Synthesis, NMR, and conformational studies of fucoidan fragments. III. Effect of benzoyl group at O-3 on stereoselectivity of glycosylation by 3-0- and 3,4-DI-0-benzoylated 2-0-benzylfucosyl bromides

Article abstract of DOI:10.1081/CAR-100108659

The effect of a benzoyl group at O-3 on stereoselectivity of glycosylation by 3-0-and 3,4-di-0-benzoylated 2-0-benzyl-L-fucopyranosyl bromides was studied by direct chemical experiments and computational chemistry. The influence of a benzoyl group at O-3 of the fucosyl donors was shown to have a larger effect on the efficiency of α-fucosylation than a benzoyl group at O-4. It is hypothesized that this is a result of the ability of a benzoyl group at O-3 to participate in glycosyl cation stabilization.

Full text of DOI:10.1081/CAR-100108659

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SYNTHESIS, NMR, AND CONFORMATIONAL STUDIES
OF FUCOIDAN FRAGMENTS. III. EFFECT OF BENZOYL
GROUP AT O-3 ON STEREOSELECTIVITY OF
GLYCOSYLATION BY 3-O- AND 3,4-DI-O-BENZOYLATED
2-O-BENZYLFUCOSYL BROMIDES
Alexey G. Gerbst a , Nadezhda E. Ustuzhanina a , Alexey A. Grachev b , Elena A.
Khatuntseva a , Dmitry E. Tsvetkov a , Dennis M. Whitfield c , Attila Berces c & Nikolay E.
Nifantiev a
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Leninsky
prospect 47, Moscow B-334, 119991, Russia
b Russian Academy of Sciences , Higher Chemical College , Moscow, Russian Federation
c National Research Council of Canada , 100 Sussex Drive, Ottawa, ON, K1A, OR6,
Canada
Published online: 19 Aug 2006.
To cite this article: Alexey G. Gerbst , Nadezhda E. Ustuzhanina , Alexey A. Grachev , Elena A. Khatuntseva , Dmitry
E. Tsvetkov , Dennis M. Whitfield , Attila Berces & Nikolay E. Nifantiev (2001) SYNTHESIS, NMR, AND CONFORMATIONAL
STUDIES OF FUCOIDAN FRAGMENTS. III. EFFECT OF BENZOYL GROUP AT O-3 ON STEREOSELECTIVITY OF GLYCOSYLATION BY
3-O- AND 3,4-DI-O-BENZOYLATED 2-O-BENZYLFUCOSYL BROMIDES, Journal of Carbohydrate Chemistry, 20:9, 821-831
To link to this article: http://dx.doi.org/10.1081/CAR-100108659
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J. CARBOHYDRATE CHEMISTRY, 20(9), 821–831 (2001)
SYNTHESIS, NMR, AND CONFORMATIONAL
STUDIES OF FUCOIDAN FRAGMENTS. III.1
EFFECT OF BENZOYL GROUP AT O-3 ON
STEREOSELECTIVITY OF GLYCOSYLATION
BY 3-O- AND 3,4-DI-O-BENZOYLATED 2-O-
BENZYLFUCOSYL BROMIDES
Alexey G. Gerbst,1 Nadezhda E. Ustuzhanina,1
Alexey A. Grachev,2 Elena A. Khatuntseva,1 Dmitry E. Tsvetkov,1
Dennis M. Whitfield,3 Attila Berces,3 and Nikolay E. Nifantiev1,*
1N. D. Zelinsky Institute of Organic Chemistry,
Russian Academy of Sciences, Leninsky prospect 47,
119991 Moscow B-334, Russia
2Higher Chemical College, Russian Academy of Sciences,
Moscow, Russian Federation
3National Research Council of Canada, 100 Sussex Drive,
Ottawa, ON, Canada, K1A, OR6
ABSTRACT
The effect of a benzoyl group at O-3 on stereoselectivity of glycosylation by 3-
O- and 3,4-di-O-benzoylated 2-O-benzyl-L-fucopyranosyl bromides was stud-
ied by direct chemical experiments and computational chemistry. The influ-
ence of a benzoyl group at O-3 of the fucosyl donors was shown to have a
larger effect on the efficiency of ꢀ-fucosylation than a benzoyl group at O-4. It
is hypothesized that this is a result of the ability of a benzoyl group at O-3 to
participate in glycosyl cation stabilization.
