Efficient synthesis of differently protected methyl (ethyl 1-thio-β-D-glucopyranosid)uronates and their evaluation as glucuronic acid donors and acceptors

Article abstract of DOI:10.1016/S0008-6215(98)00106-2

Methyl [ethyl 2-O-acetyl-3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxne-1,3-diyl)-1-thio-β-D -glucopyranosid] uronate (7), and its 2-O-benzoyl and -pivaloyl analogues, 13 and 14, have been synthesised from methyl 2,3,4-tri-O-acetyl-α-D-glucopyranosyluronate bromide, via formation and rearrangement of a 1,2-thioorthoester, in a stereospecific and high-yielding manner. Dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST)-promoted glycosylations with these derivatives as donors gave high to excellent yields (59-95%) of exclusively β-linked disaccharides in coupling with monosaccharide accepters. Removal of the tetraisopropyldisiloxyl acetal with tetrabutylammonium fluoride in tetrahydrofuran from one of the obtained disaccharides gave a 3',4'-diol, which was used as acceptor in a DMTST-promoted coupling with ethyl 2,3,4-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside as donor to give trisaccharides, albeit with low regioselectivity (3-O-linked 38%, 4-O-linked 57%).

Full text of DOI:10.1016/S0008-6215(98)00106-2

Carbohydrate Research 308 (1998) 287±296
Ecient synthesis of di€erently protected
methyl (ethyl 1-thio-ꢀ-d-
glucopyranosid)uronates and their evaluation as
glucuronic acid donors and acceptors
Christian Krog-Jensen, Stefan Oscarson*
Department of Organic Chemistry, Arrhenius Laboratory, University of Stockholm, S-106 91
Stockholm, Sweden
Received 3 November 1997; accepted 21 March 1998
Abstract
Methyl [ethyl 2-O-acetyl-3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-1-thio-ꢀ-d-gluco-
pyranosid]uronate (7), and its 2-O-benzoyl and -pivaloyl analogues, 13 and 14, have been syn-
thesised from methyl 2,3,4-tri-O-acetyl-ꢁ-d-glucopyranosyluronate bromide, via formation
and rearrangement of a 1,2-thioorthoester, in a stereospeci®c and high-yielding manner.
Dimethyl(methylthio)sulfonium tri¯uoromethanesulfonate (DMTST)-promoted glycosylations
with these derivatives as donors gave high to excellent yields (59±95%) of exclusively ꢀ-linked
disaccharides in coupling with monosaccharide acceptors. Removal of the tetraisopropyldisiloxyl
acetal with tetrabutylammonium ¯uoride in tetrahydrofuran from one of the obtained disac-
charides gave a 30,40-diol, which was used as acceptor in a DMTST-promoted coupling with ethyl
2,3,4-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-ꢀ-d-glucopyranoside as donor to give trisacchar-
ides, albeit with low regioselectivity (3-O-linked 38%, 4-O-linked 57%). # 1998 Elsevier Science
Ltd. All rights reserved
Keywords: Thioglycoside; Carbohydrates; Glycosylation; Uronic acid
1. Introduction
Streptococcus pneumoniae, Cryptococcus neoformans
and Haemophilus in¯uenzae), all containing term-
inal or internal ꢀ-linked glucuronic acid residues,
development of new and more e€ective uronic acid
donors became necessary. The known fully acy-
lated bromide and thioglycoside glucuronate
donors gave only low yields in the couplings and
the use of the fully benzylated analogues gave low
stereoselectivity. Therefore, a new thioglycoside
donor, methyl (ethyl 2-O-benzoyl-3,4-di-O-benzyl-
1-thio-ꢀ-d-glucopyranosid)uronate was constructed,
Uronic acids are abundant in Nature as residues
in many polysaccharides and glycoconjugates, e.g.,
proteoglycans and bacterial capsular poly-
saccharides [1]. In a programme directed towards
the synthesis of biologically relevant structures
from a number of capsular polysaccharides (i.e.,
* Corresponding author. Fax: 00-468-154-908.
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00106-2

288
C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
in which the use of a 2-O-acyl participating group
ensured ꢀ-selectivity, whereas the alkyl group at
O-3 and O-4 rendered activity to the donor, and
high yields of ꢀ-linked disaccharides were obtained
in couplings even with unreactive carbohydrate
monosaccharide acceptors [2]. However, since
benzylation of glucuronic acid esters is a problem
and also the stereospeci®c formation of ꢀ-thiogly-
cosides of glucuronic acid is not trivial, the synth-
esis of this donor was most ecient starting from a
glucose derivative, ethyl 3-O-benzyl-4,6-O-benzyli-
glucuronic acid, an ꢁ,ꢀ-mixture is obtained in a
poor yield. Other methods to stereospeci®cally
synthesise the ꢀ-linked thioglycoside are described
in the literature, namely, displacement by a
thioalkylate ion on an ꢁ-bromide [4] or rearrange-
ment of a preformed ꢀ-xanthate [5]. We now
describe another approach, namely, a Lewis acid
rearrangement of a preformed thioorthoester,
which stereospeci®cally and almost quantitatively
yields the ꢀ-thioglycoside. The thioorthoester 2 was
formed from the easily available glycosyl bromide
1 [6] by treatment with collidine and ethyl mercap-
tan (98% yield) [7] (Scheme 1). Treatment of 2 with
dene-1-thio-ꢀ-d-glucopyranoside, in
a
six-step
protocol, in an overall yield of 26%. Although
many intermediates are crystalline and all steps are
easily performed in large scale, we felt that
improvements in the synthesis of these types of
donors would be of value. Accordingly, we now
describe simple and high-yielding syntheses of
similar glucuronic acid donors, with silyl pro-
tecting groups at O-3 and O-4, starting from
glucuronic acid and the evaluation of these
new donors in dimethyl(methylthio)sulfonium
tri¯uoromethanesulfonate (DMTST)-promoted
couplings with unreactive carbohydrate acceptors.
a
catalytic amount of trimethylsilyl tri¯ate
(TMSOTf) yielded the ꢀ-thioglycoside 8 in 95%
yield. The orthoester intermediate also allows the
easy introduction of the protection pattern desired
for the more reactive type of donors. Compound 2
is deacetylated with methanolic sodium methoxide
to give the 3,4-diol 3 (96%), which then can be
protected with silyl ether groups. Treatment of 3
with either tert-butyldimethylsilyl (TBDMS) or
tetraisopropyldisiloxyl (TIPS) chloride and imida-
zole in N,N-dimethylformamide gave the fully
protected derivatives 4 (75%) and 5 (96%),
respectively. Rearrangements of the thioortho-
esters in 4 and 5 by treatment with TMSOTf,
once more, gave almost quantitative yields of the
ꢀ-thioglycosides 6 (95%) and 7 (99%) (Scheme 1).
