Synthesis of the C-disaccharide α-C(1→3)-L-fucopyranoside of N-acetylgalactosamine

Article abstract of DOI:10.1081/CAR-100108286

Radical C-glycosidation of racemic 5-exo-benzeneselenyl-6-endo-chloro-3-methylidene-7-oxabicyclo[2.2.1]heptan-2-one ((±)-2) with α-acetobromofucose (3) provided a mixture of α-C-fucosides that were reduced with NaBH₄ to give two diastereomeric alcohols that were separated readily. One of them ((-)-6) was converted into (-)-methyl 2-acetamido-4-O-acetyl-2,3-dideoxy-3-C-(3′,4′,5′-tri-O-acetyl- 2′,6′-anhydro-1′ ,7′-dideoxy-α-L-glycero-D-galacto-heptitol-1′ -C-yl)-α -D-galactopyranuronate ((-)-11) and then into (-)-methyl 2-acetamido-2,3-dideoxy-3-C-(2′,6′-anhydro-1′,7′-dideoxy -a-L-glycero-D-galacto-heptitol-1′ -C-yl)-β -D-galactopyranoside ((-)-1), a new α-C(1→3)-L-fucopyranoside of N-acetylgalactosamine. Its ¹H NMR data shows that this C-disaccharide (α-L-Fucp-(1→3)CH₂-β-D-Ga1NAc-OMe) adopts a major conformation in solution similar to that expected for the corresponding O-linked disaccharide, i.e., with antiperiplanar σ(C-3′,C-2′) and σ(C-1′,C-3) bonds.

Full text of DOI:10.1081/CAR-100108286

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SYNTHESIS OF THE C-DISACCHARIDE α-C(1→3)-L-
FUCOPYRANOSIDE OF N-ACETYLGALACTOSAMINE
Cécile Viodé a & Pierre Vogel b
a Section de Chimie de l'Université de Lausanne , BCH, Lausanne-Dorigny, CH-1015,
Switzerland
b Section de Chimie de l'Université de Lausanne , BCH, Lausanne-Dorigny, CH-1015,
Switzerland
Published online: 16 Aug 2006.
To cite this article: Cécile Viodé & Pierre Vogel (2001) SYNTHESIS OF THE C-DISACCHARIDE α-C(1→3)-L-FUCOPYRANOSIDE
OF N-ACETYLGALACTOSAMINE , Journal of Carbohydrate Chemistry, 20:7-8, 733-746
To link to this article: http://dx.doi.org/10.1081/CAR-100108286
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J. CARBOHYDRATE CHEMISTRY, 20(7&8), 733–746 (2001)
SYNTHESIS OF THE C-DISACCHARIDE
ꢀ-C(1→3)-L-FUCOPYRANOSIDE OF
N-ACETYLGALACTOSAMINE1
Cécile Viodé2 and Pierre Vogel*
Section de Chimie de l’Université de Lausanne,
BCH, CH-1015 Lausanne-Dorigny Switzerland
ABSTRACT
Radical C-glycosidation of racemic 5-exo-benzeneselenyl-6-endo-chloro-3-
methylidene-7-oxabicyclo[2.2.1]heptan-2-one ((ꢁ)-2) with ꢀ-acetobromofu-
cose (3) provided a mixture of ꢀ-C-fucosides that were reduced with NaBH4 to
give two diastereomeric alcohols that were separated readily. One of them ((ꢂ)-
6) was converted into (ꢂ)-methyl 2-acetamido-4-O-acetyl-2,3-dideoxy-3-C-
(3ꢃ,4ꢃ,5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-
heptitol-1ꢃ-C-yl)-ꢀ -D-galactopyranuronate ((ꢂ)-11) and then into (ꢂ)-methyl
2-acetamido-2,3-dideoxy-3-C-(2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-
galacto-heptitol-1ꢃ-C-yl)-ꢄ -D-galactopyranoside ((ꢂ)-1), a new ꢀ-C(1→3)-L-
1
fucopyranoside of N-acetylgalactosamine. Its H NMR data shows that this
C-disaccharide (ꢀ-L-Fucp-(1→3)CH2-ꢄ-D-GalNAc-OMe) adopts a major con-
formation in solution similar to that expected for the corresponding O-linked
disaccharide, i.e., with antiperiplanar ꢅ(C-3ꢃ,C-2ꢃ) and ꢅ(C-1ꢃ,C-3) bonds.
INTRODUCTION
Carbohydrate mimetics are potentially useful molecular tools for biology,3
and may become leads for drug discovery.4 In particular, C-linked disaccharides
and oligosaccharides containing them offer the advantage of being resistant to
acidic and enzymatic hydrolysis.5 They are potential inhibitors of glycosidases
and glycosyltransferases.6 They represent non-hydrolyzable epitopes.7 Kishi and
co-workers have prepared blood group mimics involving ꢀ-C(1→2)-L-fucopyra-
nosides of D-galactopyranosides and analogs.8 The first examples of ꢀ-C(1→3)-L-
733
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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734
VIODÉ AND VOGEL
Scheme 1.
fucopyranosides have been prepared by Sinaÿ and co-workers; they did not de-
scribe the corresponding non-protected derivatives.9 Applying our first method to
the synthesis of C-disaccharides10 based on Giese’s radical C-glycosidation11 of 3-
methylidene-7-oxabicyclo[2.2.1]heptan-2-one derivatives (Scheme 1) we have
now obtained the disaccharide mimic (ꢂ)-1 (ꢀ-L-Fucp-(1→3)CH2-ꢄ-D-GalNAcp-
OMe) for the first time in which ꢀ-L-fucopyranose is C-linked at C-3 of methyl
ꢄ-D-N-acetylgalactosaminepyranoside.12 The 1H NMR data recorded for (ꢂ)-1 al-
low us to define its preferred conformation in methanolic solution.
SYNTHESIS
Following the procedure of Pasquarello et al.6d utilizing enone concentra-
tions of ca. 0.16 molar and Ph3SnH as reducing agent, Giese’s radical fucosidation
of racemic enone (ꢁ)-2 (derived12a from the Diels-Alder adduct of furan to 1-
cyanovinyl acetate13) with ꢀ-L-bromoacetofucose (3), obtained from L-fucose via
peracetylation and subsequent treatment with HBr in AcOH,14 provided the ex-
pected mixture of diastereomeric ꢀ-C-fucosides 4 and 5 in low yield (less than
26%). Using Bu3SnH/AIBN instead of Ph3SnH/AIBN was less successful. We fi-
nally found that the radical C-fucosidation could give a reproducible yield of 78%
when a 1:1 mixture of Ph3SnH/AIBN was added slowly (syringe, 90 min) to a boil-
ing 0.64 molar solution of a 1:1 mixture of (ꢁ)-2 and AIBN in benzene. The C-fu-
cosides 4 and 5 could not be separated by the usual chromatographic techniques,
thus the crude reaction mixture was directly submitted to the ketone reduction with
NaBH4 in methanol and tetrahydrofuran. This provided a 1:1 mixture (95%) of
endo-alcohols (ꢂ)-6 and (ꢂ)-7 that were readily separated by flash chromatogra-
phy on silica gel and isolated pure in 40 and 35.5% yield, respectively. In order to
assign the structures of these diastereomeric C-fucosides we repeated the C-fu-
cosidation with the enantiomerically enriched enone (ꢂ)-2 (50% e.e., obtained by
incomplete resolution of (ꢁ)-2 with (1R,2R)-diphenylethylenediamine15) that led
to a 3:1 mixture of C-fucosides 4 and 5 and then to a 3:1 mixture of (ꢂ)-6 and (ꢂ)-
7 (Scheme 2).
Oxidative elimination of the benzeneselenyl group of (ꢂ)-6 with
metachloroperbenzoic acid in CH2Cl2 provided the chloroalkenol (ꢂ)-8 (91%) that
was acetylated under standard conditions (Ac2O/pyridine, DMAP) to give endo ac-
etate (ꢂ)-9 in 85% yield. Acid-promoted ring opening of (ꢂ)-9 with trifluo-