*Corresponding author. Fax: ꢁ7-095-1358784; E-mail: nen@ioc.ac.ru
821
Copyright © 2002 by Marcel Dekker, Inc.
www.dekker.com

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GERBST ET AL.
INTRODUCTION
It is known that protective groups in the glycosyl donor influence the stereo-
chemistry of glycosylation. Mechanistic studies revealing the origin of this influ-
ence were focused mainly on the “1,2-trans” directing effect of acyl substituents at
O-2 (see Ref. 2 and papers cited herein) which is widely employed in oligosaccha-
ride synthesis. However, there is some experimental evidence that acyl groups at
other positions may also influence the stereoselectivity of glycosylation. Particu-
larly such effects were observed for 4-O-acylated fucosyl bromides1,3,4 and
ethylthio galactosides5 with a non-participating group at O-2.
Recently,1 by using a series of 2,3-di-O-benzylated fucosyl bromides bearing
substituted benzoyl groups at O-4, we have shown that the stereochemical outcome
of a glycosylation reaction depends on the electronegativity of the substituents of
the benzoyl group at O-4. These data in combination with molecular mechanics
calculations suggest that the acyl group at O-4, e.g., in bromide 1, may share the
positive charge in the initial glycosyl cation I by forming a stabilized bicyclic
cationic intermediate II (Fig. 1). Such intramolecular interaction favors further nu-
cleophilic attack from the ꢀ-side as compared with the case of glycosyl cation I
whose interaction with nucleophile is not specifically stereocontrolled from ꢀ- or
ꢂ-sides.
In the course of the synthesis of fucoidan fragments6 we investigated the gly-
cosylation of allyl 3,4-di-O-isopropylidene-ꢀ-L-fucopyranoside 97 by 3-O- and
3,4-di-O-benzoylated 2-O-benzyl-L-fucopyranosyl bromides 6 and 7.6 In this pa-
per we present the results of these reactions and theoretical calculations of plausi-
ble intermediates which demonstrate a larger influence on the efficiency of ꢀ-fu-
cosylation of a benzoyl group at O-3 in a fucosyl donor than of that at O-4.
RESULTS AND DISCUSSION
To prepare fucosyl bromide 6, allyl fucoside 28 was regioselectively 3-O-p-
methoxybenzylated via a stannylidene derivative to give diol 3, which was further
2,4-di-O-benzylated (BnBr, NaH, DMF), de-O-methoxybenzylated in the presence
Figure 1. Delocalization of the positive charge in the initial glycosyl cation I via intramolecular
participation of benzoyl group at O-4.

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FUCOIDAN FRAGMENTS. III
823
of 90% aqueous trifluoroacetic acid, and finally 3-O-benzoylated to give com-
pound 4. The presence of the benzoyl group at O-3 was confirmed by the down-
field chemical shift of H-3 in the 1H NMR spectrum of 4.
The target bromide 6 was obtained by deallylation of allyl glycoside 4 in the
presence of PdCl2 in methanol followed by bromination of the formed semiacetal
5 with CBr4 in the presence of Ph3P.
Glycosylations of acetonide 9 by fucosyl bromides 6 and 7 were performed
in CH2Cl2 in the presence of Hg(CN)2 and a catalytic amount of HgBr2. The same
reaction conditions were used in our previous1 work to investigate the effect of the
substituent at O-4 on the stereoselectivity of ꢀ-fucosylation.
Glycosylation of acetonide 9 with 3-O- and 3,4-di-O-benzoylated fucosyl bro-
mides 6 and 7 gave the pairs of 1,2-cis- and 1,2-trans-linked disaccharide products
(10,12 and 11,13) in the ratio of 13:1 and ꢃ20:1, respectively (Table 1, Entries 1,2).
