Synthesis of imino-C-disaccharides related to sucrose

Article abstract of DOI:10.1081/CAR-100108281

Stabilised ylides 1 and 10, prepared from perbenzylated and peracetylated allyl C-glucopyranosides, respectively, were reacted with differently protected D-serinal; osmylation of the obtained α,β-unsaturated ketones 3 and 12, followed by intramolecular re

Full text of DOI:10.1081/CAR-100108281

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SYNTHESIS OF IMINO-C-DISACCHARIDES RELATED TO
SUCROSE
Barbara La Ferla a , Laura Cipolla a , Francesco Peri a & Francesco Nicotra b
a Department of Biotechnology and Biosciences , University of Milano-Bicocca , Piazza
della Scienza, Milano, 2-I-20126, Italy
b Department of Biotechnology and Biosciences , University of Milano-Bicocca , Piazza
della Scienza, Milano, 2-I-20126, Italy
Published online: 16 Aug 2006.
To cite this article: Barbara La Ferla , Laura Cipolla , Francesco Peri & Francesco Nicotra (2001) SYNTHESIS OF IMINO-C-
DISACCHARIDES RELATED TO SUCROSE , Journal of Carbohydrate Chemistry, 20:7-8, 667-680
To link to this article: http://dx.doi.org/10.1081/CAR-100108281
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J. CARBOHYDRATE CHEMISTRY, 20(7&8), 667–680 (2001)
SYNTHESIS OF IMINO-C-DISACCHARIDES
RELATED TO SUCROSE1
Barbara La Ferla, Laura Cipolla, Francesco Peri,
and Francesco Nicotra*
Department of Biotechnology and Biosciences, University of
Milano-Bicocca, Piazza della Scienza 2–I-20126 Milano, Italy
ABSTRACT
Stabilised ylides 1 and 10, prepared from perbenzylated and peracetylated al-
lyl C-glucopyranosides, respectively, were reacted with differently protected
D-serinal; osmylation of the obtained ꢀ,ꢁ-unsaturated ketones 3 and 12, fol-
lowed by intramolecular reductive amination, afforded different imino-C-dis-
accharides 14, 15, 18, and 19 related to sucrose.
INTRODUCTION
The significant role that carbohydrates play in a variety of biological pro-
cesses of pharmaceutical relevance has stimulated the interest in compounds that
could interfere in carbohydrate metabolism and in carbohydrate-based recognition
phenomena. In this context, great efforts have been devoted recently to the synthe-
sis of glycomimetics,2,3 such as iminosugars and C-glycosides, that can act as in-
hibitors of carbohydrate processing enzymes and/or as stable analogues of glycidic
entities.
The synthesis of sucrose mimetics is particularly attractive, due to the serious
and widespread sucrose metabolism disorders, such as diabete mellitus. Further-
more, from a synthetic point of view, stable analogues of sucrose, in which a car-
bon atom substitutes the interglycosidic oxygen, are challenging synthetic targets,
both the anomeric centres of the disaccharide being involved in the C-glycosidic
linkage.
667
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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LA FERLA ET AL.
The synthesis of C-glycosidic analogues of sucrose has already been reported
by Kishi4,5 and our group;6,7 our analogues showed no inhibition of invertase and
very weak inhibition of ꢀ-glucosidase from yeast. These results prompted us to
synthesize imino-C-glycosides related to sucrose, taking advantage of the well
known property of iminosugars to inhibit glycosidases, as mimics of the oxonium
ion transition state of the enzymatic reaction.8
To our knowledge, no examples of synthesis of imino-C-disaccharides re-
lated to sucrose have been reported. We decided to perform the synthesis of mimet-
ics in which the nitrogen atom is part of the fructosidic moiety of the disaccharide.
Towards this aim we exploited the synthetic strategy already optimised for the C-
disaccharide,6,7 using protected D-serinal (Scheme 1) in place of protected D-glyc-
eraldehyde.
RESULTS AND DISCUSSION
The ꢀ-C-glucosidic stabilised ylide 1 (Scheme 1), synthesised as already re-
ported,6,7 was reacted with N-benzyloxycarbonyl-N,O-isopropylidene-D-serinal 2.
The reaction afforded 3 in 83% yield, whose E-double9 bond was submitted to cat-
alytic osmylation in order to introduce the two hydroxyl groups with a relative syn
stereochemistry. In terms of absolute stereochemistry, the reaction was expected to
afford the (3S,4R)-product 4a preferentially. Indeed it is well established that elec-
trophiles attack double bonds with allylic heteroatom from the less hindered face,
in a conformation where the heteroatom lies in the same plane of the double
bond.10 The reaction afforded, however, the desired product 4a with a very low
stereoselection (1.6:1).
The stereochemistry of the new stereocentres of compound 4a was deter-
mined after acetylation to compound 5 and cleavage of the isopropylidene protect-
ing group with FeCl3-SiO2,11 which resulted in the formation of the pyranosidic
structure 6 (Scheme 2). The 1H NMR coupling constants of 6 allow the determi-
nation of the relative orientation of the hydrogen atoms in the cycle (see experi-
Scheme 1.

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SYNTHESIS OF IMINO-C-DISACCHARIDES
669
Scheme 2.
mental). In order to enhance the stereoselection, stoichiometric osmylation in the
presence of chiral auxiliaries such as quinuclidine12 or the Sharpless ligand
(DHQD)2-PHAL (AD-mix-ꢁ)13 was performed. However, in the first case the
stereochemical outcome of the reaction was surprisingly reversed, the 3R,4S prod-
uct being preferentially obtained (75% d.e.), whereas in the second case no stere-
oselection was observed. The synthesis was then performed with the mixture of di-
astereoisomers obtained by catalytic osmylation.
We studied the possibility of performing the reductive aminocyclization
without affecting the protecting groups of the glucose moiety. However, any at-
tempt to effect an acidic hydrolysis of the carbobenzyloxy protecting groups of 5
resulted in the degradation of the product. To overcome this problem, the protect-
ing groups of both the C-glucopyranosyl ylide and D-serinal were modified. Start-
ing from polyacetylated allyl C-glucopyranoside 714 (Scheme 3), ylide 10 was syn-
thesised and reacted with O-diphenyl-tert-butyl-silyl-N-Fmoc-D-serinal 11,
affording compound 12 in 87 % yield (no traces of the Z isomer were detected).
The catalytic osmylation of 12 proceeded without stereoselection, giving a 1:1
mixture of 13a and 13b (Scheme 3) which could be separated by flash chromatog-
raphy (the stereochemistry was attributed only after cyclization).
The amino group of 13a was deprotected with piperidine, and the obtained la-
bile hemiaminal was reduced. Different reduction conditions were investigated
(catalytic hydrogenation with Pd/C or PtO2, NaBH3CN), and the best results were
obtained using 3 equivalents of NaBH(OAc)3, dry MgSO4, and acetic acid (6
equivalents) in 1,2-dichloroethane as solvent. Under these conditions compound
13a (the isomer with the correct stereochemistry) afforded a 25:75 mixture of the
imino-C-disaccharides 14 and 15, in 65% overall yield. These compounds show
complex NMR spectra due to the equilibrium between two conformers of the
pyrrolidine ring, nevertheless the stereochemistry of C-2,3,4 of 14 and 15 was de-
termined by NOE experiments. The stereochemical outcome of the reduction sug-
gests coordination of the 3-OH group with the boron atom of the reducing agent,
inducing the hydride attack preferentially from the ꢁ-face of the intermediate
imine.
In a parallel approach, O-diphenyl-tert-butyl-silyl-N-Fmoc-D-serinal 11 re-
acted with compound 1 affording compound 16 in 87% yield (Scheme 4). Catalytic

