The behaviour of deoxyhexose trihaloacetimidates in selected glycosylations

Article abstract of DOI:10.1016/j.carres.2007.02.009

Armed deoxyhexose glycosyl donors are very reactive and sometimes too uncontrollably activated in glycosylation reactions; yields can be thereby reduced, especially when unreactive glycosyl acceptors are involved. In this paper, the behaviour of a range o

Full text of DOI:10.1016/j.carres.2007.02.009

Carbohydrate Research 342 (2007) 1021–1029
The behaviour of deoxyhexose trihaloacetimidates
in selected glycosylations
Daniela Comegna, Emiliano Bedini,* Annalida Di Nola, Alfonso Iadonisi
and Michelangelo Parrilli
`
Dipartimento di Chimica Organica e Biochimica, Universita di Napoli ‘Federico II’, Complesso Universitario Monte S.Angelo,
Via Cintia 4, 80126 Napoli, Italy
Received 5 December 2006; received in revised form 8 February 2007; accepted 9 February 2007
Available online 16 February 2007
Abstract—Armed deoxyhexose glycosyl donors are very reactive and sometimes too uncontrollably activated in glycosylation
reactions; yields can be thereby reduced, especially when unreactive glycosyl acceptors are involved. In this paper, the behaviour
of a range of deoxyhexose trihaloacetimidate (trichloro- and N-phenyl trifluoro-) donors is compared in some selected glycosylations
towards biologically relevant targets. The selected N-phenyl trifluoroacetimidates often afforded best results in terms of both donor
synthesis and glycosylation yield.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Glycosylations; Deoxysugars; Glycosyl N-phenyl trifluoroacetimidates; Glycosyl trichloroacetimidates
1. Introduction
such as Lewis X,5 a Globo H moiety,6 saponins glycolip-
ids,4c,7 glycosylated antibiotics8 and fragments of several
lipopolysaccharides.9 Interestingly, in some cases the
installation of the N-phenyl trifluoroacetimidate leaving
group at the anomeric position of the glycosyl donor
was demonstrated to be preferable: for example, the
N-glycosylation of the amide group of some asparagine
building blocks was firstly performed in high yields with
glycosyl N-phenyl trifluoroacetimidates, whereas ana-
loguous trichloroacetimidate donors gave unsatisfactory
yields.10 Besides, the observation that also some O- and
C-glycosylations proceed with better yields when con-
ducted with glycosyl N-phenyl trifluoroacetimidates in
place of glycosyl trichloroacetimidates9,11 prompted us
to explore this feature in the case of deoxyhexose gly-
cosylations. These reactions are not always high-yielding
due to the lower electron-withdrawing effect caused by
the absence of one or more hydroxyls, which can some-
times increase too much the rate of leaving group release
at the anomeric position. Actually, few scattered results
were previously reported about this behaviour.9a–c
A more accurate comparative study of deoxyhexose
glycosylations with trichloro- and N-phenyl trifluoro-
acetimidates is now presented. The examples are
Deoxyhexoses are commonly found as constituents of
O-antigenic lipopolysaccharides1 (they are the major
constituents of O-chains from phytopathogenic bacte-
ria),2 as well as components of various glycoproteins,
glycolipids and other glycoconjugates as cardioglyco-
sides, natural antibiotics and anticancer agents.3 Since
the biological role of the deoxyhexose moiety in oligo-
saccharides seems important, the synthesis of deoxy-
hexose-containing oligosaccharides is a major target in
carbohydrate chemistry.
The key reactions in oligosaccharide synthesis consist
in glycosylations, which involve the coupling between a
glycosyl acceptor and a glycosyl donor. Thioglycosides
and trichloroacetimidates are frequently used as glycosyl
donors in oligosaccharide synthesis. Recently, structural
analogues of glycosyl trichloroacetimidates, namely gly-
cosyl N-phenyl trifluoroacetimidates,4 were successfully
used as novel glycosyl donors and exploited in the syn-
thesis of biologically relevant oligosaccharide sequences
*
Corresponding author. Tel.: +39 081 674153; fax: +39 081 674393;
e-mail: ebedini@unina.it
0008-6215/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.02.009

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D. Comegna et al. / Carbohydrate Research 342 (2007) 1021–1029
restricted to the synthesis of building blocks of interest
for the synthesis of biologically relevant probes.
