Synthesis of a (1→3)-linked α-L-fucose tetrasaccharide

Article abstract of DOI:10.1135/cccc20041768

Orthoester-protected benzyl and methyl 1-thiofucopyranosides could be opened to give fucopyranosides unblocked at position 3. Convergent glycosylations of such donors and acceptors led to the corresponding disaccharides, and their block condensation could

Full text of DOI:10.1135/cccc20041768

1768
Ludewig, Thiem:
SYNTHESIS OF A (1→3)-LINKED α-L-FUCOSE TETRASACCHARIDE
1
2,
Michael LUDEWIG and Joachim THIEM *
Institut für Organische Chemie, Universität Hamburg,
Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany;
1
2
e-mail: michael.ludewig.ml@bayer-ag.de, joachim.thiem@chemie.uni-hamburg.de
Received April 8, 2004
Accepted August 29, 2004
Dedicated to Professor Miloslav Černý on the occasion of his 75th birthday in recognition of his
outstanding contributions to carbohydrate chemistry.
Orth oester-protected ben zyl an d m eth yl 1-th iofucopyran osides could be open ed to give
fucopyran osides un blocked at position 3. Con vergen t glycosylation s of such don ors an d ac-
ceptors led to th e correspon din g disacch arides, an d th eir block con den sation could be elabo-
rated to give th e (1→3)-lin ked α-L-fucose tetrasacch aride. Com poun ds of th is structure are of
in terest with regard to th e role of fucose in m etastasis developm en t in lun g tissue.
Keyw ord s: Fucose; Orth oesters; Th ioglycosides; Oligosacch arides; Carboh ydrates;
α,(1→3)-Fucose tetrasacch aride; Glycosidation s.
Placed at strategic sites of m an y biological active oligosacch arides, fucose
h as proved to play a particular im portan t role in in flam m atory diseases an d
can cer developm en t1. In th e latter case, fucose m etabolism is typically acti-
vated an d th e sugar is foun d to be en rich ed in cell-surface oligosacch a-
rides2–4. In lun g tissue, fucose-specific lectin s are con sidered to be respon si-
ble for in teractin g with dissem in ated fucose-presen tin g can cer cells an d are
th erefore con n ected with th e colon isation process of lun g tissue with m e-
tastasis5. It was observed th at blockin g of th ese lectin s was m ore efficien t
with th e fucose-con tain in g polym er fucoidin th an with fucose itself6, an d
th is stim ulated our in terest in th e developm en t of a variety of derivatised,
oligom eric an d m ultivalen t fucose derivatives7–10. Recen tly, fucoidin was
discussed to be dom in an tly built of α,(1→3)-lin kages11.
Oligom ers of fucose were previously obtain ed by Flowers et al. wh o syn -
th esised all possible fucobiosides12–15. In th e case of th e α-fucosyl-(1→3)-
α-fucose, th ey perform ed th e Koen igs–Kn orr reaction an d used regio-
selective ben zylation as th e protection group strategy. (1→2)-Oligom ers
were obtain ed by Matta et al.16,17 an d ourselves7 by usin g various iso-
propyliden ated th io don ors, an d van Boom et al. in vestigated th e syn th esis
of (1→4)-α-fucose oligom ers em ployin g th ioglycoside don ors18. Syn th esic
Collect. Czech. Chem. Commun. (Vol. 69) (2004)
doi:10.1135/cccc20041768

(1→3)-Linked α-L-Fucose Tetrasaccharide
1769
an d NMR studies of sulfated an d n on -sulfated α-fucose (1→3)-trisacch arides
as fragm en ts of fucoidin were reported recen tly19
.
Th is paper reports on th e con vergen t syn th esis of fucose oligom ers with
an α-glycoside lin kage pattern . To en able furth er elon gation up to th e
tetrasacch aride, we in vestigated th e protectin g group strategy via orth o-
esters20 as well as regioselective glycosylation s.
RESULTS AND DISCUSSION
Except for h eterogen eous prom oters21, th e axial 4-OH group in galacto-
con figurated sugars is m uch less reactive an d th is m ay be advan tageous-
ly used. By sim ple tem porary in troduction of an isopropyliden e group
in to ben zyl α-fucopyran oside22 an d protection of th e 2-position with a
4-m eth oxyben zyl group (PMB), a suitable acceptor for regioselective
glycosylation s was obtain ed. Treatm en t of th is derivative 3 with on e equiv-
alen t of th iodon or7 4 un der m ild glycosylatin g con dition s (CuBr2/t-Bu4NBr)
led to disacch aride 5 wh ich was acetylated to give 6 to facilitate an alysis
(Sch em e 1).
OBn
OBn
Me
Me
O
O
PMBCl, NaH, DMF
OPMB
OH
O
O
O
O
H2SO4 (aq.)
dioxane
2
1
OBn
Me
SMe
O
Me
HO
O
OPMB
+
OPMB
O
HO
O
Bu4NBr, CuBr2
3
DMF, CH2Cl2
4
OBn
Me
O
OPMB
O
RO
O
Me
OPMB
5, R = H
6, R = OAc
pyridine
Ac2O
O
O
SCHEME 1
Regioselective glycosylation at th e equatorial 3-position of fucopyran ose
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1770
Ludewig, Thiem:
Surprisin gly, th e resultin g disacch aride con tain ed som e α,(1→4)-lin ked
product (5%) an d a con siderable am oun t of β,(1→3)-glycoside (ca. 25%).
Th us, to avoid purification problem s in th e growin g sacch aride ch ain , it
was decided to protect th e 4-position with a ben zoate group via an
orth oester. In a on e-pot syn th esis, treatm en t of th e un protected fuco-
pyran osides 7 an d 8 with trieth yl orth oben zoate gave th e correspon din g
diastereom eric 3,4-orth oesters 9 an d 10, an d th eir subsequen t 4-m eth oxy-
ben zylation at position 2 led to th e fully protected glycosides 11 an d 12
(Sch em e 2).
By subsequen t stereoselective open in g of th e orth oesters with out isola-
tion or purification of an y in term ediate, th e 3-OH free fucopyran osides 13
an d 14 were obtain ed. In th is way, from both th e ben zyl an d m eth yl
1-th iofucopyran osides, all n ecessary buildin g blocks for th e con struction of
oligom ers could be prepared. In th e case of th e th iom eth yl don or, a
TBDMS-group was in troduced in to th e 3-position of 14 to give fully pro-
tected th iofucopyran oside 15. Attem pts to use com poun d 12 directly as a
R
PhC(OEt)3, TosOH
CH2Cl2
R
Me
Me
HO
O
O
OH
OH
O
HO
O
OEt
9, R = α-OBn
10, R = β-SMe
7, R = α-OBn
8, R = β-SMe
Ph
PMBCl, NaH
DMF
R
R
Me
Me
O
O
AcOH, 80%
OPMB
OPMB
O
HO
O
BzO
OEt
11, R = α-OBn
12, R = β-SMe
13, R = α-OBn
14, R = β-SMe
Ph
TBDMSCl,
imidazole,
DMF
Br
Me
CuBr2, CH2Cl2
Me
SMe
O
O
OPMB
OPMB
OTBDMS
OTBDMS
BzO
BzO
16
15
SCHEME 2
Regioselective protection of fucopyran osides via th e orth oester route
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

(1→3)-Linked α-L-Fucose Tetrasaccharide
1771
glycosylation reagen t proved to be difficult sin ce th e orth oester ten ded to
open in g un der glycosylation con dition s. Neverth eless, glycosylation of 13
could be perform ed un der basic con dition s wh ich , h owever, led to th e un -
desired correspon din g β-glycoside 17 (Sch em e 3).
