Synthesis of building blocks of human milk oligosaccharides. Fucosylated derivatives of the lacto- and neolacto-series.

Article abstract of DOI:10.1016/S0008-6215(02)00164-7

The synthesis of protected fucosylated derivatives of a Galbeta(1-->3)GlcNAc and of lactosamine Galbeta(1-->4)GlcNAc building blocks contained in human milk oligosaccharides is described. Both chemical and enzymatic methods have been exploited for selective protection of the disaccharide. Fucosylation of the appropriate derivatives allowed an easy and relatively short access to different products from common precursors.

Full text of DOI:10.1016/S0008-6215(02)00164-7

Carbohydrate Research 337 (2002) 1333–1342
www.elsevier.com/locate/carres
Synthesis of building blocks of human milk oligosaccharides.
Fucosylated derivatives of the lacto- and neolacto-series
Barbara La Ferla,a Davide Prosperi,a,c Luigi Lay,a Giovanni Russo,a,c,* Luigi Panzab
aDipartimento di Chimica Organica e Industriale, Uni6ersita` degli Studi di Milano, 6ia G. Venezian, I-21-20133 Milan, Italy
bDipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche (DISCAFF), Uni6ersita` del Piemonte Orientale, 6iale Ferrucci,
I-33-28100 No6ara, Italy
cIstituto di Scienze e Tecnologie Molecolari, CNR, 6ia G. Venezian, I-21-20133 Milan, Italy
Received 24 April 2002; accepted 19 June 2002
Abstract
The synthesis of protected fucosylated derivatives of a Galb(1“3)GlcNAc and of lactosamine Galb(1“4)GlcNAc building
blocks contained in human milk oligosaccharides is described. Both chemical and enzymatic methods have been exploited for
selective protection of the disaccharide. Fucosylation of the appropriate derivatives allowed an easy and relatively short access to
different products from common precursors. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Building block; Human milk; Oligosaccharide derivatives, synthesis; Lewisx; N-Acetyl lactosamine; Lipases
1. Introduction
Careful examination of the structures of the complex
oligosaccharides of human milk revealed that a great
number of these contain the disaccharidic units
Human milk is extremely rich in oligosaccharides,
more than 130 different compounds having been iso-
lated and identified so far.1,2 The biological significance
of these compounds has largely been unappreciated, as
they were thought to be nutritionally irrelevant and
merely by-products due to the presence of large
amounts of glycosyl transferases in the milk synthetic
pathway.
Recently the great importance of these compounds
has been demonstrated for breast-fed infants; during
the lactation period, the oligosaccharides, among their
other biological roles, inhibit bacterial adhesion to the
epithelial cells’ surface, which has been recognized as a
crucial initial step in the infectious process.3–9 However,
it is still not clear which of the many oligosaccharides
exert this function. In a project devoted to the identifi-
cation of such compounds, after the synthesis of trisac-
charides containing the lactose unit,10 we focussed on
the synthesis of oligosaccharide derivatives of the lacto-
and neolacto-series contained in human milk.
Galb(1“3)GlcNAc
and
lactosamine
Galb(1“
4)GlcNAc, the first bearing one/two a-fucose unit(s)
linked to position 2 of Gal and/or position 4 of Glc-
NAc (structures 1, 2, 3 of Fig. 1), while the second is
fucosylated in position 3 of GlcNAc and/or 2 of Gal
(structures 4, 5 of Fig. 1). Among the fucosylated
derivatives of N-acetyl lactosamine, trisaccharides
Lewisx and H-antigen and the tetrasaccharide Lewisy,
three of the most important blood group antigens, have
been extensively studied both from the biological, as
well as a chemical point of view. Syntheses of Lewisx,
Lewisy and H-antigens have employed various strate-
gies, building blocks and protecting groups.11–21 Lewisx
is present as such and as a core structure of many
complex oligosaccharides of human milk.
Thus in order to prepare an array of the more
complex oligosaccharides, we planned an efficient strat-
egy to synthesize these units as common building blocks
to which the proper peripheric unit(s) can be linked.
Moreover, we intended to exploit the enzymatic ma-
nipulation of the hydroxyl groups by regioselective
introduction of acyl protecting groups, so demonstrat-
ing that such a strategy can be a useful alternative to
more classical chemical methods.
* Corresponding author. Tel.: +39-02-50314060; fax: +
39-02-50314061
E-mail address: giovanni.russo@unimi.it (G. Russo).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00164-7

1334
B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
In the present paper, we describe the synthesis of the
extremely reactive totally benzylated derivative (Scheme
2).
protected fucosylated derivatives of the lacto-series,
corresponding to compounds 1, 2 and 3 (Fig. 1), to-
gether with that of the neolacto-series, corresponding to
compounds 4 and 5. All these protected structures are
useful building blocks for the preparation of more
complex oligosaccharides contained in human milk.
Compound 16, the protected derivative of 2, was
obtained according to the pathway described in Scheme
3. The acetates were removed from the galactose unit of
8 and the free primary position was efficiently silylated
by the introduction of a t-butyldiphenylsilyl group.
Position 3% and 4% of the obtained compound 14 were
then protected with an isopropylidene group affording
acceptor 15, useful for the achievement of the desired
trisaccharide 16. In fact, compound 15 was glycosylated
with the same fucosyl donor 11 in the presence of
TMSOTf to give compound 16 in 66% yield.
2. Results and discussion
The lacto series.—The synthetic strategy adopted for
the easy preparation of the target molecules was based
on the fucosylation of a common disaccharidic building
block precursor 8. This compound was obtained from
two easily available monosaccharides (6 and 7, Scheme
1), according to a procedure already described by
Toepfer and Schmidt,22 and was further elaborated to
obtain the single target molecules.
Finally, difucosylated compound 20, corresponding
to deprotected tetrasaccharide 3 (Scheme 4), was ob-
tained exploiting the result of a recently reported
study24 on selective enzymatic protection of compound
The synthetic strategy planned the manipulation of
compound 8 to introduce, both by chemical and enzy-
matic methods, the appropriate protecting groups in
order to obtain the different glycosyl acceptors for the
fucosylation reactions.
Compound 12, the protected derivative of 1, was
synthesized in a straightforward manner. Removal of
the benzylidene group from 8 followed by a selective
acetylation of the primary position at low temperature
with acetyl chloride afforded acceptor 10 in 80% yield,
which was fucosylated using the efficient donor 1123
and TMSOTf as promoter, in excellent yield (99%). The
partially acetylated fucosyl donor 11 is much more
stable and easy to use with respect to the corresponding
Scheme 2.
Scheme 3.
Fig. 1.
Scheme 1.
Scheme 4.

B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
1335
17, which can be easily obtained by deacetylation of 9.
Using lipase from Candida antarctica (CAL) and
vinylacetate25–27 in MeCN as solvent, it was possible to
protect selectively the two primary positions of com-
pound 17. The 3% and 4% hydroxyl groups of the ob-
tained compound 18 were then protected by the
introduction of an isopropylidene group affording diol
19. Such compound was used as acceptor for the syn-
thesis of the desired tetrasaccharide, employing again
donor 11 and TMSOTf as Lewis acid. Difucosylated
compound 20 was obtained in an excellent 91% yield.
The neolacto-series.—Searching for an efficient syn-
thetic strategy for the trisaccharide 30 and the tetra-
saccharide 34, we projected two differently protected
disaccharidic precursors 27 and 28 (Scheme 5), easily
available from a common monosaccharidic moiety,
azido glucose 21.28 This was converted into two glyco-
syl acceptors differently protected at C-3, compounds
24 and 25, that were reacted with donor 2628 affording
protected azidolactoses 27 and 28 in 56% and 95%
yield, respectively.
the benzyl group was removed29 with SnCl4 and the
obtained compound 29 was readily fucosylated with
donor 11, using TMSOTf as promoter, affording the
trisaccharide 30, the protected form of 4, in 90% yield
(Scheme 6).
Finally, disaccharide 27 was used for the synthesis of
the protected form of tetrasaccharide 5. Compound 27
(Scheme 7) was fully deacetylated with sodium methox-
ide to compound 31, then 3%,4% positions were protected
as isopropylidene acetal. The reaction conditions (ace-
tone, CSA and Sikkon) were chosen in order to induce
the formation of the 3%,4%- (thermodynamic control)
versus the 4%,6%-acetonide. In fact, the 3%,4% product 32 is
obtained in 85% yield, while the 4%,6% protected com-
pound is obtained only in 15% yield. Compound 32 was
selectively acetylated on the two primary positions with
acetylchloride at low temperature affording acceptor 33
in 71% yield, which was finally fucosylated. Due to the
unexpected lability of the acceptor during the glycosyla-
tion, many attempts were done both adopting the in-
verse and the direct fucosylation procedure, changing
the Lewis acid (TMSOTf, BF3·Et2O) and the tempera-
ture. The best conditions were found in the direct
procedure using TMSOTf (0.01 equiv) at −20 °C. Un-
der these conditions, tetrasaccharide 34 was obtained in
55% yield.
Compound 28, containing a benzyl group at C-3,
allowed to have selective access to position 3. In fact,
In conclusion, the use of a common precursor and an
appropriate choice of the protecting groups and
method for their introduction (either chemical or enzy-
matic) allowed the easy preparation of two families of
fucosylated derivatives of the lacto- and neolacto-series
in protected form. These compounds represent useful
building blocks which can be exploited, through selec-
tive manipulation of the protective groups, to prepare a
wide array of complex oligosaccharides of human milk.