L-Fucose was the deoxyhexose on which we focused
major attention, since it is the most relevant natural
deoxyhexose and L-fucose containing oligosaccharides
have potential application in many biomedical fields.12
Other deoxyhexoses treated in this study were D-bacil-
losamine (2,4-diacetamido-2,4,6-trideoxy-D-glucose), 3-
fucosamine (3-acetamido-3,6-dideoxy-D-galactose) and
D-tyvelose (D-arabino-hexose), which are peculiar
constituents of bacterial O-antigens.13
deactivated support such as Brockman grade 2 alumina
immediately after the work-up of the reaction. The
anomeric configuration of the N-phenyl trifluoroacetim-
idate group was strictly dependent on the nature of the
reacting hemiacetal, whereas the trichloroacetimidate
function was always a-configurated.19
Glycosylation experiments were conducted, unless
otherwise stated, by adding the promoter to a CH2Cl2
solution of donor and acceptor at ꢀ70 °C. The solution
was then allowed to warm up spontaneously (see Section
3 for details). Preliminary screenings evidenced that less
reactive N-phenyl trifluoroacetimidate donors are best
activated with TMSOTf, whereas the milder BF3ÆOEt2
worked better with armed trichloroacetimidate counter-
parts. The results are summarized in Table 2: in the case
of fucosylations, N-phenyl trifluoroacetimidate donor 2
provided better or at least comparable yields with
respect to trichloro-analogue 1.17 The difference in yield
was particularly marked with an unreactive glycosyl
acceptor such as glucosamine derivative 9 (entries 1
and 2), whose hydroxyl function at C-4, well known to
be scarcely nucleophilic,20 was even more unreactive in
this case due to the presence of an adjacent electron-
withdrawing Cbz group. The low reactivity of 9 did
not match with the rapid activation of the fucosyl
trichloroacetimidate donor; disaccharide 10 was thus
obtained in low yield, together with perbenzylated
fucose hemiacetal 11, trichloroacetamide 12 and perbenz-
ylated L-Fuc-(1!1)-L-Fuc disaccharide 13. These
byproducts resulted from the trapping of the fucosyl
oxocarbenium ion with nucleophilic species, more reac-
tive than 9, which were in situ generated by the activa-
tion of the trichloroacetimidate donor (Scheme 1).
Some yield improvements could be usually achieved
with fucosyl trichloroacetimidate donors by applying
the ‘inverse procedure’,21 since the oxocarbenium ion
is generated slowly in the presence of an excess of accep-
tor, which traps the intermediate before it can react with
other species. We tested such protocol to ascertain if an
improvement in yield was possible in glycosylations with
donor 1 (entries 3–5). The best result was obtained by
using TMSOTf as activating agent in Et2O (entry 5),
even though no significant yield improvement was
observed, whereas a-stereoselectivity was strongly
enhanced in Et2O as well as in CH2Cl2.