It is worth noting that both these reactions were much more stereoselective as com-
pared with the results of fucosylation with both 2,3,4-tri-O-benzylated fucosyl bro-
mide 8 (Table 1, Entry 4) and 4-O-benzoylated 2,3-di-O-benzylfucosyl bromide 1
(Table 1, Entry 3). These results provide evidence that a benzoyl group at O-3 has
a more pronounced ꢀ-stereocontrolling effect than that of a benzoyl group at O-4.
To investigate possible intramolecular interactions which may favor ꢀ-stere-
oselectivity of glycosylation by fucosyl bromides 6 and 7 we performed molecular

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GERBST ET AL.
Table 1. Stereoselectivity of Fucosylation of Acetonide 3 and Glycosyl Cation Stabilization Energy
Values (kcal/mol) for Fucosyl Bromides 1 and 6–8
Stabilization
Energy
Ratio of ꢀ- and
ꢂ-disaccharide
Substituent
O-3 O-4
Bz Bn
Fucosyl
Donor
Entry
Products
Intermediate
MMꢁ
DFT
1
2
6
7
13:1
20:1
III
II
III
I
8.9
9.9
4.1
01
14.3
n.d.
n.d.
1.4
Bz
Bz
3
4
8
1
Bn
Bn
Bn
Bz
1:1
3.5:1
II
3.61
7.3
mechanics calculations by employing the MMꢁ force field (developed by Hyper-
Cube using Allinger’s MM2 as basis9). The calculations revealed transformation
of non-stabilized monocyclic glycosyl cations of type I into bicyclic ones in which
the positive charge is stabilized by intramolecular interaction with benzoate
groups. In the case of monobenzoylated bromide 6, stabilization involves the for-
mation of the intermediate of type III while in the case of dibenzoate 7 two sorts
of stabilized intermediates of types II and III are possible (Fig. 2). Both stabilized
intermediates (II, III) are not able to interact with nucleophiles from the ꢂ-side
while the ꢀ-side is readily accessible to nucleophilic attack.
Figure 2. Structures and 3D models of glycosyl cation intermediates of types I–III.

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FUCOIDAN FRAGMENTS. III
825
It has been suggested before,10 that substituents on the axial O-4 of a fucosyl
cation could interact with the anomeric carbon as in our type II cations. Such an
interaction requires the pyranose ring to adopt an unfavourable B1,4 ring confor-
mation. Similarly, for the formation of type III cations, the pyranose ring must
adopt a conformation that allows O-3 to become pseudo-axial and therefore also
appears unfavourable.
However, the molecular mechanics calculations show that a cation type III
formed from 6 is indeed much more stable than the open type I cation (Table 1, En-
try 1). Since molecular mechanics is designed to find structures of neutral com-
pounds with “normal” bond lengths, bond angles, dihedral angles etc., we decided
to further study these hypothetical intermediates at a higher level of calculation,
namely using Density Functional Theory (DFT) calculations.11–13 Thus, the struc-
tures found by MMꢁ calculations were used as input and reoptimized using the
Amsterdam Density Functional implementation of DFT as described previously.14
It is expected that such calculations are as accurate as the model and therefore the
differences between calculated and experimental results will reflect the neglect of
solvent, counterions etc. in the calculations. It is readily apparent that trends ob-
served with the MMꢁ force field are reproduced by the DFT calculations. Most
importantly the cations of type III are predicted to be more stable than those of type
II (Table 1, Entry 1 versus Entry 4).
Further insight was obtained by performing conformational analysis of the
ring conformations of cations I to III (Table 2). As expected all cations of type I
prefer the 3H4 ring conformation. Similarly cation II prefers the B1,4 conformation.
Cations III exhibit the E4 ring conformation that puts O-3 in a pseudo-axial posi-
tion that allows participation with C-1. Surprisingly, this change only requires
small changes to the ring conformation as E4 is close in conformational space to
3H4. This can be seen by the small changes in the Cremer-Pople parameters be-
tween I and III (Table 2).