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SYNTHESIS OF N-ACETYLGALACTOSAMINE
735
romethanesulfonic acid in acetonitrile led to a chloroallylic cation intermediate6
that was quenched with MeCN to give, after aqueous work-up, the acetamide (ꢂ)-
10 (Ritter reaction) in 48% yield, together with several products of decomposition.
Ozonolysis of the chloroalkene moiety of (ꢂ)-10 was troublesome, leading to un-
tractable polymeric material in the absence of NaHCO3. When the ozonolysis was
carried out with a 1:1 mixture of (ꢂ)-10 and NaHCO3 at–78°C, the methyl uronic
ester (ꢂ)-11 was obtained in modest yield (21%).
Since we wanted to avoid the formation of galactofuranuronic derivatives
during the protection of the hemiacetal (ꢂ)-11, we applied Schmidt’s glycosida-
tion method16 for its conversion into the methyl galactopyranoside derivative (ꢂ)-
13. Thus, treatment of (ꢂ)-11 with Cl3CCN and NaH generated the corresponding
trichloroacetimidate 12 (1H NMR:ꢆH ꢇ 8.82 ppm (NH); 5.54 ppm/doublet, H-
C(1)) that was not isolated but directly treated with anhydrous methanol and
BF3ꢈEt2O in CH2Cl2 at 0°C. This furnished the totally protected C-disaccharide
(M)-13 in 79% yield. Its 1H NMR data confirmed its structure and especially the
methyl ꢄ-D-galactopyranoside configuration. The reduction of (ꢂ)-13 with an
excess of LiBH4 in THF provided, after treatment with DOWEX 50x8 acidic ion
exchange resin, the desired C-fucoside (ꢂ)-1 in 70% yield.
Scheme 2.

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736
VIODÉ AND VOGEL
Figure 1. Newman Projections for (ꢂ)-1 along C-1ꢃ, C-2!
CONFORMATIONAL STUDIES
For C(1→2)-ꢀ -fucosides, Kishi and co-workers8 have found that the major
conformers have antiperiplanar orientation of the (ꢅ(C-2ꢃ,C-3ꢃ) bond of the fucose
moiety with the ꢅC(C-1ꢃ,C-2) bond of the C-disaccharide. Depending on substitu-
tion of the “aglycone” part, various conformers or rotamers about bond ꢅ(C-1ꢃ,C-
2) are possible, all of them can be suited in a diamond lattice (optimal staggered
conformations). The 1H NMR spectrum (400 MHz, CD3OD) of (ꢂ)-1 shows for
the proton signals assigned to Hꢀ-1ꢃ (ꢆH ꢇ 1.94 ppm) and Hꢄ-1ꢃ (ꢆH ꢇ 1.70 ppm)
of the methano linker that Hꢀ-1ꢃ is antiperiplanar with H-2ꢃ and with H-3 as the
vicinal coupling constants 3J(Hꢀ-1ꢃ,H-2ꢃ) ꢇ 11ꢁ0.5 Hz and 3J(Hꢀ-1ꢃ,H-3) ꢇ 9ꢁ1
Hz were measured (double irradiation experiments). For proton Hꢄ-1ꢃ much
3
3
smaller vicinal coupling constants J(Hꢄ-1ꢃ,H-3) ꢀ J(Hꢄ-1ꢃ,H-2ꢃ) ꢇ 3ꢁ0.3 Hz
2
were found, with a geminal coupling constant J(Hꢀ-1ꢃ,Hꢄ-1ꢃ) ꢇ 14.6ꢁ0.2 Hz.
These data are consistent with both rotamers Aꢃ and Bꢃ about the ꢅ(C-2ꢃ,C-1ꢃ)
bond (Figure 1), not with conformer Cꢃ. Nuclear Overhauser Effects were required
to distinguish between conformers Aꢃ and Bꢃ and for the assignment of configura-
1
tion of protons Hꢀ and Hꢄ. Strong NOE’s were observed in the 2D NOESY H
NMR spectrum of (ꢂ)-1 between the signal pairs assigned to Hꢀ-1ꢃ/H-6ꢃ (ꢆH ꢇ
3.96 ppm) Hꢀ-1ꢃ/H-4 (3.77 ppm), and Hꢄ-1ꢃ/H-3 (1.76 ppm), H-1 (4.28 ppm)/H-5
(3.56 ppm) H-1/H-3, H-1/H-5 and H-4 (3.67 ppm)/H-6ꢃ (3.96 ppm) thus confirm-
ing chair conformations for both the ꢀ-L-fucopyranoside and ꢄ-D-galactopyranosyl
moieties. The data were consistent only with the conformation represented in Fig-
ure 2 for which Hꢀ-1ꢃ is proR and Hꢀ-1ꢃ proS, and in which the bonds ꢅ(C-3ꢃ,
Figure 2. Representations of the most stable conformer of (ꢂ)-1 ↔ strong NOE, ⇔medium NOE,
←→ weak NOE)

ORDER
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SYNTHESIS OF N-ACETYLGALACTOSAMINE
737
C-2ꢃ) and ꢅ(C-1ꢃ,C-3) are antiperiplanar. The large NOE observed for signals of
H-6ꢃ and H-4 as well as the vicinal coupling constants that H-3ꢃ has with Hꢀ-1ꢃ and
Hꢄ-1ꢃ confirmed that H-3 is antiperiplanar or nearly antiperiplanar with Hꢀ-1ꢃ
(Figure 2). If other conformers are equilibrating with that shown in Figure 2, their
proportion must not represent more than 15–20%.
CONCLUSION
Giese radical ꢀ-L-fucosidation of racemic 5-exo-benzeneselenyl-6-endo-
chloro-3-methylidene-7-oxabicyclo[2.2.1]heptan-2-one ((ꢁ)-2) with ꢀ-acetobro-
mofucose (3) is a more delicate reaction than the corresponding C-glucosidation,
C-galactosidation and C-mannosidation. A good yield in the C-fucosidation of
(ꢁ)-2 can be obtained if one uses Ph3SnH and high concentrations of (ꢁ)-2 and 3.
One of the diastereomeric C-fucosides so obtained has been converted into various
(1→3)-C-linked disaccharides linking ꢀ-L-fucopyranose and 2-acetamido-2-de-
oxy-D-galactopyranuronic and–D-galactopyranoside derivatives though a methano
linker. The preferred conformation of the new C-disaccharide (ꢂ)-1 (ꢀ-L-Fucp-
(1→3)CH2-ꢄ-D-GalNAcp-OMe) in solution is similar to that expected for the
corresponding O-linked disaccharide and similar to that reported by Kishi and
co-workers for C-disaccharides linking ꢀ-L-fucopyranose at C-2 of hexoses
through methano linkers. In particular, it implies antiperiplanar ꢅ(C-3ꢃ,C-2ꢃ) and
ꢅ(C-1ꢃ,C-3) bonds.
EXPERIMENTAL
General methods. Most procedures were not optimized. All solvents were
distilled prior to use: THF from Na and benzophenone; CH2Cl2 and pyridine form
CaH2; MeOH from Mg. Solutions after reactions and extractions were concen-
trated on a rotatory evaporator under reduced pressure. Liquid/solid flash chro-
matography (FC): columns of silica gel (0.040–0.64 ꢉm, Merck No. 9385 silica
gel 60, 240–400 mesh) or Lobar columns (Merck SiO2, or RP-8). Thin-layer chro-
matography (TLC) for reaction monitoring: Merck silica gel 60 F254 plates; detec-
tion by UV light. Pancaldi reagent ((NH4)6MoO4, Ce(SO4)2, H2SO4, H2O), or
KMnO4. Reagents were from Fluka or Aldrich and used without purification. Melt-
ing points are reported uncorrected; Tottoli (Büchi SMP-20) apparatus. Optical
rotations: Jasco-DIP-370 polarimeter. UV/VIS spectra: Kontron-Uvikon-811 or
Hewlett-Packard-HP8450 A spectrometer; ꢊin nm (ꢋ [dm3molꢂ1cmꢂ1]). IR
1
spectra: Perkin-Elmer-1420 or Beckman-IR4230 spectrometer; v in cmꢂ1. H
˜
NMR spectra: Bruker-DPX-400, or Bruker-ARX-400 spectrometer, ꢆ in ppm rel
1
to internal Me4Si (0.00 ppm) or to the solvent’s residual H signals (CHCl3,
ꢆ 7.27; C6HD5, ꢆ 7.16; CHD2COCD3, ꢆ 1.95; CD2HCN, ꢆ 2.50; CHD2SOCD3,
ꢆ 2.50; CHD2OD, ꢆ 3.31) as internal reference; in D2O, internal reference
Me3SiCH2CH2CH2SO3Na (ꢆ(Me3Si) 0), all 1H signal assignments were confirmed