2. Results and discussion
The hemiacetal building blocks used as starting material
for the synthesis of the trihaloacetimidates were func-
tionalized with arming protecting groups. The choice
of screening almost exclusively armed donors was
dictated by the fact that biologically relevant oligosaccha-
rides contain mainly a-linked deoxyhexoses: therefore,
in the case of galacto- or gluco-configurated deoxyhex-
oses such as fucose, 3-fucosamine and bacillosamine, a
non-participating protecting group at position C-2 was
necessary. On the other hand, armed glycosyl donors
are faster activated in glycosylation reactions; this fea-
ture, which is due to the decrease of the electron-with-
drawing effect caused by the presence of one or more
deoxy functions, often renders the glycosyl donor too
uncontrollably reactive. This could be detrimental for
glycosylation yields, especially when quite unreactive
glycosyl acceptors are involved. Partially acylated 2-O-
benzylated donors are routinely adopted to face this
problem,14 but their preparation entails longer synthetic
sequences as compared with the synthesis of fully benzyl-
ated donors.15
Glycosyl N-phenyl trifluoroacetimidates were readily
synthesized from the corresponding hemiacetals with
CF3C(NPh)Cl and a stoichiometric amount of NaH in
CH2Cl2,4b whereas trichloroacetimidate donors were ob-
tained by applying the Schmidt protocol16 with Cl3CCN
and catalytic DBU in CH2Cl2. Interestingly, in every
case N-phenyl trifluoroacetimidate donors were ob-
tained in higher or at least the same yield as compared
with the trichloro-counterparts (Table 1). No tests with
other bases were conducted to increase trichloroacetim-
idate yields, since such bases (NaH, K2CO3) were
already employed in the synthesis of compound 1 with
worse results.ꢀ Actually, one of the most relevant causes
of this difference in yields was the higher lability of
glycosyl trichloroacetimidates to the chromatographical
process, even when it was conducted on a partially
Minor differences in efficiency between trichloro- and
N-phenyl trifluoroacetimidate donors were observed
with more nucleophilic acceptors, such as 14 and 16
(entries 6–9). Interestingly, the attempted coupling
between 2 and 16 by TMSOTf activation surprisingly
afforded no disaccharide 17; actually, acceptor 16 gave
acyl migration from the anomeric position to O-2.ꢁ
However, this problem was recently circumvented by
ꢀ Compound 1 was obtained in 65% yield using DBU as base,17
whereas a 50% yield was reported with NaH17 as well as K2CO3.19
ꢁ This rearrangement occurred extensively also by treating 18 alone
with TMSOTf (0.02 equiv) at ꢀ78 °C.

D. Comegna et al. / Carbohydrate Research 342 (2007) 1021–1029
Table 1. Synthesis of trihaloacetimidate deoxyhexose donors from hemiacetals
1023
Entry
Deoxyhexose
Donor
Trichloroacetimidate yielda
(%) (a/b ratio)c
N-Phenyl trifuluoracetimidate yieldb
(%) (a/b ratio)c
1
L-Fucose
65 (only a)
99 (only b)
2
3
4
D-Bacillosamine
75 (only a)
64 (only a)
53 (only a)
75 (1:2)d
77 (only a)
74 (3:1)
D-Tyvelose
D-Fucos-3-amine
a Reaction conditions: Cl3CCN, DBU, CH2Cl2, rt.
b Reaction conditions: CF3C(NPh)Cl, NaH, CH2Cl2, 0 °C to rt.
c Measured by 1H NMR, unless otherwise stated.
d Measured after separation of the two anomers.
using a milder promoter, such as Bi(OTf)3, which
allowed the formation of disaccharide 1722 in high yield
and stereoselectivity (75%, a/b >10).23 Little differences
in yields were obtained for glycosylations involving
bacillosamine and tyvelose trichloro- or N-phenyl tri-
fluoroacetimidate donors 3–6 (entries 10–14). The good
outcome in tyvelose glycosylations is remarkable, since
in the past the use of 3,6-dideoxyhexose thioglycosides
was preferred with respect to trichloroacetimidates,24
in spite of a more laborious preparation. The last two
entries in Table 2 report previously published results
concerning 3-fucosamine donors 7 and 8:9a in this case
only the glycosylation conducted with the N-phenyl
trifluoroacetimidate donor proceeded.
The major a-stereoselectivity observed in glycosyl-
ations with glycosyl N-phenyl trifluoroacetimidates might
be explained by taking into account that such donors re-
quire harsher conditions for their activation with respect
to their trichloroacetimidate counterparts; this would
favour a SN1-type mechanism and therefore a-stereo-
selectivity, whichever the glycosyl acceptor is. Instead,
the milder conditions (BF3ÆOEt2 in CH2Cl2 at lower
temperature), which are necessary for the activation of
armed deoxyhexose a-trichloroacetimidate donors,
would render the mechanism more dependent on the
reactivity of the glycosyl acceptor. Indeed, with an
armed acceptor such as 14, b-disaccharides were pre-
dominantly obtained in agreement with a SN2-type
mechanism via a tight ion pair.19 On the contrary, less
reactive acceptors such as 9 or 16 favour a SN1 type
mechanism, affording predominantly a-products.
