2-Haloethyl 1-thioglycosides as new tools in glycoside syntheses. Part 1: Preparation, characteristics, general reactions

Article abstract of DOI:10.1135/cccc20041843

2-Haloethyl 1-thioglycosides are excellent leaving groups when the 2-haloethyl function is activated with silver salts or Lewis acids. These thioglycosides can be synthesized on the original Cerny route or for better compatibility with the needs of a more complex glycoside synthesis, in stepwise procedures via 2-(2-tetrahydropyran-2-yloxy)ethyl glycosides or trityl 1-thioglycosides. The initial step in glycosidation reaction presumably proceeds via a thiiranium ion, which is responsible for their increased reactivity compared with normal thioethers as leaving groups in glycoside syntheses. Basic features of this new system with respect to reactivity and selectivity in disaccharide syntheses are described.

Full text of DOI:10.1135/cccc20041843

2-Haloethyl 1-Thioglycosides
1843
2-HALOETHYL 1-THIOGLYCOSIDES AS NEW TOOLS IN GLYCOSIDE
SYNTHESES. PART 1: PREPARATION, CHARACTERISTICS, GENERAL
REACTIONS
1
2,
Andreas KRÜGER, Jutta PYPLO-SCHNIEDERS , Hartmut REDLICH * and
Pär WINKELMANN
3
Organisch-Chemisches Institut der WWU Münster, Corrensstrasse 40, 48149 Münster, Germany;
1
2
3
e-mail: pyplou@uni-muenster.de, redlich@uni-muenster.de, winkelp@uni-muenster.de
Received April 13, 2004
Accepted July 28, 2004
Dedicated to Professor Miloslav Černý on the occasion of his 75th birthday.
2-Haloeth yl 1-th ioglycosides are excellen t leavin g groups wh en th e 2-h aloeth yl fun ction is
activated with silver salts or Lewis acids. Th ese th ioglycosides can be syn th esized on th e
origin al Čern ý route or for better com patibility with th e n eeds of a m ore com plex glycoside
syn th esis, in stepwise procedures via 2-(2-tetrah ydropyran -2-yloxy)eth yl glycosides or trityl
1-th ioglycosides. Th e in itial step in glycosidation reaction presum ably proceeds via a
th iiran ium ion , wh ich is respon sible for th eir in creased reactivity com pared with n orm al
th ioeth ers as leavin g groups in glycoside syn th eses. Basic features of th is n ew system with
respect to reactivity an d selectivity in disacch aride syn th eses are described.
Keyw ord s: Glycosides; Th ioglycosides; Carboh ydrates; Disacch arides; Glycosidation ; Pro-
tectin g groups; Leavin g groups.
In 2-h aloeth yl 1-th ioglycosides, a class of com poun ds first syn th esized an d
described by Čern ý et al.1 in 1959, th e C–h alogen bon d in th e aglycon is
easily h ydrolyzed, as it was dem on strated by th e sam e group2 in 1975. Th e
often observed ease of such type of reaction s, widely used in gen eral ch em -
istry, is a con sequen ce of a β-position ed h etero atom relative to a leavin g
group, wh ich supports th e bon d cleavage (an ch im eric assistan ce)3. Th e re-
action is regarded to proceed via a th iiran ium ion , wh ich is open ed in a sec-
on d step by th e n ucleoph ile.
As sh own in Sch em e 1, th e attack of th e n ucleoph ile on th e th iiran ium
ion gen erated from 2-h aloeth yl 1-th ioglycosides m ay proceed at th e two
equivalen t position s of th e rin g, resultin g in com poun ds m en tion ed above.
If th e carbon of th e C–S bon d of th e th iiran ium ion is attacked by a
n ucleoph ile, for exam ple an alcoh ol, a glycoside sh ould be form ed un der
Collect. Czech. Chem. Commun. (Vol. 69) (2004)
doi:10.1135/cccc20041843

1844
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
expellin g a n eutral eth ylen e sulfide. Herein we describe, th at th is way can
be favoured by th e reaction con dition s to such an exten t, th at glycosides
are th e on ly products. With th at, 2-h aloeth yl 1-th ioglycosides represen t a
n ew type of leavin g groups in glycoside syn th eses, in wh ich th e an om eric
sulfur is activated from a “rem ote” position (rem ote activation )4.
O
O
- Br
S
S
Br
thiiranium ion
H2O
O
S
OH
SCHEME 1
Substition reaction of 2-h aloeth yl 1-th ioglycosides via th iiran ium ion s accordin g to Čern ý
Sch em e 2 in dicates a large variety of possible m an ipulation s at th e leav-
in g group. Besides th e oxidation state of th e sulfur, th e eth ylen e m oiety al-
lows differen t substitution pattern to in fluen ce th e reaction . Th e leavin g
group can be arran ged in th e way th at it fits best to a prom otor. In th is pa-
per we describe various appraoch es to 2-h aloeth yl 1-th ioglycosides, reflect-
in g th eir availability for m ore com plex glycoside syn th eses an d th eir reac-
tion with in reactive h ydroxy groups of carboh ydrate derivatives to yield
disacch arides5. In th e followin g paper we will report a m ore com plex syn -
th esis of a spacered tetrasacch aride based on th e m eth ods described h ere.
influence of substituents
degree of oxidation
O
R
R
R
promoter
LG
OR
S
R
ROH
type of
activity
leaving group
SCHEME 2
Possible m an ipulation s at th e leavin g groups
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1845
New Preparations of 2-Haloethyl 1-Thioglycosides by the Černý Route
Th e origin al procedure seem s to be in depen den t of th e con figuration of th e
startin g m aterial. Th ere are n o sign ifican t differen ces startin g from th e un -
protected 1-th iols with th e con figuration s sh own in Sch em e 3 (gluco-,
galacto- or manno-con figuration ) to obtain eith er th e 2-brom o- (4β 1, 5β 2,
6α) or 2-ch loroeth yl products (7β, 8β)6 in h igh yield. As it will be sh own
later, th ese com poun ds can be used directly in glycoside syn th esis, but th ey
do n ot allow an y furth er m an ipulation at th e glycosyl residue, due to th e
m en tion ed reactivity of th eir aglycon ic part.