ORDER
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738
VIODÉ AND VOGEL
by double irradiation experiments or by 2D COSY-DQF or COSY-45 spectra. 13
C
NMR spectra: same instruments as above (100.61 MHz); ꢆ in ppm rel to internal
Me4Si (0.00 ppm) or to the solvent’s C signal (CDCl3, ꢆ 77.0; C6D6, ꢆ 128.4;
(CD3)2CO, ꢆ 29.8; CD3CN, ꢆ 1.3; (CD3)2SO, ꢆ 39.5; CD3OD, ꢆ 49.2) as internal
reference, coupling constants J in Hz (ꢁ0.5 Hz). MS (Nermag R-10–10C, chemi-
cal ionization (NH3) mode, m/z (amu) (% rel. base peak (100%)). Elemental anal-
ysis: Ilse Beetz, D-96301 Kronach, Germany.
(ꢌ)-(1S,3S,4 R,5R,6R)-5-exo-Benzeneselenyl-6-endo-chloro-3-endo-[(3ꢃ,
4ꢃ,5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-
1ꢃ-C-yl)]-7-oxabicyclo[2.2.1]hept-2-one (4) and (ꢌ)-(1R,3R,4S,5S,6S)-5-exo-
benzeneselenyl-6-endo-chloro-3-endo-[(3ꢃ,4ꢃ,5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhydro-
1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-C-yl)]-7-oxabicyclo[2.2.1]hept-
2-one (5). A solution of Ph3SnH (1.89 g, 5.39 mmol), AIBN (68 mg, 0.65
mmol) in benzene (12 mL) was added slowly in 90 min (syringe) to a boiling so-
lution of (ꢁ)-212a (1.3 g, 4.15 mmol) 314 (1.9 g, 5.39 mmol) in anhydrous ben-
zene (4 mL). After the end of the addition boiling was continued for 1 h. The so-
lution was cooled to 20°C and KF (1.8 g) was added. The mixture was boiled
overnight, cooled to 20°C and the solid residue was filtered off (Celite). The so-
lution was concentrated in vacuo and purified by FC (Ø ꢇ 6.5 cm, h ꢇ 18 cm,
1:3 EtOAc/light petroleum ether): 1.9 g (78%), 1:1 mixture of 4 and 5, white
powder, mp 65°C.
3:1 Mixture of 4 and 5: same procedure as above using (ꢂ)-2 with 50% e.e.
Yield: 78%, Rf (1:3 EtOAc/light petroleum ether) ꢇ 0.45, white powder. UV
(MeCN): ꢊmax ꢇ 196 (ꢋ ꢇ 4500), 217 (1950). IR (KBr): ꢍ 2985, 1750, 1630, 1480,
1
1440, 1370, 1245, 1225, 1110, 1055, 915, 740, 695, 465 cmꢂ1. H NMR (400
MHz, CDCl3) of 4:ꢆH 7.63–7.62 (m, 2H), 7.40–7.35 (m, 3H), 5.30–5.15 (m, 3H,
H-3ꢃ,4ꢃ,5ꢃ), 4.88 (d, 1H, 3J ꢇ 6.1 Hz, H-4), 4.53 (d, 1H, 3J ꢇ 5.7 Hz, H-1), 4.34
(dd, 1H, 3J ꢇ 5.7, 3.3 Hz, H-6), 4.02 (qd, 1H, 3J ꢇ 6.4, 1.5 Hz, H-6ꢃ), 3.95 (ddd,
1H, 3J ꢇ 10.5, 6.1, 4.4 Hz, H-3), 3.44 (d, 1H, 3J ꢇ 3.3 Hz, H-5), 2.80 (ddd, 1H, 3
J ꢇ 12.7, 6.1, 3.3 Hz, H-2ꢃ), 2.30 (ddd, 1H, 2J ꢇ 15.6, 3J ꢇ 12.7, 4.4 Hz, H-1ꢃa),
2.18, 2.02, 2.00 (3s, 9H, 3 AcO), 1.28 (ddd, 1H, 2J ꢇ 15.6, 3J ꢇ 10.5, 3.3 Hz, H-
1ꢃb), 1.15 (d, 3H, 3J ꢇ 6.4 Hz, H-7ꢃ). 13C NMR (100.6 MHz, CDCl3) of 4:ꢆC 207.1
1
(s, C-2), 173.4, 173. 1, 172.8 (3s, 3 COO), 134.8 (d, J(C,H) ꢇ 161 Hz), 129.7
(d, 1J(C,H) ꢇ 158 Hz), 128.8 (d, 1J(C,H) ꢇ 161 Hz), 85.0 (d, 1J(C,H) ꢇ 164 Hz,
1
1
C-4), 83.4 (d, J(C,H) ꢇ 173 Hz, C-1), 70.5 (d, J(C,H) ꢇ 153 Hz, C-2ꢃ), 70.3
1
1
(d, J(C,H) ꢇ 150 Hz, C-6ꢃ), 68.2, 67.8 (2d, J(C,H) ꢇ 141 Hz, C-3ꢃ,4ꢃ), 65.9
(d, 1J(C,H) ꢇ 143 Hz, C-5ꢃ), 58.4 (d, 1J(C,H) ꢇ 168 Hz, C-6), 49.3 (d, 1J(C,H) ꢇ
133 Hz, C-3), 46.7 (d, 1J(C,H) ꢇ 149 Hz, C-5), 22.3 (t, 1J(C,H) ꢇ 132 Hz), 20.7
(3q, 1J(C,H) ꢇ 130 Hz, Ac), 16.1 (q, 1J(C,H) ꢇ 128 Hz, C-7ꢃ). CI-MS (NH3): m/z
606 (100, [MꢌNH4]ꢌ), 589 (44, [MꢌH]ꢌ), 553 (29), 395 (45), 353 (11), 251 (51),
157 (10), 111 (15), 77 (19).
Anal. Calcd for C25H29ClO9Se (588.07): C 51.07, H 4.97; Found: C 51.13,
H 5.04.