We assumed that formation of such ꢂ-hindered intermediates leads to ꢀ-se-
lectivity. In this case the amount of ꢀ-anomer should be approximately proportional
to the amount of forms II or III, i. e., to their stability compared to that of form I.
This stability can be estimated in terms of computational chemistry as the energy
difference between these forms. We called this difference “stabilization energy”.1
Such stabilization energies are an estimate of the enthalpic contributions and
do not include entropy factors necessary to estimate free energies. Both the calcu-
Table 2. Results of the Conformational Analysis of Cations I–III According to the IUPAC
Descriptors15
Cremer-Pople Parameters
Cation
Conformation
Q
ꢄ
ꢅ
I
II
III
3H4 (1.093), 2,5B(0.121), 3S1 (0.060)
B1,4 (0.824), 2S0 (0.209), 1C4 (0.080)
E4 (1.044), 0S2 (0.111), B1,4 (0.003)
0.81
0.93
0.78
ꢆ17
ꢆ12
ꢆ10
48
85
48

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826
GERBST ET AL.
lation of entropies and the experimental determination of free energies remain as
challenges for further refinement of the existing model.
The 3D structures of cations of types I–III predicted by DFT calculations are
presented in Figure 2. The calculated energy values for intermediate cations
formed from fucosyl bromides 1 and 6–8 are shown in Table 1. Comparison of the
data from Entries 1–4 shows correlation between the stabilization energies for
cations of types I and III and experimental ꢀ/ꢂ selectivity of fucosylations. This
correlation strongly supports the hypothesis that stabilization of an intermediate
glycosyl cation by a benzoyl group at O-3 or O-4 assists the formation of the 1,2-
cis-linked disaccharide.
The stabilization energy for cation III was always higher than for cation II
(Table 1, Entries 1, 2, 4). This explains the higher ꢀ-selectivity of fucosylation with
3-O-benzoylated fucosyl bromides 6 and 7 and shows that the benzoyl group at O-
3 in fucose influences the ꢀ-selectivity of glycosylation more effectively than that
at O-4. It is possible to expect that intramolecular participation of 3-O-benzoyl
groups is one of key stereoelectronic factors which control the previously observed
ꢀ-glycosylation by per-O-benzoylated D-galactopyranosyl16 and L-fucopyranosyl
bromides.17,18
CONCLUSION
The results presented here show that stereoselectivity of glycosylation with
fucosyl bromides is strongly influenced by the presence of benzoyl protective
groups at O-3, which were shown to effectively stabilize the intermediate glycosyl
cation. Computer modeling with MMꢁ and DFT can be employed for the estima-
tion of intramolecular participation of protecting groups in stabilization of cationic
intermediates. This approach may be useful for the explanation and prediction of
selectivity of some glycosylation reactions.
EXPERIMENTAL
General Methods. TLC was performed on Silica Gel 60 F254 (Merck) with
toluene-EtOAc (A, 3:1; B, 2:1), and with detection by charring with H3PO4. Col-
umn chromatography was performed on Silica Gel L 63–200 mkm (Fluka) by gra-
dient elution with toluene-EtOAc. Optical rotations for synthesized compounds
were determined with a Jasco DIP-360 digital polarimeter at 26–30°C. All solvents
used for syntheses were purified according to conventional procedures.6,16 NMR
spectra for compounds 3–5, 9–11 were recorded in CDCl3 on Bruker spectrome-
ters WM-250 and AM-300 at 303 K. One and two dimensional spectra were ac-
quired using standard Bruker software for ASPECT-2000. Molecular mechanics
calculations were performed using the MMꢁ force field9 as implemented in Hy-
perChem 5.01 program19 with the built-in dielectric constant ꢇ of 1.5. Electrostatic

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FUCOIDAN FRAGMENTS. III
827
terms of the total energy were considered in point atomic charges approximation,
as it satisfactorily describes ionic structures. Values of partial atomic charges were
obtained from AM119,20 semi-empirical calculations. All geometry optimization
procedures were carried out till the RMS gradient reached the value of ꢀ0.1
kcal/mol Å. To obtain energy values for the non-stabilized cations, we chose as
starting geometry a model with torsion angle (H3-C3)M(O3-C) set to 0°. Conse-
quently, when computing values for the stabilized cations, this angle was set to
180°. After the structures were optimized using MMꢁ via the Polak-Ribiere algo-
rithm, single point energy calculations were carried out without changing the force
field. In all the calculations, we observed only slight changes of torsion values (not
more than 15°). The reported DFT calculations were carried out with the Amster-
dam Density Functional (ADF) program version 2.3 derived from the work of
Baerends et al,11 and developed at the Free University of Amsterdam12 and at the
University of Calgary.13 Details can be found in Ref. 2. The basis set used was dou-
ble zeta with a single polarization function. The conformational analysis of 6-
membered rings was performed as outlined in Ref. 15.