O
O
(i) or (ii)
84-96%
Hal
4 X OAc
4 X OAc
SH
S
1-3
4-6 Hal = Br; 7-8 Hal= Cl
1, 4, 7 β−D-gluco
2, 5, 8 β−D-galacto
3, 6 α-D-manno
(i) 1,2-dibromomethane, K2CO3, H2O, acetone; (ii) 1-bromo-2-chloroethane, K2CO3, H2O, acetone
SCHEME 3
Preparation of 2-h aloeth yl 1-th ioglycosides from 1-th iols (an alogue Čern ý)
New Routes to 2-Haloethyl 1-Thioglycosides
For m ore advan ced application s of 2-h aloeth yl 1-th ioglycosides in glyco-
side syn th eses, it is n ecessary th at th eir reactivity at th e glycosyl residue be
dim in ish ed durin g syn th etic m an ipulation s. Th ere are several option s for
th is purpose: An in terestin g on e is in dicated in Sch em e 4. In stead of usin g
th e dih alo com poun ds for th e alkylation of th e 1-un protected th iols,
2-brom oeth an ol can be used to yield th e correspon din g 2-h ydroxyeth yl
6
1-th ioglycosides of type 9 . Th e h ydroxy group in th e aglycon part of th e
m olecule can be protected as a n orm al reactive h ydroxy group, for exam ple
as a tetrah ydropyran yl (THP) eth er 10. Th e sam e product is directly avail-
able from th e THP eth er of 2-brom oeth an ol (13)7 an d th e 1-un protected
th iol fun ction in 1. Such com poun ds can be deacetylated for exam ple,
reesterified to a tetraben zoate 11 or reben zylated to a tetraben zyl eth er 12,
allowin g th erefore sm all variation s in th e aglycon part of th e m olecule. Th e
use of th e THP eth er as a protection group for th e h ydroxy group in th e
aglycon part h as th e advan tage th at th is fun ction can be tran sform ed di-
rectly in to a brom o fun ction (4β, 14, 15) by applyin g th e m ild Appel sys-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1846
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
tem 8 PPh 3/CBr4. Th is allows to reactivate th e leavin g group at an appropri-
ate tim e in syn th esis.
OR
O
(i)
RO
RO
1
S
RO
OR´
1
9
R=Ac; R´=H
(iii)
DHP, PPTS, 92 %
10 R=Ac; R´=THP
11 R=Bz; R´=THP (95%)
12 R=Bn; R´=THP (90%)
+
84 %
(iv)
(v)
OTHP
Br
Br
13
(ii)
OR
10
11
12
(vi)
O
OH
RO
RO
S
RO
Br
4
R=Ac (77%)
14 R=Bz (78%)
15 R=Bn (69%)
(i) 2-bromoethanol, K2CO3, H2O, acetone; (ii) DHP, PPTS, CH2Cl2, quant.;
(iii) K2CO3, H2O, acetone; (iv) 1. NaOMe, MeOH, 2. BzCl, pyridine;
(v) 1. NaOMe, MeOH, 2. BnBr, NaH, DMF; (vi) PPh2/CBr4, CH2Cl2
SCHEME 4
Preparation of 2-brom oeth yl 1-th ioglycosides from THP eth ers
In th is study, m ost of th e n ewly described 2-h aloeth yl 1-th ioglycosides
are syn th esized startin g from th e 1-un protected th iol an d usin g th e trityl
group as an in term ediate protection for th e an om eric cen tre. Th e acetylated
9
S-trityl-protected com poun ds (16 , 20 10, 23 11) are available from th e un -
protected th iols usin g two differen t procedures. Un der basic con dition s
with trityl ch loride in pyridin e or in dich lorom eth an e an d trieth ylam in e
(Sch em e 5, (i), (ii)) or to advan tage, un der n early n eutral con dition s with
trityl alcoh ol an d a catalytic am oun t of CF3CO2H (Sch em e 5, (iii))12. As
sum m arized in Sch em e 5, th e average yields are excellen t for th e isolated
products 16, 20 an d 23 an d in depen den t of th e con figuration of th e start-
in g m aterials. Th e S-trityl-protected an om eric cen tre allows for exam ple
deacetylation at th e glycosyl residue, in corporation of a ben zyliden e acetal
with ben zaldeh yde an d sulfuric acid (40) in a typical stron g acidic proce-
dure, or ben zylation with NaH/ben zyl brom ide as th e typical stron g basic
procedure (41). Th e yields for both reaction s are excellen t, in dicatin g th at
th e S-trityl protected an om eric cen tre allows a large variety of syn th etic m a-
n ipulation s on th e glycosyl part of th e m olecule.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1847
Th e cleavage to th e 1-un protected th iols (1–3 an d 26 13–32) is easily car-
ried out with th e system CF3CO2H/Et3SiH in dich lorom eth an e described by
Pearson et al.14 Th e subsequen t gen eration of th e 2-h aloeth yl 1-th ioglyco-
sides proceeds in h igh yields usin g th e Čern ý route (14, 15, 33, 34 an d
35–39), as sum m arized in Sch em e 5.