Glycosylation of acceptor 13 with don or 15 un der activation of copper(II)
brom ide an d tetrabutylam m on ium brom ide gave stereospecifically th e
α-lin ked disacch aride 19. However, deprotection of th e 3-position in th e
term in al sugar rin g turn ed out to be difficult sin ce th e ben zoate ten ded to
m igrate to th e equatorial position . A deprotection un der acid con dition s
with out affectin g th e PMB group could n ot be realised. Also, em ployin g
fluoride-con tain in g acetic acid buffer did n ot result in an y reaction . Fin ally,
th is could be overcom e by rem ovin g both th e TBDMS group togeth er with
th e ben zoate com pletely, followed by its re-in troduction via an orth oester
to give com poun d 19.
For furth er elon gation of th e disacch aride acceptor 19, a disacch aride do-
n or was con structed. Usin g copper(II) brom ide, don or 15 was con verted
in to th e correspon din g brom ide 16, an d th is subsequen tly coupled to th e
th io acceptor 14 with tetrabutylam m on ium brom ide as catalyst to give th e
disacch aride don or 18 in good yields. Treatm en t of 14 un der glycosylation
con dition s led to a disacch aride in reason able yields as well. However, sin ce
it proved to be im possible to in troduce a TBDMS group at th e 3′-position
even wh en usin g TBDMSOTf, th is was n ot furth er in vestigated.
OBn
Me
SMe
Me
O
O
+
OPMB
OPMB
O
HO
O
BzO
OEt
Ph
13
12
1) NIS, DTBMP
2) HOAc, H2O
OBn
Me
O
OPMB
BzO
Me
O
O
OPMB
17
HO
BzO
SCHEME 3
Glycosylation usin g an fucopyran osyl don or un der basic con dition s
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

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Ludewig, Thiem:
Th e decreased reactivity of th e 3′-position was also eviden t in acceptor 19
sin ce its glycosylation with disacch aride don or 18 un der com m on activa-
tion of copper(II) brom ide/tetrabutylam m on ium brom ide did n ot give an y
couplin g product at all. Meth yl triflate as prom otor, h owever, led to th e
stereoselective form ation of tetrasacch aride 20 in good yield (Sch em e 4).
Br
OBn
Me
Me
SMe
Me
Me
+
SMe
OPMB
O
OTBDMS
16
O
O
OTBDMS
15
O
OPMB
OPMB
OPMB
+
HO
HO
BzO
BzO
BzO
BzO
14
13
1) CuBr2, Bu4NBr, CH2Cl2, DMF
2) TBAF, ether
Bu4NBr, CH2Cl2, DMF
3) PhC(OEt)3, TosOH, CH2Cl2
4) HOAc, 80%
OBn
Me
SMe
OPMB
Me
O
O
OPMB
O
O
BzO
O
BzO
Me
Me
O
OPMB
OPMB
18
19
MeOTf, CH2Cl2
OTBDMS
HO
BzO
BzO
OBn
Me
O
OPMB
O
BzO
O
Me
OPMB
O
BzO
O
Me
SMe
OPMB
O
BzO
O
Me
OPMB
20
OTBDMS
BzO
SCHEME 4
Con vergen t block syn th esis of a fucosetetrasacch aride derivative
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

(1→3)-Linked α-L-Fucose Tetrasaccharide
1773
CONCLUSIONS
Em ploym en t of orth oesters an d th eir regioselective open in g provided a
sim ple an d efficien t approach to obtain fucopyran ose derivatives with un -
blocked position s 3. Alth ough th e resultin g axial ben zoate ten ded to m i-
grate to th e th erm odyn am ically m ore stable equatorial position , th is did
n ot occur un der glycosylation con dition s or with silyl-protected deriva-
tives. However, it rem ain ed difficult to rem ove silyl groups with out affect-
in g th e ben zoate.
Th e reactivity of th e 3-OH group appeared to be con siderably reduced
in disacch arides. Com paratively bulky protective groups at th e 2- an d 4-
position s did n eith er affect th e deprotection of a TBDMS group n or glyco-
sylation in th e m on osacch aride. However, in order to perform th ese reac-
tion s for th e correspon din g disacch aride, a m uch m ore effective activation
via a stron g m eth ylatin g agen t h ad to be em ployed for th e form ation of th e
tetrasacch aride.
EXPERIMENTAL
Optical rotation s (in 10–1 deg cm 2 g–1) were determ in ed with a Perkin –Elm er 241 polari-
m eter. NMR spectra were recorded on a Bruker AMX-400 or Bruker DRX-500 in strum en t
with tetram eth ylsilan e (TMS) as referen ce. Ch em ical sh ifts are given in ppm (δ-scale), cou-
plin g con stan ts (J) in Hz. All reaction s were m on itored by TLC on silica gel (60F254, Merck)
with detection by UV or 10% eth an olic sulfuric acid. Flash ch rom atograph y was carried out
with silica gel 60 (230–400 m esh , 40–63 µm , Merck). Microan alyses were m ade in th e
Microan alytical Laboratory, Departm en t of Ch em istry, Un iversity of Ham burg.