ORDER
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SYNTHESIS OF N-ACETYLGALACTOSAMINE
739
(ꢂ)-(1S,2R,3S,4R,5R,6R)-5-exo-Benzeneselenyl-6-endo-chloro-3-endo-
[(3ꢃ,4ꢃ,5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-hep-
titol-1ꢃ-C-yl)]-7-oxabicyclo[2.2.1]hept-2-endo-ol ((ꢂ)-6) and (ꢂ)-(1R,2S,3R,
4S,5S,6S)-5-exo-benzeneselenyl-6-endo-chloro-3-endo-[(3ꢃ,4ꢃ,5ꢃ-tri-O-acetyl-
2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-C-yl)]-7-oxabi-
cyclo[2.2.1]hept-2-endo-ol ((ꢂ)-7). NaBH4 (83 mg, 2.2 mmol) was added por-
tionwise to a stirred solution of a 1:1 mixture of 4 and 5 (0.5 g, 0.85 mmol) in 1:1
MeOH/THF (20 mL) cooled to 0°C. After the end of the reduction (control by
TLC, ca. 5 min), 1 N aq HCl (6.5 mL) was added. The solvent was evaporated, and
the residue was extracted with CH2Cl2 (30 mL, 3 times). The combined org. ex-
tracts were dried (MgSO4), and the solvent was evaporated giving 477 mg (95%)
of a 1:1 mixture of (ꢂ)-6 and (ꢂ)-7. FC (Ø ꢇ 6.5 cm, h ꢇ 20 cm, 7:3 Et2O/light
petroleum ether) gave a first fraction of (ꢂ)-7 (498 mg, 35.5 %) and a second frac-
tion of (ꢂ)-6 (564 mg, 40%).
Data of (ꢂ)-6: white powder, mp 132°C (Et2O/pentane), Rf (7:3 Et2O/light
petroleum ether) ꢇ 0.17. [ꢀ]D25 ꢇ ꢂ54, [ꢀ] ꢇ ꢂ57, [ꢀ] ꢇ ꢂ65, [ꢀ]
ꢇ
25
577
25
546
25
435
ꢂ110, [ꢀ]42055 ꢇ ꢂ131 (c 1.0, CH2Cl2). UV (MeCN): 198 (11100), 217 (6200), 273
(1650). IR (KBr): ꢍ 3475, 2985, 1750, 1635, 1440, 1370, 1225, 1055, 915 cmꢂ1
.
1H NMR (400 MHz, CDCl3):ꢆH 7.63–7.61 (m, 2H), 7.35–7.32 (m, 3H), 5.27–5.25,
5.23–5.19 (2m, 3H, H-3ꢃ,4ꢃ,5ꢃ), 4.58 (d, 1H, 3J ꢇ 5.2 Hz, H-4), 4.49–4.46 (m, 2H,
H-1,2), 4.29 (m, 1H, H-6), 4.08 (qd, 1H, 3J ꢇ 6.8, 2.8 Hz, H-6ꢃ), 3.96 (ddd, 1H, 3
J ꢇ 12.0, 5.5, 2.8 Hz, H-2ꢃ), 3.45 (d, 1H, 3J ꢇ 4.9 Hz, H-5), 2.90 (br. s, 1H, OH),
2.30 (m, 1H, H-3), 2.10–2.00 (2s, ꢌ m, 7H, 2 Ac, H-1ꢃb), 1.34 (ddd, 1H, 2J ꢇ 14.8,
3J ꢇ 8.6, 3.0 Hz, H-1ꢃa), 1.15 (d, 3H, 3J ꢇ 6.8 Hz, H-7ꢃ). 13C NMR (100.6 MHz,
CDCl3):ꢆC 170.4, 170.0, 169.8 (3s, COO), 135.2, 129.4, 128.6 (3d, 1J(C,H) ꢁ161
Hz), 129.0 (s), 88.3 (d, 1J(C,H) ꢇ 163 Hz, C-4), 78.9 (d, 1J(C,H) ꢇ 142 Hz, C-1),
1
1
73.3 (d, J(C,H) ꢇ 159 Hz, C-2), 17.2 (d, J(C,H) ꢇ 145 Hz, C-2ꢃ), 69.9
1
1
(d, J(C,H) ꢇ 148 Hz, C-3ꢃ), 68.6 (2d, J(C,H) ꢇ 155 Hz, C-4ꢃ,5ꢃ), 66.8
(d, 1J(C,H) ꢇ 141 Hz, C-6ꢃ), 62.9 (d, 1J(C,H) ꢇ 164 Hz, C-6), 46.6 (d, 1J(C,H) ꢇ
150 Hz, C-5), 41.3 (d, 1J(C,H) ꢇ 132 Hz, C-3), 21.1 (t, 1J(C,H) ꢇ 124 Hz, C-1ꢃ),
20.8, 20.75, 20.7 (3q, 1J(C,H) ꢇ 130 Hz, CH3CO), 15.6 (q, 1J(C,H) ꢇ 127 Hz, C-
7ꢃ). CI-MS (NH3): m/z 608 (73, [MꢌNH4]ꢌ), 591 (46, [MꢌH]ꢌ), 590 (34, Mꢌ•),
416 (100).
Anal. Calcd for C25H31ClO9Se (589.92): C 50.90, H 5.30; Found: C 50.91,
H 5.25.
Data of (ꢂ)-7: white powder, mp 116°C (Et2O/pentane). Rf (7:3 Et2O/light
petroleum ether) ꢇ 0.25. [ꢀ]D25 ꢇ ꢂ34, [ꢀ] ꢇ ꢂ37, [ꢀ] ꢇ ꢂ42, [ꢀ]42355 ꢇ
25
20
577
546
ꢂ67, [ꢀ]42055 ꢇ ꢂ78 (c 0.55, CH2Cl2). UV (MeCN): 198 (11000), 216 (5700), 238
(2050), 273 (1630). IR (KBr): ꢍ 3480, 3060, 2985, 2940, 1745, 1635, 1480, 1440,
1370, 1225, 1130, 1055, 1025, 905, 740, 695, 470 cmꢂ1. H NMR (400 MHz,
1
CDCl3):ꢆH 7.67–7.65 (m, 2H), 7.38–7.34 (m, 3H), 5.24 (dd, 1H, 3J ꢇ 9.0, 5.5 Hz,
H-3ꢃ), 5.17 (dd, 1H, 3J ꢇ 3.2, 2.7 Hz, H-5ꢃ), 5.11 (dd, 1H, 3J ꢇ 9.0, 3.2 Hz, H-4),
4.55 (d, 1H, 3J ꢇ 5.5 Hz, H-4), 4.45 (m, 2H, H-1,2), 4.32 (m, 1H, H-6), 4.24 (ddd,
3
3
1H, J ꢇ 11.0, 5.5, 2.8 Hz, H-2ꢃ), 3.71 (qd, 1H, J ꢇ 6.0, 2.5 Hz, H-6ꢃ), 3.65