Since di€erent acyl groups as 2-O-participating
groups in couplings with the 3,4-benzylated donors
markedly a€ected the yields of coupling products
2. Results and discussion
Synthesis of 1,2-trans-thioglycosides are usually
easily performed using the peracylated mono-
saccharide together with an alkyl thiol and a Lewis
acid [3]. However, if these conditions are used on
Scheme 1. (i) EtSH, collidine, CH2Cl2; (ii) MeO , MeOH; (iii) TIPS-Cl or TBDMS-Cl, imidazole, DMF; (iv) TMSOTf, EtSH,
CH2Cl2; (v) K2CO3, MeOH; (vi) BzCl or PivCl, pyridine; (vii) Ac2O, pyridine.

C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
289
[2], the acetyl groups in compounds 6 and 7 were
changed into a benzoyl or a pivaloyl group for
evaluation. After deacetylation of 6 with metha-
nolic sodium methoxide only one product was
obtained (!9, 98%) which was benzoylated to give
10 (85%) (Scheme 1). However, as was evident
Cryptococcus neoformans capsular polysaccharide
structures [10] and used in the evaluation of the
corresponding 3,4-O-benzylated donors [2], and 2-
(4-nitrophenyl)ethyl 4,6-O-benzylidene-2-deoxy-2-
phthalimido-ꢀ-d-glucopyranoside (16), of interest
as a model for proteoglycan synthesis, were chosen
as acceptors with DMTST [11] as promoter.
1
from H NMR analysis [ꢂ 5.35 (t, 1 H, H-3)], 10
was not the expected 2-O-benzoyl derivative but
instead the 3-O-benzoyl derivative, due to a com-
plete 3-O!2-O-migration of the TBDMS group
under the basic deprotection [8]. Several other
conditions were tried but all gave 9 as the major
product. Deacetylation of the TIPS-protected
derivate 7 using sodium methoxide gave a mixture
of the 2-OH compound 11 (71%) and the 4-OH
analogue (24%) in which the TIPS-acetal had
migrated to the 2,3-position (Scheme 1). The
structure of the latter compound was con®rmed by
acetylation to give derivative 12 [1H NMR, ꢂ 5.13
(dd, 1 H, H-4)]. However, if potassium carbonate
was used as base instead, the TIPS migration could
be avoided, and compound 11 was obtained in
98% yield. Benzoylation or pivaloylation of 11,
with the corresponding acid chloride in pyridine
gave compounds 13 (98%) and 14 (84%), which
together with derivative 7 were evaluated as
glycosyl donors.
With acceptor 15 all three donors (1.5 equiv), 7,
13 and 14, gave high yields of ꢀ-linked disac-
charides, 17 (69%), 18 (87%), and 19 (53%)
(Scheme 2) . These yields can be compared with the
ones obtained with the 3,4-O-benzylated donors
and the same acceptor, which were 25% (2-O-Ac),
68% (2-O-Bz) and 31% (2-O-Piv), respectively [2].
Here too, the 2-O-benzoylated donor was found to
be best, but the acetylated and the pivaloylated
donors also gave acceptable coupling yields. As
was found earlier, an increase of the benzoylated
donor from 1.5 to 2.5 equiv raised the coupling
yield even further, and a 95% yield of disaccharide
18 was obtained. However, if this approach was
tried with the acetylated and pivaloylated donors,
13 and 14, the coupling yield actually decreased or
only slightly improved (17, 45%; 19, 59%) and a
glucuronic acid dimer, which had also been iso-
lated as a byproduct in the couplings using 1.5
equiv of donor, now became a major product. 50%
of the acetylated donor and 45% of the pivaloy-
lated donor was transformed into dimers. NMR
Methyl 3-O-benzyl-4,6-O-benzylidene-ꢁ-d-man-
nopyranoside (15) [9], relevant for the synthesis of
Scheme 2.

290
C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
studies suggested the structures 20 and 21 for the
dimers formed.
ꢀ-d-glucopyranoside (32) [12] and DMTST as
promoter (Scheme 3). Diol 26, when coupled with
1.1 equiv of 32 gave an inseparable mixture of tri-
saccharides 28 and 29 (1:1, 69%). The benzoylated
diol 27 was coupled with 2.2 equiv of donor to
give 57% of the 4-O-linked trisaccharide 30
together with 38% of the 3-O-linked trisaccharide
31, of which the linkages were established through
benzoylation of 30 and identi®cation of the down-
®eld shifted H-30. Thus, high yields of trisacchar-
ides can be obtained but with low regioselectivity.
To improve the regioselectivity, various tin activa-
tion procedures [13,14] of acceptor 27 were tried,
but so far this has only resulted in low coupling
yields and the formation of the 3,4-linked tetra-
saccharide as major coupling product.
Couplings with acceptor 16, using 1.5 equiv of
the three donors, produced even higher yields of ꢀ-
linked disaccharides, 22 (75%), 23 (89%) and 24
(73%) (Scheme 2). In none of these couplings any
dimer formation was observed.
Thus, 13 seems to be a most attractive ꢀ-selective
glucuronic acid donor, with compounds 7 and 14
as interesting alternatives. Their value as donors in
more complex oligosaccharide synthesis, however,
has to be tested. Apart from their easy accessibility
and good donor properties these derivatives also
contain another advantageous feature inherent in
their protecting group pattern. The acyl and the
silyl protecting group can be chemoselectively
removed to produce partially protected derivatives,
which then can be used as acceptors in continued
oligosaccharide synthesis. To evaluate this pro-
spect, selective deprotection of 22 and 23 was
attempted. Debenzoylation of 23 with methanolic
sodium methoxide gave a mixture of products,
yet this time not a silyl migration had occurred
but opening of the phthalimido moiety. This
could be closed again by treatment with tri-
¯uoroacetic acid anhydride, and the resulting 20-O-
tri¯uoroacetylated derivative easily deacylated
with potassium carbonate to give compound 25
(73%). The use of potassium carbonate from the
onset, circumvented the problem and gave in a
slow (4 days) but clean reaction 25 in 80% yield.
Desilylation of 22 and 23 was performed with
tetrabutylammonium ¯uoride in tetrahydrofuran
to produce the 3,4-diols 26 (62%) and 27 (76%),
respectively.
3. Experimental
General methods.ÐThese were as described [15].
Methyl 3,4-di-O-acetyl-1,2-O-(1-thioethyl)ethyl-
idene-a-d-glucopyranuronate (2).ÐEthyl mercap-
tan (9.9 mL, 134 mmol) and dry sym-collidine
(24.1 mL, 182 mmol) were added to a solution of
methyl
2,3,4-tri-O-acetyl-ꢁ-d-glucopyranosylur-
onate bromide (1; 49 g, 122 mmol) [6] in distilled
MeNO2 (150 mL) containing 3 A molecular sieves
(3 g), and the mixture was stirred for 30 min under
N2. Tetrabutylammonium bromide (31.3 g,
97.1 mmol) was then added, and the mixture was
stirred in the dark under N2 for another 17 h at
elevated temperature (50 ꢀC). The reaction mixture
was cooled to 0 ꢀC and sym-collidine hydro-
bromide precipitated by addition of dry Et2O
(200 mL). Filtration through a bilayer plug of
Celite and silica gel followed by concentration gave
a residue, which was puri®ed by silica gel chroma-
tography (9:1 toluene±EtOAc+0.5% pyridine) to
Investigating these 3,4-diols as acceptors, i.e.,
in terms of the regioselectivities attainable, gly-
cosylation reactions were performed with ethyl
3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-
Scheme 3.