Ben zyl 3,4-O-Isopropyliden e-2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (2)
Com poun d 1 (1.18 g, 4.01 m m ol) was dissolved in DMF (30 m l) an d treated with sodium
h ydride (240 m g, 8 m m ol, 80% in paraffin oil) at 0 °C. After stirrin g for 30 m in , 4-m eth oxy-
ben zyl ch loride (0.7 m l, 5.16 m m ol) was slowly added an d th e m ixture was stirred overn igh t
in th e m eltin g ice bath . Th e solven t was th en evaporated in vacuo, th e residue dissolved in
eth yl acetate an d wash ed with water an d a sodium h ydrogen carbon ate solution . After dryin g
with an h ydrous m agn esium sulfate an d evaporation of th e filtered solution , colum n ch ro-
m atograph y (petroleum eth er–eth yl acetate 5:1) yielded 1.56 g (3.76 m m ol, 94%) of a wh ite
am orph ous solid: [α ]2D0 –131.5 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 7.35 (m , 5 H, Bn );
7.21 (m , 2 H, PMB); 6.81 (m , 2 H, PMB); 4.80 (d, 1 H, J1,2 = 3.6, H-1); 4.70 (d, 1 H, J = 12.7,
Bn ); 4.65 (d, 1 H, J = 12.2, Bn ); 4.57 (d, 1 H, J = 12.2, Bn ); 4.53 (d, 1 H, J = 12.7, Bn ); 4.35
(dd, 1 H, J2,3 = 7.8, J3,4 = 5.6, H-3); 4.11 (dq, 1 H, J4,5 = 2.5, J5,6 = 6.6, H-5); 4.03 (dd, 1 H,
J3,4 = 5.6, J4,5 = 2.5, H-4); 3.79 (s, 3 H, OMe); 3.50 (dd, 1 H, J1,2 = 3.6, J2,3 = 7.8, H-2); 1.41 (s,
3 H, iPr); 1.34 (s, 3 H, iPr); 1.30 (d, 3 H, J5,6 = 6.6, H-6). For C24H30O6 (414.5) calculated:
69.55% C, 7.30% H; foun d: 69.31% C, 7.41% H.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

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Ludewig, Thiem:
Ben zyl 2-O-(4-Meth oxyben zyl)-α-L-fucopyran oside (3)
Com poun d 2 (500 m g, 1.19 m m ol) was treated with a m ixture of dioxan e an d 1% aqueous
sulfuric acid (25 m l, 1:1) an d stirred overn igh t. Subsequen tly, barium carbon ate was added
an d after 2-h stirrin g, th e solids were filtered off. After evaporation of th e solven t, 443 m g
(1.18 m m ol, 99%) of a wh ite solid rem ain ed as product: [α ]2D0 –138.9 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): 7.35 (m , 5 H, Bn ); 7.20 (m , 2 H, PMB); 6.83 (m , 2 H, PMB); 4.88 (d, 1 H,
J1,2 = 3.6, H-1); 4.68 (d, 1 H, J = 12.2, Bn ); 4.51 (d, 1 H, J = 12.2, Bn ); 4.50 (d, 1 H, J = 11.7,
Bn ); 4.43 (d, 1 H, J = 11.7, Bn ); 4.04 (ddd ≈ dt, 1 H, J2,3 = 8.7, J3,4 = J3,OH = 3.0, H-3); 3.98
(dq, 1 H, J4,5 < 1.0, J5,6 = 6.6, H-5); 3.79 (ddd ≈ m , 1 H, H-4); 3.79 (s, 3 H, OMe); 3.68 (dd,
1 H, J1,2 = 3.6, J2,3 = 8.7, H-2); 2.58 (d, 1 H, J3,OH = 3.0, OH-3); 2.40 (d, 1 H, J4,OH = 2.0,
OH-4); 1.27 (d, 3 H, J5,6 = 6.6, H-6). For C21H26O6 (374.4) calculated: 67.36% C, 7.00% H;
foun d: 67.07% C, 7.12% H.
Ben zyl 3,4-O-Isopropyliden e-2-O-(4-m eth oxyben zyl)-α-L-fucopyran osyl-
(1→3)-2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (5)
Acceptor 3 (350 m g, 0.93 m m ol) an d don or 4 (280 m g, 0.80 m m ol)7 were coevaporated
twice with toluen e, set un der argon an d stirred in dich lorom eth an e–DMF (10 m l, 1:1) to-
geth er with m olecular sieve (4A, 500 m g) for 1 h . Subsequen tly, tetrabutylam m on ium bro-
m ide (1200 m g, 3.72 m m ol) an d, 1 h later, copper(II) brom ide (840 m g, 3.76 m m ol) were
added, an d th e m ixture was stirred overn igh t. Th e m ixture was th en filtered th rough Celite,
diluted with eth yl acetate an d wash ed with a sodium h ydrogen carbon ate solution an d brin e,
dried with an h ydrous m agn esium sulfate, filtered an d evaporated. Colum n ch rom atograph y
(toluen e–eth yl acetate 5:1) furn ish ed 249 m g (0.37 m m ol, 46%) of th e disacch aride as
colourless syrup, wh ich con tain ed approxim ately 25% of β-lin ked product an d 5% of
(1→4)-lin ked product: [α ]2D0 –107.8 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 7.30 (m , 5 H,
Bn ); 7.25 (m , 2 H, PMB); 7.18 (m , 2 H, PMB); 6.85 (m , 2 H, PMB); 6.81 (m , 2 H, PMB); 4.82
(d, 1 H, J1,2 = 3.5, H-1); 4.80 (d, 1 H, J = 12.1, Bn -a); 4.72 (d, 1 H, J1′,2′ = 3.6, H-1′); 4.67 (d, 1 H,
J = 12.2, Bn -b); 4.59 (d, 1 H, J = 12.1, Bn -a); 4.57 (d, 1 H, J = 12.2, Bn -b); 4.46 (d, 1 H, J =
11.7, Bn -c); 4.42 (d, 1 H, J = 11.7, Bn -c); 4.37 (dq, 1 H, J4′,5′ = 2.5, J5′,6′ = 6.6, H-5′); 4.36 (dd,
1 H, J2′,3′ = 7.6, J3′,4′ = 5.6, H-3′); 4.00 (dd, 1 H, J2,3 = 9.6, J3,4 = 3.0, H-3); 3.88 (m , 2 H, H-4′,
H-5); 3.79 (s, 6 H, 2 × OMe); 3.75 (dd ≈ m , 1 H, J1,2 = 3.6, H-2); 3.70 (ddd ≈ m , 1 H, H-4);
3.48 (dd, 1 H, J1′,2′ = 3.6, J2′,3′ = 7.6, H-2′); 1.44 (s, 3 H, iPr); 1.34 (s, 3 H, iPr); 1.25 (d, 3 H,
J5,6 = 6.6, H-6); 1.19 (d, 3 H, J5′,6′ = 6.6, H-6′). 13C NMR (100 MHz, CDCl3): 159.45 (PMB);
159.25 (PMB); 137.54 (Bn ); 127.00–130.00 (Bn , PMB); 113.89 (PMB); 113.70 (PMB); 108.66
(iPr); 95.92 (C-1*); 94.02 (C-1*); 76.51, 76.21, 75.88, 74.92, 74.23, 68.17, 65.08, 63.36 (2 ×
C-2, 2 × C-3, 2 × C-4, 2 × C-5); 72.81 (PMB); 72.67 (PMB); 69.21 (Bn ); 55.28 (2 × OMe);
28.34 (iPr); 26.43 (iPr); 16.29 (C-6*); 16.16 (C-6*). For C38H48O11 (680.8) calculated: 67.04% C,
7.11% H; foun d: 67.03% C, 7.28% H.