Conclusively, in Table 2 some selected glycosylations
involving deoxyhexoses are reported. Good yields were
obtained with N-phenyl trifluoroacetimidate glycosyl
donors, which gave in some cases even better results
with respect to trichloroacetimidate donors. This could
be ascribed to a slower formation of the oxocarbenium
ion, which can be therefore trapped with more efficiency
even by a low reactive glycosyl acceptor. Actually, the
conditions (temperature, acidity of the activator: see
Table 2 for details) necessary for the activation of
N-phenyl trifluoroacetimidate donors were relatively
harsher than for trichloro-ones. This would favour the
formation of the thermodynamic a-configurated

Table 2. Glycosylation reactions of deoxyhexosyl trihaloacetimidate donors
Entry
Acceptor
Donora Solvent
Promoter
T (°C)
Yieldd (%)
Product
Natural target
Lewis A
(a/b ratio)e
1
1
CH2Cl2
BF3ÆOEt2
ꢀ70 to ꢀ30 °C 28 (4:3)f
2
3
9
9
2
1
CH2Cl2
CH2Cl2
TMSOTf
TMSOTf
(inverse procedure)
BF3ÆOEt2
(inverse procedure)
TMSOTf
ꢀ50 to ꢀ30 °C 71 (only a)
10a
—
Lewis A
ꢀ70 °C to rt
ꢀ70 °C to rt
ꢀ70 °C to rt
No product
17 (>10:1)f
30 (only a)
4
5
9
9
1
1
CH2Cl2
Et2O
10
Lewis A
Lewis A
10a
(inverse procedure)
6
7
1
2
CH2Cl2
CH2Cl2
BF3ÆOEt2
ꢀ70 to ꢀ50 °C 69 (2:3)
ꢀ50 to ꢀ30 °C 85 (3:2)
O-Antigen from
Pseudomonas fluorescens
IMV472
14
TMSOTf
15a
O-Antigen from
Pseudomonas fluorescens
IMV472
8
9
1
2
CH2Cl2
CH2Cl2
BF3ÆOEt2
ꢀ70 to ꢀ50 °C 68 (6:1)f
Lewis A, B
16
14
TMSOTf
ꢀ70 °C to rt
No product
—
O-Antigens from
Pseudomonas aeruginosa
O1, O3, O13, O14
10
3
CH2Cl2
BF3ÆOEt2
ꢀ70 to ꢀ50 °C 85 (1:1)f
Pseudomonas aeruginosa
NCTC 8505
Shewanella algae BrY

1118
14
4a
4b
CH2Cl2
TMSOTf
TMSOTf
0 °C
0 °C
75 (only a)
86 (only a)
18a
18a
O-Antigens from
Pseudomonas aeruginosa
O1, O3, O13, O14
Pseudomonas aeruginosa
NCTC 8505
Shewanella algae BrY
O-Antigens from
1218
14
CH2Cl2
Pseudomonas aeruginosa
O1, O3, O13, O14
Pseudomonas aeruginosa
NCTC 8505
Shewanella algae BrY
13
5b
CH2 Cl2 BF3ÆOEt2
ꢀ70 to ꢀ20 °C 89 (3:2)
O-Antigen from
Salmonella enterica sv.
enteritidis
14
19
6b
7c
8c
CH2Cl2
CH2Cl2
CH2Cl2
TMSOTf
BF3ÆOEt2
TMSOTf
ꢀ70 °C to rt
ꢀ70 °C to rt
0 °C to rt
79 (5:2)
20
O-Antigen from
Salmonella enterica sv.
enteritidis
159a
No product
65 (62:38)f
—
169a
21
O-Antigens from
Pseudomonas fluorescens
ATCC49271
Pseudomonas syringae pv.
tabaci MV 223
Pseudomonas syringae pv.
coriandricola GFPB2028
a 1.4 equiv in respect to the acceptor, unless otherwise stated.
b 1.8 equiv in respect to 19.
c 1.1 equiv in respect to 21.
d Isolated yield.
e Measured after separation of the two anomers unless otherwise stated.
f Measured by 1H NMR.

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D. Comegna et al. / Carbohydrate Research 342 (2007) 1021–1029
Scheme 1. Disaccharide product and byproducts formation in glycosylation of 1 with 9.
disaccharide, which is very often required in biological-
targeted glycosylations involving deoxyhexoses, what
might be the glycosyl acceptor. Although generalization
of these results would still require a larger panel of
examples, we feel that they could be of interest in
selected glycosylations involving deoxyhexose donors
and unreactive glycosyl acceptors.