C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
291
give 2 (47 g, 98%); [ꢁ]d+6.1ꢀ (c 1.0, CHCl3); 13C
NMR (CDCl3): ꢂ 15.0 (MeCH2S), 20.7 (MeCO),
24.9 (MeCH2S), 27.4 (Me orthoester), 52.8 (MeO),
68.2, 68.7, and 72.7 (C-2±5), 96.9 (C-1), 117.0 (C
orthoester), 168.8, 168.9, and 169.3 (MeCO,
COOMe). Anal. Calcd for C15H22O9S: C, 47.61; H,
5.86. Found: C, 47.56; H, 5.84.
(17.8 g, 95%); [ꢁ]d 19ꢀ (c 1.0, CHCl3); NMR
(CDCl3): 13C, ꢂ
4.8, 4.7, 4.6, and 4.4
(MeSi), 14.8 (MeCH2S), 17.9 (Me3CSi), 21.1
(MeCO), 23.8 (MeCH2S), 25.6, 25.7, and 25.8
(Me3CSi), 52.2 (MeO), 72.5, 73.4, 74.4, 79.9, and
80.0 (C-1±5), 169.6 and 169.7 (MeCO, COOMe);
1H, ꢂ 4.30 (d, 1 H, J 2.8 Hz, H-1). Anal. Calcd for
C23H46O7Si2S: C, 52.84; H, 8.87. Found: C, 52.70;
H, 8.89.
Methyl 1,2-O-(1-thioethyl)ethylidene-a-d-gluco-
pyranuronate (3).ÐMethanolic
1 M NaOMe
(4.5 mL) was added to a solution of 2 (47 g,
120 mmol) in dry MeOH (200 mL). The reaction
mixture was left for 10 h, then carefully neutralized
by addition of Dowex H+ ion-exchange resin, ®l-
tered, concentrated, and puri®ed on a silica gel
column (3:1 toluene±EtOAc+1% pyridine). Crys-
tallization from EtOAc±light petroleum bp 40±
60 C gave 3 (33.9 g, 96%); mp 80±83 C; [ꢁ]d
+34ꢀ (c 1.0, CHCl3); 13C NMR (CDCl3+pyr-
idine-d6): ꢂ 15.0 (MeCH2S), 24.7 (MeCH2S), 28.1
(Me orthoester), 52.7 (MeO), 70.4, 70.7, 72.8, and
76.6 (C-2±5), 96.9 (C-1), 116.9 (C orthoester), 170.9
(COOMe). Anal. Calcd for C11H18O7S: C, 44.89;
H, 6.16. Found: C, 44.99; H, 6.11.
Methyl [ethyl 2-O-acetyl-3,4-O-(1,1,3,3-tetraiso-
propyl-1,3-disiloxane-1,3-diyl)-1-thio-b-d-glucopyrano-
sid]uronate (7).ÐTetraisopropyldisiloxyl ꢀchloride
(10 g, 31 mmol) was added to a cooled (0 C) solu-
tion of 3 (7.8 g, 26 mmol) and imidazole (8.5 g,
125 mmol) in DMF (30 mL). The mixture was
allowed to attain room temperature and stirred
overnight under N2, then diluted by toluene and
washed with NaHCO3 (aq sat, 3 times) and water,
dried (Na2SO4), ®ltered, concentrated and co-
concentrated twice with toluene. The residue was
puri®ed on a silica gel column (10:1 light petroleum
bp 60±70 ꢀC±EtOAc+1% pyridine) to yield methyl
3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-
1, 2 - O - (1 - thioethyl)ethylidene - ꢁ - d - glucopyran-
uronate (5; 13.6 g, 96%); [ꢁ]d+80ꢀ (c 1.0, CHCl3);
13C NMR (CDCl3): ꢂ 12.0, 12.2, 12.7, and 12.9
CHSi), 15.1 (MeCH2S), 17.1 and 17.2 (Me2CHSi),
24.8 (MeCH2S), 28.7 (Me orthoester), 52.2 (MeO),
72.8, 73.6, 78.8, and 79.2 (C-2±5), 98.6 (C-1), 115.2
orthoester), 169.3 (COOMe). HRMS: 559.2196
[M+Na]+. The thioorthoester 5 (13.4 g, 25 mmol)
was rearranged as described for 4 (silica gel chroma-
tography, 15:ꢀ1 toluene±EtOAc) to give 7 (13.3 g,
99%); [ꢁ]d 1 (c 1.0, CHCl3); NMR (CDCl3): 13C, ꢂ
12.2, 12.8, and 12.9 (CHSi), 14.6 (MeCH2S), 17.1
and 17.2 (Me2CHSi), 20.8 (MeCO), 23.7 (MeCH2S),
52.3 (MeO), 71.2, 74.4, 78.4, 79.5, and 83.6 (C-1±5),
168.4 and 169.2 (MeCO, COOMe); 1H, ꢂ 4.43 (d, 1
H, J 9.8 Hz, H-1). Anal. Calcd for C23H44O8Si2S:
C, 51.46; H, 8.26. Found: C, 51.57; H, 8.34.