Ben zyl 3,4-O-Isopropyliden e-2-O-(4-m eth oxyben zyl)-α-L-fucopyran osyl-
(1→3)-4-O-acetyl-2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (6)
Com poun d 5 (230 m g, 0.34 m m ol) was acetylated with a m ixture of pyridin e–acetic acid
an h ydride (15 m l, 1:1) overn igh t. Th e liquids were rem oved in vacuo to furn ish 223 m g
(0.31 m m ol, 91%) of a syrupy product m ixture: [α ]2D0 –121.1 (c 1.0, CHCl3). Isom er 6α:
1H NMR (400 MHz, CDCl3): 7.3 (m , 5 H, Bn ); 7.23 (m , 2 H, PMB); 7.18 (m , 2 H, PMB); 6.86
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

(1→3)-Linked α-L-Fucose Tetrasaccharide
1775
(m , 2 H, PMB); 6.82 (m , 2 H, PMB); 5.36 (dd ≈ d, 1 H, J3,4 = 3.6, J4,5 < 1.0, H-4); 5.01 (d, 1 H,
J1′,2′ = 3.6, H-1′); 4.87 (d, 1 H, J1,2 = 3.6, H-1); 4.70 (d, 1 H, J = 2.7, Bn -a); 4.63 (d, 1 H, J =
12.2, Bn -b); 4.60 (d, 1 H, J = 12.7, Bn -a); 4.57 (d, 1 H, J = 12.2, Bn -b); 4.54 (d, 1 H, J = 11.2,
Bn -c); 4.48 (d, 1 H, J = 11.2, Bn -c); 4.39 (dq, 1 H, J4′,5′ = 2.5, J5′,6′ = 6.6, H-5′); 4.26 (dd, 1 H,
J2′,3′ = 8.1, J3′,4′ = 5.6, H-3′); 4.24 (dd, 1 H, J2,3 = 8.1, J3,4 = 3.6, H-3); 4.01 (dq, 1 H, J4,5 < 1.0,
J5,6 = 6.6, H-5); 3.79 (s, 6 H, 2 × OMe); 3.79 (m , 1 H, H-2); 3.71 (dd, 1 H, J3′,4′ = 5.6, J4′,5′
=
2.5, H-4′); 3.43 (dd, 1 H, J1′,2′ = 3.6, J2′,3′ = 8.1, H-2′); 1.97 (s, 3 H, OAc); 1.30 (s, 3 H, iPr);
1.28 (s, 3 H, iPr); 1.19 (d, 3 H, J5,6 = 6.6, H-6*); 1.04 (d, 3 H, J5,6 = 6.6, H-6*). 13C NMR
(100 MHz, CDCl3): 170.92 (OAc); 159.17 (2 × PMB); 137.57 (Bn ); 130.63, 129.81, 129.71,
129.08, 129.04, 128.46, 128.41, 128.35, 128.23, 128.03, 127.76, 125.31 (Bn , PMB); 113.67
(PMB); 113.60 (PMB); 108.59 (iPr); 96.60 (C-1*); 92.48 (C-1*); 75.44, 74.64, 69.99, 68.95,
65.08, 63.36 (2 × C-2, 2 × C-3, 2 × C-4); 64.78, 62.93 (2 × C-5); 72.52 (PMB); 71.81 (PMB);
69.62 (Bn ); 55.29 (OMe); 55.27 (OMe); 28.09 (iPr); 26.38 (iPr); 20.68 (OAc); 16.44 (C-6*);
16.17 (C-6*). Isom er 6β: 1H NMR (400 MHz, CDCl3): 5.31 (dd ≈ d, 1 H, J3,4 = 3.6, J4,5 < 1.0,
H-4); 4.81 (d, 1 H, J1,2 = 3.6, H-1*); 4.31 (dd, 1 H, J2,3 = 10.1, J3,4 = 3.6, H-3); 3.91 (dd, 1 H,
J3′,4′ = 5.6, J4′,5′ = 2.5, H-4′); 3.87 (dd, 1 H, J1,2 = 3.6, J2,3 = 10.1, H-2); 3.30 (dd ≈ t, 1 H, J1,2
J2,3 = 7.6, H-2). α(1→4)-product: 1H NMR (400 MHz, CDCl3): 5.19 (dd, 1 H, J2,3 = 10.7, J3,4
3.1, H-3).
=
=
Meth yl (R,S)-3,4-O-(α-Eth oxyben zyliden e)-2-O-(4-m eth oxyben zyl)-
1-th io-β-L-fucopyran oside (12)
A solution of com poun d 8 (1.0 g, 5.15 m m ol)17 in dich lorom eth an e (20 m l) was treated
with a speck of 4-toluen esulfon ic acid before trieth yl orth oben zoate (3.4 m l, 15 m m ol) was
slowly added. After stirrin g th e m ixture overn igh t, a sm all am oun t of sodium h ydroxide was
added an d th e solven t was rem oved. Th e residue was evaporated twice with toluen e an d dis-
solved in an h ydrous DMF (20 m l). Sodium h ydride (0.45 g, 15 m m ol) was added, an d after
stirrin g th e m ixture for 20 m in , 4-m eth oxyben zyl ch loride (2.23 m l, 16.44 m m ol) was
dropped slowly in to th e solution . After stirrin g for an oth er n igh t, m eth an ol (1 m l) was
added an d, 20 m in later, th e solven t was rem oved in vacuo. Th e residue was again dissolved
in dich lorom eth an e, wash ed with water an d brin e, dried over an h ydrous m agn esium sulfate
an d filtered. Th e solven t was rem oved an d th e crude product was purified by colum n ch ro-
m atograph y (petroleum eth er–eth yl acetate 4:1) to give 640 m g (1.43 m m ol, 28%) of pure
syrupy product (diastereom eric m ixture) an d an oth er 1.9 g of crude product: [α ]2D0 –5.1 (c 1.0,
CHCl3). 1H NMR (400 MHz, CDCl3): 7.64–7.28 (m , 5 H, Ph ); 7.10 (m , 2 H, PMB); 6.75 (m ,
2 H, PMB); 4.59 (d, 1 H, J = 11.2, Bn ); 4.51 (dd ≈ t, 1 H, J2,3 = J3,4 = 6.2, H-3); 4.45 (dd, 1 H,
J3,4 = 6.2, J4,5 = 2.0, H-4); 4.42 (d, 1 H, J = 11.2, Bn ); 4.21 (d, 1 H, J1,2 = 10.2, H-1); 3.88 (dq,
1 H, J4,5 = 2.0, J5,6 = 6.6, H-5); 3.76 (s, 3 H, OMe); 3.50 (dt, 1 H, Jd = 7.1, Jt = 9.7, O-CH2);
3.38 (dt, 1 H, Jd = 7.1, Jt = 9.5, O-CH2); 3.24 (d, 1 H, J1,2 = 10.2, J2,3 = 6.6, H-2); 2.02 (s, 3 H,
SMe); 1.51 (d, 3 H, J5,6 = 6.6, H-6); 1.19 (dd ≈ t, 3 H, J = 7.1, OEt).