O
Ph
O
40 R=H (81%)
41 R=Bn (95%)
O
STr
STr
RO
OR
j)
(i)
1
1
O
(iv)
(v) or (vi)
O
O
(ii)
Hal
S
SH
4 X OR
4 X OR
1
2
3
4 X OR
(iii)
1
β−
D
-gluco
16 R=Ac (82%)
17 R=Bz (96%)
18 R=Piv (70%)
19 R=Bn (90%)
14(β) R=Bz, Hal=Br (78%)
33(β) R=Bz, Hal=Cl (95%)
34(β) R=Piv, Hal=Br (92%)
15(β) R=Bn, Hal=Br (69%)
35(β) R=Bn, Hal=Cl (90%)
(vii):
(viii):
(ix):
26 R=Bz (α+β; 89%)
27 R=Piv (β; 92%)
28 R=Bn (β; 86%)
β−D-galacto
20 R=Ac (91%)
(vii): 21 R=Bz (95%)
2
29 R=Bz (β; 88%)
30 R=Bn (β; 88%)
36(β)
37(β)
R=Bz, Hal=Br (92%)
R=Bn, Hal=Br (85%)
(ix):
22 R=Bn (86%)
α−D-manno
23 R=Ac (84%)
24 R=Bz (93%)
25 R=Bn (76%)
3
(vii):
(ix):
31 R=Bz (α; 87%)
32 R=Bn (α; 83%)
38(α)
39(α)
R=Bz, Hal=Br (89%)
R=Bn, Hal=Br (80%)
(i) TrCl, pyridine; (ii) TrCl, Et3N, CH2Cl2; (iii) TrOH, CF3COOH, CH2Cl2; (iv) CF3COOH, Et3SiH, CH2Cl2;
(v) 1,2-dibromoethane, K2CO3, H2O, acetone; (vi) 1-bromo-2-chloroethane, K2CO3, H2O, acetone;
(vii) 1. NaOMe, MeOH, 2. BzCl, pyridine; (viii) 1. NaOMe, MeOH, 2. PivCl, pyridine; (ix) 1. NaOMe,
MeOH, 2. BnBr, NaH, DMF; (x) 1. NaOMe, MeOH, 2. PhCHO, H2SO4, DMF
SCHEME 5
Preparation of 2-brom oeth yl 1-th ioglycosides from trityl 1-th ioglycosides
A sin gular result (Sch em e 6) dem on strates th e differen ces between a
S-trityl-protected an d a 2-ch loroeth yl-protected an om eric cen tre 7β. Both
allow deacetylation of th e glycosyl residue. Wh ile th e form er allows th e
ben zyliden ation at th e glycosyl part un der stron g acidic con dition s
(Sch em e 4, (xi)), th e latter can on ly be isopropyliden ated in a fast reaction
to com poun d 42. Th is com poun d suffers from elim in ation in a clean reac-
tion durin g ben zylation with NaH/Bn Br in DMF in th e aglycon ic part to
yield th e S-vin yl eth er 43. In terestin gly, th is com poun d sh owed a very low
reactivity in th e syn th esis with th ioglycosides un der th e reaction con di-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1848
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
tion s, n orm ally supportin g th e glycoside syn th esis. Th e vin yl group in 43
can be refun ction alized by h ydroboration to th e 2-h ydroxyeth yl m oiety
(44) an d by brom in ation with th e Classon 15 system Br2/ClPPh 2/im idazole.
O
O
O
O
(i)
(ii)
O
O
7β
S
S
BnO
HO
OBn
OH
Cl
43
42
O
O
O
BnO
(iii)
S
R
OBn
R=OH
R=Br
44
45
(iv)
(i) 1. NaOMe, MeOH, 2. 2,2-dimethoxypropane, TsOH, 72%; (ii) NaH, BnBr, DMF, 82%;
(iii) BH3·SMe2/H2O2, 72%; (iv) Br2, ClPPh2, imidazole, 85%
SCHEME 6
2-Haloeth yl com poun ds with varyin g protectin g groups
Applications of 2-Bromoethyl Thioglycosides in Glycoside Syntheses
Com pared to th e correspon din g ch loro com poun ds th e 2-brom oeth yl
1-th ioglycosides sh ow, as it can be expected, always a h igh er reactivity.
Here, on ly th is type of com poun ds is regarded. In a basic experim en t, com -
poun d 4β reacts in n itrom eth an e with 1.5 equivalen ts of th e very reactive
cycloh exan ol un der th e prom otion of silver triflate in a sm ooth reaction to
two differen t com poun ds. On e is th e substitution product at th e eth ylen e
m oiety (47) (30%), th e oth er is cycloh exyl glycoside 46 16 (40%) (Sch em e 7).
Th e m ost strikin g aspect of th is reaction is th e α-con figuration of th e
form ed cycloh exyl glycoside. Th is fits very good with th e idea, as already
discussed, th at th e reaction proceeds via a th iiran ium ion , wh ich , if at-
tacked by th e n ucleoph ile at th e eth ylen e m oiety, leads to th e substitution
product 47, or, if attacked by th e n ucleoph ile at th e an om eric cen tre an d
expellin g th e n eutral an d very soft th iiran e, results in glycoside 46. Th e lat-
ter process h as to be so fast an d dom in an t th at th e expected n eigh borin g
group participation of th e ester fun ction at C-2 does n ot take place. Th is ef-
fect could n o lon ger be observed if th e ester fun ction s were ch an ged in th e
glycosyl acceptor (for exam ple ben zoates or pivalates) or if th e reactivity of
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1849
th e glycosyl don or was m uch lower com pared to cycloh exan ol. Neverth e-
less th is basic fin din g in dicates th e n ew type of assistan ce in th e glyco-
sidation process.