ORDER
REPRINTS
740
VIODÉ AND VOGEL
(d, 1H, 3J ꢇ 5.5 Hz, H-5), 2.55 (br. s, 1H, OH), 2.46 (m, 1H, H-3), 2.14, 2.07, 2.04
(3s, 9H, 3 Ac), 1.82 (ddd, 1H, 2J ꢇ 14.5, 3J ꢇ 8.0, 2.8 Hz, H-1ꢃb), 1.50 (ddd, 1H,
3
3
2J ꢇ 14.5, J ꢇ 11.0, 7.0 Hz, H-1ꢃa), 1.45 (d, 3H, J ꢇ 6.0 Hz, H-7ꢃ).13C NMR
(100.6 MHz, CDCl3):ꢆC ꢇ 170.4, 170.0, 169.3 (3s, COO), 135.0, 129.4, 128.5
(3d), 128.0 (s), 89.1 (d), 78.5 (d), 73.2 (d), 71.1 (d), 69.9, 68.6, 68.4, 66.5 (4d,
C-3ꢃ,4ꢃ,5ꢃ,6ꢃ), 63.2 (d, C-6), 46.5 (d, C-3), 41.2 (d, C-5), 21.1 (t, C-1ꢃ), 20.8, 20.75,
20.7 (3q, Ac), 15.7 (q, C-7ꢃ). CI-MS (NH3): m/z 608 (73, [MꢌNH4]ꢌ), 591 (46,
[MꢌH]ꢌ), 590 (34, M•ꢌ), 416 (100).
(ꢂ)-(1S,2R,3S,4R)-6-Chloro-3-endo-[(3ꢃ,4ꢃ,5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhy-
dro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-C-yl)]-7-oxabicy-
clo[2.2.1]hept-5-en-2-endo-ol ((ꢂ)-8). Metachloroperbenzoic acid (145 mg,
0.59 mmol) was added portionwise to a solution of (ꢂ)-6 (316 mg, 0.535 mmol) in
anhydrous CH2Cl2 stirred at ꢂ78°C. After stirring at ꢂ78°C for 3 h, then at 20°C
for 15 h, CH2Cl2 (20 mL) was added. The solution was washed with sat aq solu-
tion of NaHCO3 (30 mL), then with brine (30 mL). After drying (MgSO4) the sol-
vent was evaporated. The crude yellowish oil was purified by FC (Ø ꢇ 2.8 cm, h
ꢇ 12 cm, 9:1 Et2O/light petroleum ether) to give 210 mg (91%) of (ꢂ)-8, white
powder, mp 58°C, Rf (9:1 Et2O/(light petroleum ether) ꢇ 0.54. [ꢀ]2D5 ꢇ ꢂ71,
[ꢀ]52757 ꢇ ꢂ63, [ꢀ]52456 ꢇ ꢂ96, [ꢀ]42355 ꢇ ꢂ161 [ꢀ]42055 ꢇ ꢂ192 (c 0.2, CHCl3). UV
(MeCN): 208 (4150). IR (KBr): ꢍ 3745, 3480, 2985, 1745, 1645, 1595, 1435, 1375,
1
3
1230, 1055, 910, 600, 465 cmꢂ1. H NMR (400 MHz, CDCl3):ꢆH 6.21 (d, 1H,
J ꢇ 1.9 Hz, H-5), 5.27 (dd, 1H, 3J ꢇ 3.7, 3.6 Hz, H-5ꢃ), 5.16 (d, 1H, 3J ꢇ 6.7 Hz,
3
3
H-4ꢃ), 5.14 (d, 1H, J ꢇ 6.7 Hz, H-3ꢃ), 4.87–4.85 (m, 1H, H-4), 4.74 (d, 1H,
J ꢇ 4.6 Hz, H-1), 4.56 (dd, 1H, 3J ꢇ 7.8, 4.6 Hz, H-2), 4.21–4.13 (m, 2H, H-2ꢃ,6ꢃ),
2.53–2.41 (br. s, 1H, OH), 2.36–2.27 (m, 1H, H-3), 2.12, 2.10, 2.05 (3s, 9H, 3 Ac),
1.69–1.61 (ddd, 1H, 2J ꢇ 15.0, 3J ꢇ 11.6, 8.3 Hz, H-1ꢃb), 1.24 (d, 3H, 3J ꢇ 6.7
Hz, H-7ꢃ), 1.22–1.16 (m, 1H, H-1ꢃa). 13C NMR (100.6 MHz, CDCl3):ꢆC 170.2,
1
169.9, 169.7 (3s, COO), 138.7 (s, C-6), 128.0 (d, J(C,H) ꢇ 180 Hz, C-5), 83.7
(d, 1J(C,H) ꢇ 161 Hz, C-1), 83.1 (d, 1J(C,H) ꢇ 165 Hz, C-4), 70.9 (d, C-2ꢃ), 69.9
(d, C-2), 69.5 (d, C-3ꢃ), 69.0 (d, C-5ꢃ), 68.5 (d, C-4ꢃ), 67.7 (d, 1J(C,H) ꢇ 131 Hz,
1
1
C-6ꢃ), 41.5 (d, J(C,H) ꢇ 138 Hz, C-3), 23.8 (t, J(C,H) ꢇ 130 Hz, C-1ꢃ), 20.8,
1
20.7, 20.6 (3q, 3Ac), 15.1 (q, J(C,H) ꢇ 128 Hz, C-7ꢃ). CI-MS (NH3): m/z 452
(40, [MꢌNH4]ꢌ), 435 (20, [MꢌH]ꢌ), 434 (21, M•ꢌ), 450 (100), 433 (54), 373
(11), 273 (10), 102 (65), 83 (22).
Anal. Calcd for C19H25ClO9 (432.12): C 52.72, H 5.82; Found: C 52.63,
H 5.83.
(ꢂ)-(1S,2R,3S,4R)-6-Chloro-3-endo-[(3ꢃ,4ꢃ,5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhy-
dro-1ꢃ,7ꢃ-dideoxy-ga-L-glycero-D-galacto-heptitol-1ꢃ-C-yl)]-7-oxabicy-
clo[2.2.1]hept-5-en-2-endo-yl Acetate ((ꢂ)-9). A mixture of (ꢂ)-8 (360 mg,
0.83 mmol), anhydrous pyridine (39 mL), acetic anhydride (0.35 mL) and
4-dimethylaminopyridine (5 mg) was stirred at 20°C for 15 h. The solvent was evap-
orated in vacuo to dryness and the residue taken in Et2O (20 mL). The solution was
washed with aq 1 N HCl (20 mL), dried (MgSO4) and the solvent evaporated to give