ꢀ
ꢀ
Methyl (ethyl 2-O-acetyl-3,4-di-O-tert-butyl-
dimethylsilyl-1-thio-b-d-glucopyranosid)uronate
(6).Ðtert±Butyldimethylsilyl
chloride
(1.1 g,
15 mmol) was added to a solution of 3 (1 g,
3.4 mmol) and imidazole (1.0 g, 7.5 mmol) in DMF
(2 mL). The mixture was stirred overnight under
N2, then diluted by toluene and washed with
NaHCO3 (aq sat, 4 times) and water, dried
(Na2SO4), ®ltered, concentrated and co-concen-
trated twice with toluene. The residue was puri®ed
on a silica gel column (9:1 light petroleum bp 60±
ꢀ
70 C±EtOAc+1% pyridine) to yield methyl 3,4-
di-O-tert±butyldimethylsilyl-1,2-O-(1-thioethyl)-
ethylidene-ꢁ-d-glucopyranuronate (4; 1.33 g, 75%);
[ꢁ]d +7ꢀ (c 1.2, CHCl3±pyridine-d6); 13C NMR
(CDCl3): ꢂ 5.0, 4.7, and 4.5 (MeSi), 15.2
(MeCH2S), 17.9 (Me3CSi), 24.5 (MeCH2S), 25.6
and 25.64 (Me3CSi), 28.2 (Me orthoester), 52.1
(MeO), 70.2, 70.8, 74.1, and 75.7 (C-2±5), 96.2 (C-
1), 117.5 (C orthoester), 170.4 (COOMe). A mix-
ture of 4 (18.8 g, 36 mmol) in freshly distilled
CH2Cl2 (100 mL) containing 4A molecular sieves
(4 g) was stirred under N2 for 30 min, whereafter
ethyl mercaptan (3 mL, 36 mmol) and TMSOTf
(652 ꢃL, 3.6 mmol) were added. After 5 min, Et3N
(1.5 mL) was added and the resulting mixture
®ltered through Celite and concentrated. The
residue was puri®ed on a silica gel column (9:1
Methyl (ethyl 2,3,4-tri-O-acetyl-1-thio-b-d-gluco-
pyranosid)uronate (8).ÐThe thioorthoester
2
(0.56 g, 1.6 mmol) was rearranged as described for
4 (silica gel chromatography, 6:1 toluene±EtOAc)
to give crystalline 8 (532 mg,ꢀ95%); [ꢁ]d 29ꢀ (c
1.0, CHCl3); mp 108.5±109.5 C (from Et2O±light
petroleum); NMR (CDCl3): 13C, ꢂ 14.7 (MeCH2S),
20.5, 20.6, and 20.7 (MeCO), 24.1 (MeCH2S), 52.9
(MeO), 69.4, 69.5, 73.2, 76.4, and 83.7 (C-1±5),
167.0, 169.3, and 170.1 (MeCO, COOMe); 1H, ꢂ 4.52
(d, 1 H, J 11.0 Hz, H-1). Anal. Calcd for C15H22O9S:
C, 47.61; H, 5.86. Found: C, 47.73; H, 5.79.
ꢀ
light petroleum bp 60±70 C±EtOAc) to give 6

292
C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
Methyl (ethyl 3-O-benzoyl-2,4-di-O-tert-butyl-
gel chromatography (10:1 toluene±EtOAc) gave 11
(45 mg, 98%); [ꢁ]d 3ꢀ (c 1.0, CHCl3); 13C NMR
(CDCl3): ꢂ 12.1, 12.2, 12.8, and 12.9 (CHSi), 15.0
(MeCH2S), 17.1, 17.2, and 17.3 (Me2CHSi), 24.3
(MeCH2S), 52.2 (MeO), 72.5, 74.0, 79.5, 80.5, and
85.7 (C-1±5), 168.6 (COOMe). HRMS: Calcd for
C21H42O7Si2S [M+Na]+: 517.2088; found:
517.2081.
Methyl [ethyl 4-O-acetyl-2,3-O-(1,1,3,3-tetraiso-
propyl-1,3-disiloxane-1,3-diyl)-1-thio-b-d-glucopyr-
anosid]uronate (12).ÐAcetylation of methyl [ethyl
2,3-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-
dimethylsilyl-1-thio-b-d-glucopyranosid)uronate
(10).ÐMethanolic 1 M NaOMe (1.5 mL) was
added to a solution of 6 (18.8 g, 36 mmol) in
MeOH (200 mL). The mixture was stirred for 5 h
and then neutralized by addition of Dowex H+
ion-exchange resin, ®ltered, concentrated, and the
residue was puri®ed on a silica gel column (10:1
toluene±EtOAc) to yield methyl (ethyl 2,4-di-O-
tert-butyldimethylsilyl-1-thio-ꢀ-d-glucopyranosid)-
uronate (9; 17.1 g, 98%); [ꢁ]d 42ꢀ (c 1.0, CHCl3);
NMR (CDCl3): 13C, ꢂ 5.3, 4.1, 4.0, and 3.8
(MeSi), 14.8 (MeCH2S), 18.0 and 18.3 (Me3CSi),
24.7 (MeCH2S), 25.7 and 26.1 (Me3CSi), 52.2
(MeO), 72.5, 74.2, 79.5, 79.8, and 86.6 (C-1±5),
168.7 (COOMe); 1H, ꢂ 4.34 (d, 1 H, J 9.2 Hz, H-1);
HRMS: 503.2258 [M+Na]+. Benzoyl chloride
(2.1 mL, 26 mmol) was added to a solution of 9
(6.2 g, 12.9 mmol) in 4:1 CH2Cl2±pyridine
diyl)-1-thio-ꢀ-d-glucopyranosid]uronate
(1.2 g,
2.4 mmol) with Ac2O in pyridine gave, after con-
ventional work-up and silica gel chromatography
(10:1 toluene±EtOAc), 12 (1.25 g, 98%); [ꢁ]d 55ꢀ
(c 1.0, CHCl3); NMR (CDCl3): 13C, ꢂ 12.1, 12.2,
12.7, and 12.8 (CHSi), 14.9 (MeCH2S), 17.16, 17.2,
17.3, and 17.4 (Me2CHSi), 20.5 (MeCO), 24.7
(MeCH2S), 52.7 (MeO), 71.3, 75.5, 76.5, 78.4, and
85.9 (C-1±5), 167.8 and 169.3 (MeCO, COOMe);
1H, ꢂ 4.42 (d, 1 H, J 9.3 Hz, H-1), 5.13 (dd, 1 H, J3,4
9, J4,5 10 Hz, H-4). HRMS: Calcd for C23H44O8Si2S
[M+Na]+: 559.2193; found: 559.2195.
ꢀ
(12.5 mL) and the mixture was stirred at 40 C for
4 days, then diluted with toluene and washed with
water, NaHCO3 (aq, sat) and water, dried
(Na2SO4), ®ltered, and concentrated. The residue
was puri®ed by silica ꢀgel chromatography (6:1 light
petroleum bp 60±70 C±EtOAc) to give 10 (6.4 g,
85%); [ꢁ]d 24ꢀ (c 1.0, CHCl3); NMR (CDCl3):
13C, ꢂ 4.9, 4.4, 3.7, and 3.6 (MeSi), 14.7
(MeCH2S), 17.7 and 17.9 (Me3CSi), 23.8
(MeCH2S), 25.1, 25.4, 25.5, and 25.8 (Me3CSi), 52.4
(MeO), 70.9, 72.4, 79.3, 80.0, and 87.0 (C-1±5),
128.2±133.0 (C aromatic), 165.2 (PhCO), 168.7
Methyl [ethyl 2-O-benzoyl-3,4-O-(1,1,3,3-tetraiso-
propyl-1,3-disiloxane-1,3-diyl)-1-thio-b-d-glucopyr-
anosid]uronate (13).ÐBenzoyl chloride (86 ꢃL,
0.75 mmol) was added to a solution of 11 (37 mg,
74.7 ꢃmol) in pyridine (1.5 mL) and the mixture
was stirred for 48 h. Conventional work-up and
puri®cation on a silica gel column (10:1 toluene±
EtOAc) gave 13 (44 mg, 98%); [ꢁ]d +23ꢀ (c 1.0,
CHCl3); NMR (CDCl3): 13C, ꢂ 12.1, 12.2, 12.76,
and 12.8 (CHSi), 14.7 (MeCH2S), 17.0, 17.1, and
17.2 (Me2CHSi), 23.7 (MeCH2S), 52.3 (MeO),
71.7, 74.5, 78.6, 79.5, and 83.7 (C-1±5), 128.3±133.0
1
(COOMe); H, ꢂ 4.50 (d, 1 H, J 9.3 Hz, H-1), 5.35
(t, 1 H, J 8.8 Hz, H-3). Anal. Calcd for C28H48O7
Si2S: C, 57.50; H, 8.27. Found: C, 57.77; H, 8.22.