OAc
O
AcO
AcO
OAc
HO
AcO
46 40%
OAc
O
AcO
AcO
AgOTf
O
S
AcO
CH3NO2
Br
4β
O
AcO
AcO
S
AcO
O
47 30%
SCHEME 7
Glycosidation reaction of 4β with cycloh exan ol
Th e basic beh aviour of β-brom oeth yl 1-S-glyosides in glycoside syn th eses
with less reactive glycosyl don ors are sum m arized in Table I. Com poun d 14
represen ts ester-fun ction alized, com poun d 15 eth er-fun ction alized glycosyl
don ors. Th e 6-un protected com poun ds carry eith er acetate groups17 (48) or
ben zyl groups18 (49), represen t th e m ore reactive glycosyl don ors, th e
4-un protected com poun d19 (50) h as in gen eral a very low reactivity. Th e
glycosidation s were carried out un der stan dard con dition s (1.0 equivalen t
of glycosyl don or, 1.2 equivalen ts of h ydroxy com poun d, 1.5 equivalen ts of
th e silver salt or a Lewis acid, room tem perature) with out an y special pre-
caution s with respect to yield an d selectivity, to m ake th e results of th e re-
action s com parable. As it can be seen in Table I, in depen den tly of th e type
of glycosyl don or an d glycosyl acceptors, th e yields are gen erally h igh or
even excellen t. In polar solven ts n itrom eth an e, dioxan e an d aceton itrile,
silver triflate is an excellen t prom oter, surprisin gly in th e less polar solven t
dich lorom eth an e Sn Cl4 is th e best. Th e don or 14 with β-con figuration al-
ways results in th e β-lin ked disacch arides (en tries 1–4), in dicatin g a n eigh -
borin g group participation durin g th e bon d form ation . Th e don or 15 with
β-con figuration , a com poun d with out th e possibility of n eigh borin g group
assistan ce, sh ows in th e solven ts n itrom eth an e, dioxan e an d dich loro-
m eth an e an in terestin gly h igh ten den cy to form th e α-lin ked disacch arides
(en tries 5, 6 an d 8). In aceton itrile th e opposite ten den cy can be observed,
in dicatin g th e occurren ce of an in term ediate n itrilium ion 20. Addition al ex-
am ples will be discussed in th e n ext paper.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1850
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
OR1
OR
O
O
R2O
RO
RO
S
R3O
RO
Br
R3O
OMe
14 R=Bz
15 R=Bn
48 R1=H, R2, R3= Ac
49 R1=H, R2, R3= Bn
50 R1, R3=Bn, R2=H
OR1
O
OR1
R1O
R1O
OR2
O
O
OR1
R1O
R1O
O
R2O
O
R2O
O
R2O
R2O
OR1
R2O
OMe
OMe
51 R1=Bz, R2=Ac
52 R1=Bz, R2=Bn
53 R1, R2=Bn
54 R1=Bz, R2=Bn
55 R1,R2=Bn
TABLE I
Selected glycosidation reaction s with stan dard h ydroxy com poun ds
Glycosyl
don or
Glycosyl
acceptor
Selectivity
(α:β)
En try
Product
Prom oter Solven t
Yield, %
1
2
3
4
5
6
7
8
14
14
14
14
15
15
15
15
48
49
50
48
49
49
49
50
5121
5222
5423
51
AgOTf
AgOTf
AgOTf
Sn Cl4
CH3NO2
CH3NO2
CH3NO2
CH2Cl2
dioxan e
CH2Cl2
CH3CN
dioxan e
78
80
71
83
81
84
92
74
0:1
0:1
0:1
0:1
6:1
4:1
1:6
8:1
5324
AgOTf
Sn Cl4
53
53
AgOTf
AgOTf
5523
2,2-Dialkyl-2-haloethyl 1-Thioglycosides
Th e results described above refer to th e basic system with out an y substitu-
en ts at th e eth ylen e m oiety in th e aglycon part. To clarify th e in fluen ce of
substituen ts in th is part of th e m olecule th e 2,2-dim eth yl-2-brom oeth yl
1-th ioglycosides 56 an d 57 were syn th esized. Th e syn th eses (Sch em e 8) fol-
low th e gen eral m eth ods already described (58–61).
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1851
OR
OR
(i)
(ii) or (iii)
O
O
1
28
RO
RO
RO
RO
S
S
OH
Hal
RO
RO
58 R=Ac, Hal=Br 79%
59 R=Ac, Hal=Cl 84%
60 R=Bn, Hal=Br 70%
61 R=Bn, Hal=Cl 73%
56 R=Ac 71%
57 R=Bn 71%
(i) 2-chloro-2-methylpropan-1-ol, K2CO3, acetone, H2O; (ii) PBr3, CHCl3; (iii) PCl3, CHCl3
SCHEME 8
Preparation of 2,2-dialkyl-2-h aloeth yl 1-th ioglycosides
In particular th e glycosyl don or 60 an d th e glycosyl acceptor 49 sh ow a
very clear result with respect to th e application of such com poun ds in
glycoside syn th eses. In gen eral, com poun ds of type 60 exh ibit a h igh er re-
activity, com pared with th e basic system . Th erefore th e glycosylation s were
carried out at lower tem peratures (Table II). In dieth yl eth er, toluen e,
n itrom eth an e, tetrah ydrofuran e, N,N-dim eth ylform am ide an d dich loro-
m eth an e, solven ts coverin g a broad spectrum of polarities, on ly th e product
of substitution in th e aglycon part, 62, could be isolated in varyin g
am oun ts (en tries 1, 2, 5–9). Th is is in good accordan ce with th e idea
th at, caused by th e substituen ts, a “h arder” electroph ilic cen tre will favour
th e attack of a “h ard” n ucleoph ile (th e OH fun ction ) in th is part of th e
m olecule. In case of aceton itrile, as it was already described for th e basic
system , th e n itrilium ion is in volved. Wh en th is is form ed, th e resultin g
reaction product is a glycoside, obtain ed with an excellen t yield an d selec-
tivity (en tries 3 an d 4).
OBn
OBn
O
O
BnO
BnO
BnO
BnO
S
Br
O
BnO
BnO
O
60
BnO
BnO
53
+
BnO
OMe
OBn
OH
O
O
BnO
BnO
BnO
BnO
S
BnO
BnO
O
OMe
O
BnO
49
62
BnO
BnO
OMe
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1852
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
TABLE II
Orien tation glycosidation reaction sa with tertiary reaction cen tre
En try
Solven t
Tem perature, °C Yield, %
Product
Selectivity (α:β)
1
2
3
4
5
6
7
8
9
Et2O
0→20
–20
72
62
89
91
70
60
34
17
75
62
62
53
53
62
62
62
62
62
–
Et2O
–
CH3CN
CH3CN
Toluen e
CH3NO2
THF
0→20
–20
1:7
1:22
–20
–
–
–
–
–
–20
–20
DMF
–20
CH2Cl2
–20
a
Gen eral procedure: 100 m g (0.14 m m ol) of 60 was glycosylated with th e h ydroxy com -
poun d 49 accordin g to Gen eral procedure 5 (see Experim en tal)
CONCLUSIONS
Th e availability of 2-h alogen oeth yl 1-th ioglyosides, origin ally described by
Čern ý et al., can be exten ded, coverin g especially th e n ecessities for
glycoside syn th eses. Th is n ew type of leavin g group in glycoside syn th eses
sh ows excellen t reactivity an d good ten den cies to selectivity.