Scheme 5.
3. Experimental
General methods.—1H and 13C NMR spectra were
recorded on Bruker AC 300 and Varian Gemini 200
spectrometers for solution. Melting points were deter-
mined with Bu¨chi apparatus and are not corrected.
Optical rotations were measured at rt with a Perkin–
Elmer 241 polarimeter. TLC was carried out on E.
Merck Silica-Gel 60 F245 plates (0.25 mm thickness),
and spots were visualized by spraying with solution
containing H2SO4 (31 mL) ammonium molybdate (21
g) and Ce(SO4)2 (1 g) in 500 mL water, followed by
heating at 110 °C for 5 min. Column chromatography
was performed by the flash procedure using E. Merck
Silica-gel 60 (230–400 mesh). Elemental analyses were
performed using the Carlo–Erba elemental analyzer
1108.
Scheme 6.
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
D-gal-
Scheme 7.
actopyranosyl-(1“3)-2-azido-4,6-O-benzylidene-2-de-

1336
B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
oxy-i-
D
-glucopyranoside (8).—Compounds 7 (429 mg,
−3.231 (CH3CO, CH3-TDS, CH3Si). Anal. Calcd for
C28H47N3O14Si: C, 49.61; H, 6.99; N, 6.20. Found: C,
49.58; H, 6.96; N, 6.17.
0.98 mmol) and 6 (1200 mg, 2.45 mmol) were mixed in
a flask under inert atmosphere and dissolved in dry
CH2Cl2 (5 ml). Then BF3·Et2O (490 mL of a 0.1 M
solution, 0.05 equiv) was added. After 15 min, the
reaction was neutralized with Et3N and the solvent was
removed under reduced pressure. Chromatographic
purification (7:3 petroleum ether–EtAcO) afforded 707
mg (94% yield) of pure compound 8. Amorphous white
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
D-gal-
actopyranosyl-(1“3)-6-O-acetyl-2-azido-2-deoxy-i-
D
-
glucopyranoside (10).—Compound 9 (474 mg, 0.70
mmol) was dissolved in dry CH2Cl2 (10 mL) under inert
atmosphere and the temperature was lowered to
−78 °C; then Py (452 mL, 5.6 mmol) and AcCl (223 mL,
3.5 mmol) were added in the order. After 1 h, MeOH
was added (1 mL) and the solvent was removed under
reduced pressure. Chromatographic purification (1:1
petroleum ether–EtAcO) afforded 400 mg (80% yield)
of pure 10. [h]D +10.2° (c 1.5, CHCl3); 1H NMR
(CDCl3): l 5.39 (d, 1 H, J3%,4% 3.3 Hz, H-4%), 5.26 (dd, 1
H, J1%,2% 7.8, J2%,3% 10.4 Hz, H-2%), 5.05 (dd, 1 H, H-3%),
4.58 (d, 1 H, H-1%), 4.52 (d, 1 H, J1,2 7.0 Hz, H-1), 4.43
(dd, 1 H, J6b,5 2.0, J6b,6a 12.0 Hz, H-6b), 4.17 (dd, 1 H,
J6a,5 7.5 Hz, H-6a), 4.20–4.00 (m, 2 H, H-6%a, 6%b), 3.99
(bt, 1 H, H-5%), 3.82, (s, 1 H, OH), 3.48 (dd, 1 H, J4,3
7.1, J4,5 9.7 Hz, H-4), 3.41 (ddd, 1 H, H-5), 3.25 (dd, 1
H, J3,2 9.8 Hz, H-3), 3.17 (dd, 1 H, H-2), 2,15, 2.10,
2.04, 2.04, 1.97 (5 s, 15 H, CH3CO), 1.60–1.80 (m, 1 H,
CH-TDS), 0.94–0.86 (m, 12 H, CH3-TDS), 0.22, 0.20
(2 s, 6 H, CH3Si); 13C NMR (CDCl3): l 170.6, 170.4,
170.0, 169.9, 169.5 (5 s, CH3CO), 102.5, 97.05 (2 d, C-1,
1%), 86.36, 73.42, 71.28, 70.63, 69.20, 68.51, 67.09, 66.86
(8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%), 63.36, 61.63 (2 t, C-6, 6%),
33.86 (d, CH-TDS), 24.78 (s, Cq-TDS), 20.73–18.31,
−2.257, −3.344 (CH3CO, CH3-TDS, CH3Si). Anal.
Calcd for C30H49N3O15Si: C, 50.05; H, 6.86; N, 5.84.
Found: C, 49.98; H, 6.79; N, 5.81.
1
solid; [h]D −21.6° (c 2, CHCl3); H NMR (CDCl3): l
7.51–7.23 (m, 5 H, H-Ar), 5.54 (s, 1 H, CHPh), 5.33 (d,
1 H, J3%,4% 3.1 Hz, H-4%), 5.26 (dd, 1 H, J1%,2% 8.0, J2%,3%
10.4 Hz, H-2%), 5.00 (d, 1 H, H-3%), 4.74 (d, 1 H, H-1%),
4.60 (d, 1 H, J1,2 7.6 Hz, H-1), 4.27 (dd, 1 H, J6b,5 4.8,
J6b,6a 10.4 Hz, H-6b), 4.09 (dd, 1 H, J6%b,5% 7.8, J6b%,6a%
11.1 Hz, H-6%b) 3.89 (dd, 1 H, J6%a,5% 5.8 Hz, H-6%a), 3.78
(t, 1 H, J6a,5 10.4 Hz, H-6a), 3.58–3.75 (m, 3 H, H-3, 4,
5%), 3.29–3.41 (m, 1 H, H-5), 3.32 (dd, 1 H, J2,3 8.5 Hz,
H-2), 2,12, 2.08, 1.98, 1.94 (4s, 12 H, CH3CO), 1.60–
1.80 (m, 1 H, CH-TDS), 0.96–0.88 (m, 12 H, CH3-
TDS), 0.22, 0.20 (2 s, 6 H, CH3Si); 13C NMR (CDCl3):
l 170.7, 170.6, 170.6, 170.0 (4 s, CO), 137.4 (s), 129.6,
128.6, 126.4 (3 d, CHAr), 101.9, 101.7, 97.95, 80.14,
79.81, 71.44, 71.09, 69.70, 69.10, 67.32, 66.85 (11 d,
C-1, 2, 3, 4, 5, 1%, 2%, 3%, 4%, 5%, CHPh), 68.92, 61.38 (2t,
C-6, 6%), 34.28 (d, CH-TDS), 25.19 (s, Cq-TDS), 21.10,
21.01, 20.94, 20.94, 20.32, 20.19, 18.87, 18.75, −1.744,
−2.826 (10q, 4 CH3CO, 6 CH3-TDS). Anal. Calcd for
C35H51N3O14Si: C, 54.88; H, 6.71; N, 5.49. Found: C,
55.00; H, 6.78; N, 5.41.