Allyl 3-O-(4-Methoxybenzyl)-ꢀ-L-fucopyranoside (3). A mixture of allyl
fucoside 2 (306 mg, 1.5 mmol), (Bu3Sn)2O (1.14 mL, 2.25 mmol) and toluene (36
mL) was refluxed until complete dissolution and then concentrated to the volume
of 18 mL. Bu4NBr (533 mg, 1.65 mmol) and 4-methoxybenzyl chloride (0.46 mL,
3.3 mmol) were added, the solution was refluxed for 3 h and then concentrated in
vacuo. Column chromatography of the residue gave amorphous 3 (297 mg, 61%):
[ꢀ]D ꢆ172° (c 3, EtOAc); RF 0.2 (solvent A); 1H NMR (CDCl3) ꢈ 1.28 (d, 3H, J5,6
ꢉ 7.0 Hz, H-6), 3.63 (dd, 1H, J3,4 ꢉ 3.4 Hz, H-3), 3.78 (d, 1H, H-4), 3.79 (s, 3H,
CH2C6H4OCH3), 3.90 (q, 1H, H-5), 3.93 (dd, 1H, J2,3 ꢉ 10.0 Hz, H-2), 4.02 (m,
1H, CH2CHBCH2), 4.19 (m, 1H, CH2CHBCH2), 4.65 (s, 2H, CH2C6H4OCH3),
4.91 (d, 1H, J1,2 ꢉ 4.3 Hz, H-1), 5.20, 5.30 (2m, 2H, CH2CHBCH2), 5.90 (m, 1H,
CH2CHBCH2), 6.87, 7.30 (2d, 4H, CH2C6H4OCH3).
Anal. Calcd for C17H24O6: C, 62.95%; H, 7.46%. Found: C, 62.76%; H,
7.41%.
Allyl 3-O-Benzoyl-2,4-di-O-benzyl-ꢀ-L-fucopyranoside (4). A solution
of 3 (290 mg, 0.89 mmol) in DMF (2.6 mL) was added at 0°C under stirring to a
60% oil suspension of NaH (100 mg, 2.49 mmol). The mixture was stirred at 0° for
30 min and benzyl bromide (0.3 mL, 2.5 mmol) was added. Stirring was continued
for 2 h at rt. The mixture was diluted with chloroform (40 mL) and washed with
water (2ꢊ500 mL). The organic layer was separated and concentrated. The solu-
tion of 90% aqueous CF3COOH (0.5 mL) in CH2Cl2 (5 mL) was added to the
residue, the mixture was kept at rt for 30 min, and then concentrated and co-evap-
orated with toluene (2ꢊ5 mL). Flash column chromatography of the residue gave
the 3-OH intermediate, which was dissolved in pyridine (2.4 mL), and benzoyl
chloride (0.1 mL, 0.78 mmol) was added. The solution was stirred at rt for 1 h, con-
centrated, diluted with CH2Cl2 (100 mL) and washed with water (2ꢊ200 mL). The

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828
GERBST ET AL.