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LA FERLA ET AL.
Scheme 3. i: NIS, DMSO-H2O; ii: PCC, CH2Cl2; iii: PPh3, Et3N, MeCN, then NaHCO3; iv: OsO4,
N-methylmorpholine-N-oxide, acetone-H2O; v, piperidine, DMF, then NaBH(OAc)3, AcOH.
osmylation of 16 gave a 1:1 mixture of inseparable diastereoisomers which were
acetylated affording compounds 17a and 17b, easily separated by flash chro-
matography. Acetylation was also effected to prevent the coordination by
NaBH(OAc)3 to the 3-OH group.
Scheme 4.

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SYNTHESIS OF IMINO-C-DISACCHARIDES
671
Figure 1.
Deprotection of the amino group of 17a with piperidine afforded a labile
hemiaminal which was directly submitted to reduction with NaHB(OAc)3. Under
these conditions, the diastereoisomer 17a afforded only compound 18 (40% yield)
(Figure 1). The stereochemistry of C-2,3,4 of 18 was attributed by NOE experi-
ments. Once more, the reduction occurred stereoselectively from the ꢁ-face of the
“pseudo-furanosidic” pyrrolidine ring, affording an imino-C-disaccharide epimer
at C-2 of sucrose.
Finally, the mixture of diastereomers 4 was submitted to catalytic hydro-
genation under slightly acidic conditions, in order to perform complete deprotec-
tion, formation of the cyclic hemiaminal, and reductive amination at once. This
sequence of reactions afforded directly the desired deprotected imino-C- disaccha-
rides. The catalytic hydrogenation was performed under different experimental
conditions, the best results being finally obtained with Pd/C, THF/MeOH/AcOH.
In these conditions compound 19 was isolated in 17% overall yield after acetyla-
tion and chromatographic purification of the crude that allowed the separation of
19 from the undesired diastereomer. It is noteworthy that the nitrogen of 19 is
methylated, a result that could be explained with the hypothesis that formaldehyde
formed during the reaction undergoes a reductive amination.
In conclusion, starting from differently protected allyl-C-glucopyranosides it
is possible to synthesise various imino-C-disaccharides related to sucrose, exploit-
ing an approach in which the furanosidic moiety of the molecule is built up on the
allylic appendage by conversion into a stabilised ylide and condensation with a
properly protected D-serinal. Depending on the reagents employed in the osmyla-
tion of the double bond and in the intramolecular reductive amination, different di-
astereoisomeric imino-C-disaccharides have been obtained.
EXPERIMENTAL
General Methods. Optical rotations were measured with a Perkin Elmer
241 digital polarimeter. NMR spectra were recorded on a Varian XL200 (200 MHz
for 1H and 50.29 MHz for 13C) and on a Bruker AC300 (300 MHz for 1H and 75.47

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LA FERLA ET AL.
MHz for 13C). Chemical shifts are expressed in parts per million downfield from
TMS. Melting points were determined on a Büchi 510 apparatus. Mass spectra
were recorded on a VG 70-70 EQ, using FAB (Naꢂ) ionization. Reactions were
followed on TLC on silica gel 60F254 (E. Merck); flash column chromatography
was performed on silica gel 60 (0.040–0.063 mm, E. Merck).
(3E)-5-Amino-1-C-(2,3,4,6-tetra-O-benzyl-ꢀ-D-glucopyranosyl)-5-N-
benzyloxycarbonyl-1,3,4,5-tetradeoxy-5,6-N,O-isopropylidene-D-glycero-hex-
3-eno-2-ulose (3). To a solution of compound 1 (2.50 g, 2.97 mmol, 1.3 equiv)
in dry MeCN (10 mL) under an inert atmosphere, compound 2 was added (0.61 g,
2.3 mmol, 1 equiv) dissolved in dry MeCN (7 mL). After 5 days the solvent was
removed under reduced pressure; chromatographic purification (petroleum
ether/acetone 8:2 v/v) afforded compound 3 (1.67 g, 2.02 mmol, 88% yield, only
1
E isomer): oil, m/z: 849 (Mꢂ23)ꢂ; 826 (M)ꢂ; [ꢀ]D ꢂ55.0° (c 0.96, CHCl3); H
NMR (300 MHz, CDCl3) ꢃ 1.54, 1.66 (2s, 6H, CH3 iPr), 2.72 (dd, 1H, J1a,1b ꢄ 15.8
Hz, J1a,1ꢅ ꢄ 8.1 Hz, H-1a), 2.90 (dd, 1H, J1b,1a ꢄ 15.8 Hz, J1b,1ꢅ ꢄ 5.0 Hz, H-1b),
3.57–3.78 (m, 7H, H-2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 6ꢅa, 6ꢅb, 6a), 4.03 (dd, 1H, J ꢄ 9.3, J ꢄ 6.5 Hz,
H-6b), 4.38–4.45 (m, 1H, H-5), 4.44 (d, 1H, J ꢄ 11.4 Hz, CHPh), 4.48 (d, 1H,
J ꢄ 10.3 Hz, CHPh), 4.53–4.63 (m, 3H, 3CHPh), 4.69–4.78 (m, 1H, H-1ꢅ), 4.78
(d, 1H, J ꢄ 11.0 Hz, CHPh), 4.80 (d, 1H, J ꢄ 10.7 Hz, CHPh), 4.89 (d, 1H,
J ꢄ 11.0 Hz, CHPh), 5.03 (bs, 2H, CH2Ph), 6.03 (d, 1H, J3,4 ꢄ 15.8 Hz, H-3), 6.60
(dd, 1H, J4,3 ꢄ 15.8, J4,5 ꢄ 7.0 Hz, H-4), 7.05–7.35 (m, HPh); 13C NMR (75.47
MHz, C6D6, 60°C) ꢃ 21.55, 24.63 (2q, CH3 iPr), 36.57 (q, C-1), 56.10 (d, C-5),
64.97,65.54, 67.81, 71.19, 71.61, 73.01, 73.23 (7t, C-6ꢅ, 6, 5CH2Ph), 69.26, 71.32,
76.50, 78.02, 80.52 (5d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ), 92.98 (s, Cq iPr), 128.01–129.00
(CHPh), 128.69, 141.52 (2d, C-3, 4), 134.91–137.50 (Cq Ph), 194.47 (s, C-2).
Anal. Calcd for C51H55NO9: C, 74.16; H, 6.71; N, 1.70. Found: C, 74.09;
H, 6.77; N, 1.69.
3,4-Di-O-acetyl-5-amino-1-C-(2,3,4,6-tetra-O-benzyl-(ꢀ-D-glucopyra-
nosyl)-5-N-benzyloxycarbonyl-1,5-dideoxy-5,6-N,O-isopropyliden-D-arabino-
hex-2-ulose (5). Compound 3 (1g, 1.16 mmol) was dissolved in 8 mL of
H2O/acetone 1/8; N-methylmorpholine-N-oxide (317 mg, 2.32 mmol, 2 equiv) and
OsO4 (3 mL of a 5 mg/mL solution in tBuOH, 0.05 equiv) were added. After 4 h
the reaction was quenched with aqueous Na2S2O3. After 30 min, the reaction mix-
ture was extracted with AcOEt, the organic layer was dried over Na2SO4, filtered
and the solvent was removed under reduced pressure. Chromatographic purifica-
tion (petroleum ether/AcOEt 65:35 v/v) afforded compounds 4a and 4b in 75%
yield (748 g, 0.87 mmol) as a mixture of inseparable diastereomers, which was di-
rectly acetylated for characterisation. The mixture of compounds 4a and 4b (748
g, 0.87 mmol) was dissolved in 9 mL of dry Py and 0.32 mL of Ac2O and a cat-
alytic amount of DMAP was added. After 90 min the solvent was removed under
reduced pressure and chromatographic purification (petroleum ether/AcOEt 7:3
v/v) afforded pure compound 5 (455 mg, 0.482 mmol, 55% yield) and the other di-
astereomer (284 mg, 0.301 mmol, 35% yield). Compound 5: m/z: 967 (M ꢂ 23)ꢂ;