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
D-gal-
actopyranosyl-(1“3)-2-azido-2-deoxy-i- -glucopy-
D
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
actopyranosyl-(1“3)-[3,4-di-O-acetyl-2-O-benzyl-h-
fucopyranosyl-(1“4)]-6-O-acetyl-2-azido-2-deoxy-i-
-glucopyranoside (12).—Compound 10 (98 mg, 0.136
D-gal-
ranoside (9).—Compound 8 was dissolved in CH2Cl2
(15 mL) and 70% CF3COOH (3 mL) was added. After
10 min, a saturated solution of Na2CO3 was added until
basic pH was reached. After phase separation, the
water layer was extracted with CH2Cl2. The combined
organic phases were washed with water, dried with
anhyd NaSO4, filtered and the solvent was removed
under reduced pressure. Chromatographic purification
(1:1 petroleum ether–EtAcO) afforded 548 mg (87%
yield) of pure 9. Amorphous white solid; [h]D +3.9° (c
L
-
D
mmol) was dissolved in dry CH2Cl2 (1 mL). The tem-
perature was lowered to 0 °C and TMSOTf (27 mL of a
0.1 M solution, 0.02 equiv) was added. Then compound
11 (131 mg, 0.273 mmol) dissolved in dry CH2Cl2 (1.5
mL) was slowly added at rt. After 1 h, the reaction was
neutralized with Et3N and the solvent was removed
under reduced pressure. Chromatographic purification
(3:2 petroleum ether–EtAcO) afforded 140 mg (99%
1
1.5, CHCl3); H NMR (CDCl3): l 5.39 (d, 1 H, J3%,4% 3.4
1
Hz, H-4%), 5.26 (dd, 1 H, J1%,2% 7.9, J2%,3% 10.5 Hz, H-2%),
5.05 (dd, 1 H, H-3%), 4.58 (d, 1 H, H-1%), 4.57 (d, 1 H,
J1,2 7.2 Hz, H-1), 4.19–4.06 (m, 2 H, H-6%a, 6%b), 4.00
(bt, 1 H, H-5%), 3.88 (dd, 1 H, J6b,5 3.7, J6b,6a 11.8 Hz,
H-6b), 3.73 (dd, 1 H, J6a,5 5.3 Hz, H-6a), 3.53 (m, 1 H,
H-5), 3.34–3.21 (m, 3 H, H-2, 3, 4), 2.18, 2.11, 2.07,
2.00 (4 s, 12 H, CH3CO), 1.60–1.80 (m, 1 H, CH-TDS),
0.94–0.88 (m, 12 H, CH3-TDS), 0.22, 0.20 (2 s, 6 H,
CH3Si); 13C NMR (CDCl3): l 170.4, 170.1, 170.1, 169.5
(5s, CH3CO), 102.4, 97.05 (2 d, C-1, 1%), 86.25, 75.28,
71.23, 70.65, 69.72, 68.56, 67.29, 66.89 (8 d, C-2, 3, 4, 5,
2%, 3%, 4%, 5%), 62.84, 61.69 (2 t, C-6, 6%), 33.85 (d,
CH-TDS), 24.77 (s, Cq-TDS), 20.45–18.31, −2.085,
yield) of pure 12. [h]D −55.1° (c 1, CHCl3); H NMR
(CDCl3): l 7.35–7.23 (m, 5 H, H-Ar), 5.38 (d, 1 H, J3%,4%
2.9 Hz, H-4%), 5.31 (d, 1 H, J3%%,4%% 2.9 Hz, H-4%%), 5.17
(dd, 1 H, J2%%,3%% 10.6 Hz, H-3%%), 5.10–4.99 (m, 4 H, H-1%,
2%, 3%, 5%%), 4.82 (d, 1 H, J1%%,2%% 3.6 Hz, H-1%%), 4.64 (d, 1
H, J 11.6 Hz, CHPh), 4.59 (d, 1 H, CHPh), 4.49 (d, 1
H, J1,2 7.3 Hz, H-1), 4.49–4.44 (m, 1 H, H-6b), 4.40
(dd, 1 H, J6%b,5% 6.0, J6%b,6%a 11.6 Hz, H-6%b), 4.23 (dd, 1
H, J6%a,5% 7.9 Hz, H-6%a), 4.15 (dd, 1 H, J6a,5 4.2, J6a,6b
12.0 Hz, H-6a), 3.89–3.82 (m, 2 H, H-5%, 2%%), 3.69 (t, 1
H, J4,3=J4,5 9.3 Hz, H-4), 3.59 (t, 1 H, J3,2 9.3 Hz,
H-3), 3.44–3.41 (m, 1 H, H-5), 3. 20 (dd, 1 H, H-2),
2.15, 2.11, 2.10, 2.04, 2.04, 1.98, 1.94 (7 s, 21 H,

B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
1337
CH3CO), 1.60–1.80 (m, 1 H, CH-TDS), 1.20 (d, 3 H,
J5%%,6%% 5.3 Hz, H-6%%), 0.96–0.88 (m, 12 H, CH3-TDS),
0.22, 0.20 (2 s, 6 H, CH3Si); 13C NMR (CDCl3): l
170.5, 170.2, 170.2, 170.2, 169.9, 169.5, 169.4 (7s, CO),
137.5 (s), 128.4–128.0 (CHAr), 100.8, 97.74, 96.93 (3 d,
C-1, 1%, 1%%), 77.05, 73.41, 73.17, 72.49, 72.03, 71.05,
70.59, 69.84, 68.87, 66.96, 64.69 (12 d, C-2, 3, 4, 5, 2%,
3%, 4%, 5%, 2%%, 3%%, 4%%, 5%%), 74.29, 61.74, 60.88 (3 t, C-6, 6%,
CH2Ph), 33.91 (d, CH-TDS), 24.78 (s, Cq-TDS), 20.73–
15.73, −2.304, −3.310 (CH3CO, CH3-TDS, CH3Si).
Anal. Calcd for C47H69N3O21Si: C, 54.26; H, 6.69; N,
4.04. Found: C, 54.30; H, 6.72; N, 4.07.
OH), 2.59 (d, 1 H, J 3.7 Hz, OH), 1.80–1.60 (m, 1 H,
CH-TDS), 1.12–0.88 (m, 21 H, CH3-TDS, CH3-tBu),
0.21, 0.18 (2 s, 6 H, CH3Si); 13C NMR (CDCl3): l
132.8–132.9 (m, CqPh), 135.6–127.8 (m, CHAr), 104.3,
97.46, 96.94 (3 d, C-1, 1%, CHPh), 85.89, 75.42, 75.42,
73.25, 71.93, 70.01, 68.56, 67.30 (8 d, C-2, 3, 4, 5, 2%, 3%,
4%, 5%), 63.14, 62.90 (2 t, C-6, 6%), 33.91 (d, CH-TDS),
26.80 (q, CH3tBu), 24.85, 19.12 (2 s, Cq-TDS, tBu),
19.98–18.38, −2.062, −3.134 (m, CH3-TDS, CH3Si).
Anal. Calcd for C43H61N3O10Si2: C, 61.76; H, 7.35; N,
5.03. Found: C, 61.71; H, 7.38; N, 4.99.
Thexyldimethylsilyl 6-O-tert-butyldiphenylsilyl-3,4-O-
isopropylidene-i-
4,6-O-benzylidene-2-deoxy-i-
D
-galactopyranosyl-(1“3)-2-azido-
-glucopyranoside (15).—
Texyldimethylsilyl
i-D
-galactopyranosyl-(1“3)-2-
-glucopyranoside
D
azido-4,6-O-benzylidene-2-deoxy-i-
D
Compound 14 (392 mg, 0.47 mmol) was dissolved in
dry MeCN (12 mL), and DMP (178 mL, 1.45 mmol)
and a catalytic amount of CSA were added; after 10
min, the reaction was neutralized with Et3N and the
solvent was removed under diminished pressure. Chro-
matographic purification (4:1 petroleum ether–EtAcO)
afforded 391 mg (95% yield) of pure 15. Amorphous
solid; [h]D −3.1° (c 0.55, CHCl3); 1H NMR (CDCl3): l
7.72–7.12 (m, 15 H, H-Ar), 5.50 (s, 1 H, CHPh), 4.61
(d, 1 H, J1%,2% 7.4 Hz, H-1%), 4.39 (d, 1 H, J1,2 8.4 Hz,
H-1), 4.24 (dd, 1 H, J6b,5% 4.9, J6b,6a 10.6 Hz, H-6b),
4.15–4.03 (m, 2 H, H-3%, 4%), 4.03–3.54 (m, 7 H, H-3, 4,
5, 6a, 2%, 6%a, 6%b), 3.36 (bt, 1 H, H-2), 3.35–3.28 (m, 1
H, H-5%), 2.99 (bs, 1 H, OH), 1.74–1.60 (m, 1 H,
CH-TDS), 1.53, 1.36 (2 s, 6 H, (CH3)2C), 1.03 (s, 9 H,
(CH3)3C), 0.91–0.88 (m, 12 H, CH3-TDS), 0.20, 0.18 (2
s, 6 H, CH3Si); 13C NMR (CDCl3): l 136.8–133.4 (m,
CqPh), 135.6–125.7 (m, CHAr), 109.7 (s), 102.8, 101.1,
97.55 (3 d, C-1, 1%, CHPh), 79.56, 78.79, 78.44, 74.35,
73.44, 72.70, 68.15, 66.44 (8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%),
68.38, 62.12 (2 t, C-6, 6%), 33.81 (d, CH-TDS), 28.17,
26.22 (2 q, CH3iPr), 26.71 (q, CH3tBu), 24.79, 19.14 (2
s, Cq-TDS, tBu), 19.85–19.37, −2.231, −3.211 (CH3-
TDS, CH3Si). Anal. Calcd for C46H65N3O10Si2: C,
63.05; H, 7.48; N, 4.80. Found: C, 63.01; H, 7.51; N,
4.83.
(13).—Compound 8 (330 mg, 0.43 mmol) was dissolved
in dry MeOH (5 mL) under inert atmosphere, and
MeNaO (43 mL of a 1 M solution in MeOH, 0.043
mmol) was added. After 30 min, the reaction was
neutralized with IR 120 resin H+ form. The resin was
then filtered and the solvent was removed under re-
duced pressure. 249 mg (97% yield) of pure 13 were
obtained. Amorphous white solid; [h]D −17.0° (c 1.5,
1
CHCl3); H NMR (CD3OD): l 5.60 (s, 1 H, CHPh),
4.73 (d, 1 H, J1,2 7.8 Hz, H-1), 4.59 (d, 1 H, J1%,2% 7.3 Hz,
H-1%), 4.24 (dd, 1 H, J6b,5 4.9, J6b,6a 10.3 Hz, H-6b), 3.79
(t, 1 H, J6a,5=J6a,6b 10.3 Hz, H-6a), 3.55 (dd, 1 H,
J2%,3%10.3 Hz, H-2%), 3.85–3.40 (m, 9 H, H-2, 3, 4, 5, 3%,
4%, 5%, 6%a, 6%b), 1.74–1.63 (m, 1 H, CH-TDS), 0.94-0.90
(m, 12 H, CH3-TDS), 0.23, 0.20 (2 s, 6 H, CH3Si); 13C
NMR (CDCl3): l 136.9 (s), 129.4–126.1 (CHAr), 103.2,
101.5, 97.49 (3 d, C-1, 1%, CHPh), 78.86, 78.57, 74.07,
73.01, 71.18, 69.70, 68.56, 66.41 (8 d, C-2, 3, 4, 5, 2%, 3%,
4%, 5%), 68.39, 61.36 (2 t, C-6, 6%), 33.91 (d, CH-TDS),
24.74 (s, Cq-TDS), 19.98–18.33, −2.185, −3.222
(CH3-TDS, CH3Si). Anal. Calcd for C27H43N3O10Si: C,
54.25; H, 7.25; N, 7.03. Found: C, 54.30; H, 7.22; N,
6.98.
