molecule is asymme-
trical, the sugar ring with the two free hydroxyl groups is designated “A,” the
other one “B” for NMR assignments. 1H NMR (500 MHz, DMSO-d6):
7.45–7.36 (m, 10H, aromatic), 5.61 [s, 1H, CH–Ph (B)], 5.56 [s, 1H, CH–
Ph (A)], 4.23–4.17 [m, 2H, H6e (A), H6e (B)], 3.99 [dd, 1H, CH2e–C1 (B), J¼
2.0, 14.5], 3.90–3.80 [m, 2H, H1 (A), H2 (A)], 3.75 [t, 1H, H3 (A), J ¼ 9.0],
3.70 [t, 1H, H6a (A), J ¼ 10.0], 3.64–3.59 [m, 2H, H6a (B), H5 (A)], 3.55–
3.30 [m, H1 (B), H3 (B), H4 (B), H5 (B), CH2–C1 (A), H4 (A)], 3.07–2.99
[m, 2H, H2 (B), CH2a–C1 (B)]; 13C NMR (500 MHz, DMSO-d6): 152.01
(C55O), 137.80, 137.53 (aromatic, quarternary), 128.93, 128.82, 128.06,
128.01, 126.36, 126.32 (aromatic), 100.94, 100.67 (CH-Ph), 80.86 [C4 (B)],
80.62 [C4 (A)], 79.38 [C1 (B)], 78.63 [C2 (A)], 73.84 [C3 (B)], 72.82 [C2
(B)], 70.52 [C5 (A)], 70.37 [C3 (A)], 69.99 [C5 (B)], 68.88 [C1 (A)], 68.00
[C6 (B)], 67.53 [C6 (A)], 51.26 [CH2–C1 (B)], 50.12 [CH2–C1 (A)].
ACKNOWLEDGEMENT
Acknowledgement is made to the Donors of the American Chemical Society
Petroleum Research Fund for support of the research given to K.M. (PRF Type
G 36892-G4).
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