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673
944 (M)ꢂ; 1H NMR (300 MHz, CDCl3) two conformers ꢃ 1.48–1.39 (m, 6H, 2CH3
iPr), 1.60 (s, 3H CH3 Ac), 1.98 (s, 3H, CH3 Ac), 2.65–3.00 (m, 2H, H-1a,1b),
4.25–3.50 (m, 9H, H-2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 6ꢅa, 6ꢅb, 5, 6a, 6b), 4.44 (d, 1H, J ꢄ 12.2 Hz,
CHPh), 4.50 (d, 1H, J ꢄ 11.0 Hz, CHPh), 4.50–4.58 (m, 3H, 3CHPh), 4.62–4.73
(m, 1H, H-1ꢅ), 4.74 (d, 1H, J ꢄ 11.4 Hz, CHPh), 4.78 (d, 1H, J ꢄ 11.0 Hz, CHPh),
4.86 (d, 1H, J ꢄ 11.4 Hz, CHPh), 5.10–5.30 (bs, 3H, CH-OAc, CH2Ph), 5.89 (bs,
1H, CH-OAc), 7.10–7.41 (m, HPh); 13C NMR (50.29 MHz, CDCl3) two conform-
ers ꢃ 20.49 (CH3 Ac), 22.90, 24.33, 25.37, 27.05 (4q, CH3 iPr), 35.76 (d, C-1),
57.89, 58.65 69.50, 72.47, 77.55, 77.94, 78.80, 81.74 (8d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 3, 4,
5), 63.52, 67.46, 69.03, 72.95, 73.46, 74.84, 75.16 (7t, C-6ꢅ, 6, 5CH2Ph), 93.32,
93.38 (2s, Cq-iPr), 127.93–128.26 (CHPh) 136.10–139.63 (CqPh), 169.41, 169.93
(2s, CO), 200.44 (s, C-2).
Anal. Calcd for C55H61NO13: C, 69.97; H, 6.51; N, 1.48. Found: C, 70.02;
H, 6.56; N, 1.47.
3,4-Di-O-acetyl-2-amino-7,11-anhydro-8,9,10,12-tetra-O-benzyl-2-N-
benzyloxycarbonyl-2,6-dideoxy-D-glycero-D-ido-D-manno-dodec-5-ulopyra-
nose (6). Compound 5 (91 mg, 0.096 mmol) was mixed with FeCl3-SiO121 (270
mg) and vigorously stirred for 16 h. Then the mixture was filtered on florisil elut-
ing with Et2O, then with EtOAc. Chromatographic purification (petroleum
ether/AcOEt 7:3 v/v) afforded 62 mg of pure compound 6 (76% yield). Compound
6: white amorphous solid; m/z: 927 (M ꢂ 23)ꢂ, 904 (M)ꢂ; [ꢀ]D ꢄ ꢆ15.7° (c 0.9,
CHCl3); 1H NMR (300 MHz, C6D6) ꢃ 1.67 (s, 3H, CH3 Ac), 1.81 (s, 3H, CH3 Ac),
1.95 (bd, 1H, J6a,6b ꢄ 14.7 Hz, H-6a), 2.51 (dd, 1H, J6b,6a ꢄ 14.7, J6b,7 ꢄ 12.0 Hz,
H-6b), 3.38 (dd, 1H, J10,11 ꢄ 9.4, J10,9 ꢄ 7.4 Hz, H-10), 3.46 (dd, 1H, J12a,12b
ꢄ 10.0, J12a,11 ꢄ 6.4 Hz, H-12a), 3.53–3.59 (m, 2H, H-8, 12b), 3.78 (t, 1H, J9,8
ꢄ J9,10 ꢄ 7.4 Hz, H-9), 4.12 (dt, 1H, J11,10 ꢄ 9.4, J11,12a ꢄ 6.4, J11,12b ꢇ 1 Hz, H-
11), 4.28 (d, 1H, J ꢄ 12.4 Hz, CHPh), 4.32 (d, 2H, J ꢄ 11.2 Hz, 2CHPh), 4.36 (d,
1H, J ꢄ 11.2 Hz, CHPh), 4.45–4.48 (m, 1H, H-2), 4.48 (d, 1H, J ꢄ 11.4 Hz,
CHPh), 4.54 (d, 1H, J ꢄ 11.5 Hz, CHPh), 4.68 (d, 1H, J ꢄ 11.2 Hz, CHPh), 4.71
(d, 1H, J ꢄ 11.5 Hz, CHPh), 4.82 (m, 1H, H-7), 5.00 (d, 1H, J ꢄ 11.3 Hz, CHPh),
5.04 (dd, 1H, J1a,1b ꢄ 12.1, J1a,2 ꢈ1 Hz, H-1a), 5.10 (d, 1H, J ꢄ 11.3 Hz, CHPh),
5.30 (bs, 1H, NH), 5.34 (dd, 1H, J1b,1a ꢄ 12.1, J1b,2 ꢄ 4.9 Hz, H-1b), 5.39 (bd, 1H,
J
4,3 ꢄ 10.3 Hz, H-4), 5.71 (dd, 1H, J3,4 ꢄ 10.3, J3,2 ꢄ 3.2 Hz, H-3), 7.10–7.33 (m,
HPh); 13C NMR (50.29 MHz, CDCl3) ꢃ 20.63, 20.93, (2q, CH3 Ac), 31.37 (t, C-6),
50.09 (d, C-2), 61.63, 66.88, 68.79, 72.95, 73.36, 74.54, 74.62 (7t, C-1, 12,
5CH2Ph), 69.06, 69.42, 71.34, 72.03, 76.81, 78.32, 80.06 (7d, C-3, 4, 7, 8, 9, 10,
11), 97.91 (d, C-5), 127.74–128.40 (CHPh), 135.60–138.27 (CqPh), 170.11, 170.40
(2s, CO).
Anal. Calcd for C52H57NO13: C, 69.09; H, 6.36; N, 1.55. Found: C, 69.11;
H, 6.41; N, 1.60.
1-C-(2,3,4,6-Tetra-O-acetyl-(ꢀ-D-glucopyranosyl)-3-iodopropan-2-ol (8).
Compound 714 (4.7 g, 12.6 mmol, 1 equiv) was dissolved in DMSO (60 mL) then
H2O (680 ꢉL, 3 equiv) and NIS (6.4 g, 28.5 mmol, 2.3 equiv) were added. After