ORDER
REPRINTS
SYNTHESIS OF N-ACETYLGALACTOSAMINE
741
336 mg (85%) of (ꢂ)-9 as a colorless powder, mp 104°C, Rf (1:1 EtOAc/light
petroleum ether) ꢇ 0.45. [ꢀ]2D5 ꢇ ꢂ65, [ꢀ] ꢇ ꢂ67, [ꢀ] ꢇ ꢂ75, [ꢀ]
ꢇ
25
577
25
546
25
435
25
405
ꢂ122, [ꢀ] ꢇ ꢂ144 (c 1.0, CHCl3). UV (MeCN): 205 (2050), 287 (220). IR
(KBr): ꢍ 2975, 1745, 1635, 1590, 1435, 1375, 1230, 1115, 1070, 1035, 912, 465
cmꢂ1. 1H NMR (400 MHz, CDCl3):ꢆH 6.22 (d, 1H, 3J ꢇ 1.9 Hz, H-5), 5.28–5.24
(m, 4H, H-4,3,5ꢃ), 5.19–5.15 (dd, 1H, 3J ꢇ 10.2, 3.3 Hz, H-4ꢃ), 4.97 (d, 1H, 3J ꢇ
4.3 Hz, H-2), 4.22–4.15 (ddd, 1H, 3J ꢇ 12.1, 5.7, 3.5 Hz, H-2ꢃ), 3.99–3.92 (qd, 1H,
3J ꢇ 6.4, 1.8 Hz, H-6ꢃ), 2.61–2.52 (m, 1H, H-3), 2.17, 2.08, 2.02 (3s, 12H, 4 Ac),
1.85–1.74 (ddd, 1H, 2J ꢇ 16.0, 3J ꢇ 12.1, 4.9 Hz, H-1ꢃb), 1.18 (d, 3H, 3J ꢇ 6.4 Hz,
H-7ꢃ), 1.08–0.97 (ddd, 1H, 2J ꢇ 16.0, 3J ꢇ 11.4, 3.5 Hz, H-1ꢃa). 13C NMR (100.6
MHz, CDCl3):ꢆC 170.7, 170.5, 170.2, 170.0 (4s, 4 COO), 137.9 (s, C-6), 128.4 (d,
C-5), 82.2 (d, C-1), 81.8 (d, C-4), 71.2 (d, C-2), 70.7 (d, C-2ꢃ), 70.5 (d, C-3ꢃ), 68.4
(d, C-5ꢃ), 68.3 (d, C-4ꢃ), 65.8 (d, C-6ꢃ), 38.4 (d, C-3), 22.9 (t, C-1ꢃ), 20.8, 20.7,
20.75, 20.6 (4q, 4 Ac), 16.1 (q, C-7ꢃ). CI-MS (NH3): m/z 492 (55, [MꢌNH4]ꢌ), 475
(20, [MꢌH]ꢌ), 415 (12), 330 (6), 273 (100), 111 (50), 102 (32), 83 (44).
Anal. Calcd for C21H27ClO10 (474.89): C 53.11, H 5.73; Found: C 53.02,
H 5.80.
(ꢂ)-(1R,2S,5R,6R)-5-Acetamido-3-chloro-2-hydroxy-6-[(3ꢃ,4ꢃ,5ꢃ-tri-O-
acetyl-2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-C-
yl)]cyclohex-3-en-1-yl Acetate ((ꢂ)-10). CF3SO3H (0.2 mL, 2.3 mmol) was
added dropwise to a stirred solution of (ꢂ)-9 (200 mg) in anhydrous MeCN (10
mL) cooled to ꢂ15°C. After stirring at ꢂ15°C for 30 min, CH2Cl2 (10 mL) was
added and the solution washed with an ice-cold sat aq solution of NaHCO3 (15 mL,
3 times). Drying (MgSO4), solvent evaporation gave 228 mg of a yellowish oil FC
(Ø ꢇ 2.2 cm, h ꢇ 15 cm, 7:3 EtOAc/light petroleum ether): 108 mg (48%) of (ꢂ)-
10, colorless powder, mp 117°C, Rf (7:3 EtOAc/light petroleum ether) ꢇ 0.29.
[ꢀ]D25 ꢇ ꢂ61, [ꢀ]52757 ꢇ ꢂ54 [ꢀ]52456 ꢇ ꢂ59, [ꢀ]42355 ꢇ ꢂ98, [ꢀ]42055 ꢇ ꢂ123 (c 1.0,
CHCl3). UV (MeCN): 206 (4300), 260 (250), 281 (260). IR (KBr): ꢍ 3560, 2985,
2940, 1750, 1655, 1535, 1435, 1375, 1230, 1110, 1060, 1030, 915, 600, 560 cmꢂ1
.
1H NMR (400 MHz, CDCl3):ꢆH 6.43 (d, 1H, 3J ꢇ 9.4 Hz, NH), 5.81 (d, 1H, 3J ꢇ
2.4 Hz, H-4), 5.20 (dd, 1H, 3J ꢇ 3.2, 1.9 Hz, H-5ꢃ), 5.15 (dd, 1H, 3J ꢇ 10.2, 5.6
Hz, H-3ꢃ), 5.07 (dd, 1H, 3J ꢇ 10.2, 3.2 Hz, H-4ꢃ), 5.02 (dd, 1H, 3J ꢇ 3.1, 2.7 Hz,
H-1), 4.58 (ddd, 1H, 3J ꢇ 9.4, 9.3, 2.4 Hz, H-5), 4.33 (br. s, 1H, OH), 4.21 (ddd,
3J ꢇ 11.3, 5.6, 3.2 Hz, H-2ꢃ), 4.00 (d, 1H, 3J ꢇ 2.76 Hz, H-2), 3.88 (qd, 1H, 3J ꢇ
6.5, 1.9 Hz, H-6ꢃ), 2.61–2.52 (m, 1H, H-3), 2.10, 2.09, 2.03, 2.00, 1.96 (5s, 15H, 5
Ac), 2.06 (m, H-6), 1.75 (m, 1H, H-1ꢃb), 1.56 (m, 1H, H-1ꢃa), 1.10 (d, 3H, 3J ꢇ 6.5
Hz, H-7ꢃ). 13C NMR (100.6 MHz, CDCl3):ꢆC 170.8, 170.4, 170.3, 170.2, 170.1 (5s,
5 COO), 132.6 (s, C-3), 129.3 (d, 1J(C,H) ꢇ 169 Hz, C-4), 75.4 (d, 1J(C,H) ꢇ 152
Hz, C-1), 72.8 (d, 1J(C,H) ꢇ 145 Hz, C-2ꢃ), 70.5 (d, 1J(C,H) ꢇ 153 Hz, C-5ꢃ), 69.8
(d, 1J(C,H) ꢇ 150 Hz, C-2), 68.1 (d, 1J(C,H) ꢇ 154 Hz, C-3ꢃ), 68.05 (d, 1J(C,H)
ꢇ 154 Hz, C-4ꢃ), 65.7 (d, 1J(C,H) ꢇ 139 Hz, C-6ꢃ), 48.7 (d, 1J(C,H) ꢇ 145 Hz,
C-5), 35.4 (d, 1J(C,H) ꢇ 128 Hz, C-6), 23.0 (t, 1J(C,H) ꢇ 128 Hz, C-1ꢃ), 23.0 (q,
1J(C,H) ꢇ 128 Hz, AcNH), 21.8, 20.7, 20.6, 20.5 (4q, 1J(C,H) ꢇ 130 Hz, 5 AcO),
15.8 (q, 1J(C,H) ꢇ 128 Hz, C-7ꢃ).