organic layer was separated and concentrated. Column chromatography of the
residue gave 4 (291 mg, 67%): [ꢀ]D ꢆ145° (c 3, EtOAc); RF 0.64 (solvent A); 1H
NMR (CDCl3) ꢈ 1.21 (d, 3H, J5,6 ꢉ 6.9 Hz, H-6), 3.96 (d, 1H, H-4), 4.07 (m, 1H,
CH2CHBCH2), 4.15 (q, 1H, H-5), 4.22 (m, 1H, CH2CHBCH2), 4.24 (dd, 1H, J2,3
ꢉ 11.0 Hz, H-2), 4.53–4.77 (m, 4H, 2ꢊCH2C6H5), 4.99 (d, 1H, J1,2 ꢉ 3.9 Hz, H-
1), 5.25, 5.40 (2m, 2H, CH2CHBCH2), 5.63 (dd, 1H, J3,4 ꢉ 3.0 Hz, H-3), 5.99 (m,
1H, CH2CHBCH2), 7.20–8.10 (m, 15H, 2ꢊCH2C6H5, OCOC6H5).
Anal. Calcd for C30H32O6: C, 73.75%; H, 6.60%. Found: C, 73.64%; H,
6.56%.
3-O-Benzoyl-2,4-di-O-benzyl-ꢀ- and -ꢂ-L-fucopyranose (5). A solution
of 4 (170 mg, 0.35 mmol) in MeOH (2.3 mL) was stirred for 3 h at rt with PdCl2
(27.8 mg, 0.14 mmol). Triethylamine (0.5 mL) was then added, and the mixture
was filtered through a Celite pad and concentrated. Column chromatography of the
residue gave the mixture of ꢀ- and ꢂ-isomers 5 (143 mg, 92%): RF 0.27 (solvent
A); 1H NMR (CDCl3) for ꢀ-isomer ꢈ 1.20 (d, 3H, J5,6 ꢉ 6.6 Hz, H-6), 3.90 (d, 1H,
J3,4 ꢉ 3.0 Hz, H-4), 4.20 (dd, 1H, J2,3 ꢉ 10.3 Hz, H-2), 4.33 (q, 1H, H-5),
4.51–5.01 (m, 4H, CH2C6H5), 5.38 (d, 1H, J1,2 ꢉ 3.6 Hz, H-1), 5.55 (dd, 1H, H-3),
7.20–7.67, 7.97–8.10 (m, 15H, 2ꢊCH2C6H5, OCOC6H5); 1H NMR (CDCl3) for ꢂ-
isomer ꢈ 1.25 (d, 3H, J5,6 ꢉ 6.4 Hz, H-6), 3.75 (q, 1H, H-5), 3.83 (d, 1H, J3,4 ꢉ 3.1
Hz, H-4), 3.92 (dd, 1H, J2,3 ꢉ 10.2 Hz, H-2), 4.51–5.01 (m, 4H, CH2C6H5), 4.72
(d, 1H, J1,2 ꢉ 7.6 Hz, H-1), 5.20 (dd, 1H, H-3), 7.20–7.67, 7.97–8.10 (m, 15H,
2ꢊCH2C6H5, OCOC6H5).
Anal. Calcd for C27H28O6: C, 72.30%; H, 6.29%. Found: C, 72.41%; H,
6.26%.