Thexyldimethylsilyl 6-O-tert-butyldiphenylsilyl-i-
galactopyranosyl-(1“3)-2-azido-4,6-O-benzylidene-2-
deoxy-i- -glucopyranoside (14).—Compound 13 (519
D-
D
Texyldimethylsilyl
fucopyranosyl-(1“2)-6-O-tert-butyldiphenylsilyl-3,4-
O-isopropylidene-i- -galactopyranosyl-(1“3)-2-azido-
4,6-O-benzylidene-2-deoxy-i- -glucopyranoside (16).—
3,4-di-O-acetyl-2-O-benzyl-h-L-
mg, 0.87 mmol) was dissolved in dry DMF (10 mL)
under inert atmosphere, and imidazole (118 mg, 1.74
mmol) and tBuDPSCl (266 mL, 1.04 mmol) were
added. After 3 h, DMF was removed under reduced
pressure, the crude was dissolved in EtAcO and washed
with a saturated solution of NH4Cl then with water.
The organic layer was dried over anhyd NaSO4, filtered
and the solvent was removed under reduced pressure.
Chromatographic purification (1:1 petroleum ether–
EtAcO) afforded 509 mg (70% yield) of pure 14. White
D
D
Compound 15 (56 mg, 0.064 mmol) was dissolved in
dry CH2Cl2 (1 mL). The temperature was lowered to
0 °C and TMSOTf (7 mL of a 0.1 M solution, 0.01
equiv) was added. Then, donor 11 (63 mg, 0.131 mmol)
dissolved in dry CH2Cl2 (1.5 mL) was slowly added.
After 1 h, the reaction was neutralized with Et3N and
the solvent was removed under reduced pressure. Chro-
matographic purification (4:1 petroleum ether–EtAcO)
afforded 50 mg (66% yield) of pure 16. Glassy solid;
[h]D −46.1° (c 2.3, CHCl3); 1H NMR (CDCl3): l
7.75–7.18 (m, 20 H, H-Ar), 5.54 (d, 1 H, J1%%,2%% 3.7 Hz,
H-1%%), 5.40 (dd, 1 H, J3%%,4%% 3.3, J3%%,2%% 10.5 Hz, H-3%%),
5.38 (s, 1 H, CHPh), 5.26 (d, 1 H, H-4%%), 4.73 (d, 1 H,
1
solid; [h]D −3.1° (c 1, CHCl3); H NMR (CDCl3): l
7.78–7.12 (m, 15 H, H-Ar), 5.42 (s, 1 H, CHPh), 4.60
(d, 1 H, J1%,2% 7.6 Hz, H-1%), 4.40 (d, 1 H, J1,2 7.6 Hz,
H-1), 4.26 (dd, 1 H, J6b,5% 4.9, J6b,6a 10.5 Hz, H-6b),
4.18–3.29 (m, 11 H, H-2, 3, 4, 5, 6a, 2%, 3%, 4%, 5%, 6%a,
6%b), 3.09 (d, 1 H, J 2.1 Hz, OH), 2.67 (d, 1 H, J 5.5 Hz,

1338
B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
1
J1%,2% 7.9 Hz, H-1%), 4.71 (d, 1 H, J 12.2 Hz, CHPh), 4.65
(d, 1 H, J1,2 7.6 Hz, H-1), 4.63 (d, 1 H, J 12.2 Hz,
CHPh), 4.51 (bq, 1 H, J6%%,5%% 6.6 Hz, H-5%%), 4.11–4.27
(m, 3 H, H-4, 3%, 4%), 3.96 (t, 1 H, J6b,5=J6b,6a 8.8 Hz,
H-6b), 3.84 (dd, 1 H, H-2%%), 3.66–3.82 (m, 5 H, H-3,
6a, 2%, 6%a, 6%b), 3.63–3.61 (m, 1 H, H-5), 3.37–3.30 (m,
1 H, H-5%), 3.33 (dd, 1 H, J2,3 9.6 Hz, H-2), 2,10, 1.99
(2 s, 6 H, CH3CO), 1.60–1.73 (m, 1 H, CH-TDS), 1.49,
1.30 (2 s, 6 H, (CH3)2C), 1.09 (d, 3 H, H-6%%), 1.05 (s, 9
H, (CH3)3C), 0.92–0.88 (m, 12 H, CH3-TDS), 0.22,
0.20 (2 s, 6 H, CH3Si); 13C NMR (CDCl3): l 170.5,
169.7 (2 s, CO), 138.2, 137.0, 133.4, 133.1 (4 s, CqPh),
135.7–126.1 (m, CHAr), 109.8 (s), 101.4, 99.53, 97.51,
95.14 (4d, C-1, 1%, 1%%, CHPh), 80.01, 79.72, 77.01, 76.31,
73.54, 73.07, 72.38, 72.02, 69.78, 68.44, 66.37, 64.64, (12
d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%, 2%%, 3%%, 4%%, 5%%), 72.50, 68.56,
62.33 (3 t, C-6, 6%, CH2Ph), 33.85 (d, CH-TDS), 27.96,
26.81, 26.40 (3 q, 2 CH3iPr, CH3tBu), 24.78, 19.19 (2 s,
Cq-TDS, tBu), 20.84, 20.68, 19.92, 19.81, 18.48, 18.37,
16.11, −2.254, −3.065 (9 q, 2 CH3CO, 6 CH3-TDS,
C-6%%). Anal. Calcd for C63H85N3O16Si2: C, 63.23; H,
7.16; N, 3.51. Found: C, 63.21; H, 7.21; N, 3.46.
1.5, CHCl3); H NMR (CD3OD): l 4.59 (d, 1 H, J1,2
7.1 Hz, H-1), 4.44 (d, 1 H, J1%,2% 7.1 Hz, H-1%), 4.40 (dd,
1 H, J6%b,5% 1.4, J6%b,6%a 11.4 Hz, H-6%b), 4.31 (dd, 1 H,
J6%a,5% 8.4 Hz, H-6%a), 4.23 (dd, 1 H, J6b,5 4.2, J6b,6a 11.7
Hz, H-6b), 4.17 (dd, 1 H, J6a,5 7.2 Hz, H-6a), 3.88–3.78
(m, 2 H, H-4%, 5%), 3.58 (bt, 1 H, H-2%), 3.52 (dd, 1 H,
J3%,4% 3.6, J3%,2% 10.3 Hz, H-3%), 3.54–3.46 (m, 1 H, H-5),
3.44–3.28 (m, 3 H, H-2, 3, 4), 2.05 (s, 6 H, CH3CO),
1.75–1.60 (m, 1 H, CH-TDS), 0.95–0.86 (m, 12 H,
CH3-TDS), 0.21, 0.18 (2 s, 6 H, CH3Si); 13C NMR
(CD3OD): l 173.0, 172.8 (2 s, CO), 105.6, 98.58 (2 d,
C-1, 1%), 85.52, 75.19, 74.72, 74.43, 72.58, 70.67, 70.39,
69.63 (8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%), 65.13, 65.02 (2 t,
C-6, 6%), 35.61 (d, CH-TDS), 26.19 (s, Cq-TDS), 21.09–
19.29, −1.535, −2.692 (CH3CO, CH3-TDS, CH3Si).
Anal. Calcd for C24H43N3O12Si: C, 48.54; H, 7.30; N,
7.08. Found: C, 48.49; H, 7.31; N, 7.07.
Thexyldimethylsilyl 6-O-acetyl-3,4-O-isopropylidene-
-galactopyranosyl)-(1“3)-6-O-acetyl-2-azido-2-
-glucopyranoside (19).—Compound 18 (260
mg, 0.437 mmol) was dissolved in dry MeCN (7 mL)
and DMP (170 mL, 1.38 mmol) and a catalytic amount
of CSA was added; after 30 min, the reaction was
neutralized with Et3N and the solvent was removed
under diminished pressure. Chromatographic purifica-
tion (3:2 petroleum ether–EtAcO) afforded 213 mg
i-
deoxy-i-
D
D
Thexyldimethylsilyl i-
D
-galactopyranosyl-(1“3)-2-
azido-2-deoxy-i- -glucopyranoside (17).—Compound
D
9 (130 mg, 0.19 mmol) was dissolved in dry MeOH (3
mL) under inert atmosphere, and MeONa (20 mL of a
1 M solution in MeOH, 0.020 mmol) was added. After
30 min, the reaction was neutralized with IR 120 resin
H+ form. The resin was then filtered and the solvent
was removed under reduced pressure. Pure compound
17 (97 mg, quant.) was obtained. Amorphous white
solid; [h]D −11.5° (c 1.4, CH3OH); 1H NMR
(CD3OD): l 4.58 (d, 1 H, J1,2 7.5 Hz, H-1), 4.48 (d, 1
H, J1%,2% 7.1 Hz, H-1%), 3.88–3.24 (m, 12 H, H-2, 3, 4, 5,
6a, 6b, 2%, 3%, 4%, 5%, 6%a, 6%b), 1.77–1.59 (m, 1 H,
CH-TDS), 0.97–0.90 (m, 12 H, CH3-TDS), 0.21 (s, 6
H, CH3Si); 13C NMR (CD3OD): l 105.1, 98.41 (2 d,
C-1, 1%), 84.02, 77.68, 76.98, 74.73, 72.65, 70.34, 70.00,
69.82 (8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%), 62.60, 62.60 (2 t,
C-6, 6%), 35.28 (d, CH-TDS), 25.87 (s, Cq-TDS), 20.60–
18.96, −1.729, −3.094 (CH3-TDS, CH3Si). Anal.