3.2. General procedure for trichloroacetimidate formation
The hemiacetal (0.50 mmol) was dissolved in CH2Cl2
(2.0 mL) and to the 0 °C cooled soln, Cl3CCN
(2.50 mmol) and DBU (0.10 mmol) were added. The
soln was stirred at rt until the reaction finished (TLC
analysis) and then concentrated. The resulting residue
was then immediately chromatographed over neutral
alumina (Brockman grade 2) gel.
3. Experimental
3.3. General procedure for N-phenyl trifluoroacetimidate
formation
3.1. General methods
1H (300 MHz) and 13C NMR (75 MHz) spectra were re-
corded on a Varian Gemini-300 NMR equipment, in
CDCl3 (internal standard, for H: CHCl3 at d 7.26; for
The hemiacetal (0.50 mmol) was dissolved in CH2Cl2
(2.0 mL) under an argon atmosphere and then cooled
to 0 °C under stirring. CF3C(NPh)Cl (0.65 mmol) and
NaH (60% oil suspension; 0.75 mmol) were added and
stirring was continued at 0 °C and eventually at rt until
the reaction finished (TLC analysis), after that the soln
was concentrated. Neutral alumina (Brockman grade
2) column chromatography afforded the pure N-phenyl
trifluoroacetimidate donor.
1
13C: CDCl3 at d 77.0). Positive MALDIMS spectra were
recorded on an Applied Biosystem Voyager DE-PRO
MALDI-TOF mass spectrometer in the positive mode:
compounds were dissolved in MeCN at a concentration
of 0.1 mg/mL and 1 lL of this soln was mixed with 1 lL
of a 20 mg/mL soln of 2,5-dihydroxybenzoic acid in 7:3
MeCN–water. Optical rotations were measured on a
JASCO P-1010 polarimeter. Elemental analysis was per-
formed on a Carlo Erba 1108 instrument. Analytical
thin layer chromatography (TLC) was performed on
aluminium plates precoated with E. Merck Silica Gel
60 F254 as the adsorbent. The plates were developed with
5% H2SO4 ethanolic soln and then heated to 130 °C.
Column chromatography was performed on Kieselgel
60 (63–200 mesh) unless otherwise stated. Solvents used
were purchased from Fluka and not further purified
before use.
3.4. General procedure for glycosylation
A mixture of acceptor (0.050 mmol) and donor (0.055–
0.100 mmol: see Table 2 for details) was coevaporated
three times with toluene, the residue was then mixed
˚
with freshly activated AW-300 4 A molecular sieves,
cooled to ꢀ70 °C and then suspended under argon in
the solvent (1.0 mL). Upon stirring, a soln of BF3ÆOEt2
or TMSOTf in CH2Cl2 (0.02 equiv of the activator in
respect to the donor) was added and the temperature

D. Comegna et al. / Carbohydrate Research 342 (2007) 1021–1029
1027
was allowed to rise spontaneously. After completion of
the reaction (TLC analysis), the mixture was neutralized
by adding Et3N. The mixture was then filtered over
Celite and concentrated to give a residue that was
purified by chromatography.
3.4.5. 2,4-Di-O-benzyl-a-D-tyvelopyranosyl N-phenyltri-
fluoroacetimidate (6). [a]D +15.6 (c 0.8, CH2Cl2). H
1
NMR (CDCl3, 300 MHz): d 7.44–6.73 (m, 15H), 6.00
(br s, 1H), 4.70 (d, Jgem = 12.6 Hz, 1H), 4.63 (d,
Jgem = 12.6 Hz, 1H), 4.53 (d, Jgem = 11.7 Hz, 1H), 4.48
(d, Jgem = 11.7 Hz, 1H), 3.91 (br s, 1H), 3.58 (m, 2H),
2.67 (br s, 1H), 2.32 (m, 1H), 1.37 (d, J6,5 = 6.0 Hz,
3H); 13C NMR (CDCl3, 75 MHz): d 138.1, 135.8
(2Cipso), 128.5–119.3 (C–Ar), 95.9 (C-1), 75.0, 74.9, 71.8,
71.3 (C-2, C-4, C-5, CH2Ph), 29.9 (C-3), 18.6 (C-6).