EXPERIMENTAL
All reaction s were m on itored by TLC on silica gel (Merck, GF254) usin g m ixtures of
cyloh exan e an d eth yl acetate (CH/EA). All solven ts were distilled. Detection was carried out
by UV spectra, reaction with 0.2% eth an olic n aph th alen e-1,3-diol solution /1 M H2SO4 (1:1)
an d h eatin g. Separation s were carried out usin g preparative colum n ch rom atograph y on
silica gel (70–230 m esh ) at n orm al pressure or on silica gel 60 (230–400 m esh ) at
0.2–0.4 MPa usin g th e solven t m ixtures m en tion ed above. Meltin g poin ts were m easured on
an electroth erm al m eltin g poin t apparatus an d were n ot corrected. Optical rotation s were
m easured on a Perkin –Elm er polarim eter 241 usin g 1 dm cells, [α ]2D0 values are given in
10–1 deg cm 2 g–1 1H NMR spectra were recorded on a Bruker WM 300 (1H: 300.13 MHz,
.
13C: 75.48 MHz) spectrom eter usin g TMS as in tern al stan dard. All spectra were an alyzed
as first-order spectra. Couplin g con stan ts (J) are given in Hz. Acetylation of rem ain in g free
OH groups led to com poun ds h avin g 1H NMR spectra wh ich could be easily an alyzed be-
cause of th e down field sh ift of th e correspon din g h ydrogen atom s. Th erefore, com poun ds
with free h ydroxy groups are ch aracterized as acetates (see Gen eral procedure 1). All evapo-
ration s were carried out at 40 °C in vacuo.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1853
Gen eral Procedure 1: Esterification (O-Acetylation , O-Pivaloylation , O-Ben zoylation )
Th e carboh ydrate com poun d (1 m m ol per equivalen t OH) was dissolved in an h ydrous pyri-
din e (3 m l). Ac2O (0.1 m l, 1.1 m m ol) or PivCl (6 equiv. per m m ol OH) or ben zoyl ch loride
(6 equiv. per m m ol OH) an d a catalytic am oun t of DMAP was added. After th e reaction was
com plete, th e m ixture was con cen trated un der reduced pressure, codistilled with toluen e
(wh en usin g ben zoyl ch loride was used, wash in g of th e organ ic layer with 10% HCl, a satu-
rated sodium h ydrogen carbon ate solution an d water were preferred) an d purified by colum n
ch rom atograph y.
Gen eral Procedure 2: De-O-acetylation
Th e carboh ydrate com poun d was dissolved in m eth an ol. Sodium m eth an olate was added
un til pH 10–11 was reach ed. After th e reaction was com plete (TLC m on itorin g), th e m ixture
was n eutralized with acid ion exch an ge resin (Dowex 50 WX8, H+-form ). Th e resin was fil-
tered off, wash ed with m eth an ol an d th e solven t was rem oved in vacuo.
Gen eral Procedure 3: O-Ben zylation
Th e carboh ydrate com poun d was dissolved in an h ydrous N,N-dim eth ylform am ide, cooled in
an ice bath an d sodium h ydride (60 or 80% dispersion in m in eral oil, 2 equiv. per OH
group) was added. After 30 m in , ben zyl brom ide (1.5 equiv. per OH group) was slowly
dropped to th e suspen sion an d stirred at room tem perature. After th e reaction was com plete
excess of sodium h ydride was destroyed with m eth an ol, an d th e solution was reduced in
h igh vacuo. Th e residue was extracted with eth yl acetate/water, th e organ ic layer dried with
an h ydrous MgSO4, filtered an d reduced. Colum n ch rom atograph y followed.
Gen eral Procedure 4: S-Alkylation of Th ioglycosides
Th e th ioglycoside (1 m m ol) was dissolved in aceton e (1–2 m l) an d th e alkylation reagen t
(2 equiv., with 1,2-dibrom oeth an e an d 1-brom o-2-ch loroeth an e 4 equiv.) was added. A solu-
tion of 1.2 m m ol K2CO3 in 1–2 m l of water was added. With acetyl derivatives, th e reaction
was quen ch ed after 1 h , oth erwise deacetylation took place. Th erefore, 10–20 m l of water was
added an d th e solution was extracted (3×) with 40 m l of eth yl acetate. Th e organ ic layer was
dried with an h ydrous MgSO4, filtered an d con cen trated. Colum n ch rom atograph y followed.
Gen eral Procedure 5: Glycosidation with Silver Salts
Un der argon atm osph ere th e glycosyl com poun d (1.0 equiv.) an d th e h ydroxy com poun d
(1.2 equiv.) were dissolved in an an h ydrous. solven t (5 m l per 100 m g) an d stirred with
powdered m olecular sieve 4A for 4 h . After th at th e silver salt (1.5 equiv.) was added an d
th e reaction m ixture was stirred in th e dark. After stirrin g overn igh t, th e reaction m ixture
was filtered over Celite, wash ed with saturated aqueous sodium h ydrogen carbon ate, dried,
con cen trated an d purified by colum n ch rom atograph y.
Gen eral Procedure 6: Glycosidation with Lewis Acids
Un der argon atm osph ere th e glycosyl com poun d (1.0 equiv.) an d th e h ydroxy com poun d
(1.2 equiv.) were dissolved in th e an h ydrous solven t (5 m l per 100 m g) an d stirred with
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1854
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
powdered m olecular sieve 4A for 4 h . After th at th e Lewis acid (1.5 equiv.) was added. After
stirrin g overn igh t, trieth ylam in e (1.0 equiv.) was added an d th e m ixture was stirred for an -
oth er h our. Th e m olecular sieves were filtered off an d th e resultin g solution was con cen -
trated an d purified by colum n ch rom atograph y.