Calcd for C20H39N3O10Si: C, 47.12; H, 7.72; N, 8.25.
Found: C, 47.15; H, 7.68; N, 8.30.
1
(77% yield) of pure 19. [h]D +34.3° (c 1.5, CHCl3); H
NMR (CDCl3): l 4.54 (d, 1 H, J1,2 7.2 Hz, H-1),
4.48–4.04 (m, 8 H, H-6a, 6b, 1%, 2%, 3%, 4%, 6%a, 6%b),
3.68–3.60 (m, 1 H, H-5%), 3.48–3.43 (m, 2 H, H-4, 5),
3.33 (dd, 1 H, J2,3 10.1 Hz, H-2), 3.22 (dd, 1 H, J3,4 7.5
Hz, H-3), 2.10, 2.08 (2 d, 6 H, CH3CO), 1.75–1.50 (m,
1 H, CH-TDS), 1.56, 1.38 (2 s, 6 H, (CH3)2C), 0.96–
0.88 (m, 12 H, CH3-TDS), 0.21 (s, 6 H, CH3Si); 13C
NMR (CDCl3): l 170.9, 170.3 (2 s, CO), 110.7 (s),
104.1, 96.88 (2 d, C-1, 1%), 87.18, 78.63, 73.54, 73.37,
72.95, 71.59, 69.44, 66.86 (8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%),
63.37, 63.14 (2 t, C-6, 6%), 33.87 (d, CH-TDS), 27.87,
26.12 (2 q, CH3iPr), 25.19 (s, Cq-TDS), 20.63–18.36,
−2.299, −3.332 (CH3CO, CH3-TDS, CH3Si). Anal.
Calcd for C27H47N3O12Si: C, 51.16; H, 7.48; N, 6.63.
Found: C, 51.13; H, 7.51; N, 6.68.
Thexyldimethylsilyl 3,4-di-O-acetyl-2-O-benzyl-h-
fucopyranosyl-(1“2)-6-O-acetyl-3,4-O-isopropylidene-
i - - galactopyranosyl - (1“3) - [3,4 - di - O-acetyl-2-O-
benzyl-h- -fucopyranosyl-(1“4)]-6-O-acetyl-2-azido-
2-deoxy-i- -glucopyranoside (20).—Compound 19 (73
mg, 0.115 mmol) was dissolved in dry CH2Cl2 (1 mL).
The temperature was lowered to 0 °C and TMSOTf (12
mL of a 0.1 M solution, 0.01 equiv) was added. Then
donor 11 (222 mg, 0.461 mmol) dissolved in dry
CH2Cl2 (2 mL) was slowly (1 h) added. After 1 h,
another equivalent of 11 (55 mg, 0.11 mmol) dissolved
in dry CH2Cl2 (1 mL) was added. After 20 min, the
reaction was neutralized with Et3N and the solvent was
removed under reduced pressure. Chromatographic
purification (4:1 petroleum ether–acetone) afforded 133
L-
Thexyldimethylsilyl 6-O-acetyl-i-
(1“3)-6-O-acetyl-2-azido-2-deoxy-i-
D
-galactopyranosyl-
-glucopyran-
D
D
L
oside (18).—Compound 17 was dissolved in MeCN (7
mL), vinylacetate (1 mL) was added and the supported
CAL was suspended. The suspension was stirred me-
chanically with a thermostatic shaking apparatus at
40 °C for 24 h, and the reaction was monitored by TLC
(9:1 EtAcO–MeOH). The enzyme was filtered, and the
solvent was removed under reduced pressure. Chro-
matographic purification (EtAcO) afforded 112 mg
(70% yield) of pure compound 18 and 10 mg (8%) of
the 6%-monoacetylated and 24 mg (16%) of the 6,2%,6%-
triacetylated compounds. Colorless oil; [h]D +4.7° (c
D

B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
1339
mg (91% yield) of pure 20. [h]D −52.4° (c 1.1, CHCl3);
1H NMR (CDCl3): l 7.49–7.22 (m, 10 H, H-Ar), 5.48
(d, 1 H, J1%%%,2%%% 3.6 Hz, H-1%%%), 5.36–5.31 (m, 2 H, H-3%%,
4%%), 5.28 (dd, 1 H, J3%%%,4%%% 3.4, J3%%%,2%%% 10.6 Hz, H-3%%%), 5.21
(d, 1 H, H-4%%%), 4.95 (bq, 1 H, J5%%,6%% 6.6 Hz, H-5%%), 4.92
(d, 1 H, J1%,2% 8.5 Hz, H-1%), 4.84 (d, 1 H, J1%%,2%% 3.7 Hz,
H-1%%), 4.73 (d, 1 H, J 12.1 Hz, CHPh), 4.63 (d, 1 H, J
12.1 Hz, CHPh), 4.62 (s, 2 H, CH2Ph), 4.52 (d, 1 H, J1,2
7.6 Hz, H-1), 4.48 (dd, 1 H, J6b,5 1.8, J6b,6a 12.7 Hz,
H-6b), 4.49–4.42 (m, 3 H, H-6%a, 6%b, 5%%%), 4.29 (dd, 1
H, J6a,5 4.6 Hz, H-6a), 4.24 (dd, 1 H, J3%,4% 5.7, J3%,2% 6.9
Hz, H-3%), 4.09 (dd, 1 H, J4%,5% 2.3 Hz, H-4%), 3.92 (dt, 1
H, J5%,6%a=J5%,6%b 6.4 Hz, H-5%), 3.88–3.82 (m, 2 H, H-2%%,
2%%%), 3.63 (bt, 2 H, H-3, 2%), 3.56 (t, 1 H, J4,3 4.5 Hz,
H-4), 3.50–3.42 (m, 1 H, H-5), 3.23 (dd, 1 H, J2,3 9.4
Hz, H-2), 2.12, 2,10, 2.08, 2.04, 1.99, 1.92 (6 s, 18 H,
CH3CO), 1.71–1.58 (m, 1 H, CH-TDS), 1.48, 1.32 (2 s,
6 H, (CH3)2C), 1.17–1.10 (m, 6 H, H-6%%, 6%%%), 0.92–0.87
(m, 12 H, CH3-TDS), 0.20, 0.19 (2 s, 6 H, CH3Si); 13C
NMR (CDCl3): l 170.9, 170.5, 170.3, 173.3, 169.4,
169.4 (6 s, CO), 138.4, 137.5 (2 s, CqPh), 128.4–127.6
(m, CHAr), 110.0 (s), 100.2, 98.56, 97.16, 96.81 (4 d,
C-1, 1%, 1%%, 1%%%), 79.77, 77.12, 76.76, 74.60, 73.77, 73.59,
73.40, 73.04, 72.29, 71.90, 71.12, 70.42, 69.83, 69.07,
64.80, 64.58 (16 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%, 2%%, 3%%, 4%%,
5%%, 2%%%, 3%%%, 4%%%, 5%%%), 74.29, 72.09, 62.90, 62.04 (4 t, C-6,
6%, 2 CH2Ph), 33.84 (d, CH-TDS), 28.01, 26.05 (2 q,
2CH3iPr), 24.89 (s, Cq-TDS), 20.90–15.72 (m, 6
CH3CO, 4 CH3-TDS, C-6%%, C-6%%%), −2.197, −3.234 (2
CH3Si). Anal. Calcd for C61H87N3O24Si: C, 57.48; H,
6.88; N, 3.30. Found: C, 57.51; H, 6.91; N, 3.27.
4%, 5%), 62.10, 60.94 (2 t, C-6, 6%), 33.80 (d, CH-TDS),
24.73 (s, Cq-TDS), 20.74–18.30, −2.440, −3.442 (6
CH3CO, 4 CH3-TDS, 2 CH3Si). Anal. Calcd for
C32H51N3O16Si: C, 50.44; H, 6.75; N, 5.52. Found: C,
50.39; H, 6.78; N, 5.47.