Ben zyl 4-O-Ben zoyl-2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (13)
Com poun d 7 (1.5 g, 5.99 m m ol)22 was processed in th e sam e way as com poun d 8 in th e
previous procedure usin g trieth yl orth oben zoate (3.95 m l, 17.4 m m ol), a speck of 4-toluen e-
sulfon ic acid, dich lorom eth an e (25 m l), an h ydrous DMF (20 m l), sodium h ydride (80% in
paraffin oil, 522 m g, 17.4 m m ol), an d 4-m eth oxyben zyl ch loride (1.62 m l, 12 m m ol). After
h avin g perform ed th e ben zylation overn igh t, acetic acid (5 m l) an d a few drops of water
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1776
Ludewig, Thiem:
were added, an d th e m ixture was stirred for an oth er n igh t. For workup, th e solven t was ex-
ch an ged for dich lorom eth an e an d wash ed with a sodium h ydrogen carbon ate solution an d
brin e, dried with an h ydrous m agn esium sulfate an d evaporated. Colum n ch rom atograph y
(petroleum eth er–eth yl acetate 2:1) yielded 1.50 g (3.13 m m ol, 52%) of th e product: [α ]D20
–119.6 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 8.02 (m , 2 H, Bz); 7.59 (m , 1 H, Bz); 7.45
(m , 2 H, Bz); 7.39 (m , 5 H, Bn ); 7.20 (m , 2 H, PMB); 6.82 (m , 2 H, PMB); 5.48 (dd ≈ d, 1 H,
J3,4 = 3.6, J4,5 < 1.0, H-4); 4.99 (d, 1 H, J1,2 = 3.1, H-1); 4.73 (d, 1 H, J = 12.2, Bn ); 4.57 (d, 1 H,
J = 12.2, Bn ); 4.52 (2 × d, 2 H, Bn ); 4.32 (dd, 1 H, J2,3 = 10.7, J3,4 = 3.6, H-3); 4.17 (dq, 1 H,
J4,5 < 1.0, J5,6 = 6.6, H-5); 3.82 (dd, 1 H, J1,2 = 3.1, J2,3 = 10.7, H-2); 3.79 (s, 3 H, OMe); 1.14
(d, 3 H, J5,6 = 6.6, H-6). For C28H30O7 (478.5) calculated: 70.28% C, 6.32% H; foun d: 70.20% C,
6.56% H.
Meth yl 4-O-Ben zoyl-2-O-(4-m eth oxyben zyl)-1-th io-β-L-fucopyran oside (14)
Com poun d 12 (100 m g, 0.22 m m ol) was dissolved in dich lorom eth an e (20 m l) an d treated
with acetic acid (1 m l). Th e solution was stirred overn igh t, wash ed twice with aqueous
NaHCO3 an d water, dried over an h ydrous m agn esium sulfate, filtered an d evaporated. Col-
um n ch rom atograph y (petroleum eth er–eth yl acetate 2:1) yielded 91 m g (0.217 m m ol, 98%)
of th e product: [α ]2D0 –60.0 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 8.09 (m , 2 H, Bz); 7.61
(m , 1 H, Bz); 7.47 (m , 2 H, Bz); 7.34 (m , 2 H, PMB); 6.86 (m , 2 H, PMB); 5.45 (dd ≈ d, 1 H,
J3,4 = 3.2, J4,5 < 1.0, H-4); 4.92 (d, 1 H, J = 10.6, PMB); 4.64 (d, 1 H, J = 10.6, PMB); 4.40 (d, 1 H,
J1,2 = 9.8, H-1); 3.90 (dd, 1 H, J2,3 = 9.1, J3,4 = 3.2, H-3); 3.85 (dq, 1 H, J4,5 < 1.0, J5,6 = 6.6,
H-5); 3.76 (s, 3 H, OMe); 3.61 (dd ≈ t, 1 H, J1,2 = 9.8, J2,3 = 9.1, H-2); 2.31 (s, 3 H, SMe); 1.25
(d, 3 H, J5,6 = 6.6, H-6). For C22H26O6S (418.5) calculated: 63.14% C, 6.26% H; foun d:
62.51% C; 6.50% H.
Meth yl 4-O-Ben zoyl-3-O-(tert-butyldim eth ylsilyl)-2-O-(4-m eth oxyben zyl)-
1-th io-β-L-fucopyran oside (15)
Com poun d 14 (2.83 g, 6.75 m m ol) was dissolved in DMF (10 m l), treated with im idazole
(1.01 g, 15.8 m m ol) an d tert-butyldim eth ylsilyl ch loride (1.58 g, 10.9 m m ol), an d stirred at
room tem perature overn igh t. For workup, th e solven t was rem oved un der reduced pressure
an d th e residue dissolved in dich lorom eth an e. Th e solution was wash ed twice with NaHCO3
solution an d water, dried over an h ydrous m agn esium sulfate, filtered an d evaporated. Th e
crude residue was purified by colum n ch rom atograph y (petroleum eth er–eth yl acetate 5:1)
to give 2.25 g (4.22 m m ol, 63%) of pure product: [α ]2D0 +10.3 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): 8.09 (m , 2 H, Bz); 7.59 (m , 1 H, Bz); 7.46 (m , 2 H, Bz); 7.35 (m , 2 H,
PMB); 6.86 (m , 2 H, PMB); 5.34 (dd ≈ d, 1 H, J3,4 = 3.6, J4,5 < 1.0, H-4); 4.78 (d, 1 H, J = 10.2,
PMB); 4.69 (d, 1 H, J = 10.2, PMB); 4.39 (d, 1 H, J1,2 = 9.7, H-1); 3.88 (dd, 1 H, J2,3 = 9.2, J3,4
=
3.6, H-3); 3.80 (s, 3 H, OMe); 3.80 (dq ≈ m , 1 H, H-5); 3.61 (dd ≈ t, 1 H, J1,2 = J2,3 = 9.5,
H-2); 2.25 (s, 3 H, SMe); 1.25 (d, 3 H, J5,6 = 6.6, H-6); 0.80 (s, 9 H, t-Bu); 0.13 (s, 3 H, SiMe);
0.08 (s, 3 H, SiMe). For C28H40O6SiS (532.8) calculated: 63.12% C, 7.57% H; foun d: 63.15% C,
7.67% H.