ORDER
REPRINTS
742
VIODÉ AND VOGEL
Anal. Calcd for C23H32ClO11 (533.17): C 51.74, H 6.04; Found: 51.56,
H 6.12.
(ꢂ)-Methyl 2-Acetamido-4-O-acetyl-2,3-dideoxy-3-C-(3ꢃ,4ꢃ,5ꢃ-tri-O-
acetyl-2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-C-yl)-ꢀ -
D-galactopyranuronate ((ꢂ)-11). Ozone (3% in O2) was bubbled through a
mixture of (ꢂ)-10 (54 mg, 0.1 mmol), MeOH (2 mL), THF (2 mL), NaHCO3 (48
mg, 0.56 mmol) cooled to ꢂ78°C. After 10 min, Me2S (two drops) was added and
the mixture stirred at ꢂ78°C for 10 min, then at 20°C for 6 h. Water (5 mL) was
added and the mixture was extracted with CH2Cl2 (20 mL, twice). Drying, solvent
evaporation, FC (Ø ꢇ 1 cm, h ꢇ 12 cm, 48.5:48.5:3 EtOAc/CH2Cl2/MeOH) gave
12 mg (21%) of (ꢂ)-11, colorless powder, Rf (48.5:48.5:3 EtOAc/CH2Cl2/MeOH)
ꢇ 0.11. [ꢀ]D25 ꢇ ꢂ45, [ꢀ]52757 ꢇ ꢂ14.5, [ꢀ]52456 ꢇ ꢂ32, [ꢀ]42355 ꢇ ꢂ54, [ꢀ]42055 ꢇ ꢂ62
(c 0.2, CH2Cl2). IR (KBr): ꢍ 3385, 2960, 1750, 1660, 1540, 1440, 1375, 1230,
1
1110, 1045, 915, 805, 600 cmꢂ1. H NMR (400 MHz, CDCl3):ꢆH 5.77 (d, 1H,
3
3J ꢇ 9.8 Hz, NH), 5.39 (br. s, 1H, H-4), 5.26, 5.25 (d, 1H, J ꢇ 3.5 Hz, H-1),
5.25–5.24 (dd, 1H, 3J ꢇ 4.0, 2.0 Hz, H-5ꢃ), 5.18 (dd, 1H, 3J ꢇ 10.2, 6.0 Hz, H-3ꢃ),
5.08 (dd, 1H, 3J ꢇ 10.2, 4.0 Hz, H-4ꢃ), 4.75 (br. s, 1H, H-5), 4.39 (ddd, 1H, 3J ꢇ
12.0, 10.0, 3.5 Hz, H-2), 4.24 (ddd, 1H, 3J ꢇ 10.6, 6.0, 4.0 Hz, H-2ꢃ) 3.95 (qd, 1H,
3J ꢇ 6.6, 2.0 Hz, H-6ꢃ), 3.74 (s, 3H, COOMe), 2.26 (m, 1H, H-3), 2.15, 2.08, 2.00,
2
3
1.98 (5s, 15H, 3 Ac), 1.67 (ddd, 1H, J ꢇ 15.4, J ꢇ 10.6, 4.4 Hz, H-1ꢃa), 1.57
(ddd, 1H, 2J ꢇ 15.4, 3J ꢇ 4.6, 4.3 Hz, H-1ꢃb), 1.17 (d, 3H, 3J ꢇ 6.6 Hz, H-7ꢃ). 13C
NMR (100.6 MHz, CDCl3):ꢆC 170.5, 170.4, 170.3, 170.0, 168.9 (5s), 91.8
(d, 1J(C,H) ꢇ 172 Hz, C-1), 72.6 (d, 1J(C,H) ꢇ 146 Hz, C-6ꢃ), 70.8 (d, 1J(C,H) ꢇ
148 Hz, C-5ꢃ), 70.5 (d, 1J(C,H) ꢇ 151 Hz, C-4ꢃ), 69.6 (d, 1J(C,H) ꢇ 138 Hz, C-
3ꢃ), 68.2 (d, 1J(C,H) ꢇ 138 Hz, C-2ꢃ), 68.1 (d, 1J(C,H) ꢇ 138 Hz, C-4), 65.8 (d,
1J(C,H) ꢇ 141 Hz, C-5), 52.6 (q, 1J(C,H) ꢇ 148 Hz, MeO), 48.2 (d, 1J(C,H) ꢇ 143
Hz, C-2), 35.5 (d, 1J(C,H) ꢇ 130 Hz, C-3), 24.0 (q, 1J(C,H) ꢇ 128 Hz, MeCONH),
23.3 (q, 1J(C,H) ꢇ 130 Hz, C-1ꢃ), 20.8, 20.7, 20.6 (3q, 1J(C,H) ꢇ 130 Hz, 3 Ac),
1
16.0 (q, J(C,H) ꢇ 128 Hz, C-7ꢃ). CI-MS (NH3): m/z 579 (9, [MꢌNH4]ꢌ), 562
(100, [MꢌHꢌ]), 561 (8, M(ꢌ), 502 (27), 442 (12).
Anal. Calcd for C23H32ClO11 (533.17): C 51.33, H 6.28; Found: C 51.23,
H 6.35.
(ꢂ)-Methyl 2-Acetamido-4-O-acetyl-2,3-dideoxy-1-O-methyl-3-C-(3ꢃ,4ꢃ,
5ꢃ-tri-O-acetyl-2ꢃ,6ꢃ-anhydro-1,7ꢃ-dideoxy-ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-
C-yl)-ꢄ-D-galactopyranuronate ((ꢂ)-13). A mixture of (ꢂ)-11 (21 mg, 0.037
mmol), anhydrous CH2Cl2 (5 mL), Cl3CCN (60 ꢉL) and NaH (3 mg) was stirred
under Ar atmosphere at 20°C for 4 h. Brine (5 mL) was added and the mixture ex-
tracted with CH2Cl2 (10 mL, 3 times). The combined org. extracts were dried
(MgSO4). Solvent evaporation provided 12 (1H NMR,ꢆH ꢇ 8.82 ppm (NH), 5.54
ppm (d, H-1)) that was directly taken in anhydrous CH2Cl2 (4 mL) and MeOH (0.1
mL). After cooling to 0°C, BF3ꢈEt2O (0.02 mL) in solution in anhydrous CH2Cl2
(1 mL) was then added slowly under stirring. After 10 min at 0°C, the mixture was
stirred at 20°C for 15 h. A sat aq solution of NaHCO3 (4 mL) was added and the
mixture extracted with CH2Cl2 (10 mL, 3 times). The combined org. extracts were