Gen eral Procedure 7: Halogen ation with Ph osph orus(III) Halides
Th e alcoh ol was dissolved in an h ydrous. ch loroform (4 m l per m m ol) an d stirred for 1 h
with powdered m olecular sieve 4A. After coolin g to 0 °C ph osph orus h alide (0.4 equiv.) was
dropped slowly to th e solution . After 60-m in coolin g it was stirred at room tem perature for
5 h . Th e reaction was quen ch ed with m eth an ol an d solid sodium h ydrogen carbon ate was
added. After filtration , th e solution was con cen trated, th e residue was extracted with di-
ch lorom eth an e, wash ed with water an d dried. Th e crude product was purified by colum n
ch rom atograph y.
Gen eral Procedure 8: Detritylation of Trityl 1-Th ioglycosides
Th e trityl 1-th ioglycoside was dissolved in an h ydrous dich lorom eth an e (5 m l per m m ol) an d
th e sam e am oun t of trifluoroacetic acid was added. Trieth ylsilan e (1.2 equiv.) was directly
given to th e solution , wh ich led to decolorization . After 10 m in th e reaction was usually
com plete. Th e m ixture was con cen trated un der reduced pressure. Th e residue was diluted
with dich lorom eth an e an d wash ed with water, saturated sodium h ydrogen carbon ate solu-
tion an d water, dried with an h ydrous MgSO4, filtered an d th e solven t was rem oved. Th e
crude product was purified by colum n ch rom atograph y.
2-Brom oeth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-glucopyran oside (4β)
a) Com poun d 1 (6.20 g, 17 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 5/1). Yield 6.97 g (87%),
wh ite crystals, m .p. 104 °C, [α ]D20 –32.1 (c 1.0 in MeOH); reported1 m .p. 106–108 °C, [α ]2D0
–29.7 (c 1.07 in CHCl3). For C16H23BrO9S (471.4) calculated: 40.77% C, 4.92% H; foun d:
40.71% C, 4.85% H.
b) Tetrabrom oeth an e (283 m g, 0.85 m m ol) was added un der argon atm osph ere to a solu-
tion of com poun d 10 (300 m g, 0.61 m m ol) in an h ydrous dich lorom eth an e. After 10 m in
th e reaction m ixture was cooled to 0 °C an d 450 m g (2.8 m m ol) triph en ylph osph in e was
added. After stirrin g at room tem perature overn igh t, th e m ixture was passed th rough a sm all
silica gel layer. Th e filtrate was con cen trated followed by a colum n ch rom atograph y (CH/EA =
5/1). Yield 221 m g (77%).
2-Brom oeth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-galactopyran oside (5β)
Com poun d 2 (4.50 g, 12.36 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 5/1). Yield 5.59 g (96%),
wh ite crystals, [α ]2D0 –5.0 (c 0.9 in CDCl3); reported2 [α ]D20 –5.7 (c 1.0 in CHCl3).
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1855
2-Brom oeth yl 2,3,4,6-Tetra-O-acetyl-1-th io-α-D-m an n opyran oside (6α)
Com poun d 3 (2.00 g, 3.27 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 6/1). Yield 2.09 g (89%),
wh ite crystals, m .p. 79–81 °C, [α ]2D0 –17.0 (c 1.0 in CHCl3).
2-Ch loroeth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-glucopyran oside (7β)
Com poun d 1 (9.84 g, 27 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e crude
product was purified by colum n ch rom atograph y (CH/EA = 5/1). Yield 10.37 g (90%), wh ite
crystals, m .p. 98 °C, [α ]2D0 –25.4 (c 1.0 in MeOH); reported6 m .p. 97–98 °C, [α ]2D0 –38 (c 0.7 in
CHCl3). For C16H23ClO9S (426.9) calculated: 45.02% C, 5.43% H; foun d: 45.27% C, 5.42% H.
2-Ch loroeth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-galactopyran oside (8β)
Com poun d 2 (0.75 g, 2.06 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 5/1). Yield 880 m g (92%),
wh ite crystals, m .p. 75–77 °C, [α ]D20 –8.6 (c 1.0 in CDCl3); reported6 m .p. 76–78 °C, [α ]2D0 –10
(c 1.2 in CHCl3).
2-Hydroxyeth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-glucopyran oside (9)
Com poun d 1 (1.00 g, 2.74 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 2/1). Yield 884 m g (79%),
colorless crystals, m .p. 70 °C, [α ]D20 –28.0 (c 1.0 in MeOH); reported6 m .p. 70–73 °C, [α ]2D0 –14
(c 0.5 in CHCl3). For C16H24O10S (408.5) calculated: 47.04% C, 5.93% H; foun d: 47.12% C,
5.98% H.
Acetate 1H NMR (300 MHz, CDCl3): 5.22 dd, 1 H, J(2,3) = 9.4, J(3,4) = 9.4 (H-3); 5.07 dd,
J(2,3) = 9.4, J(1,2) = 10.0 (H-2); 5.02 dd, J(3,4) = 9.4, J(4,5) = 9.8 (H-4); 4.54 d, J(1,2) = 10.0
(H-1); 4.25 m , 2 H (CH2OCOCH3); 4.22 dd, J(5,6) = 5.0, J(6,6′) = 12.2 (H-6); 4.14 dd, 1 H,
J(5,6′) = 2.6, J(6,6′) = 12.2 (H-6′); 3.72 ddd, 1 H, J(4,5) = 9.8, J(5,6) = 5.0, J(5,6′) = 2.6 (H-5);
2.89 m , 2 H (SCH2); 2.08, 2.06, 2.05, 2.02, 2.00 5 × s, 5 × 3 H (5 × OAc). 13C NMR (75 MHz,
CDCl3): 170.63, 170.60, 170.20, 169.54, 169.36 (OAc), 83.61 (C-1), 75.98, 73.71, 69.74,
68.20 (C-2, C-3, C-4, C-5), 63.57, 62.02 (CH2OAc or C-6), 28.69 (SCH2), 20.82, 20.76, 20.72,
20.65, 20.55 (OCOCH3).