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(1→3)-Linked α-L-Fucose Tetrasaccharide
1777
4-O-Ben zoyl-3-O-(tert-butyldim eth ylsilyl)-2-O-(4-m eth oxyben zyl)-
α-L-fucopyran osyl Brom ide (16)
Com poun d 15 (500 m g, 0.94 m m ol) was set un der argon , dissolved in dich lorom eth an e
(20 m l) an d stirred for 2 h togeth er with m olecular sieve (4A, 300 m g). Subsequen tly,
copper(II) brom ide (628 m g, 2.81 m m ol) was added. After stirrin g th e solution overn igh t,
th e solids were filtered off, an d th e solution was wash ed with aqueous NaHCO3 an d wa-
ter, dried over an h ydrous m agn esium sulfate an d evaporated. Th is furn ish ed 401 m g
(0.71 m m ol, 75%) of th e product, wh ich was used with out furth er purification : [α ]2D0 –257.5
(c 3.0, CHCl3). 1H NMR (400 MHz, CDCl3): 7.93 (m , 2 H, Bz); 7.51 (m , 1 H, Bz); 7.38 (m ,
2 H, Bz); 7.21 (m , 2 H, PMB); 6.80 (m , 2 H, PMB); 5.96 (d, 1 H, J1,2 = 4.0, H-1); 5.31 (dd,
1 H, J3,4 = 3.5, J4,5 = 1.0, H-4); 4.58 (d, 1 H, J = 11.7, PMB); 4.51 (d, 1 H, J = 11.7, PMB); 4.34
(dq ≈ q, 1 H, J4,5 = 1.0, J5,6 = 6.1, H-5); 4.17 (dd, 1 H, J2,3 = 9.6, J3,4 = 3.5, H-3); 3.82 (dd, 1 H,
J1,2 = 4.0, J2,3 = 9.6, H-2); 3.73 (s, 3 H, OMe); 1.16 (d, 3 H, J5,6 = 6.1, H-6); 0.69 (s, 9 H, t-Bu);
0.09 (s, 3 H, SiMe); 0.02 (s, 3 H, SiMe).
Ben zyl 4-O-Ben zoyl-2-O-(4-m eth oxyben zyl)-β-L-fucopyran osyl-
(1→3)-4-O-ben zoyl-2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (17)
Com poun d 12 (158 m g, 0.36 m m ol) an d com poun d 13 (126 m g, 0.28 m m ol) were m ixed
an d evaporated twice with toluen e. Th e m ixture was dissolved in dich lorom eth an e (10 m l)
an d m olecular sieve (4A, 200 m g) an d 2,6-di-tert-butyl-4-m eth ylpyridin e (206 m g, 1.0 m m ol)
were added un der argon . After stirrin g for 1 h , th e solution was cooled to –20 °C an d
N-iodosuccin im ide (225 m g, 1.0 m m ol) was added. Th e solution was stirred overn igh t, acetic
acid (2 m l) an d water (1 m l) were added, an d th e m ixture was stirred for an oth er n igh t. For
workup, som e aqueous NaHCO3 was added an d th e organ ic layer was wash ed with water,
dried over an h ydrous m agn esium sulfate, filtered an d evaporated. Th e rem ain in g crude
product was purified by colum n ch rom atograph y (petroleum eth er–eth yl acetate 2:1) to give
56 m g (0.066 m m ol, 24%) of th e product as colourless syrup: [α ]2D0 –197.4 (c 1.5, CHCl3).
1H NMR (400 MHz, CDCl3): 8.13 (m , 2 H, Bz); 8.04 (m , 2 H, Bz); 7.54 (m , 2 H, Bz); 7.40 (m ,
9 H, Bz, Bn ); 7.18 (m , 2 H, PMB); 6.91 (m , 2 H, PMB); 6.79 (m , 2 H, PMB); 6.62 (m , 2 H,
PMB); 5.66 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5 < 1.0, H-4*); 5.34 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5 < 1.0,
H-4*); 4.94 (d, 1 H, J1,2 = 3.6, H-1); 4.90 (d, 1 H, J1′,2′ = 7.6, H-1′); 4.74 (d, 1 H, J = 12.2,
Bn -a); 4.69 (d, 1 H, J = 11.2, Bn -b); 4.63 (d, 1 H, J = 12.2, Bn -a); 4.62 (d, 1 H, J = 11.7, Bn -c);
4.51 (dd, 1 H, J2,3 = 10.2, J3,4 = 3.5, H-3*); 4.44 (d, 1 H, J = 11.7, Bn -c); 4.31 (d, 1 H, J = 11.2,
Bn -b); 4.21 (dq ≈ q, 1 H, J4,5 < 1.0, J5,6 = 6.6, H-5*); 4.04 (dd, 1 H, J2,3 = 10.2, J3,4 = 3.5,
H-3*); 3.77 (m , 2 H, H-2, H-5*); 3.77 (s, 3 H, OMe); 3.67 (s, 3 H, OMe); 3.37 (dd, 1 H, J1′,2′
7.6, J2′,3′ = 10.2, H-2′); 1.19 (d, 3 H, J5,6 = 6.6, H-6*); 1.17 (d, 3 H, J5,6 = 6.6, H-6*).
=
Meth yl 4-O-Ben zoyl-3-O-(tert-butyldim eth ylsilyl)-2-O-(4-m eth oxyben zyl)-α-L-fucopyran osyl-
(1→3)-4-O-ben zoyl-2-O-(4-m eth oxyben zyl)-1-th io-β-L-fucopyran oside (18)
Com poun d 14 (381 m g, 0.91 m m ol) was evaporated with toluen e an d stirred in a m ixture of
dich lorom eth an e–DMF (10 m l, 1:1) togeth er with m olecular sieve (4A, 500 m g) for 1 h un der
argon . Subsequen tly, tetrabutylam m on ium brom ide (665 m g, 2.07 m m ol) an d acceptor 16
(401 m g, 0.71 m m ol) were added, an d th e m ixture was stirred overn igh t. For workup, th e so-
lids were filtered off, th e solution was wash ed with aqueous NaHCO3 an d water, dried over
an h ydrous m agn esium sulfate, filtered an d evaporated. Th e crude product was purified by
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1778
Ludewig, Thiem:
colum n ch rom atograph y (petroleum eth er–eth yl acetate 10:1) to give 320 m g (0.35 m m ol,
49%) of a colourless syrup: [α ]2D0 –100.9 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 8.03 (m ,
2 H, Bz); 7.97 (m , 2 H, Bz); 7.56 (m , 2 H, Bz); 7.44 (m , 4 H, Bz); 7.36 (m , 2 H, PMB); 7.06
(m , 2 H, PMB); 6.89 (m , 2 H, PMB); 6.68 (m , 2 H, PMB); 5.66 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5.0,
H-4*); 5.28 (d, 1 H, J1′,2′ = 3.6, H-1′); 5.22 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5 < 1.0, H-4*); 4.93 (d, 1 H,
J = 10.2, Bn -a); 4.77 (d, 1 H, J = 10.2, Bn -a); 4.44 (d, 1 H, J1′,2′ = 9.7, H-1′); 4.43 (d, 1 H, J =
11.7, Bn -b); 4.30 (d, 1 H, J = 11.7, Bn -b); 4.26 (m , 2 H, 2 × H-3); 3.98 (dd, 1 H, J1′,2′ = 3.6,
J2′,3′ = 9.7, H-2′); 3.82 (s, 3 H, OMe); 3.76 (s, 3 H, OMe); 3.85–3.72 (m , 3 H, H-2, 2 × H-5);
2.29 (s, 3 H, SMe); 1.22 (d, 3 H, J5,6 = 6.6, H-6*); 0.99 (d, 3 H, J5,6 = 6.6, H-6*); 0.69 (s, 9 H,
t-Bu); 0.04 (s, 3 H, SiMe); –0.03 (s, 3 H, SiMe). 13C NMR (100 MHz, CDCl3): 166.39 (Bz);
166.29 (Bz); 159.51 (Bz); 158.80 (Bz); 133.05, 132.83, 130.38, 129.99, 129.95, 129.78,
129.29, 128.37, 128.28 (Bz, PMB); 113.95 (PMB); 113.37 (PMB); 93.87 (C-1′); 85.47 (C-1);
76.15, 75.94, 75.00, 74.56, 73.51, 69.60, 69.53, 65.40 (2 × C-2, 2 × C-3, 2 × C-4, 2 × C-5);
75.27 (PMB); 71.68 (PMB); 55.35 (OMe); 55.18 (OMe); 25.64 (t-Bu); 17.82 (t-Bu); 16.85
(C-6*); 16.20 (C-6*); 12.66 (SMe); –4.75 (SiMe); –4.97 (SiMe). For C49H62O12SSi (903.2) calcu-
lated: 65.16% C, 6.92% H; foun d: 64.88% C, 7.13% H.