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LA FERLA ET AL.
24 h an aqueous solution of Na2S2O3 was added until the reaction became colour-
less. The reaction mixture was then extracted with Et2O, the organic layer dried
over Na2SO4 and concentrated to dryness. Chromatographic purification
(petroleum ether/AcOEt 1/1, v/v) afforded 5.6 g of pure compound 8 as a mixture
1
of diastereomers (86% yield). Compound 8: H NMR (200 MHz, CDCl3) ꢃ
1.60–1.90 (m, 2H, H-1a, 1b), 2.10 (m, 12H, 4CH3 Ac), 2.55 (s, 1H, OH), 2.85 (s,
1H, OH), 3.25–3.40 (m, 2H, H-3a, 3b), 3.60–4.50 (m, 6H, H-1ꢅ, 5ꢅ, 6ꢅa, 6ꢅb, 2),
4.90–5.00 (m, 1H, H-4ꢅ), 5.00–5.15 (m, 1H, H-2ꢅ), 5.20–5.40 (m, 1H, H-3ꢅ); 13
C
NMR (50.29 MHz, CDCl3) ꢃ 13.80, 14.10 (2t, C-1), 22.02 (CH3 Ac), 32.41 (t,
C-3), 62.44 (t, C-6ꢅ), 67.46, 68.22, 68.84, 69.63, 69.89, 70.13, 71.05 (7d, C-1ꢅ, 2ꢅ,
3ꢅ, 4ꢅ, 5ꢅ, 2), 169.43, 169.70, 170.51, 170.73 (4s, CO).
Anal. Calcd for C17H25IO10: C, 39.55; H, 4.88. Found: C, 39.58; H, 4.91.
1-C-(2,3,4,6-Tetra-O-acetyl-(ꢀ-D-glucopyranosyl)-3-(triphenyl-ꢊ5-phos-
phanyliden)-propan-2-one (10). A solution of compound 8 (3.7 g, 7.16 mmol)
in dry CH2Cl2 (40 mL), was added, under an inert atmosphere, to a mixture of PCC
(2.3 g, 10.8 mmol, 1.5 equiv) and 4Å powdered molecular sieves. After 18 h the
mixture was filtered first on a celite pad and then on silica gel (petroleum
ether/AcOEt 1/1, v/v, ꢂ1% Et3N). Compound 9 (3.37 g, 92% yield) was immedi-
ately used for the next step. PPh3 (1.89 g, 7.20 mmol) and Et3N (170 ꢉL, 1.22
mmol) were dissolved in dry MeCN (44 mL), then compound 9 (3.3 g, 6.4 mmol)
dissolved in dry MeCN (40 mL) was added. After 3.5 h the solvent was removed
under reduced pressure, the crude was dissolved in AcOEt and washed sequentially
with a saturated solution of NaHCO3 and H2O, dried over Na2SO4, filtered and the
solvent removed. Purification by flash chromatography (AcOEt) afforded 2.8 g
(67% yield) of pure compound 10. Yellow solid, mp 125–128°C; [ꢀ]D ꢄ ꢂ5.6° (c
1, CHCl3); 1H NMR (200 MHz, CDCl3) ꢃ 1.90–2.00 (m, 12H, 4CH3 Ac), 2.54 (dd,
1H, J1a, 1b ꢄ 14.3, J1a,1ꢅ ꢄ 4.2 Hz, H-1a), 2.78 (m, 1H, H-1b), 4.05–4.25 (m, 3H,
H-5ꢅ, 6ꢅa, 6ꢅb), 4.72–4.82 (m, 1H, H-1ꢅ), 5.05 (t, 1H, J4ꢅ,3ꢅ ꢄ J4ꢅ,5ꢅ ꢄ 8.0 Hz, H-4ꢅ),
5.15 (dd, 1H, J2ꢅ,3ꢅ ꢄ 8.8, J2ꢅ,1ꢅ ꢄ 5.6 Hz, H-2ꢅ), 5.28 (bt, 1H, H-3ꢅ), 7.40–7.80 (m,
15H, HPh). 13C NMR (50.29 MHz, CDCl3) ꢃ 20.50 (CH3 Ac), 29.50 (t, C-1), 37.96
(d, C-3), 62.39 (t, C-6ꢅ), 68.91, 69.17, 70.03, 70.78, 71.52 (5d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ),
128.00–133.00 (CHPh), 169.45, 170.01, 170.13, 170.64 (4s, CO), 187.40 (s, C-2).
Anal. Calcd for C35H37O10P: C, 64.81; H, 5.75. Found: C, 64.79; H, 5.77.
(3E)-1-C-(2,3,4,6-Tetra-O-acetyl-(ꢀ-D-glucopyranosyl)-5-amino-1,3,4,5-
tetradeoxy-5-N-fluorenylmethoxycarbonyl-6-O-diphenyl-tert-butylsilyl-D-
glycero-hex-3-eno-2-ulose (12). Compound 10 (286 mg, 0.44 mmol), dissolved
in dry MeCN (5 mL), was added to a solution of 11 (302 mg, 0.55 mmol, 1.25
equiv) in dry MeCN (10 mL). After 48 h the solvent was removed under reduced
pressure and chromatographic purification (petroleum ether/AcOEt 6/4, v/v) af-
forded 353 mg of pure compound 12 (87% yield). Compound 12: amorphous solid;
1
[ꢀ]D ꢄ ꢂ17.2° (c 1, CHCl3); H NMR (200 MHz, CDCl3) ꢃ 1.10 (s, 9H, tBu),
1.90–2.00 (m, 12H, 4CH3 Ac), 2.90 (m, 2H, H-1a, 1b), 3.70–3.90 (m, 3H, H-5ꢅ, 6a,
6b), 4.00–4.14 (m, 3H, H-6ꢅa, 6ꢅb, CHFmoc), 4.40–4.55 (m, 3H, H-5, CH2Fmoc),