MALDIMS for C28H28F3NO4 (m/z): Mr(calcd) 499.20,
Mr(found) 522.26 (M+Na)+. Anal. Calcd: C, 67.32; H,
5.65; N, 2.80. Found: C, 67.45; H, 5.75; N, 2.86.
3.4.1. 3-O-Benzyl-2,4-diazido-a-D-glucopyranosyl trichlo-
roacetimidate (3). [a]D +55.3 (c 1.4, CH2Cl2); 1H NMR
(300 MHz, CDCl3): d 8.76 (s, 1H), 7.50–7.33 (m, 5H),
6.36 (d, J = 3.4 Hz, 1H), 4.92 (s, 2H), 3.85 (m, 2H),
3.66 (dd, J = 10.0, 3.4 Hz, 1H), 3.24 (t, J = 10.0 Hz,
1H), 1.36 (d, J = 6.2 Hz, 3H). 13C NMR (75 MHz,
CDCl3): d 160.7 (C@N), 136.9 (Cipso), 128.6–128.2 (C–
Ar), 94.5 (C-1), 78.3, 75.5, 69.4, 68.0, 63.2 (C-2, C-3,
C-4, C-5, OCH2Ph), 18.4 (C-6). Anal. Calcd: C, 40.15;
H, 3.59; N, 21.85. Found: C, 40.29; H, 3.56; N, 21.68.
3.4.6. tert-Butyldiphenylsilyl (2,3,4-tri-O-benzyl-a-L-
fucopyranosyl)-(1!4)-6-O-benzyl-3-O-benzyloxycarbonyl-
2-deoxy-2-(2,2,2-trichloroethoxycarbonylamino)-b-D-gluco-
pyranoside (10a). [a]D ꢀ35.1 (c 1.0, CH2Cl2); 1H NMR
(300 MHz, CDCl3): d 7.73–7.12 (m, 35H), 5.13 (d,
J = 12.0 Hz, 1H), 5.06–5.00 (m, 3H), 4.88 (d,
J = 11.6 Hz, 1H), 4.75 (d, J = 11.6 Hz, 1H), 4.72–4.62
(m, 4H), 4.59 (d, J = 11.6 Hz, 1H), 4.56 (d,
J = 11.6 Hz, 1H), 4.51 (d, J = 12.0 Hz, 1H), 4.45 (d,
J = 8.0 Hz, 1H), 4.32 (d, J = 12.3 Hz, 1H), 4.25 (d,
J = 12.3 Hz, 1H), 3.97 (dd, J = 9.9, 3.6 Hz, 1H), 3.92–
3.83 (m, 2H), 3.72–3.65 (m, 3H), 3.43 (br d,
J = 6.4 Hz, 1H), 3.37 (br s, 1H), 3.12 (dd, J = 9.6,
2.0 Hz, 1H), 1.01 (s, 9H), 0.96 (d, J = 6.4, 3H). 13C
NMR (75 MHz, CDCl3): d 155.2, 153.8 (2C@O),
138.1–127.3 (C–Ar), 98.7, 96.1 (C-1A, C-1B), 95.4
(C(CH3)3) 79.5, 78.0, 75.9, 75.2, 74.6, 74.5, 74.2, 74.1,
73.4, 72.7, 69.8, 67.7, 67.2, 60.4, 58.5 (C-2A, C-2B, C-
3A, C-3B, C-4A, C-4B, C-5A, C-5B, C-6A, 5OCH2Ph,
OCH2CCl3), 26.7 (C(CH3)3), 16.4 (C-6B). MALDIMS
for C67H72Cl3NO13Si (m/z): Mr(calcd) 1231.38,
Mr(found) 1254.58 (M+Na)+. Anal. Calcd: C, 65.23;
H, 5.88; N, 1.14. Found: C, 65.35; H, 5.68; N, 1.16.