Methyl [ethyl 3,4-O-(1,1,3,3-tetraisopropyl-1,3-
disiloxane-1,3-diyl)-1-thio-b-d-glucopyranosid]-
uronate (11).ÐMethod A: Compound 7 (8.5 g,
15.8 mmol) was deacetylated, as described for 6,
for 48 h. Silica gel chromatography (10:1 toluene±
EtOAc) gave 11 (5.55 g, 71%) together with methyl
[ethyl 2,3-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-
1,3-diyl)-1-thio-ꢀ-d-glucopyranosid]uronate (1.9 g,
24%); [ꢁ]d 70ꢀ (c 1.0, CHCl3); NMR (CDCl3):
13C, ꢂ 12.1, 12.2, 12.76, and 12.8 (CHSi), 15.0
(MeCH2S), 17.18, 17.2, and 17.4 (Me2CHSi), 24.9
(MeCH2S), 52.6 (MeO), 71.9, 75.2, 77.8, 80.8, and
86.4 (C-1±5), 169.2 (COOMe); 1H, ꢂ 4.45 (d, 1 H, J
9.2 Hz, H-1). Method B: Potassium carbonate
(0.4 mL of a solution of 5 g K2CO3 in 100 mL
MeOH) was added to a solution of 8 (50 mg,
93 ꢃmol) in dry MeOH (3 mL), and the mixture
was stirred for 48 h. Work-up as above and silica
1
(C aromatic), 165.0 (PhCO), 168.4 (COOMe); H,
ꢂ 5.3 (t, 1 H, H-2). Anal. Calcd for C28H46O8Si2S:
C, 56.15; H, 7.74. Found: C, 56.32; H, 7.86.
Methyl [ethyl 2-O-pivaloyl-3,4-O-(1,1,3,3-tetraiso-
propyl-1,3-disiloxane-1,3-diyl)-1-thio-b-d-glucopyr-
anosid]uronate (14).ÐTrimethylacetyl chloride
(0.63 mL, 5 mmol) was added to a solution of 11
(250 mg, 0.5 mmol) in pyridine (15 mL) and the
mixture was stirred for 24 h, when 4-pyrrolidino-
pyridine (0.1 equiv) was added. After a further
24 h, conventional work-up and puri®cation on a
silica gel column (9:1 toluene±EtOAc) yielded 14
(244 mg, 84%); [ꢁ]d 13ꢀ (c 1.0, CHCl3); 13C NMR
(CDCl3): ꢂ 12.4, 12.7, and 13.1 (CHSi), 14.7
(MeCH2S), 17.1, 17.2, 17.3, 17.5, and 17.7
(Me2CHSi), 23.6 (MeCH2S), 27.3 (Me3CCO), 38.8

C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
293
(Me3CCO), 52.3 (MeO), 70.8, 74.5, 78.3, 79.4, and
83.8 (C-1±5), 168.5 (COOMe), 176.7 (Me3CCO).
Anal. Calcd for C26H50O8Si2S: C, 53.94; H, 8.71.
Found: C, 54.11; H, 8.67.
General glycosidation procedure.ÐThe donor
(1.5 equiv) and acceptor (1 equiv) were dissolved in
CH2Cl2 (5 mL) and crushed 4 A molecular sieves
(0.3 g) was added and the mixture stirred under N2
for 30 min, whereafter DMTST (4 equiv) was
added. After an additional 12 h, Et3N (1.5 mL) was
added and the mixture was ®ltered through Celite
and concentrated. The residue was puri®ed directly
by silica gel chromatography.
using the general procedure (silica gel chromato-
graphy, 9:1 toluene±EtOAc) to give 18 (46 mg,
87%). If instead 2.5 equiv of 13 was reacted with
15 (23 mg, 56 ꢃmol) the disaccharide 18 was
obtained in 95% yield (51 mg); [ꢁ]d +10ꢀ (c 1.1,
CHCl3); NMR (CDCl3): 13C, ꢂ 12.2, 12.8, and 12.9
(CHSi), 17.0, 17.1, 17.16, and 17.20 (Me2CHSi),
52.2 and 54.8 (MeO), 63.9, 68.6, 71.9, 73.4, 74.3,
74.5, 76.2, 76.3, 77.2, and 78.2 (C-2±6,20±50,
PhCH2), 99.3, 100.7, and 101.4 (C-1,10, PhCH),
125.3±138.8 (C aromatic), 164.7 (PhCO), 168.2
1
(COOMe); H, ꢂ 4.55 (d, 1 H, J 1.7 Hz, H-1), 4.75
(d, 1 H, J 8.0 Hz, H-10).
Methyl {methyl [2-O-acetyl-3,4-O-(1,1,3,3-tetra-
isopropyl-1,3-disiloxane-1,3-diyl)-b-d-glucopyrano-
syl]uronate}-(1!2)-3-O-benzyl-4,6-O-benzylidene-
Methyl {methyl [2-O-pivaloyl-3,4-O-(1,1,3,3-tetra-
isopropyl-1,3-disiloxane-1,3-diyl)-b-d-glucopyrano-
syl]uronate}-(1!2)-3-O-benzyl-4,6-O-benzylidene-
a-d-mannopyranoside (19).ÐDonor 14 (50 mg,
86 ꢃmol) and 15 (24 mg, 58 mmol) were coupled
using the general procedure (silica gel chromato-
graphy, 9:1 toluene±EtOAc) to give 19 (29 mg,
53%) together with 30 mg of the suggested
dimer {methyl [2-O-pivaloyl-3,4-O-(1,1,3,3-tetra-
isopropyl-1,3-disiloxane-1,3-diyl)-b-d-glucopyrano-
syl]uronate}-(1!2)-1-O-pivaloyl-3,4-O-(1,1,3,3-
tetraisopropyl-1,3-disiloxane-1,3-diyl)-a-d-gluco-
pyranuronate (21).