2-(Tetrah ydropyran -2-yloxy)eth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-glucopyran oside (10)
From the alcohol 9 5: Com poun d 9 (900 m g, 2.20 m m ol) was dissolved in an h ydrous di-
ch lorom eth an e (15 m l), 3,4-dih ydro-2H-pyran e (0.3 m l, 3.30 m m ol) an d pyridin ium tosylate
(PPTS) (55 m g, 0.22 m m ol) were added an d th e solution was stirred overn igh t. For work-up
20 m l dieth yl eth er was added, th e organ ic layer was wash ed with h alf-con cen trated sodium
ch loride solution an d dried with an h ydrous MgSO4, filtered an d con cen trated in vacuo. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 4/1). Yield 996 m g (92%),
colorless syrup, diastereom eric m ixture (1:1), [α ]2D0 –28.0 (c 1.0 in MeOH). Selected 1H NMR
data: 4.65–4.58 m (H-1, THP acetal-H); 3.96–3.80 (THP-CH2); 3.73–3.65 m (H-5), 3.64–3.59 m
(CH2OTHP); 3.55–3.45 m (THP-CH2); 3.03–2.90 m (SCH2′); 2.85–2.73 m (SCH2); 2.07, 2.04,
2.01 1.99 4 × s (4 × OAc); 1.90–1.35 m (THP-CH2). 13C NMR (75 MHz, CDCl3, double sig-
n als): 98.99, 98.71 (THP acetal-C), 83.78, 83.68 (C-1), 75.88, 73.90, 70.06 (C-2, C-3, C-4),
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1856
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1857
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1858
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
68.35 (C-5), 67.37, 67.24, 62.32, 62.12 (THP-C-6, C-6), 30.52, 29.93, 29.76, 26.89, 25.37
(THP-C-3, THP-C-4, SCH2, CH2OTHP), 20.96, 20.64, 20.54 (OCOCH3), 19.45, 19.31
(THP-C-4).
From the thiol 1: Com poun d 1 (2.40 g, 6.59 m m ol) was alkylated accordin g to Gen eral
procedure 4 with 2-[(2-brom oeth yl)oxy)]tetrah ydropyran (13; 2.76 g, 13.2 m m ol). Th e crude
product was purified by colum n ch rom atograph y (CH/EA = 4/1). Yield 2.27 g (84%), color-
less syrup.
2-[2-(Brom oeth yl)oxy]tetrah ydropyran (13)
2-Brom oeth an ol (3.0 m l, 42.3 m m ol) was dissolved in an h ydrous dich lorom eth an e (30 m l),
3,4-dih ydro-2H-pyran (5.79 m l, 63.5 m m ol) an d pyridin ium tosylate (PPTS) (1.06 g,
4.23 m m ol) were added, an d th e solution was stirred overn igh t. For work-up dieth yl eth er
(30 m l) was added, th e organ ic layer was wash ed with h alf con cen trated sodium ch loride so-
lution an d dried with an h ydrous MgSO4, filtered an d con cen trated in vacuo. Th e crude
product was purified by colum n ch rom atograph y (CH/EA = 3/1). Yield 8.84 g (quan tita-
tively), colorless syrup. 1H NMR (300 MHz, CDCl3): 4.58–4.64 m , 1 H (OCHO); 3.95 ddd,
1 H, J = 6.4, J′ = 6.6, J′′ = 11.4 (CH2′Br); 3.78–3.88 m , 1 H (THP-CH2); 3.70 ddd, 1 H, J = 6.4,
J′ = 6.6, J′′ = 11.4 (CH2Br); 3.40–3.51 m , 3 H (THP-CH2, CH2OTHP, CH2′OTHP); 1.41–1.87 m ,
6 H (THP-CH2). 13C NMR (75 MHz, CDCl3): 98.22 (THP-C-2), 67.45 (CH2OTHP), 62.13
(THP-C-6), 30.69 (CH2Br), 30.35 (THP-C-3), 24.78 (THP-C-5), 19.16 (THP-C-4).
2-(Tetrah ydropyran -2-yloxy)eth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-glucopyran oside (11)
Th e peracetylated THP eth er 10 (500 m g, 1.01 m m ol) was deacetylated accordin g to Gen eral
procedure 2. After th at, th e crude product was ben zoylated accordin g to Gen eral procedure
1. Th e crude product was purified by colum n ch rom atograph y (CH/EA = 4/1). Yield 714 m g
(95%), colorless syrup, diastereom eric m ixture (1:1). For C41H40O11S (740.9) calculated:
66.46% C, 5.45% H; foun d: 66.55% C, 5.59% H.
Selected 1H NMR data: 8.10–7.24
m (arom . H); 4.65–4.57 m (H-1, THP acetal-H);
3.95–3.80 (THP-CH2); 3.73–3.65 m (H-5); 3.66–3.59 m (CH2OTHP); 3.53–3.45 m (THP-CH2);
2.93–3.08 m (SCH2′); 2.88–2.79 m (SCH2); 1.91–1.39 m (THP-CH2). 13C NMR (75 MHz,
CDCl3, double sign als): 165.94, 165.21, 164.34, 163.92 (OCOPh ), 133.14, 133.09, 132.89,
132.61 (Ci), 129.97–125.69 (arom . C), 98.90, 98.67 (THP acetal-C), 78.75 (C-1), 70.82, 69.89,
68.67, 68.52 (C-2, C-3, C-4, C-5), 67.17, 66.24, 62.30, 61.98 (THP-C-6, C-6), 30.52, 30.11,
29.93, 29.46, 26.85, 25.37 (THP-C-3, THP-C-5, SCH2, CH2OTHP), 19.35, 19.12 (THP-C-4).
2-(Tetrah ydropyran -2-yloxy)eth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-glucopyran oside (12)
Th e peracetylated THP eth er 10 (500 m g, 1.01 m m ol) was deacetylated accordin g to Gen eral
procedure 2. After th at, th e crude product was ben zylated accordin g to Gen eral procedure 3.