ORDER
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SYNTHESIS OF IMINO-C-DISACCHARIDES
675
4.81 (m, 1H, H-1ꢅ), 5.00 (t, 1H, J4ꢅ,3ꢅ ꢄ J4ꢅ,5ꢅ ꢄ 8.5 Hz, H-4ꢅ), 5.15 (dd, 1H, J2ꢅ,3ꢅ
ꢄ 8.5, J2ꢅ,1ꢅ ꢄ 5.3 Hz, H-2ꢅ), 5.27 (t, 1H, J3ꢅ,2ꢅ ꢄ J3ꢅ,4ꢅ ꢄ 8.5 Hz, H-3ꢅ), 6.25 (d, 1H,
J
3,4 ꢄ 15.8 Hz, H-3), 6.80 (dd, 1H, J4,3 ꢄ 15.8, J4,5 ꢄ 4.9 Hz, H-4), 7.30–7.70 (m,
19H, HPh, NH).
Anal. Calcd for C51H57NO13Si: C, 66.58; H, 6.24; N, 1.52. Found: C, 66.60;
H, 6.31; N, 1.57.
1-C-(2,3,4,6-Tetra-O-acetyl-(ꢀ-D-glucopyranosyl)-5-amino-1,5-dideoxy-
5-N-fluorenylmethoxycarbonyl-6-O-diphenyl-tert-butylsilyl-D-arabino-hex-2-
ulose (13a) and 1-C-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl)-5-amino-1,5-
dideoxy-5-N-fluorenylmethoxycarbonyl-6-O-diphenyl-tert-butylsilyl-D-xylo-h
ex-2-ulose (13b). Compound 12 (229 mg, 0.325 mmol) was dissolved in 2 mL
of H2O/acetone 1/8; then N-methylmorpholine-N-oxide (88 mg, 0.65 mmol) and
OsO4 (0.8 mL of a solution 5 mg/mL in tBuOH, 0.05 equiv) was added. After 6 h
the reaction was quenched with aqueous Na2S2O3. After stirring 30 min the reac-
tion mixture was extracted with AcOEt, the organic layer was dried over Na2SO4,
filtered and the solvent removed under reduced pressure. Chromatographic purifi-
cation (petroleum ether/AcOEt 6:4 v/v) afforded 57 mg of compound 13a, 111 mg
of 13b and 119 mg of the mixture of the two which was separated by medium pres-
sure chromatography (petroleum ether/AcOEt 65:35 v/v). The total yield of the re-
action was 92% and the ratio of the two diastereomers 1/1. Compound 13a: oil; m/z
1
978 (Mꢂ23)ꢂ, 955 (M)ꢂ; H NMR (300 MHz, CDCl3) ꢃ 1.10 (s, 9H, tBu),
1.90–2.15 (m, 12H, 4CH3 Ac), 2.92 (dd, 1H, J1a,1b ꢄ 15.9, J1a,1ꢅ ꢄ 9.7 Hz, H-1a),
3.00–3.05 (m, 1H, H-1b), 3.60–4.50 (m, 10H, H-5ꢅ, 6ꢅa, 6ꢅb, 4, 5, 6a, 6b, CHFmoc,
CH2Fmoc), 4.80–4.82 (m, 1H, H-1ꢅ), 4.98 (t, 1H, J4ꢅ,3ꢅ ꢄ J4ꢅ,5ꢅ ꢄ 8.7 Hz, H-4ꢅ),
5.18 (dd, 1H, J2ꢅ,3ꢅ ꢄ 9.1, J2ꢅ,1ꢅ ꢄ 5.5 Hz, H-2ꢅ), 5.26 (bt, 1H, H-3ꢅ), 5.27–5.35 (m,
1H, H-3), 7.30–7.70 (m, 19H, HPh, NH); 13C NMR (75.47 MHz, CDCl3) ꢃ 20.62
(CH3 Ac), 26.91 (CH3 tBu), 37.15 (t, C-1), 47.18 (d, CHFmoc), 54.00 (d, C-5),
62.03, 64.40, 67.21 (3t, C-6ꢅ, 6, CH2Fmoc), 68.35, 68.64, 69.33, 69.97, 70.12,
70.31, 71.98 (7d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 3, 4), 119.99–135.51 (CHPh), 132.45–143.88
(CqPh), 156.99, 169.42, 169.42, 169.92, 170.69 (5s, CO), 206.79 (s, C-2).
Anal. Calcd for C51H59NO15Si: C, 64.20; H, 6.23; N, 1.47. Found: C, 64.25;
H, 6.19; N, 1.51.
Compound 13b: mp 102–104°C; m/z 978 (Mꢂ23)ꢂ; [ꢀ]D ꢄ ꢂ15.4° (c 1,
CHCl3); 1H NMR (200 MHz, CDCl3) ꢃ 1.10 (s, 9H, tBu), 2.00 (m, 12H, 4CH3 Ac),
2.30–2.40 (m, 2H, OH), 2.92 (dd, 1H, J1a,1b ꢄ 16.7, J1a,1ꢅ ꢄ 5.1 Hz, H-1a), 3.25
(dd, 1H, J1b,1a ꢄ 16.7, J1b,1ꢅ ꢄ 9.0 Hz, H-1b), 3.65–4.50 (m, 10H, H-5ꢅ, 6ꢅa, 6ꢅb,
4, 5, 6a, 6b, CHFmoc, CH2Fmoc), 4.81 (m, 1H, H-1ꢅ), 5.00 (t, 1H, J4ꢅ,3ꢅ ꢄ J4ꢅ,5ꢅ
ꢄ 8.5 Hz, H-4ꢅ), 5.15 (dd, 1H, J2ꢅ,3ꢅ ꢄ 8.7, J2ꢅ,1ꢅ ꢄ 5.5 Hz, H-2ꢅ), 5.25 (dd, 1H, J3ꢅ,4ꢅ
ꢄ 8.5, J3ꢅ,2ꢅ ꢄ 8.7 Hz, H-3ꢅ), 5.36 (d, 1H, J3,4 ꢄ 8.4 Hz, H-3), 7.30–7.70 (m, 19H,
HPh, NH). 13C NMR (50.29 MHz, CDCl3) ꢃ 20.59 (CH3 Ac), 26.98 (CH3 tBu),
29.60 (t, C-1), 47.11 (d, CHFmoc), 53.23 (d, C-5), 62.00, 64.41, 67.24 (2t, C-6ꢅ, 6,
CH2Fmoc), 68.47, 68.47, 69.26, 69.26, 70.00, 70.11, 71.97 (7d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ,
3, 4), 120.00–135.41 (CHAr), 141.20, 143.42 (2s, Cq Ph) 169.40–170.60 (CO),
207.20 (s, C-2).