Ben zyl 4-O-Ben zoyl-2-O-(4-m eth oxyben zyl)-α-L-fucopyran osyl-(1→3)-4-O-ben zoyl-
2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (19)
Acceptor com poun d 13 (333 m g, 0.74 m m ol), don or com poun d 15 (500 m g, 0.94 m m ol),
m olecular sieve (4A, 1.0 g), tetrabutylam m on ium brom ide (665 m g, 2.07 m m ol), an d copper(II)
brom ide (457 m g, 2.07 m m ol) un der argon in dich lorom eth an e–DMF (10 m l, 1:1) were
treated an d worked up as described for th e syn th esis of disacch aride 5. Colum n ch rom atog-
raph y (petroleum eth er–eth yl acetate 5:1) furn ish ed 454 m g (0.47 m m ol, 64%) of th e
disacch aride as a colourless syrup. Th is com poun d (410 m g, 0.43 m m ol) an d a 1 M solution
of tetrabutylam m on ium fluoride in THF (5 m l) were stirred at room tem perature overn igh t.
Th e solven t was evaporated an d th e residue dissolved in dich lorom eth an e, wash ed with wa-
ter, dried with an h ydrous m agn esium sulfate, filtered an d evaporated. Th e crude product
was purified by colum n ch rom atograph y (petroleum eth er–eth yl acetate 2:1) to yield 43 m g
of th e product 19 (0.051 m m ol, 12%), 20 m g of th e 3-O-ben zylated product (0.024 m m ol,
5%) an d 262 m g of th e product with out ben zoate at th e n on -reducin g en d (0.352 m m ol,
82%).
Th e latter (230 m g, 0.321 m m ol) was dissolved in dich lorom eth an e (10 m l) an d treated
with trieth yl orth oben zoate (0.22 m l, 0.983 m m ol) an d a speck of 4-toluen esulfon ic acid
an d stirred at room tem perature for 2 h . Acetic acid (5 m l) an d water (1 m l) were added an d
th e solven t was rem oved after 1-h stirrin g. Colum n ch rom atograph y (petroleum eth er–eth yl
acetate 2:1) yielded 156 m g (0.184 m m ol, 57%) of th e product resultin g in an overall
am oun t of 199 m g (0.235 m m ol, 55%): [α ]2D0 –122.5 (c 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3): 8.04 (m , 2 H, Bz); 7.94 (m , 2 H, Bz); 7.58 (m , 2 H, Bz); 7.40 (m , 9 H, Bz, Bn ); 7.23
(m , 2 H, PMB); 7.05 (m , 2 H, PMB); 6.84 (m , 2 H, PMB); 6.69 (m , 2 H, PMB); 5.68 (dd ≈ d, 1 H,
J3,4 = 3.5, J4,5 = 1.0, H-4*); 5.41 (d, 1 H, J1′,2′ = 3.6, H-1′); 5.29 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5
<
1.0, H-4*); 4.97 (d, 1 H, J1,2 = 3.6, H-1); 4.74 (d, 1 H, J = 12.2, Bn -a); 4.64 (d, 1 H, J = 12.2,
Bn -a); 4.61 (d, 1 H, J = 11.2, Bn -b); 4.55 (d, 1 H, J = 11.2, Bn -b); 4.50 (d, 1 H, J = 11.7, Bn -c);
4.46 (dd ≈ m , 1 H, J3,4 = 3.5, H-3*); 4.42 (dq ≈ m , 1 H, J4,5 < 1.0, J5,6 = 6.6, H-5*); 4.32 (d, 1 H,
J = 11.7, Bn -c); 4.20 (dd, 1 H, J2,3 = 10.2, J3,4 = 3.5, H-3*); 4.15 (dq ≈ q, 1 H, J4,5 < 1.0, J5,6
=
6.6, H-5*); 4.00 (dd, 1 H, J1,2 = 3.6, J2,3 = 10.2, H-2*); 3.81 (s, 3 H, OMe); 3.82 (dd ≈ m , 1 H,
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

(1→3)-Linked α-L-Fucose Tetrasaccharide
1779
H-2*); 3.71 (s, 3 H, OMe); 1.11 (d, 3 H, J5,6 = 6.6, H-6*); 1.08 (d, 3 H, J5,6 = 6.6, H-6*).
13C NMR (100 MHz, CDCl3): 171.25 (Bz); 166.47 (Bz); 159.39 (Bz); 159.23 (Bz); 137.60,
133.64, 133.19, 132.97, 130.27, 130.20, 130.01, 129.87, 129.76, 129.49, 129.47, 128.56,
128.40, 128.31, 128.00, 127.80 (Bn , Bz, PMB); 113.85, 113.77 (PMB); 97.72 (C-1*); 92.20
(C-1*); 74.97, 74.25, 73.80, 70.25, 70.06, 67.88 (2 × C-2, 2 × C-3, 2 × C-4); 72.65, 71.45,
69.69 (2 × PMB, Bn ); 65.26 (2 × C-5); 55.32 (OMe); 55.16 (OMe); 16.25 (C-6*); 16.13 (C-6*).