3.4.2. 3-O-Benzyl-2,4-diazido-a-D-glucopyranosyl N-phen-
yltrifluoroacetimidate (4a). [a]D +126.2 (c 1.4,
CH2Cl2). 1H NMR (CDCl3, 300 MHz): d 7.46–6.84
(m, 10H, H–Ar), 6.34 (br s, 1H, H-1), 4.92 (s, 2H,
CH2Ph), 3.84–3.58 (m, 3H, H-2, H-3, H-5), 3.22 (t,
1H, 1H, J4,3 = J4,5 = 9.6 Hz, H-4), 1.37 (d, 3H,
J6,5 = 6.0 Hz, H-6); 13C NMR (CDCl3, 75 MHz): d
143.1, 136.8 (2Cipso), 128.7–118.2 (C–Ar), 93.4 (C-1),
78.5 (C-3), 75.7, 69.3, 67.9, 63.1 (C-2, C-4, C-5,
OCH2Ph), 18.4 (C-6). MALDIMS for C21H20F3N7O3
(m/z): Mr(calcd) 475.16, Mr(found) 498.03 (M+Na)+.
Anal. Calcd: C, 53.05; H, 4.24; N, 20.62. Found: C,
53.00; H, 4.26; N, 20.74.
3.4.3. 3-O-Benzyl-2,4-diazido-b-D-glucopyranosyl N-phen-
yltrifluoroacetimidate (4b). [a]D +98.9 (c 1.4, CH2Cl2).
1H NMR (CDCl3, 300 MHz): d 7.45–6.87 (m, 10H),
5.49 (br m, 1H), 4.93 (d, Jgem = 10.8 Hz, 1H), 4.87
(d, Jgem = 10.8 Hz, 1H), 3.65 (t, J3,2 = J3,4 = 9.0 Hz,
1H), 3.34–3.15 (m, 3H), 1.39 (d, J6,5 = 6.2 Hz, 3H);
13C NMR (CDCl3, 75 MHz): d 143.0, 136.9 (2Cipso),
128.7–119.2 (C–Ar), 95.3 (C-1), 81.2 (C-3), 75.6,
71.8, 67.2, 65.4 (C-2, C-4, C-5, CH2Ph), 18.2 (C-6).
MALDIMS for C21H20F3N7O3 (m/z): Mr(calcd)
475.16, Mr(found) 497.94 (M+Na)+. Anal. Calcd: C,
53.05; H, 4.24; N, 20.62. Found: C, 52.89; H, 4.30; N,
20.86.
3.4.7. Methyl (2,3,4-tri-O-benzyl-a-L-fucopyranosyl)-
(1!3)-2-O-allyl-4-O-benzyl-a-L-rhamnopyranoside (15a).
[a]D ꢀ38.6 (c 0.7, CH2Cl2); 1H NMR (300 MHz,
CDCl3): d 7.39–7.10 (m, 20H), 5.91 (m, 1H), 5.29 (dd,
J = 17.0, 2.1 Hz, 1H), 5.17–5.08 (m, 2H), 5.00 (d,
J = 11.6 Hz, 1H), 4.85 (d, J = 12.2 Hz, 1H), 4.77–4.63
(m, 7H), 4.53 (d, J = 11.8 Hz, 1H), 4.14–3.97 (m, 4H),
3.72–3.63 (m, 3H), 3.52 (t, J = 9.6 Hz, 1H), 3.34 (m,
4H), 1.27 (d, J = 6.2 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H).
13C NMR (75 MHz, CDCl3): d 139.0, 138.9, 138.8,
138.6 (4Cipso), 135.1 (OCH2CH@CH2), 128.3–127.2
(C–Ar), 116.7 (OCH2CH@CH2), 99.7, 98.0 (C-1A, C-
1B), 79.9, 79.3, 78.9, 78.3, 78.0, 76.2, 74.8, 74.7, 73.0,
72.9, 71.5, 67.8, 66.9 (C-2A, C-2B, C-3A, C-3B, C-4A,
C-4B, C-5A, C-5B, 4OCH2Ph, OCH2CH@CH2), 54.7
(OCH3), 18.0, 16.8 (C-6A, C-6B). MALDIMS for
C44H52O9 (m/z): Mr(calcd) 724.36, Mr(found) 747.50
3.4.4. 2,4-Di-O-benzyl-a-D-tyvelopyranosyl trichloroacet-
imidate (5). [a]D +58.0 (c 0.9, CH2Cl2). 1H NMR
(CDCl3, 300 MHz): d 7.40–7.24 (m, 10H), 6.19 (br s,
1H), 4.74–4.41 (m, 4H), 3.92 (m, 1H), 3.78 (br s, 1H),
3.53 (dq, J = 9.8, 6.0 Hz, 1H), 2.28 (dt, J = 13.2,
3.0 Hz, 1H), 1.82 (ddd, J = 13.2, 10.2, 3.0 Hz, 1H),
1.19 (d, J = 6.0 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d 160.5 (C@N), 138.0, 137.7 (2Cipso), 94.9 (C-1), 74.6,