If instead 2.5 equiv of 14 (100 mg, 173 ꢃmol) was
reacted with 15 (29 mg, 69 ꢃmol), 59% of the di-
saccharide 19 (38 mg) was obtained together with
the dimer 21 (45 mg). 19: [ꢁ]d +11ꢀ (c 1.4, CHCl3);
NMR (CDCl3): 13C, ꢂ 12.3, 12.4, 12.7, and 13.1
(CHSi), 17.1, 17.2, 17.3, 17.5, and 17.7 (Me2CHSi),
27.2 and 27.3 (Me3CCO), 38.9 (Me3CCO), 52.2
and 54.8 (MeO), 64.2, 68.8, 71.4, 72.6, 74.1, 74.3,
75.4, 75.9, 77.3, and 78.0 (C-2±6,20±50, PhCH2),
99.4, 100.4, and 101.4 (C-1,10, PhCH), 126.1-138.8
(C aromatic), 168.1 (COOMe), 176.3 (Me3CCO);
1H, ꢂ 4.55 (d, 1 H, J 8.5 Hz, H-10), 4.59 (d, 1 H, J
1.3 Hz, H-1). Anal. Calcd for C45H68O14Si2: C,
60.78; H, 7.71. Found: C, 60.50; H, 7.64.
a-d-mannopyranoside (17).ÐDonor
7
(50 mg,
93 ꢃmol) and methyl 3-O-benzyl-4,6-O-benzyli-
dene-ꢁ-d-mannopyranoside (15; 26 mg, 62 ꢃmol)
[9] were coupled using the procedure described
above (silica gel chromatography 9:1 toluene±
EtOAc) to give 17 (38 mg, 69%) together with 5 mg
of the suggested dimer {methyl [2-O-acetyl-3,4-O-
(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-ꢀ-d-
glucopyranosyl]uronate}-(1!2)-1-O-acetyl-3,4-O-
(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-ꢁ-d-
glucopyranuronate (20).
If instead 2.5 equiv of 7 (50 mg, 93 ꢃmol) was reac-
ted with 15 (16 mg, 37 ꢃmol), 45% of the disaccharide
17 (15 mg) was obtained together with the dimer 20
(25 mg); 17: [ꢁ]d +6ꢀ (c 0.9, CHCl3); NMR (CDCl3):
13C, ꢂ 12.2, 12.8, and 12.9 (CHSi), 17.1 and 17.2
(Me2CHSi), 20.6 (MeCO), 52.2 and 54.9 (MeO),
64.1, 68.8, 71.8, 72.5, 74.0, 74.3, 76.0, 76.1, and 78.1
(C-2±6,20±50, PhCH2), 99.6, 100.5, and 101.5 (C-1,10,
PhCH), 126.1±138.7 (C aromatic), 168.0 and 168.8
(MeCO, COOMe); 1H, ꢂ 4.52 (d, 1 H, J 8.0 Hz, H-
10), 4.65 (s, 1 H, H-1). Anal. Calcd for C42H62O14Si2:
C, 59.55; H, 7.38. Found: C, 61.06; H, 7.80.
20: [ꢁ]d +30ꢀ (c 1.0, CHCl3); NMR (CDCl3):
13C, ꢂ 12.1, 12.4, and 12.8 (CHSi), 17.1 and 17.4
(Me2CHSi), 20.9 (MeCO), 52.3 (MeO), 72.8, 73.0,
74.2, 74.5, 75.5, 76.2, and 77.4 (C-2±5), 90.9 (C-
1ꢁ), 101.0 (C-1ꢀ), 168.0, 168.8, 169.0, and 169.2
21: [ꢁ]d +67ꢀ (c 0.3, CHCl3); NMR (CDCl3):
13C, ꢂ 12.3, 12.4, 12.5, 12.7, 12.72, 12.8, 13.0, and
13.2 (CHSi), 17.0, 17.1, 17.2, 17.3, 17.4, 17.6, and
17.7 (Me2CHSi), 27.0, 27.2, and 27.3 (Me3CCO),
38.7 and 39.0 (Me3CCO), 52.4 (MeO), 73.0, 73.2,
73.8, 74.2, 74.4, 74.5, 75.7, and 79.4 (C-2±5), 90.7
(C-1ꢁ), 100.2 (C-1ꢀ), 168.3 and 169.1 (COOMe),
176.0 (Me3CCO); 1H, ꢂ 4.58 (d, 1 H, J 6 Hz, H-1ꢀ),
6.28 (d, 1 H, J 3.5 Hz, H-1ꢁ); MS (FAB+): m/z
1051.4 [M+H]+, 1073.6 [M+Na]+.
1
(MeCO, COOMe); H, ꢂ 4.72 (d, 1 H, J 7.9 Hz,
H-1ꢀ), 6.23 (d, 1 H, J 3.8 Hz, H-1ꢁ); MS (FAB+):
m/z 989.6 [M+Na]+.
Methyl {methyl [2-O-benzoyl-3,4-O-(1,1,3,3-tetra-
isopropyl-1,3-disiloxane-1,3-diyl)-b-d-glucopyrano-
syl]uronate}±(1!2)-3-O-benzyl-4,6-O-benzylidene-
a-d-mannopyranoside (18).ÐDonor 13 (50 mg,
84 ꢃmol) and 15 (23 mg, 56 ꢃmol) were coupled
2-(4-Nitrophenyl)ethyl {methyl [2-O-acetyl-3,4-
O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-

294
C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
b-d-glucopyranosyl]uronate}-(1!3)-4,6-O-benzyl-
idene-2-deoxy-2-phthalimido-b-d-glucopyranoside
2-(4-Nitrophenyl)ethyl {methyl [3,4-O-(1,1,3,3-
tetraisopropyl-1,3-disiloxane-1,3-diyl)-b-d-glucopyr-
anosyl]uronate}-(1!3)-4,6-O-benzylidene-2-deoxy-
2-phthalimido-b-d-glucopyranoside (25).ÐMethod A:
Potassium carbonate (0.5 mL of a solution of 5 g
K2CO3 in 100 mL MeOH) was added to a solution
of 23 (40 mg, 36 ꢃmol) in MeOH (5 mL), and the
mixture was stirred for 4 days with an addition of
the same amount of base each day. The reaction
mixture was neutralized with Dowex H+ ion-
exchange resin, ®ltered, concentrated, and the resi-
due was puri®ed on a silica gel column (6:1 toluene±
EtOAc) to yield 25 (28 mg, 80%).
(22).ÐDonor
7
(259 mg, 550 ꢃmol) and 16
(213 mg, 366 ꢃmol) were coupled using the general
procedure (silica gel chromatography, 6:1 toluene±
EtOAc) to give 22 (290 mg, 75%); [ꢁ]d 24ꢀ (c 1.0,
CHCl3); NMR (CDCl3): 13C, ꢂ 11.9, 12.1, 12.6, and
12.7 (CHSi), 16.9, 17.0, and 17.1 (Me2CHSi), 20.0
(MeCO), 35.3 (PhCH2CH2O), 52.0 (MeO), 55.0,
66.6, 68.6, 69.0, 72.8, 74.2, 75.2, 75.4, and 80.9 (C-
2±6,20±50, PhCH2CH2O), 98.5, 100.2, and 101.3 (C-
1,10, PhCH), 123.0±146.6 (C aromatic), 168.4
(MeCO, COOMe); 1H, ꢂ 4.42 (d, 1 H, J 8.1 Hz, H-
10), 5.08 (d, 1 H, J 8.8 Hz, H-1). Anal. Calcd for
C50H64O17Si2N2: C, 58.81; H, 6.32. Found: C,
58.90; H, 6.20.