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
actopyranosyl)-(1“4)-6-O -acetyl-2-azido-3-O-benzyl-
2-deoxy-i- -glucopyranoside (28).—Compounds 25
D-gal-
D
(258 mg, 0.54 mmol) and 26 (344 mg, 0.70 mmol) were
mixed in a flask under inert atmosphere and dissolved
in dry CH2Cl2 (6 mL). Then TMSOTf (54 mL of a 0.1
M solution in CH2Cl2, 0.01 equiv) was added. After 3
h, the reaction was neutralized with Et3N and the
solvent was removed under diminished pressure. Chro-
matographic purification (7:3 petroleum ether–EtAcO)
afforded 413 mg (95% yield) of pure 28. Amorphous
white solid; [h]D −2.3° (c 0.66, CHCl3); 1H NMR
(CDCl3): l 7.40–7.21 (m, 5 H, HAr), 5.30 (d, 1 H, J3%,4%
3.0 Hz, H-4%), 5.18 (dd, 1 H, J1%,2% 7.9, J2%,3% 10.5 Hz,
H-2%), 4.95 (dd, 1 H, H-3%), 4.92 (d, 1 H, J 10.9 Hz,
CHPh), 4.82 (d, 1 H, J 10.9 Hz, CHPh), 4.62 (d, 1 H,
H-1%), 4.47 (d, 1 H, J1,2 7.6 Hz, H-1), 4.43 (dd, 1 H, J6b,5
1.8, J6b,6a 11.7 Hz, H-6b), 4.05 (dd, 1 H, J6%b,5% 6.7,
J6%b,6%a 11.0 Hz, H-6%b), 3.69 (dd, 1 H, J6%a,5% 8.0 Hz,
H-6%a), 3.84 (dd, 1 H, J6a,5 6.2 Hz, H-6a), 3.73–3.67 (m,
2 H, H-3, 5%), 3.46 (ddd, 1 H, J5,4 8.0 Hz, H-5), 3.37 (bt,
1 H, H-4), 3.29 (dd, 1 H, J2,3 9.3 Hz, H-2), 2.16. 2.11,
2.06, 1.97 (4 s, 15 H, CH3CO), 1.78–1.57 (m, 1 H,
CH-TDS), 0.94–0.88 (m, 12 H, CH3-TDS), 0.20, 0.18
(2 s, 6 H, CH3Si); 13C NMR (CDCl3): l 170.3, 170.0,
170.0, 170.0, 169.3 (5 s, CO), 138.2 (s), 128.3–127.3
(CHAr), 100.8, 96.69 (2 d, C-1, 1%), 80.83, 77.93, 72.73,
70.93, 70.70, 69.55, 68.45, 66.78 (8 d, C-2, 3, 4, 5, 2%, 3%,
4%, 5%), 74.69, 62.43, 60.65 (3 t, C-6, 6%, CH2Ph), 33.86
(d, CH-TDS), 24.73 (s, Cq-TDS), 20.52–18.27, −2.353,
−3.392 (5 CH3CO, 4 CH3-TDS, 2 CH3Si). Anal. Calcd
for C37H55N3O15Si: C, 54.86; H, 6.85; N, 5.19. Found:
C, 54.91; H, 6.88; N, 5.22.
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
actopyranosyl-(1“4)-3,6-di-O-acetyl-2-azido-2-deoxy-
i- -glucopyranoside (27).—Compounds 24 (719 mg,
D-gal-
D
1.67 mmol) and 26 (1.23 g, 2.50 mmol) were mixed in a
flask under inert atmosphere and dissolved in dry
CH2Cl2 (8 mL). Then TMSOTf (333 mL of a 0.1 M
solution in CH2Cl2, 0.02 equiv) was added. After 40
min the reaction was neutralized with Et3N and the
solvent was removed under diminished pressure. Chro-
matographic purification (3:2 petroleum ether–EtAcO)
afforded 707 mg (56% yield) of pure 27. Amorphous
white solid; [h]D +2.5° (c 1.1, CHCl3); 1H NMR
(CDCl3): l 5.33 (d, 1 H, J3%,4% 3.3 Hz, H-4%), 5.10 (dd, 1
H, J1%,2% 7.6, J2%,3% 10.3 Hz, H-2%), 4.97 (dd, 1 H, J3,4 8.6,
J3,2 10.3 Hz, H-3), 4.96 (d, 1 H, H-3%), 4.58 (d, 1 H, J1,2
7.7 Hz, H-1), 4.46 (d, 1 H, H-1%), 4.46 (dd, 1 H, J6b,5
2.0, J6b,6a 11.7 Hz, H-6b), 4.21–4.05 (m, 3 H, H-6a, 6%a,
6%b), 3.87 (bt, 1 H, J 6.6 Hz, H-5%), 3.67 (t, 1 H, J4,5 8.6
Hz, H-4), 3.62–3.51 (m, 1 H, H-5), 3.32 (dd, 1 H, H-2),
2.16, 2.09, 2.08, 2.07, 2.04, 1.98 (6 s, 18 H, CH3CO),
1.78–1.57 (m, 1 H, CH-TDS), 0.94–0.88 (m, 12 H,
CH3-TDS), 0.20, 0.18 (2 s, 6 H, CH3Si); 13C NMR
(CDCl3): l 170.2, 170.2, 170.2, 170.0, 169.4, 168.8 (6 s,
CO), 100.8, 96.67 (2d, C-1, 1%), 76.45, 71.79, 70.87,
70.66, 70.37, 69.08, 66.66, 66.43 (8 d, C-2, 3, 4, 5, 2%, 3%,
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
D-gal-
actopyranosyl-(1“4)-6-O-acetyl-2-azido-2-deoxy-i-
D
-
glucopyranoside (29).—Compound 28 (400 mg, 0.493
mmol) was dissolved in dry CH2Cl2 (20 mL) under inert
atmosphere. Then SnCl4 (0.115 mL, 0.986 mmol) was
added. After 24 h, another 2 equiv (0.115 mL) of SnCl4
were added and the reaction was left stirring for 12 h.
Then, the reaction mixture was poured in an ice cold
saturated solution of NaHCO3 and a solution of
sodium and potassium tartrate was added. The organic
layer was washed with HCl 5% and water, dried over
Na2SO4, filtered, and the solvent was removed under
reduced pressure. Chromatographic purification (7:3
petroleum ether–EtAcO) afforded 170 mg (48% yield)
of pure 29. Amorphous white solid; [h]D +18.2° (c
1
0.60, CHCl3); H NMR (CDCl3): l 5.37 (d, 1 H, J3%,4%
3.2 Hz, H-4%), 5.21 (dd, 1 H, J1%,2% 8.1, J2%,3% 10.4 Hz,
H-2%), 4.99 (dd, 1 H, H-3%), 4.53 (d, 1 H, H-1%), 4.45 (d,

1340
B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
Thexyldimethylsilyl i-
D
-galactopyranosyl-(1“4)-2-
1 H, J1,2 7.8 Hz, H-1), 4.26 (dd, 1 H, J6b,5 1.5, J6b,6a 11.7
Hz, H-6b), 4.22–4.10 (m, 3 H, H-5%, 6%a, 6%b), 3.98 (dd,
1 H, J6a,5 6.5 Hz, H-6a), 3.54 (dd, 1 H, J3,4 8.1, J3,2 9.6
Hz, H-3), 3.50–3.46 (m, 1 H, H-5), 3.40 (t, 1 H, J4,5 8.1
Hz, H-4), 3.22 (dd, 1 H, H-2), 2.18, 2.11, 2.09, 2.00 (4
s, 15 H, CH3CO), 1.72–1.57 (m, 1 H, CH-TDS), 0.92–
0.88 (m, 12 H, CH3-TDS), 0.19, 0.16 (2 s, 6 H, CH3Si);
13C NMR (CDCl3): l 170.4, 170.4, 169.8, 169.8, 169.4
(CO), 102.0, 96.35 (2 d, C-1, 1%), 82.82, 73.70, 71.68,
71.48, 70.75, 68.71, 67.68, 66.83 (8 d, C-2, 3, 4, 5, 2%, 3%,
4%, 5%), 62.68, 61.79 (2 t, C-6, 6%), 33.91 (d, CH-TDS),
24.83 (s, Cq-TDS), 20.98–11.37, −2.341, −3.374 (5
CH3CO, 4 CH3-TDS, 2 CH3Si). Anal. Calcd for
C30H49N3O15Si: C, 50.05; H, 6.86; N, 5.84. Found: C,
50.00; H, 6.88; N, 5.79.
azido-2-deoxy-i- -glucopyranoside (31).—Compound
D
27 (500 mg, 0.656 mmol) was dissolved under inert
atmosphere in dry MeOH (10 mL). Then NaOMe (65
mL of a 1 M solution in MeOH, 0.1 equiv) was added.
After 15 min, the reaction was neutralized with IR 120
resin (H+ form), filtered, and the solvent was removed
under reduced pressure. Compound 31 was recovered
in quantitative yield (334 mg). Amorphous glassy solid;
[h]D −10.7° (c 2.6, MeOH); 1H NMR (CD3OD): l
4.56 (d, 1 H, J1,2 7.8 Hz, H-1), 4.38 (d, 1 H, J1%,2% 7.4 Hz,
H-1%), 3.85–3.30 (m, 11 H, H-3, 4, 5, 6a, 6b, 2%, 3%, 4%, 5%,
6%a, 6%b), 3.10 (dd, 1 H, J2,3 9.7 Hz, H-2), 1.71–1.67 (m,
1 H, CH-TDS), 0.94–0.91 (m, 12 H, CH3-TDS), 0.22,
0.21 (2 s, 6 H, CH3Si); 13C NMR (CD3OD): l 107.2,
99.88 (2 d, C-1, 1%), 82.79, (8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%),
62.10, 60.94 (2 t, C-6, 6%), 33.80 (d, CH-TDS), 24.73 (s,
Cq-TDS), 20.74–18.30, −2.440, −3.442 (6 CH3CO, 6
CH3-TDS). Anal. Calcd for C20H39N3O10Si: C, 47.14;
H, 7.71; N, 8.25. Found: C, 46.98; H, 7.69; N, 8.27.