Allyl 2-O-(3-O-Benzoyl-2,4-di-O-benzyl-ꢀ- (10) and -ꢂ-L-fucopyra-
nosyl)-3,4-O-isopropylidene-ꢀ-L-fucopyranoside (12). A solution of semiac-
etal 5 (90 mg, 0.26 mmol), PPh3 (89 mg, 0.34 mmol) and CBr4 (113 mg, 0.34
mmol) in 3 mL of CH2Cl2 was refluxed for 3 h and then cooled to room tempera-
ture to give a solution of bromide 6 which was used in the next step without any
purification. A mixture of acetonide 9 (43 mg, 0.17 mmol), Hg(CN)2 (66 mg, 0.26
mmol), HgBr2 (catalytic amount), and molecular sieves 4 Å (370 mg) in CH2Cl2 (3
mL) was stirred for 1 h at 20°C under Ar. Using a syringe, a solution of fucosyl
bromide 6 was added portionwise during 1 h. The mixture was stirred for 24 h, then
filtered through Celite, diluted with CH2Cl2, washed with satd aq KBr and
NaHCO3 solutions and concentrated. Column chromatography of the residue gave
the mixture (94 mg, 82%) of ꢀ- and ꢂ-isomers 10 and 12 13:1 (1H NMR)
Data of 10: RF 0.51 (solvent A); 1H NMR (CDCl3) ꢈ 1.18 (d, 3H, J5ꢋ,6ꢋ ꢉ 6.2
Hz, H-6ꢋ), 1.28 (d, 3H, J5,6 ꢉ 6.2 Hz, H-6), 1.34, 1.38 (2ꢊs, 2ꢊ3H, C(CH3)2), 3.88
(dd, 1H, J2,3 ꢉ 8.0 Hz, H-2), 3.97 (d, 1H, J3ꢋ,4ꢋ ꢉ 5.3 Hz, H-4ꢋ), 4.04 (m, 1H,
CH2CHBCH2), 4.09 (d, 1H, J3,4 ꢉ 6.0 Hz, H-4), 4.18 (m, 1H, CH2CHBCH2),
4.24 (dd, 1H, J2ꢋ,3ꢋ ꢉ 10.5 Hz, H-2ꢋ), 4.39 (dd, 1H, H-3), 4.50–4.70 (m, 4H,
2ꢊCH2C6H5), 4.95 (d, 1H, J1,2 ꢉ 3.9 Hz, H-1), 5.11 (d, 1H, J1ꢋ,2ꢋ ꢉ 4.0 Hz, H-1ꢋ),

ORDER
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FUCOIDAN FRAGMENTS. III
829
5.13–5.35 (m, 2H, CH2CHBCH2), 5.64 (dd,1H, H3ꢋ), 5.86 (m, 1H,
CH2CHBCH2), 7.10–8.10 (m, 15H, 2ꢊCH2C6H5, OCOC6H5).
Data of 12: RF 0.56 (solvent A); 1H NMR (CDCl3) ꢈ 1.19 (d, 3H, J5ꢋ,6ꢋ ꢉ 6.2
Hz, H-6ꢋ), 1.38 (d, 3H, J5,6 ꢉ 6.2 Hz, H-6), 1.38, 1.50 (2ꢊs, 2ꢊ3H, C(CH3)2), 3.65
(m, 1H, CH2CHBCH2), 3.77 (s, 1H, H-4ꢋ), 3.91 (t, 1H, J2ꢋ,3ꢋ ꢉ 7.7 Hz, H-2ꢋ), 3.97
(dd, 1H, J2,3 ꢉ 8.1 Hz, H-2), 4.06 (d, 1H, J3,4 ꢉ 5.3 Hz, H-4), 4.18 (m, 1H,
CH2CHBCH2), 4.42 (dd, 1H, H-3), 4.50–5.00 (m, 4H, 2ꢊCH2C6H5), 4.91 (d, 1H,
J1ꢋ,2ꢋ ꢉ 7.7 Hz, H-1ꢋ), 5.02 (d, 1H, J1,2 ꢉ 3.3 Hz, H-1), 5.15 (d, 1H, H-3ꢋ),
5.16–5.35 (m, 2H, CH2CHBCH2), 5.93 (m, 1H, CH2CHBCH2), 7.25–8.10 (m,
15H, 2ꢊCH2C6H5, OCOC6H5).
Anal. Calcd. for C39H46O10: C, 69.42%; H, 6.87%. Found: C, 69.50%; H,
6.95%.