ORDER
REPRINTS
SYNTHESIS OF N-ACETYLGALACTOSAMINE
743
dried (MgSO4). Solvent evaporation, FC (Ø ꢇ 1 cm, h ꢇ 15 cm, 50:48:2
EtOAc/CH2Cl2/MeOH) gave 17 mg (79%) of (ꢂ)-13, colorless powder, Rf
(50:48:2 EtOAc/CH2Cl2/MeOH) ꢇ 0.19. [ꢀ]D25 ꢇ ꢂ143, [ꢀ]52757 ꢇ ꢂ150, [ꢀ]52456 ꢇ
25
435
25
405
ꢂ173, [ꢀ] ꢇ ꢂ283, [ꢀ] ꢇ ꢂ327 (c 0.03, EtOH). IR (KBr): ꢍ 2960, 1745,
1655, 1375, 1230, 1060 cmꢂ1. 1H NMR (400 MHz, CDCl3):ꢆH 5.51 (d, 1H, 3J ꢇ
8.0 Hz, NH), 5.33 (d, 1H, 3J ꢇ 2.0 Hz, H-4), 5.22 (dd, 1H, 3J ꢁ3.0, 2.0 Hz, H-5ꢃ),
5.15 (dd, 1H, 3J ꢇ 10.0, 6.0 Hz, H-3ꢃ), 5.07 (dd, 1H, 3J ꢇ 10.0, 3.0 Hz, C-4ꢃ), 4.52
(d, 1H, 3J ꢇ 8.0 Hz, H-1), 4.28 (d, 1H, 3J ꢇ 2.0 Hz, H-5), 4.24 (ddd, 1H, 3J ꢇ 10.0,
5.0, 4.9 Hz, H-2ꢃ), 3.94 (qd, 1H, 3J ꢇ 6.5, 2.0 Hz, H-6ꢃ), 3.76 (m, 1H, H-2), 3.53
(s, 3H, MeO), 2.35 (m, 1H, H-3), 2.13, 2.07, 2.04, 2.00, 1.96 (5s, 15H, 5 Ac), 1.68
(ddd, 1H, 2J ꢇ 15.4, 3J ꢇ 10.0, 4.9 Hz, H-1ꢃa), 1.61 (ddd, 1H, 2J ꢇ 15.4, 3J ꢇ 5.0,
4.4 Hz, H-1ꢃb), 1.16 (d, 3H, 3J ꢇ 6.5 Hz, H-7ꢃ). 13C NMR (100.6 MHz, CDCl3):ꢆC
170.6, 170.5, 170.4, 170.0 (5s, 4 COO ꢌ CONH), 167.7 (s, C-6), 102.7 (d, 1J(C,H)
1
1
ꢇ 170 Hz, C-1), 75.2 (d, J(C,H) ꢇ 142 Hz, C-5), 72.1 (d, J(C,H) ꢇ 149 Hz,
1
1
C-2ꢃ), 70.2 (2d, J(C,H) ꢇ 153 Hz, C-4,5ꢃ), 68.3, 68.1 (2d, J(C,H) ꢇ 162 Hz,
C-3,4ꢃ), 66.1 (d, 1J(C,H) ꢇ 145 Hz, C-2), 40.0 (d, 1J(C,H) ꢇ 127 Hz, C-3), 23.5
1
1
(t, J(C,H) ꢇ 126 Hz, C-1ꢃ), 20.8, 20.7 (5q, J(C,H) ꢇ 130 Hz, 5 Ac), 15.7
(q, J(C,H) ꢇ 126 Hz, C-7ꢃ). CI-MS (NH3): m/z 593 (9, [MꢌNH4]ꢌ), 576 (56,
1
[MꢌH]ꢌ), 575 (25, M(ꢌ), 544 (27, [MꢌH-MeOH]ꢌ), 424 (12), 179 (9).
Anal. Calcd for C25H37NO14 (575.56): C 52.17, H 6.48; Found: C 52.36,
H 6.32.
(ꢂ)-Methyl 2-Acetamido-2,3-dideoxy-3-C-(2ꢃ,6ꢃ-anhydro-1ꢃ,7ꢃ-dideoxy-
ꢀ-L-glycero-D-galacto-heptitol-1ꢃ-C-yl)-ꢄ -D-galactopyranoside ((ꢂ)-1). A 2
M solution of LiBH4 in anhydrous THF (0.3 mL) was added dropwise under Ar at-
mosphere to a stirred solution of (ꢂ)-13 (47.3 mg, 0.082 mmol) in anhydrous THF
(8 mL) cooled at 0°C. After stirring at 0°C for 1 h, then at 20°C for 15 h, H2O (4
mL) was added and the solvent was evaporated to dryness (lyophilisation). The
residue was taken in MeOH (2 mL) and filtered through a column (Ø ꢇ 1 cm, h ꢇ
5 cm) of DOWEX 50x8 (acidic) prewashed with 1:10 HCl/H2O (20 mL), then H2O
(20 mL, 3 times) and MeOH (20 mL, twice). Elution with MeOH provided 22 mg
(70%) of (ꢂ)-1, colorless powder, mp 134–138°C (dec.). [ꢀ]D25 ꢇ ꢂ78, [ꢀ]52757 ꢇ
25
25
25
ꢂ74, [ꢀ] ꢇ ꢂ86, [ꢀ] ꢇ ꢂ130, [ꢀ] ꢇ ꢂ158 (c 0.05, EtOH). IR (KBr):
546
435
405
ꢍ 3745, 3445, 2985, 1745, 1650, 1540, 1455, 1395, 1080 cmꢂ1. 1H NMR (400 MHz,
MeOH-d4):ꢆH 4.28 (d, 1H, 3J ꢇ 8.4 Hz, H-1), 3.97 (ddd, 1H, 3J(H-1ꢃ(proR),H-2ꢃ)
ꢇ 8.5–10, 3J(H-2ꢃ,H-3ꢃ) ꢇ 5.0, 3J(H-1ꢃ(proS) ꢇ 3.0 Hz, H-2ꢃ), 3.96 (qd, 1H, 3J ꢇ
6.5, 3.0 Hz, H-6ꢃ), 3.90 (dd, 1H, 3J(H-1,H-2) ꢇ 8.4, 3J(H-2,H-3) ꢇ 9.0 Hz, H-2),
3.86 (br. dd, 1H, 3J(H-3ꢃ,H-4ꢃ) ꢇ 8.8, 3J(H-2ꢃ,H-3ꢃ) ꢇ 5.0 Hz, H-3ꢃ), 3.77 (dd, 1H,
3J(H-3,H-4) ꢇ 6.5, J(H-4,H-5) ꢇ 4.5 Hz, H-4), 3.73 (dd, 1H, J(H-5ꢃ,H-6ꢃ)
ꢁ3J(H-4ꢃ,H-5ꢃ) ꢁ3.0 Hz, H-5ꢃ), 3.67 (dd, 1H, 3J(H-3ꢃ,H-4ꢃ) ꢇ 8.8, 3J(H-4ꢃ,H-5ꢃ)
ꢇ 3.0 Hz, H-4ꢃ), 3.56 (dd, 1H, 3J ꢇ 6.5, 4.5 Hz, H-5), 3.50 (br. s, 2H, H-6), 3.39 (s,
3
3
3
3H, MeO), 2.01 (s, 3H, AcNH), 1.94 (m, 1H, H-1ꢃ(proR)), 1.76 (m, 1H, J(H-
1ꢃ(proR),H-3) ꢇ 11.0, 3J(H-2,H-3) ꢇ 9.0, 3J(H-3,H-4) ꢇ 6.5, 3J(H-1ꢃ(proS),H-3)
ꢇ 3.0 Hz, H-3), 1.70 (m, 1H, 2J ꢇ 14.6, 3J(H-1ꢃ(proS),H-2ꢃ) ꢁ3J(H-1ꢃ(proS),H-3)
ꢇ 3.0 Hz, H-1ꢃ(proS)), 1.26 (d, 3H, J ꢇ 6.5 Hz, H-7ꢃ). 13C NMR (100.6 MHz,
3
1
MeOH-d4):ꢆC 174.3 (1s, CONH), 105.6 (d, J(C,H) ꢇ 174 Hz, C-1), 84.9, 79.7,

ORDER
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VIODÉ AND VOGEL
72.2, 70.3, 69.4, 68.2, 56.7 (7d, C-2ꢃ,3ꢃ,4ꢃ,4,5,5ꢃ,6ꢃ), 63.0 (t, C-6), 52.3 (d, 1J(C,H)
ꢇ 138 Hz, C-2), 49.8 (q, MeO), 45.2 (d, 1J(C,H) ꢇ 129 Hz, C-3), 23.5 (t, C-1ꢃ), 22.6
(q, 1J(C,H) ꢇ 128 Hz, MeCONH), 16.5 (q, 1J(C,H) ꢇ 128 Hz, C-7ꢃ). CI-MS (NH3):
m/z 347 (23, [M-MeOH]ꢌ), 77 (100). electrospray MS: m/z 380 [MꢌHꢌ], 348
[MꢌH-MeOH]ꢌ. HRMScalcdforC16H29NO9Na:402.174002;found:402.173143
ACKNOWLEDGMENTS
We thank the Swiss National Science Foundation, the Fonds Herbette (Lau-
sanne) and the Office Fédéral de l’enseignement et de la Science (European pro-
ject COSTD13/0001/99) for financial support. We thank Prof. I. Robina, Mr. M.
Rey and F. Sepúlveda for technical help.
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Accepted September 18, 2001

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