ORDER
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676
LA FERLA ET AL.
Anal. Calcd for C51H59NO15Si: C, 64.20; H, 6.23; N, 1.47. Found: C, 64.18;
H, 6.25; N, 1.50.
1-C-(2,3,4,6-tetra-O-acetyl-(ꢀ-D-glucopyranosyl)-1,2,5-trideoxy-2,5-
imino-6-O-diphenyl-tert-butylsilyl-D-gluco-hexitol (14) and 1-C-(2,3,4,6-tetra-
O-acetyl-ꢀ-D-glucopyranosyl)-1,2,5-trideoxy-2,5-imino-6-O-diphenyl-tert-
butylsilyl-D-manno-hexitol (15): Compound 13a (198 mg, 0.207 mmol) was
dissolved in dry DMF (4 mL) under an inert atmosphere, and piperidine (27 ꢉL,
0.27 mmol, 1.3 equiv) was added. After 30 min the solvent was removed under re-
duced pressure. The crude was dissolved in dry 1,2-dichloroethane (6 mL) and an-
hydrous MgSO4 (411 mg, 3.41 mmol) was added; after 5 min AcOH (79 ꢉL, 6.7
equiv) was added and the reaction was allowed to stir for 10 min, then
NaBH(OAc)3 (162 mg, 0.77 mmol) was added. After 4 h the reaction was neu-
tralised with a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2,
the organic layer was dried over Na2SO4, filtered and the solvent removed under
reduced pressure. Chromatographic purification (petroleum ether/acetone
1:1→0:1 v/v) afforded 59 mg (41% yield) of pure compound 15 and 20 mg (13%
yield) of pure compound 14. Compound 14: two conformers, m/z 716 (Mꢂ1)ꢂ; 1H
NMR (200 MHz, CDCl3) ꢃ 1.10 (s, 9H, tBu), 1.62–1.90 (m, 2H, H-1a, 1b),
1.98–2.13 (m, 12H, 4CH3 Ac), 3.39–3.59 (m, 2H, H-2, 5), 3.84–4.42 (m, 8H,
H-1ꢅ, 5ꢅ, 6ꢅa, 6ꢅb, 3, 4, 6a, 6b), 4.85–5.09 (m, 2H, H-2ꢅ, 4ꢅ), 5.27, 5.30 (2t, 1H,
J ꢄ 8.9, J ꢄ 8.0 Hz, H-3ꢅ), 7.35–7.70 (m, 10H, HPh); 13C NMR (50.29 MHz, C6D6)
ꢃ 19.91 (CH3 Ac), 25.20, 25.67 (2t, C-1), 26.69 (CH3 tBu), 56.60, 57.49, 60.13,
69.02, 69.35, 70.23, 70.59, 70.70, 71.56, 78.00, 78.55, 79.15 (12d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ,
5ꢅ, 2, 3, 4, 5), 62.20, 63.99 (2t, C-6ꢅ, 6), 128.00–135.66 (CHPh), 169.01, 169.35,
169.52, 169.98 (4s, CO);
Anal. Calcd for C36H49NO12Si: C, 60.40; H, 6.90; N, 1.96. Found: C, 60.42;
H, 6.88; N, 2.00.
Compound 15: two conformers, m/z 716 (Mꢂ1)ꢂ; [ꢀ]D ꢄ ꢂ31.2° (c 0.9,
1
CHCl3); H NMR (300 MHz, CDCl3, 50°C) ꢃ 1.10 (s, 9H, tBu), 1.69 (ddd, 1H,
J1a,1b ꢄ 14.6, J ꢄ 7.1, J ꢄ 2.7 Hz, H-1a), 1.84 (ddd, 1H, J1b,1a ꢄ 14.6, J ꢄ 4.9,
J ꢄ 3.4 Hz, H-1b), 1.94–2.13 (m, 12H, 4CH3 Ac), 2.90–3.05 (m, 1H, H-5), 3.38
(m, 1H, H-2), 3.74–4.25 (m, 7H, H-5ꢅ, 6ꢅa, 6ꢅb, 3, 4, 6a, 6b), 4.33 (m, 1H, H-1ꢅ),
4.93 (t, 1H, J4ꢅ,3ꢅ ꢄ J4ꢅ,5ꢅ ꢄ 8.6 Hz, H-4ꢅ), 5.05 (m, 1H, H-2ꢅ), 5.26, 5.28 (2t, 1H,
J3ꢅ,2ꢅ ꢄ J3ꢅ,4ꢅ ꢄ 8.6 Hz, H-3ꢅ), 7.35–7.80 (m, 10H, HPh); 13C NMR (75.47 MHz,
C6D6, 60°C) ꢃ 19.87 (CH3 Ac), 26.85 (CH3 tBu), 30.21, 30.57 (2t, C-1), 62.00,
64.41 (2t, C-6ꢅ, 6), 60.53, 69.04, 69.21, 70.01, 70.42, 70.63, 70.63, 72.13, 78.69,
79.14, 82.44, 83.02 (12d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 2, 3, 4, 5), 127.840–135.70 (CHPh),
133.40 (Cq Ph), 168.87, 169.27, 169.80, 169.95 (4s, CO).
Anal. Calcd for C36H49NO12Si: C, 60.40; H, 6.90; N, 1.96. Found: C, 60.39;
H, 6.91; N, 1.98.
(3E)-1-C-(2,3,4,6-Tetra-O-benzyl-(ꢀ-D-glucopyranosyl)-5-amino-1,3,4,5-
tetradeoxy-5-N-fluorenylmethoxycarbonyl-6-O-diphenyl-tert-butylsilyl-D-
glycero-hex-3-eno-2-ulose (16). To a solution of compound 1 (1.64 g, 1.94