73.4, 71.2, 71.1, 70.8 (C-2, C-4, C-5, 2OCH2Ph), 29.6
(C-3), 17.9 (C-6). Anal. Calcd: C, 55.89; H, 5.12; N,
2.96. Found: C, 55.99; H, 5.10; N, 2.88.

1028
D. Comegna et al. / Carbohydrate Research 342 (2007) 1021–1029
(M+Na)+. Anal. Calcd: C, 72.90; H, 7.23. Found: C,
73.15; H, 7.07.
(d, J = 6.0 Hz, 3H). 13C NMR (75 MHz, CDCl3): d
139.1, 138.8, 138.5, 138.4, 138.2 (5Cipso), 129.7–127.2
(C–Ar), 99.4, 98.9 (C-1A, C-1B), 76.9, 76.6, 75.5, 75.1,
74.9, 74.3, 74.2, 73.3, 72.7, 72.6, 71.7, 71.3, 69.6 (C-2A,
C-2B, C-3A, C-4A, C-4B, C-5A, C-5B, C-6A, 5OCH2Ph),
54.7 (OCH3), 33.7 (C-3B), 18.4 (C-6B). MALDIMS for
C48H54O9 (m/z): Mr(calcd) 774.38, Mr(found) 797.45
(M+Na)+. Anal. Calcd: C, 74.39; H, 7.02. Found: C,
74.28; H, 7.10.
3.4.8. Methyl (2,3,4-tri-O-benzyl-b-L-fucopyranosyl)-
(1!3)-2-O-allyl-4-O-benzyl-a-L-rhamnopyranoside (15b)
[a]D ꢀ26.2 (c 0.7, CH2Cl2); 1H NMR (300 MHz,
CDCl3): d 7.41–7.10 (m, 20H), 5.78 (m, 1H), 5.16 (dd,
J = 17.0, 2.1 Hz, 1H), 5.09–4.99 (m, 4H), 4.86 (d,
J = 11.8 Hz, 1H), 4.76 (s, 2H), 4.66 (d, J = 2.0 Hz,
1H), 4.64 (d, J = 11.6 Hz, 1H), 4.54 (d, J = 7.6 Hz,
1H), 4.53 (d, J = 12.0 Hz, 1H), 4.27 (dd, J = 9.6,
3.2 Hz, 1H), 4.09 (m, 2H), 3.86 (dd, J = 9.4, 7.6 Hz,
1H), 3.72 (dd, J = 3.2, 2.0 Hz, 1H), 3.67–3.55 (m, 4H),
3.47 (q, J = 6.6 Hz, 1H), 3.32 (s, 3H), 1.33 (d,
J = 6.2 Hz, 3H), 1.17 (d, J = 6.6 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d 139.0, 138.8, 138.7, 138.5 (4Cipso),
135.1 (OCH2CH@CH2), 128.5–127.0 (C–Ar), 116.9
(OCH2CH@CH2), 100.8, 99.0 (C-1A, C-1B), 82.9, 79.6,
79.5, 76.8, 76.6, 75.0, 74.8, 74.7, 72.9, 72.1, 72.0, 70.4,
67.6 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B,
4OCH2Ph, OCH2CH@CH2), 54.5 (OCH3), 18.0, 16.8
(C-6A, C-6B). MALDIMS for C44H52O9 (m/z):
Mr(calcd) 724.36, Mr(found) 747.38 (M+Na)+. Anal.
Calcd: C, 72.90; H, 7.23. Found: C, 73.09; H, 7.16.
Acknowledgements
We thank Centro di Metodologie Chimico-Fisiche of
the University Federico II of Naples for the NMR spec-
tra, and MIUR, Rome (Progetti di Ricerca di Interesse
Nazionale 2004, M.P.), for the financial support.
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