For C49H52O13 (848.9) calculated: 69.33% C, 6.17% H; foun d: 69.04% C, 6.52% H.
Ben zyl 4-O-Ben zoyl-3-O-(tert-butyldim eth ylsilyl)-2-O-(4-m eth oxyben zyl)-
α-L-fucopyran osyl-(1→3)-4-O-ben zoyl-2-O-(4-m eth oxyben zyl)-α-L-fucopyran osyl-
(1→3)-4-O-ben zoyl-2-O-(4-m eth oxyben zyl)-α-L-fucopyran osyl-(1→3)-4-O-ben zoyl-
2-O-(4-m eth oxyben zyl)-α-L-fucopyran oside (20)
Don or disacch aride 18 (45 m g, 49.8 (m ol) an d acceptor disacch aride 19 (57 m g, 67.1 µm ol)
were coevaporated twice with toluen e, dissolved in dich lorom eth an e (3 m l) an d stirred for
1 h togeth er with a fresh ly activated m olecular sieve (4A, 300 m g). Th en , m eth yl triflate
(0.2 m l of a 10% solution in dich lorom eth an e, 0.2 m m ol) was added an d th e solution was
stirred overn igh t un der argon . For workup, first trieth ylam in e (0.1 m l) an d, after 1-h stir-
rin g, a sm all am oun t of solid sodium h ydrogen carbon ate were added. Th e m ixture was evap-
orated togeth er with silica gel an d th e residue purified by colum n ch rom atograph y (petro-
leum eth er–eth yl acetate 3:1) yielded 56 m g (32.8 µm ol, 66%) of a syrupy product: [α ]D20
–444.2 (c 2.6, CHCl3). 1H NMR (500 MHz, CDCl3): 8.02 (m , 2 H, Bz); 7.97 (m , 2 H, Bz); 7.91
(m , 2 H, Bz); 7.86 (m , 2 H, Bz); 7.54 (m , 4 H, 4 × Bz); 7.38 (m , 13 H, 4 × Bz, Bn ); 7.24 (m , 2 H,
PMB); 7.08 (m , 2 H, PMB); 7.03 (m , 2 H, PMB); 6.98 (m , 2 H, PMB); 6.83 (m , 2 H, PMB);
6.72 (m , 2 H, PMB); 6.69 (m , 2 H, PMB); 6.64 (m , 2 H, PMB); 5.63 (dd ≈ d, 1 H, J3,4 = 3.5,
J4,5 < 1.0, H-4d); 5.49 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5 < 1.0, H-4a); 5.27 (d, 1 H, J1,2 = 3.5, H-1a);
5.21 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5 < 1.0, H-4b); 5.11 (d, 1 H, J1,2 = 3.5, H-1b); 5.03 (d, 1 H,
J1,2 = 3.5, H-1c); 5.00 (dd ≈ d, 1 H, J3,4 = 3.5, J4,5 < 1.0, H-4c); 4.92 (d, 1 H, J1,2 = 3.6, H-1d);
4.74 (d, 1 H, J = 12.3, Bn -a); 4.64 (m ≈ d, 2 H, Bn -a, Bn -b); 4.60 (d, 1 H, J = 11.7, Bn -b); 4.52
(d, 1 H, J = 11.0, Bn -c); 4.48 (d, 1 H, J = 11.3, Bn -d); 4.42 (dd, 1 H, J2,3 = 10.4, J3,4 = 3.6,
H-3d); 4.36 (dq, 1 H, J4,5 < 1.0, J5,6 = 6.6, H-5a); 4.32 (m , 4 H, Bn -c, Bn -d, Bn -e, H-3a); 4.19
(dd, 1 H, J2,3 = 10.2, J3,4 = 3.6, H-3b); 4.10 (m , 4 H, Bn -e, H-5b, H-5c, H-5d); 4.04 (dd ≈ m ,
1 H, J2,3 = 10.5, J3,4 = 3.5, H-3c); 4.01 (dd ≈ m , 1 H, J1,2 = 3.6, H-2d); 3.98 (dd, 1 H, J1,2 = 3.5,
J2,3 = 10.4, H-2a); 3.88 (dd, 1 H, J1,2 = 3.5, J2,3 = 10.1, H-2b); 3.80 (s, 3 H, OMe); 3.78 (s, 3 H,
OMe); 3.76 (s, 3 H, OMe); 3.75 (s, 3 H, OMe); 3.63 (dd, 1 H, J1,2 = 3.5, J2,3 = 9.6, H-2c); 1.09
(d, 3 H, J5,6 = 6.6, H-6*); 1.06 (d, 3 H, J5,6 = 6.6, H-6*); 0.78 (d, 3 H, J5,6 = 6.6, H-6*); 0.72 (d,
3 H, J5,6 = 6.6, H-6*); 0.64 (s, 9 H, t-Bu); –0.12 (s, 3 H, SiMe2); –0.20 (s, 3 H, SiMe2).
13C NMR (100 MHz, CDCl3): 166.37 (OBz); 166.28 (OBz); 159.36 (OBz); 159.05 (OBz);
158.95 (OBz); 158.67 (OBz); 137.61, 133.12, 132.97, 132.73, 130.47, 130.41, 130.18, 130.10,
130.06, 130.03, 129.99, 129.95, 129.88, 129.86, 129.79, 129.76, 129.73, 129.41, 129.37,
128.41, 128.38, 128.28, 128.20, 128.17, 128.02, 127.78 (Bn , Bz, PMB); 113.83 (PMB); 113.58
(2 × PMB); 113.22 (PMB); 96.90 (C-1d); 93.34 (C-1a); 93.17 (C-1b); 93.00 (C-1c); 75.11
(C-4c); 73.95 (C-2c); 73.56 (C-2d); 73.21 (C-2a); 72.68 (Bn -b); 72.27 (Bn -c); 72.15 (C-2b);
71.58 (Bn -d); 71.18 (Bn -e); 70.88 (C-3d); 70.75 (C-3a); 70.43 (C-3b); 70.21 (C-4d); 70.15
(C-4a, C-4b); 69.66 (Bn -a); 69.48 (C-3c); 65.34 (C-5a, C-5*); 65.02 (C-5*); 64.82 (C-5*); 55.26
(OMe); 55.21 (2 × OMe); 55.12 (OMe); 25.60 (t-Bu); 17.74 (t-Bu); 16.28 (C-6*); 16.28 (C-6*);
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1780
Ludewig, Thiem:
16.25 (C-6*); 16.00 (C-6*); –4.92 (2 × SiMe). Maldi-Tof (M = 1702.01): 1605.57 (M –
(Bz/PMB) + Na); 1621.57 (M – (Bz/PMB) + K); 1725.66 (M + Na); 1741.64 (M + K).
Support of this work by the Fonds der Chemischen Industrie including a doctoral scholarship to
M. Ludewig is gratefully acknowledged.
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