ORDER
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SYNTHESIS OF IMINO-C-DISACCHARIDES
677
mmol, 1 equiv) in dry MeCN (8 mL) under an inert atmosphere, compound 11
(1.64 g, 2.98 mmol, 1.53 equiv), dissolved in dry MeCN (8 mL), was added. After
20 h the solvent was removed under reduced pressure; chromatographic purifica-
tion (petroleum ether/AcOEt 75:25 v/v) afforded 1.86 g of compound 16 (86%
yield, only E isomer). Oil, [ꢀ]Dꢄ ꢂ6.4° (c 1, CHCl3); 1H NMR (300 MHz, CDCl3)
ꢃ 1.10 (s, 9H, tBu), 2.83 (dd, 1H, J1a,1b ꢄ 15.8, J1a,1ꢅ ꢄ 7.3 Hz, H-1a), 2.97 (dd, 1H,
J
1a,1b ꢄ 15.8, J1b,1ꢅ ꢄ 4.8 Hz, H-1b), 3.57–4.90 (m, 21H, H-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 6ꢅa,
6ꢅb, 5, 6a, 6b, CHFmoc, CH2Fmoc, 8CHPh), 6.19 (d, 1H, J3,4 ꢄ 15.8 Hz; H-3),
6.69 (dd, 1H, J3,4 ꢄ 15.8, J4,5 ꢄ 4.9 Hz, H-4), 7.10–7.80 (m, 19H, HPh, NH); 13
C
NMR (75.47 MHz, CDCl3) ꢃ 26.69 (s, Cq tBu), 26.81 (CH3 tBu), 37.94 (t, C-1),
47.24 (d, CHFmoc), 50.43 (d, C-5), 61.98, 65.22, 68.97, 73.25, 73.49, 74.91, 75.28
(7t, C-6ꢅ, 6, 4CH2Ph, CH2Fmoc), 70.53, 72.71, 77.75, 79.31, 82.09 (5d, C-1ꢅ, 2ꢅ,
3ꢅ, 4ꢅ, 5ꢅ), 120.00–138.10 (C-3, 4, CHAr), 138.29–144.41 (CqAr), 198.30 (s, C-2).
Anal. Calcd for C71H73NO9Si: C, 76.66; H, 6.61; N, 1.26. Found: C, 76.70;
H, 6.63; N, 1.30.
1-C-(2,3,4,6-Tetra-O-benzyl-(ꢀ-D-glucopyranosyl)-3,4-di-O-acetyl-5-
amino-1,5-dideoxy-5-N-fluorenylmethoxycarbonyl-6-O-diphenyl-tert-butylsi-
lyl-D-arabino-hex-2-ulose (17a) and 1-C-(2,3,4,6-tetra-O-benzyl-(-D-glucopy-
ranosyl)-3,4-di-O-acetyl-5-amino-1,5-dideoxy-5-N-fluorenylmethoxycarbony
l-6-O-diphenyl-tert-butylsilyl-D-xylo-hex-2-ulose (17b). Compound 16 (1.78
g, 1.59 mmol) was dissolved in 10 mL of H2O/acetone 1/8; then N-methylmor-
pholine-N-oxide (540 mg, 3.99 mmol) and OsO4 (4 mL of a 5 mg/mL solution in
tBuOH, 0.05 equiv) were added. After 4 h the reaction was heated to 40°C; after 2
h the reaction was quenched with aqueous Na2S2O3 and allowed to stir for 30 min.
The reaction mixture was then extracted with AcOEt, the organic layer was dried
over Na2SO4, filtered and the solvent removed under reduced pressure. Chromato-
graphic purification (petroleum ether/AcOEt 65:35 v/v) afforded 1.56 g (85%
yield) of a 1/1 mixture of the two inseparable diastereomers. 82 mg of the mixture
(0.07 mmol) was dissolved in 90 mL of CH2Cl2 then Ac2O (0.07 mL, 100 equiv)
and DMAP (8.7 mg, 1 equiv) were added. After 5 min the reaction was quenched
with MeOH; then the solvent was removed under reduced pressure and medium
pressure chromatographic purification (toluene/AcOEt 9:1 v/v) afforded com-
pounds 17a (39 mg, 46% yield) and compound 17b (35 mg, 44% yield).
1
Compound 17a: oil, [ꢀ]D ꢄ ꢂ15.0° (c 1, CHCl3); H NMR (300MHz,
CDCl3) ꢃ 1.05 (s, 9H, CH3 tBu), 1.82 (s, 3H, CH3 Ac), 1.95 (s, 3H, CH3 Ac), 2.15
(m, 1H, H-1a), 2.97 (m, 1H, H-1b), 3.53–3.83 (m, 8H, H-2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 6ꢅa, 6ꢅb, 6a,
6b), 4.16–4.87 (m, 13H, H-1ꢅ, 5, CH2Fmoc, CHFmoc, 8CHPh), 5.30–5.50 (m, 2H,
H-3, 4), 7.07–7.80 (m, 19H, HPh, HN); 13C NMR (50.29 MHz, CDCl3)ꢃ: 20.35,
20.50 (CH3 Ac), 26.86 (CH3 tBu), 29.64 (s, Cq tBu), 35.03 (t, C-1), 47.04 (d, CHF-
moc), 51.57 (d, C-5), 62.50, 67.19, 69.03, 72.70, 73.29, 74.80, 75.12 (7t, C-6ꢅ, 6,
4CH2Ph, CH2Fmoc), 68.88, 69.66, 72.44, 76.01, 77.40, 78.67, 81.51 (7d, C-1ꢅ, 2ꢅ,
3ꢅ, 4ꢅ, 5ꢅ, 3, 4), 119.90–135.50 (CHAr), 132.50, 132.60, (2s, Cq Si-Ph), 132.80,
132.90, 138.10, 138.60 (4s, Cq Ph), 143.60, 141.30 (2s, Cquat Fmoc), 169.50,
170.00 (2s, CO), 201.80 (s, C-2).