Thexyldimethylsilyl 2,3,4,6-tetra-O-acetyl-i-
actopyranosyl-(1“4)-[3,4-di-O-acetyl-2-O-benzyl-h-
fucopyranosyl-(1“3)]-6-O-acetyl-2-azido-2-deoxy-i-
-glucopyranoside (30).—Compound 29 (100 mg, 0.139
D-gal-
L
-
D
mmol) was dissolved in dry CH2Cl2 (1 mL), the solu-
tion was cooled to 0 °C and TMSOTf (28 mL of a 0.1
M solution in CH2Cl2) was added. The ice bath was
then removed and donor 11 (100 mg, 0.208 mmol)
dissolved in dry CH2Cl2 (2 mL), was added in 30 min.
The reaction was neutralized with Et3N, and the solvent
was removed under reduced pressure. Chromatographic
purification (3:2 petroleum ether–EtAcO) afforded 130
mg (90% yield) of pure 30. Amorphous white solid; [h]D
Thexyldimethylsilyl
3,4-O-isopropylidene-i-
D-gal-
actopyranosyl-(1“4)-2-azido-2-deoxy-i-
D
-glucopyra-
noside (32).—Compound 31 (110 mg, 0.216 mmol) was
dissolved in dry acetone (3 mL) under inert atmo-
sphere; then Sikkon (200 mg) and a catalytic amount of
CSA were added and the reaction was heated to reflux.
After 1 h, the reaction was neutralized with Et3N and
the solvent was removed under diminished pressure.
Chromatographic purification (10:1 EtAcO–MeOH)
afforded 99 mg (84%) of pure 32 (thermodynamic
product), and 20 mg (16%) of the 4%,6%-isopropylidene
regioisomer. Amorphous solid; 1H NMR (CDCl3): l
4.56 (d, 1 H, J1,2 7.7 Hz, H-1), 4.35 (d, 1 H, J1%,2% 8.4 Hz,
H-1%), 4.16 (dd, 1 H, J4%,5% 1.5, J4%,3% 6.0 Hz, H-4%), 4.10 (t,
1 H, J3%,2% 6.0 Hz, H-3%), 4.02–3.85 (m, 5 H, H-6a, 6b, 2%,
6%a, 6%b), 3.64 (t, 1 H, J3,2 9.4 Hz, H-3), 3.61 (t, 1 H, J
8.6 Hz, H-5%), 3.49 (t, 1 H, J 9.4 Hz, H-4), 3.37 (dt, 1 H,
J 3.6 Hz, H-5), 3.22 (dd, 1 H, H-2), 1.76–1.58 (m, 1 H,
CH-TDS), 1.52, 1.55 (2 s, 6 H, (CH3)2C), 0.94–0.88 (m,
12 H, CH3-TDS), 0.21, 0.18 (2 s, 6 H, CH3Si); 13C
NMR (CDCl3): l 110.6(s), 102.9, 96.91 (2 d, C-1, 1%),
81.39, 79.28, 74.15, 73.99, 73.70, 73.15, 73.15, 67.95 (8
d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%), 62.30, 61.93 (2 t, C-6, 6%),
33.90 (d, CH-TDS), 27.96, 26.12 (2 q, CH3iPr), 24.74
(s, Cq-TDS), 19.87–18.35, −2.128, −3.276 (4 CH3-
TDS, 2CH3Si). Anal. Calcd for C23H43N3O10Si: C,
50.26; H, 7.88; N, 7.64. Found: C, 50.31; H, 7.85; N,
7.67.
1
−48.3° (c 1.0, CHCl3); H NMR (CDCl3): l 7.48–7.21
(m, 5 H, HAr), 5.58 (d, 1 H, J1%%,2%% 3.7 Hz, H-1%%), 5.40
(d, 1 H, J3%,4% 3.2 Hz, H-4%), 5.33 (d, 1 H, J3%%,4%% 3.1 Hz,
H-4%%), 5.18 (dd, 1 H, J3%%,2%% 10.5 Hz, H-3%%), 5.06 (bt, 1
H, H-2%), 4.95 (dd, 1 H, J2%,3% 10.5 Hz, H-3%), 4.90 (bq, 1
H, H-5%%), 4.77 (d, 1 H, J 12.3 Hz, CHPh), 4.62 77 (d,
1 H, CHPh), 4.61 (bd, 1 H, H-6b), 4.54 (d, 1 H, J1,2 7.5
Hz, H-1), 4.46 (dd, 1 H, J6%b,5% 6.2, J6%b,6%a 11.5 Hz,
H-6%b), 4.45 (d, 1 H, J1%,2% 7.6 Hz, H-1%), 4.30 (dd, 1 H,
J6%a,5% 7.7 Hz, H-6%a), 3.99 (dd, 1 H, J6a,5 5.8, J6b,6a 11.8
Hz, H-6a), 3.89–3.85 (m, 1 H, H-2%%), 3.82–3.79 (m, 1
H, H-5%), 3.80 (t, 1 H, J4,3=J4,5 9.7 Hz, H-4), 3.56 (t, 1
H, J3,2 9.7 Hz, H-3), 3.46–3.39 (m, 1 H, H-5), 3.40 (dd,
1 H, H-2), 2.15, 2.07, 2.06, 2.01, 2.00, 1.93 (6 s, 21 H,
CH3CO), 1.70–1.57 (m, 1 H, CH-TDS), 1.16 (d, 3 H,
J6%%,5%% 6.5 Hz, H-6%%), 0.87–0.84 (m, 12 H, CH3-TDS),
0.15, 0.14 (2 s, 6 H, CH3Si); 13C NMR (CDCl3): l
170.6, 170.5, 170.4, 170.0, 169.8, 169.7, 168.9 (7 s, CO),
138.0 (s), 128.2–127.7 (CHAr), 100.7, 97.16, 96.81 (3 d,
C-1, 1%, 1%%), 74.69, 74.23, 73.30, 72.90, 71.97, 71.17,
70.94, 70.19, 69.03, 68.86, 66.72, 64.17 (12 d, C-2, 3, 4,
5, 2%, 3%, 4%, 5%, 2%%, 3%%, 4%%, 5%%), 72.55, 61.75, 60.83 (3 t,
C-6, 6%, CH2Ph), 33.91 (d, CH-TDS), 24.78 (s, Cq-
TDS), 20.73–15.77, −2.371, −3.169 (C-6%%, 7 CH3CO,
4 CH3-TDS, 2 CH3Si). Anal. Calcd for C47H69N3O21Si:
C, 54.26; H, 6.69; N, 4.04. Found: C, 54.30; H, 6.73; N,
3.99.
Thexyldimethylsilyl 6-O-acetyl-3,4-O-isopropylidene-
i-
oxy-i-
D
-galactopyranosyl-(1“4)-6-O-acetyl-2-azido-2-de-
-glucopyranoside (33).—Compound 32 (196
D
mg, 0.356 mmol) was dissolved in dry CH2Cl2 (5 mL)
under inert atmosphere and the solution was cooled to
−78 °C. Then Py (230 mL) and AcCl (152 mL) were
added. After 6 h, MeOH (1 mL) was added to the
reaction mixture and the temperature raised to rt; then

B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
1341
a saturated solution of NaHCO3 was added, the or-
ganic layer was washed with HCl 5%, dried over
Na2SO4, filtered, and the solvent was removed under
diminished pressure. Chromatographic purification (1:1
petroleum ether–EtAcO) afforded 159 mg (71% yield)
of pure compound 33. Yellow oil; [h]D +29° (c 0.9,
CH-TDS), 1.45, 1.32 (2 s, 6 H, (CH3)2C), 1.11 (d, 3 H,
J6%%,5%% 6.6 Hz, H-6%%), 1.07 (d, 3 H, J6%%%,5%%% 6.5 Hz, H-6%%%),
0.89–0.87 (m, 12 H, CH3-TDS), 0.20, 0.19 (2 s, 6 H,
CH3Si); 13C NMR (CDCl3): l 170.6–169.6 (CO), 138.1
(CqPh), 128.3–127.7 (m, CHAr), 110.3 (s), 100.7, 97.17,
97.17, 95.77 (4 d, C-1, 1%, 1%%, 1%%%), 79.43, 76.31, 75.85,
75.38, 73.58, 73.58, 73.01, 72.90, 72.14, 71.68, 71.46,
69.95, 69.49, 69.03, 64.75, 64.12 (16 d, C-2, 3, 4, 5, 2%,
3%, 4%, 5%, 2%%, 3%%, 4%%, 5%%, 2%%%, 3%%%, 4%%%, 5%%%), 72.61, 72.14,
62.85, 62.16 (4 t, C-6, 6%, 2 CH2Ph), 33.91 (d, CH-TDS),
28.01, 26.11 (2 q, 2 CH3iPr), 24.72 (s, Cq-TDS), 20.96–
15.78 (m, 6 CH3CO, 4 CH3-TDS, C-6%%, C-6%%%), −2.253,
−3.224 (2 CH3Si). Anal. Calcd for C61H87N3O24Si: C,
57.48; H, 6.88; N, 3.30. Found: C, 57.53; H, 6.90; N,
3.32.