Allyl 2-O-(3,4-Di-O-benzoyl-2-O-benzyl-ꢀ (11) and ꢂ-L-fucosyl)-3,4-O-
isopropylidene-ꢀ-L-fucopyranoside (13). Glycosylation of acetonide 9 (100
mg, 0.40 mmol) by fucosyl bromide 7 [prepared from 3,4-di-O-benzoyl-2-O-ben-
zyl-ꢀ-L-fucopyranose6 (277 mg, 0.6 mmol) as described above for bromide 6] was
performed analogous to preparation of 10 and 12 to give the mixture (223 mg,
81%) of ꢀ- and ꢂ-isomers 11 and 13 20:1 (1H NMR)
Data of 11: RF 0.73 (solvent B); 1H NMR (CDCl3) ꢈ 1.20 (d, 3H, J5ꢋ,6ꢋ ꢉ 6.2
Hz, H-6ꢋ), 1.40 (d, 3H, J5,6 ꢉ 6.2 Hz, H-6), 1.43, 1.60 (2ꢊs, 2ꢊ3H, C(CH3)2), 3.93
(dd, 1H, J2,3 ꢉ 8.1 Hz, H-2), 4.06 (m, 1H, CH2CHBCH2), 4.15 (dd, 1H, J3,4 ꢉ 5.8
Hz, H-4), 4.20 (dd, 1H, J2ꢋ,3ꢋ ꢉ 10.5 Hz, H-2ꢋ), 4.22 (m, 1H, CH2CHBCH2), 4.23
(q, 1H, H-5), 4.45 (dd, 1H, H-3), 4.70 (q, 1H, H-5ꢋ), 4.71 (s, 2H, CH2C6H5), 5.01
(d, 1H, J1,2 ꢉ 3.6 Hz, H-1), 5.16–5.35 (m, 2H, CH2CHBCH2) 5.23 (d, 1H, J1ꢋ,2ꢋ
ꢉ 3.4 Hz, H-1ꢋ), 5.74 (d, 1H, J3ꢋ,4ꢋ ꢉ 3.0 Hz, H-4ꢋ), 5.85 (dd, 1H, H-3), 5.90 (m,
1H, CH2CHBCH2), 7.25–8.00 (m, 15H, 2ꢊCH2C6H5, OCOC6H5); 13C NMR
(CDCl3) ꢈ 15.9 (C-6ꢋ), 16.2 (C-6), 26.3, 28.4 (C(CH3)2), 63.4 (C-5), 64.8 (C-5ꢋ),
68.4 (CH2CHBCH2), 70.7 (C-3ꢋ), 72.3 (CH2C6H5), 72.5 (C-4ꢋ), 72.9 (C-2ꢋ), 74.1
(C-2), 74.6 (C-3), 76.1 (C-4), 76.7–77.3 (CDCl3), 94.9 (C-1), 95.6 (C-1ꢋ), 108.7
(C(CH3)2), 117.9 (CH2CHBCH2), 127.6–137.9 (CH2C6H5, 2ꢊOCOC6H5); 165.4,
165.9 (2ꢊOCOC6H5).
Data of 13: RF 0.75 (solvent B); 1H NMR (CDCl3) ꢈ 4.00 (dd, 1H, J1,2 ꢉ 3.7
Hz, H-2), 4.48 (dd, 1H, J2,3 ꢉ 8.8 Hz, H-3), 4.99 (d, 1H, J1ꢋ,2ꢋ ꢉ 7.9 Hz, H-1ꢋ), 5.11
(d, 1H, J1,2 ꢉ 3.6 Hz, H-1); 13C NMR (CDCl3) ꢈ 15.9 (C-6ꢋ), 16.2 (C-6), 26.7, 29.7
(C(CH3)2), 97.5 (C-1), 104.0 (C-1ꢋ), 108.7 (C(CH3)2), 117.2 (CH2CHBCH2).
Anal. Calcd for C39H44O11: C, 68.01%; H, 6.44%. Found: C, 68.14%; H,
6.56%.
ACKNOWLEDGMENTS
This work was supported by the Russian Foundation for Basic Research
(grants 98-03-33025a and 01-03-33059).

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Received March 22, 2001
Accepted October 19, 2001

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