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REPRINTS
678
LA FERLA ET AL.
Anal. Calcd for C75H79NO13Si: C, 73.21; H, 6.47; N, 1.14. Found: C, 73.14;
H, 6.43; N, 1.10.
Compound 17b: oil, [ꢀ]D ꢄ ꢂ9.5° (c 1, CHCl3); 13C NMR (75.47 MHz,
CDCl3) ꢃ 20.45, 20.45 (CH3 Ac), 26.92 (CH3 tBu), 29.68 (s, Cq tBu), 36.28 (t,
C-1), 47.14 (d, CHFmoc), 53.01 (d, C-5), 62.96, 66.95, 68.91, 73.07, 73.42, 74.80,
75.27 (7t, C-6ꢅ, 6, 4CH2Ph, CH2Fmoc), 69.09, 69.65, 72.38, 76.43, 77.64, 78.59,
82.25 (7d, C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 3, 4), 119.90–135.50 (CHAr), 132.60, 132.60 (Cq Si-
Ph), 137.80, 138.00, 138.30, 138.60 (4s, Cq Ph), 143.80, 141.30 (s, Cq Fmoc),
169.80, 170.40 (2s, CO), 200.80 (s, C-2).
Anal. Calcd for C75H79NO13Si: C, 73.21; H, 6.47; N, 1.14. Found: C, 73.12;
H, 6.43; N, 1.10.
1-C-(2,3,4,6-Tetra-O-benzyl-(ꢀ-D-glucopyranosyl)-3,4-di-O-acetyl-1,2,5-
trideoxy-2,5-imino-6-O-diphenyl-tert-butylsilyl-D-manno-hexitol (18). Com-
pound 17a (90 mg, 0.073 mmol) was dissolved in dry DMF (0.7 mL) under an in-
ert atmosphere, and piperidine (7 ꢉL) was added. After 30 min the solvent was
removed under reduced pressure. The crude was dissolved in dry 1,2-dichlo-
roethane (1.5 mL) and Na2SO4 (420 mg, 2.94 mmol) was added. After 5 min
AcOH (42 ꢉL, 10 equiv) was added and the reaction was allowed to stir for 10 min,
then NaBH(OAc)3 (63 mg, 0.29 mmol) was added. After 4 h the reaction was neu-
tralised with a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2;
the organic layer was dried over Na2SO4, filtered and the solvent removed under
reduced pressure. Chromatographic purification (petroleum ether/AcOEt 83:17
→75:25 v/v) afforded 30 mg (41% yield) of compound 18. Compound 18: oil, m/z
992 (M)ꢂ; 1H NMR (300 MHz, CDCl3) ꢃ 1.30 (s, 9H, CH3 tBu), 1.90 (s, 3H, CH3
Ac), 2.00 (s, 3H, CH3 Ac), 1.20–2.10 (m, 2H, H-1a, 1b), 3.05 (m, 1H, H-5),
3.33–3.41 (m, 1H, H-2), 3.52–3.88 (m, 8H, H-2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 6ꢅa, 6ꢅb, 6a, 6b),
4.12–4.20 (m, 1H, H-1ꢅ), 4.37 (d, 1H, J ꢄ 12.0 Hz, CHPh), 4.45 (d, 1H, J ꢄ 11.1
Hz, CHPh), 4.52 (d, 1H, J ꢄ 12.0 Hz, CHPh), 4.59 (d, 1H, J ꢄ 11.7 Hz, CHPh),
4.66 (d, 1H, J ꢄ 11.7 Hz, CHPh), 4.77 (d, 1H, J ꢄ 11.1 Hz, CHPh), 4.79 (d, 1H,
J ꢄ 10.9 Hz, CHPh), 4.89 (d, 1H, J ꢄ 10.9 Hz, CHPh), 5.04 (d, 1H, J4,5 ꢄ 4.6 Hz,
H-4), 5.23 (d, 1H, J3,2 ꢄ 4.0 Hz, H-3), 7.10–7.70 (m, 19H, HPh, HN); 13C NMR
(75.47 MHz, CDCl3) ꢃ 20.77 (CH3 Ac), (s, Cq tBu), 26.88 (CH3 tBu), 24.10, 29.66
(t, C-1, Cq tBu), 58.69, 65.61, 71.56, 72.67, 78.31, 79.07, 79.81, 80.31, 82.25 (9d,
C-1ꢅ, 2ꢅ, 3ꢅ, 4ꢅ, 5ꢅ, 2, 3, 4, 5), 63.89, 69.27, 73.00, 73.42, 74.80, 75.33 (6t, C-6ꢅ, 6,
4CH2Ph), 127.50–135.60 (CHPh), 133.20 (Cq Si-Ph), 138.20, 138.40, 138.70 (Cq
Ph), 169.70, 169.85 (CO).
Anal. Calcd for C57H69NO9Si: C, 68.99; H, 7.01; N, 1.41. Found C, 68.90;
H, 7.03; N, 1.43.
1-C-(2,3,4,6-Tetra-O-acetyl-(ꢀ-D-glucopyranosyl)-3,4,6-tri-O-acetyl-
1,2,5-trideoxy-2,5-imino-N-methyl-D-gluco-hexitol (19). The mixture of di-
astereomers 4a and 4b (228 mg, 0.26 mmol) was dissolved in THF/MeOH and hy-
drogenated using Pd/C as catalyst. After 4 days AcOH was added and the reaction
was prolonged for 4 more days. The catalyst was filtered over a celite pad, and the

ORDER
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SYNTHESIS OF IMINO-C-DISACCHARIDES
679
solvent was removed under reduced pressure. The crude was then dissolved in Py
and Ac2O and a catalytic amount of DMAP were added. After 6 h the solvent was
removed. Chromatographic purification (petroleum ether/AcOEt 6/4, 1/1, v/v) af-
forded 28 mg of pure compound 7 (17% yield). Compound 7: oil, m/z 618 (M)ꢂ;
[ꢀ]D ꢄ ꢂ26.2° (c 1, CHCl3); 1H NMR (300 MHz, CDCl3) ꢃ 1.71 (bdd, 1H, J1a,1b
ꢄ 15.5, J1a,2 ꢄ 6.5 Hz, H-1b), 1.90–2.11 (m, 21H, 7CH3 Ac), 2.22 (ddd, 1H, J1b,1a
ꢄ 15.5, J1b,1ꢅ ꢄ 10.3, J1a,2 ꢄ 2.6 Hz, H-1a), 2.30 (s, 3H, N-CH3), 2.45–2.53 (m,
1H, H-2), 2.95–4.20 (m, 5H, H-5ꢅ, 6ꢅa, 6ꢅb, 6a, 6b), 4.50 (bdd, 1H, J1ꢅ,1a ꢄ 10.3,
J1ꢅ,2ꢅ ꢄ 5.8 Hz, H-1ꢅ), 4.95 (t, 1H, J4ꢅ,3ꢅ ꢄ J4ꢅ,5ꢅ ꢄ 9.4 Hz, H-4ꢅ), 5.00–5.15 (m, 3H,
H-2ꢅ, 3, 4), 5.22 (t, 1H, J3ꢅ,2ꢅ ꢄ J3ꢅ,4ꢅ ꢄ 9.4 Hz, H-3ꢅ); 13C NMR (75.47 MHz,
CDCl3) ꢃ 20.63 (q, CH3 Ac), 24.56 (t, C-1), 39.29 (q, CH3-N), 61.74, 62.44 (2t, C-
6ꢅ, 6), 64.95, 68.84, 68.97, 69.40, 69.55, 69.88, 70.43, 75.91, 78.63 (9d, C-1ꢅ, 2ꢅ,
3ꢅ, 4ꢅ, 5ꢅ, 2, 3, 4, 5), 169.00–170.60 (CO).
Anal. Calcd for C27H39NO15: C, 52.51; H, 6.36; N, 2.27. Found C, 52.49;
H, 6.38; N, 2.29.
ACKNOWLEDGMENTS
We thank MURST (COFIN 2000, MM03155477) for the financial support
and Dr. Enrico Caneva for the NMR spectra.
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Received March 7, 2001
Accepted September 7, 2001

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