1
CHCl3); H NMR (CDCl3): l 4.49 (bd, 1 H, J 12.2 Hz,
H-6b), 4.45 (d, 1 H, J1,2 8.0 Hz, H-1), 4.40 (dd, 1 H,
J6%b,5% 2.5, J6%b,6%a 12.0 Hz, H-6%b), 4.27 (dd, 1 H, J6%a,5 9.3
Hz, H-6%a), 4.20 (d, 1 H, J1%,2% 8.2 Hz, H-1%), 4.14 (dd, 1
H, J6a,5 6.1 Hz, H-6a), 4.12–4.07 (m, 2 H, H-3%, 4%), 3.57
(bt, 1 H, H-5%), 3.51 (t, 1 H, J 9.6 Hz, H-3), 3.48–3.43
(m, 1 H, H-5), 3.30 (bt, 1 H, H-4), 3.19 (dd, 1 H, H-2),
2.11, 2.05 (2 s, 6 H, CH3CO), 1.70–1.57 (m, 1 H,
CH-TDS), 1.49, 1.31 (2 s, 6 H, (CH3)2C), 0.88–0.86 (m,
12 H, CH3-TDS), 0.20, 0.18 (2 s, 6 H, CH3Si); 13C
NMR (CDCl3): l 171.0, 170.9 (2 s, CO), 110.7 (s),
103.5, 96.33 (2 d, C-1, 1%), 82.65, 79.08, 73.95, 73.19,
73.01, 72.55, 71.22, 67.66 (8 d, C-2, 3, 4, 5, 2%, 3%, 4%, 5%),
63.52, 63.25 (2 t, C-6, 6%), 33.96 (d, CH-TDS), 27.96,
26.17 (2 q, CH3iPr), 24.89 (s, Cq-TDS), 20.79–18.37,
−2.204, −3.296 (2 CH3CO, 4 CH3-TDS, 2 CH3Si).
Anal. Calcd for C27H47N3O12Si: C, 51.17; H, 7.47; N,
6.63. Found: C, 51.22; H, 7.44; N, 6.62.
Acknowledgements
This work was supported by the EU-NOFA project
(grant Fair CT973142), MURST (Ministero dell’Uni-
versita` e della Ricerca Scientifica e Tecnologica) and
CNR (Consiglio Nazionale delle Ricerche).
Thexyldimethylsilyl 3,4-di-O-acetyl-2-O-benzyl-h-
fucopyranosyl-(1“2)-6-O-acetyl-3,4-O-isopropylidene-
i- -galactopyranosyl- (1“4)-[3,4-di-O-acetyl-2-O-
benzyl-h- -fucopyranosyl-(1“3)]-6-O-acetyl-2-azido-
2-deoxy-i- -glucopyranoside (34).—Compound 33 (64
L-
References
D
L
1. Newburg, D. S.; Neubaur, S. H. Handbook of Milk
Composition; Academic: San Diego, CA, 1995; pp 273–
349.
2. Stahl, B.; Thurl, S.; Zeng, J.; Karas, M.; Hillenkamp, F.;
Steup, M.; Sawatzki, G. Anal. Biochem. 1994, 223, 218–
226.
3. Coppa, G. V. Abstract of Papers, Milanopediatria 2000,
Milan, Italy, May 2000.
4. Ofek, I.; Beachey, E. H. Ad6. Intern. Med. 1980, 25,
503–532.
5. Boedeker, E. C. Gastroenterology 1982, 83, 489–492.
6. Gothefors, L.; Olling, S.; Winberg, J. Acta Pediatr.
Scand. 1975, 64, 807–812.
7. Andersson, B.; Porras, O.; Hanson, L. A.; Lagergard, T.;
Svanborg-Eden, C. J. Infect. Dis. 1986, 153, 232–237.
8. Holmgren, J.; Svennerholm, A. M.; Lindblad, M. Infect.
Immun. 1983, 39, 147–154.
9. Crane, J. K.; Azar, S. S.; Stam, A.; Newburg, D. S. J.
Nutr. 1994, 124, 2358–2364.
10. La Ferla, B.; Lay, L.; Poletti, L.; Russo, G.; Panza, L. J.
Carbohydr. Chem. 2000, 19, 331–347.
11. Nicolaou, K. C.; Hummel, C. W.; Iwabuchi, Y. J. Am.
Chem. Soc. 1992, 114, 3126–3128.
12. Jacquinet, J. C.; Sinay¨, P. J. Chem. Soc., Perkin Trans. 1
1979, 314–318.
13. Be´har, V.; Danishefsky, S. J. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1468–1470 and references therein.
14. Ichikawa, Y.; Lin, Y.-C.; Dumas, D. P.; Shen, G.-J.;
Garcia-Junceda, E.; Williams, M. A.; Bayer, R.;
Ketcham, C.; Walker, L. E.; Paulson, J. C.; Wong, C.-H.
J. Am. Chem. Soc. 1992, 114, 9283–9298 and references
therein.
D
mg, 0.101 mmol) and donor 11 (146 mg, 0.30 mmol)
were mixed in a flask under inert atmosphere and
dissolved in dry CH2Cl2 (4 mL). At −20 °C TMSOTf
(20 mL of a 0.05 M solution in CH2Cl2, 0.01 equiv) was
added. After 5 min, 3 equiv (146 mg) of donor were
added slowly and after 10 min 2 more equiv. The
reaction was neutralized with Et3N and the solvent was
removed under reduced pressure. Chromatographic
purification (3:2 petroleum ether–EtAcO) afforded 70
mg (55% yield) of pure 34. Amorphous white solid; [h]D
1
−64.9° (c 0.9, CHCl3); H NMR (CDCl3): l 7.45–7.22
(m, 10 H, H-Ar), 5.58 (d, 1 H, J1%%%,2%%% 3.5 Hz, H-1%%%),
5.48 (d, 1 H, J1%%,2%% 3.6 Hz, H-1%%), 5.32 (dd, 1 H, J3%%%,4%%%
3.2, J3%%%,2%%% 10.7 Hz, H-3%%%), 5.29 (d, 1 H, J4%%,3%% 3.4 Hz,
H-4%%), 5.23 (d, 1 H, H-4%%%), 5.14 (dd, 1 H, J3%%,2%% 10.6 Hz,
H-3%%), 4.93 (bq, 1 H, J5%%%,6%%% H-5%%%), 4.81 (d, 1 H, J 12.5
Hz, CHPh), 4.67 (d, 1 H, J 10.0 Hz, CHPh), 4.63 (d, 1
H, J 10.0 Hz, CHPh), 4.60 (d, 1 H, J 12.5 Hz, CHPh),
4.62–4.57 (m, 1 H, H-6b), 4.59 (d, 1 H, J1,2 7.1 Hz,
H-1), 4.53–4.45 (m, 2 H, H-6%a, 6%b), 4.30 (d, 1 H, J1%,2%
8.2 Hz, H-1%), 4.33–4.24 (m, 2 H, H-6a, 5%%), 4.12 (bt, 1
H, H-3%), 4.09 (dd, 1 H, J4%,5% 1.6 Hz, H-4%), 3.89–3.84
(m, 1 H, H-5), 3.84 (dd, 1 H, H-2%%%), 3.82 (dd, 1 H,
H-2%%), 3.76 (t, 1 H, J4,3=J4,5 9.0 Hz, H-4), 3.58 (dd, 1
H, J2%,3% 6.9 Hz, H-2%), 3.55–3.48 (m, 1 H, H-5), 3.48 (t,
1 H, J2,3 9.0 Hz, H-3), 3.43 (dd, 1 H, H-2), 2.10, 2.07,
2.05, 1.96, 1.93 (5 s, 18 H, CH3CO), 1.71–1.58 (m, 1 H,
15. (a) Toepfer, A.; Schmidt, R. R. Tetrahedron Lett. 1992,
33, 5161–5164;

1342
B. La Ferla et al. / Carbohydrate Research 337 (2002) 1333–1342
(b) Toepfer, A.; Kinzy, W.; Schmidt, R. R. Liebigs Ann.
Chem. 1994, 449–464.
16. Windmu¨ller, R.; Schmidt, R. R. Tetrahedron Lett. 1994, 35,
7927–7930.
17. Jain, R. K.; Vig, R.; Locke, R. D.; Mohammad, A.; Matta,
K. L. Chem. Commun. 1996, 65–67.
18. Randolph, J. T.; Danishefsky, S. J. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1470–1473.
19. Nilsson, M.; Norberg, T. Carbohydr. Res. 1988, 183, 71–82.
20. Gege, C.; Vogel, J.; Bendas, G.; Rothe, U.; Schmidt, R.
R. Chem. Eur. J. 2000, 6, 111–122.
21. Hummel, G.; Schmidt, R. R. Tetrahedron Lett. 1997, 38,
1173–1176.
22. Toepfer, A.; Schmidt, R. R. J. Carbohydr. Chem. 1993, 12,
809–822.
23. Manzoni, L.; Lay, L.; Schmidt, R. R. J. Carbohydr. Chem.
1998, 17, 739–758 and references therein.
24. La Ferla, B.; Lay, L.; Russo, G.; Panza, L. Tetrahedron:
Asymmetry 2000, 11, 3647–3651.
25. Degueil-Castaing, M.; De Jeso, B.; Drouillard, S.; Maillard,
B. Tetrahedron Lett. 1987, 28, 953–954.
26. Wang, Y.-F.; Wong, C.-H. J. Org. Chem. 1988, 53,
3127–3129.
27. Cottaz, S.; Apparu, C.; Driguez, H. J. Chem. Soc., Perkin
Trans I 1991, 9, 2235–2241.
28. Toepfer, A.; Schmidt, R. R. J. Carbohydr. Chem. 1993, 12,
809–822.
29. Hori, H.; Nishida, Y.; Ohrui, H.; Meguro, H. J. Org. Chem.
1989, 54, 1346–1353.