Method B. NaOMe (1.5 mL, 1 M in MeOH) was
added to a solution of 23 (41 mg, 35.8 ꢃmol) in
MeOH (5 mL). After 12 h the reaction mixture was
neutralized with Dowex H+ ion-exchange resin,
®ltered, and concentrated. The residue was dis-
solved in pyridine (15 mL) and tri¯uoroacetic
2-(4-Nitrophenyl)ethyl {methyl [2-O-benzoyl-
3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-
b-d-glucopyranosyl]uronate}-(1!3)-4,6-O-benzyl-
idene-2-deoxy-2-phthalimido-b-d-glucopyranoside
(23).ÐDonor 13 (50 mg, 84 ꢃmol) and acceptor 16
(32 mg, 55 ꢃmol) were coupled using the general
procedure (silica gel chromatography, 6:1 toluene±
EtOAc) to give 23 (55 mg, 89%); [ꢁ]d 8ꢀ (c 1.0,
CHCl3); NMR (CDCl3): 13C, ꢂ 11.8, 12.1, 12.4, and
12.7 (CHSi), 16.8, 16.9, 17.0, and 17.1 (Me2CHSi),
35.2 (PhCH2CH2O), 52.1 (MeO), 54.5, 66.3, 68.6,
69.0, 73.8, 74.3, 75.1, 76.0, 77.3, and 81.6 (C-2±
6,20±50, PhCH2CH2O), 98.3, 100.2, and 101.6 (C-
1,10, PhCH), 122.9±146.5 (C aromatic), 164.1
ꢀ
anhydride (5 mL) was added at 0 C. After 1 h,
MeOH (1 mL) was added and the mixture was
diluted with CH2Cl2 and washed with water, 1 M
HCl and water, dried (Na2SO4), ®ltered, and con-
centrated. The residue was dissolved in MeOH
(5 mL) and potassium carbonate was added
(0.5 mL of a solution of 5 g K2CO3 in 100 mL
MeOH). After 30 min, the reaction mixture was
neutralized with Dowex H+ ion-exchange resin,
®ltered, concentrated, and puri®ed on a silica gel
column (6:1 toluene±EtOAc) to yield 25 (27.3 mg,
73%); [ꢁ]d 34ꢀ (c 1.0, CHCl3); NMR (CDCl3):
13C, ꢂ 11.9, 12.1, 12.5, and 12.9 (CHSi), 16.8, 17.0,
17.1, and 17.2 (Me2CHSi), 35.4 (PhCH2CH2O),
51.9 (MeO), 55.5, 66.5, 68.6, 69.2, 72.2, 74.0, 75.6,
75.8, 78.6, and 80.3 (C-2±6,20±50, PhCH2CH2O),
98.8, 101.4, and 103.2 (C-1,10, PhCH), 123.0±149.8
(C aromatic), 168.4 (COOMe); 1H, ꢂ 5.16 (d, 1 H, J
8.6 Hz, H-1). Anal. Calcd for C48H62O16Si2N2: C,
58.88; H, 6.38. Found: C, 58.66; H, 6.22.
2-(4-Nitrophenyl)ethyl [methyl (2-O-acetyl-b-d-
glucopyranosyl)uronate]-(1!3)-4,6-O-benzylidene-
2-deoxy-2-phthalimido-b-d-glucopyranoside (26).Ð
Tetrabutylammonium ¯uoride (260 ꢃL from a
stock solution of 8.3 g QF-(H2O)3 in 23 mL THF)
was added to a solution of 22 (93 mg, 88 ꢃmol) in
THF (1.5 mL). After 45 min the mixture was care-
fully concentrated. The crude product was puri®ed
in two steps: (1) silica gel chromatography in acet-
onitrile; (2) the still not pure product was puri®ed
again on a silica gel column by gradient elution
(9:1!6:1!3:1!1:1 toluene±EtOAc) to give 26
(44 mg, 62%); [ꢁ]d 38ꢀ (c 1.4, CHCl3); NMR
1
(PhCO), 168.6 (COOMe); H, ꢂ 4.74 (d, 1 H, J 8.4
Hz, H-10), 4.99 (t, 1 H, H-2'), 5.03 (d, 1 H, J 8.8
Hz, H-1). Anal. Calcd for C55H66O17Si2N2: C,
61.20; H, 6.16. Found: C, 60.94; H, 6.14.
2-(4-Nitrophenyl)ethyl {methyl [2-O-pivaloyl-3,4-
O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-b-d-
glucopyranosyl]uronate}-(1!3)-4,6-O-benzylidene-
2-deoxy-2-phthalimido-b-d-glucopyranoside (24).Ð
Donor 14 (101 mg, 174 ꢃmol) and acceptor 16 (67 mg,
116 ꢃmol) were coupled using the general procedure
(silica gel chromatography, 6:1 toluene±EtOAc) to
give 24 (93 mg, 73%); [ꢁ]d 20ꢀ (c 1.5, CHCl3); NMR
(CDCl3): 13C, ꢂ 12.3, 12.4, 12.6, and 12.9 (CHSi),
16.9, 17.0, 17.1, 17.3, 17.5, and 17.6 (Me2CHSi), 26.8
(Me3CCO), 35.3 (PhCH2CH2O), 38.3 (Me3CCO),
52.1 (MeO), 55.3, 66.5, 68.7, 68.9, 73.4, 74.1, 74.4,
74.9, 77.3, and 80.8 (C-2±6,20±50, PhCH2CH2O),
98.2, 98.9, and 101.7 (C-1,10, PhCH), 123.0±146.6 (C
aromatic), 168.6 (COOMe), 175.8 (Me3CCO); 1H, ꢂ
4.62 (d, 1 H, J 8.1 Hz, H-10), 5.13 (d, 1 H, J 8.6 Hz,
H-1). Anal. Calcd for C53H70O17Si2N2: C, 59.86;
H, 6.64. Found: C, 58.87; H, 6.64.

C. Krog-Jensen, S. Oscarson/Carbohydrate Research 308 (1998) 287±296
295
(CDCl3): 13C, ꢂ 20.0 (MeCO), 35.3 (PhCH2CH2O),
52.6 (MeO), 54.9, 66.5, 68.7, 69.1, 71.7, 73.0, 73.4,
74.5, 75.5, and 81.0 (C-2±6,20±50, PhCH2CH2O),
98.4, 100.0, and 101.6 (C -1,10, PhCH), 123.0±146.5
(C aromatic), 169.4 and 169.7 (MeCO, COOMe);
1H, ꢂ 4.45 (d, 1 H, J 8.1 Hz, H-1'), 5.1 (d, 1 H, J 8.8
Hz, H-1). HRMS: Calcd for C38H38O16N
[M+Na]+: 801.2119; found: 801.2127.
169.3, 169.5, 169.8, 170.5, and 170.53 (MeCO,
COOMe); 1H, ꢂ 5.23 (d, 0.5 H, J 8.6 Hz, H-100), 5.3
(d, 0.5 H, J 8.6 Hz, H-100). Anal. Calcd for
C58H57O25N3: C, 58.24; H, 4.80. Found: C, 57.96;
H, 4.87.
2-(4-Nitrophenyl)ethyl (3,4,6-tri-O-acetyl-2-
deoxy-2-phthalimido-b-d-glucopyranosyl)-(1!4)-
[methyl (2-O-benzoyl-b-d-glucopyranosyl)uronate]-
(1!3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-b-
d-glucopyranoside (30) and 2-(4-nitrophenyl)ethyl
(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-b-d-gluco-
pyranosyl)-(1!3)-[methyl (2-O-benzoyl-b-d-gluco-
pyranosyl)uronate]-(1!3)-4,6-O-benzylidene-2-
deoxy-2-phthalimido-b-d-glucopyranoside (31).Ð
Acceptor 27 (23 mg, 26.5 ꢃmol) was coupled with
donor 32 (26.5 mg, 53 ꢃmol) as described for
acceptor 26, to give the 4-O-linked trisaccharide 30
(19 mg, 57%) and the 3-O-linked trisaccharide 31
(14 mg, 38%). 30: [ꢁ]d 14ꢀ (c 1.5, CHCl3); NMR
(CDCl3): 13C, ꢂ 20.2, 20.4, and 20.6 (MeCO), 35.3
(PhCH2CH2O), 51.7 (MeO), 54.3, 54.7, 62.2, 66.4,
68.6, 69.0, 70.0, 71.6, 72.7, 72.8, 73.1, 75.8, 77.2, 81.1,
and 82.0 (C-2±6,20±50,200-600, PhCH2CH2O), 98.4,
98.6, 99.5, and 101.1 (C-1,10,100, PhCH), 123.0±146.4
(C aromatic), 164.5 and 166.9 (PhCO), 169.5, 169.8,
and 170.5 (MeCO, COOMe); 1H, ꢂ 4.61 (d, 1 H, J 8.1
Hz, H-10), 5.02 (d, 1 H, J 8.4 Hz, H-1), 5.35 (d, 1 H, J
8.7 Hz, H-100). Anal. Calcd for C63H59O25N3: C,
60.14; H, 4.73. Found: C, 60.19; H, 5.12.
2-(4-Nitrophenyl)ethyl [methyl (2-O-benzoyl-b-d-
glucopyranosyl)uronate]-(1!3)-4,6-O-benzylidene-
2-deoxy-2-phthalimido-b-d-glucopyranoside (27).Ð
The TIPS-group was removed from disaccharide
23 (155 mg, 139 ꢃmol) as described above for 26 to
give 27 (93 mg, 76%); [ꢁ]d 39ꢀ (c 1.2, CHCl3);
NMR (CDCl3): 13C, ꢂ 35.3 (PhCH2CH2O), 52.6
(MeO), 54.6, 66.4, 68.8, 69.0, 71.8, 73.5, 73.8, 74.6,
76.1, and 81.5 (C-2±6,20±50, PhCH2CH2O), 98.3,
100.0, and 101.9 (C-1,10, PhCH), 122.9±146.5 (C
1
aromatic), 165.0 (PhCO), 169.4 (COOMe); H, ꢂ
4.7 (d, 1 H, J 8.1 Hz, H-10), 5.07 (d, 1 H, J 8.4 Hz,
H-1). Anal. Calcd for C43H40O16N2: C, 61.43; H,
4.79. Found: C, 61.60; H, 4.89.
2-(4-Nitrophenyl)ethyl (3,4,6-tri-O-acetyl-2-deoxy-
2-phthalimido-b-d-glucopyranosyl)-(1!4)-[methyl
(2-O-acetyl-b-d-glucopyranosyl)uronate]-(1!3)-
4,6-O-benzylidene-2-deoxy-2-phthalimido-b-d-gluco-
pyranoside (28) and 2-(4-nitrophenyl)ethyl (3,4,6-
tri-O-acetyl-2-deoxy-2-phthalimido-b-d-glucopyr-
anosyl)-(1!3)-[methyl (2-O-acetyl-b-d-glucopyr-
anosyl)uronate]-(1!3)-4,6-O-benzylidene-2-deoxy-
31: [ꢁ]d 10ꢀ (c 1.2, CHCl3); NMR (CDCl3):
13C, ꢂ 20.2 and 20.4 (MeCO), 35.2 (PhCH2CH2O),
52.5 (MeO), 54.4, 54.8, 62.1, 66.4, 68.7, 68.8, 70.2,
70.3, 71.7, 74.3, 75.3, 77.2, 81.0, and 84.6 (C-2±
6,20±50,200-600, PhCH2CH2O), 98.0, 98.3, 99.5, and
101.7 (C-1,10,100, PhCH), 122.9±146.5 (C aromatic),
163.5 (PhCO), 168.3, 169.3, 169.6, and 170.4
2-phthalimido-b-d-glucopyranoside
(29).ÐEthyl
3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-ꢀ-
d-glucopyranoside [12] (32; 15 mg, 30 ꢃmol) and 26
(23 mg, 28.3 ꢃmol) were dissolved in CH2Cl2
(5 mL), 4A molecular sieves (0.5 g) were added, and
the mixture was stirred under N2 for 1 h. The mix-
ꢀ
1
ture was cooled to 40 C and DMTST (29 mg,
(MeCO, COOMe); H, ꢂ 4.6 (d, 1 H, J 8.1 Hz, H-
113 ꢃmol) wasꢀadded. The reaction mixture was
stirred at 20 C for 12 h and then an additional
4 h at room temperature. Et3N (0.5 mL) was added,
and the mixture was ®ltered through Celite, con-
centrated, and puri®ed by silica gel chromato-
graphy (1:1 toluene±EtOAc) to give 28 and 29 as
an inseparable 1:1 mixture (24 mg, 68 %); NMR
(CDCl3): 13C, ꢂ 19.6, 20.2, 20.3, 20.4, and 20.6
(MeCO), 35.3 (PhCH2CH2O), 51.7 and 52.6 (OMe),
54.2, 54.9, 55.1, 61.8, 62.1, 66.5, 68.5, 68.7, 69.0,
69.02, 70.0, 70.05, 71.6, 71.7, 71.8, 72.7, 72.8, 74.3,
74.8, 75.0, 77.2, 80.4, 80.7, 82.0, and 83.6 (C-2±
6,20±50,200-600, PhCH2CH2O), 97.9, 98.3, 98.4, 98.7,
99.7, 100.1, 101.2, and 101.5 (C-1,10,100, PhCH),
123.0±149.8 (C aromatic), 166.9, 167.9, 168.1, 169.0,
10), 4.93 (d, 1 H, J 8.8 Hz, H-1), 5.35 (d, 1 H, J 8.4
Hz, H-100).
Acknowledgements
We thank Professor Per J. Garegg for his interest
in this work and the Swedish Natural Science
Research Council for ®nancial support.
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