Th e crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 633 m g
(90%), colorless syrup, diastereom eric m ixture (1:1). Selected 1H NMR data: 7.75–7.18 m
(arom . H); 5.17–4.80 m (Ph CH2); 4.70–4.55 m (H-1, THP acetal-H); 4.05–3.63 m (H-2, H-3,
H-4, H-6, THP-CH2); 3.61–3.33 m (H-5, CH2OTHP); 3.08–2.97 m (SCH2′); 2.93–2.78 m
(SCH2); 1.91–1.30 m (THP-CH2). 13C NMR (75 MHz, CDCl3, double sign als): 138.35, 138.00,
137.87, 137.62 (Ci), 129.41–127.68 (arom . C), 98.90, 98.76 (THP acetal-C), 87.41 (C-1),
85.69, 81.14, 79.06, 78.23 (C-2, C-3, C-4, C-5), 75.76, 75.61, 75.32, 73.40 (Ph CH2), 68.97
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1859
(C-6), 63.90, 62.54 (THP-C-6, C-6), 31.71, 30.54, 25.37 (THP-C-3, THP-C-5, SCH2), 19.42,
19.33 (THP-C-4).
2-Brom oeth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-glucopyran oside (14)
Un der argon atm osph ere tetrabrom oeth an e (410 m g, 1.23 m m ol) was added to a solution of
com poun d 11 (650 m g, 0.88 m m ol) in an h ydrous dich lorom eth an e. After 10 m in th e reac-
tion m ixture was cooled to 0 °C an d triph en ylph osph in e (645 m g, 2.39 m m ol) was added.
After stirrin g at room tem perature overn igh t, th e m ixture was passed th rough a sm all silica
gel layer. Th e filtrate was reduced, a colum n ch rom atograph y followed (CH/EA = 8/1). Yield
487 m g (78%), colorless crystals, m .p. 112–115 °C, [α ]2D0 +23.8 (c 1.0 in CHCl3). For
C
36H31BrO9 (719.6) calculated: 60.08% C, 4.35% H; foun d: 60.22% C, 4.30% H.
2-Brom oeth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-glucopyran oside (15)
Tetrabrom oeth an e (510 m g, 1.5 m m ol) was added un der argon atm osph ere to a solution of
com poun d 12 (750 m g, 1.10 m m ol) in an h ydrous dich lorom eth an e. After 10 m in th e reac-
tion m ixture was cooled to 0 °C an d triph en ylph osph in e (830 m g, 2.8 m m ol) was added.
After stirrin g at room tem perature overn igh t, th e m ixture was passed th rough a sm all silica
gel layer. Th e filtrate was reduced, a colum n ch rom atograph y followed (CH/EA = 12/1).
Yield 503 m g (69%), colorless crystals, m .p. 121–123 °C, [α ]2D0 +47.6 (c 1.0 in CHCl3). For
C
36H39BrO5S (663.7) calculated: 65.14% C, 5.93% H; foun d: 65.20% C, 5.84% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-glucopyran oside (16)
a) Preparation with pyridin e. Com poun d 1 (30.0 g, 82.4 m m ol) was dissolved in an -
h ydrous pyridin e (500 m l), trityl ch loride (40.0 g, 140.1 m m ol, 1.7 equiv.) an d catalytic
am oun t of 4-(dim eth ylam in o)pyridin e were added. Th e solution was h eated for several
h ours un der reflux (black solution ). After coolin g down to room tem perature, water (400 m l)
was added an d th e resultin g solution was con cen trated an d codistilled with toluen e. Th e res-
idue was diluted with dich lorom eth an e an d wash ed with water, dried with an h ydrous
MgSO4, filtered an d purified by colum n ch rom atograph y (CH/EA = 3/1). Yield 32.5 g (69%),
colorless crystals, m .p. 176–178 °C (EtOH), [α ]2D0 –6.1 (c 1.0 in CHCl3); reported9 m .p.
182–183 °C, [α ]2D0 –2.0 (c 1.0 in CHCl3). For C33H34O9S (606.7) calculated: 65.32% C, 5.66% H;
foun d: 65.42% C, 5.69% H.
b) Preparation with trieth ylam in e. Com poun d 1 (25.0 g, 68.6 m m ol) was dissolved in an -
h ydrous dich lorom eth an e (200 m l) an d trityl ch loride (23.0 g, 82.3 m m ol, 1.2 equiv.) was
added. Un der stirrin g, trieth ylam in e (14.3 m l, 102.9 m m ol, 1.5 equiv.) was dropped slowly
to th e reaction m ixture. After th e reaction was com plete (TLC m on itorin g) th e m ixture was
n eutralized with 2 M h ydroch loric acid, wash ed several tim es with water, dried with an -
h ydrous MgSO4, filtered an d con cen trated. Th e product was crystallized from eth an ol. Yield
31.7 g (76%).
c) Preparation with trifluoroacetic acid. Com poun d 1 (25.0 g, 68.6 m m ol) was dissolved
in an h ydrous dich lorom eth an e (150 m l) an d trityl ch loride (21.5 g, 82.3 m m ol, 1.2 equiv.)
was added. Trifluoroacetic acid (50 m l) was given in on e portion to th e reaction m ixture,
wh ich becam e brown . After 20 m in th e reaction was usually com plete. Th e m ixture was
con cen trated un der reduced pressure. Th e residue was diluted with dich lorom eth an e an d
wash ed with water, saturated sodium h ydrogen carbon ate solution an d again with water,
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1860
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
dried with an h ydrous MgSO4, filtered an d th e solven t was rem oved. Th e product was crys-
tallized from eth an ol. Yield 34.1 g (82%).
Triph en ylm eth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-galactopyran oside (20)
Preparation with trifluoroacetic acid. Com poun d 2 (35.0 g, 96.15 m m ol) was dissolved in
an h ydrous dich lorom eth an e (150 m l) an d trityl ch loride (30.0 g, 115.4 m m ol, 1.2 equiv.)
was added. Trifluoroacetic acid (150 m l) was given in on e portion to th e reaction m ixture,
wh ich directly got brown . After 20 m in th e reaction was usually com plete. Th e m ixture was
con cen trated un der reduced pressure. Th e residue was diluted with dich lorom eth an e an d
wash ed with water, saturated sodium h ydrogen carbon ate solution an d again with water,
dried with an h ydrous MgSO4, filtered an d th e solven t was rem oved. Th e crude product was
purified by colum n ch rom atograph y (CH/EA = 3/1). Yield 53.02 g (91%), m .p. 81–82 °C, [α ]D20
–10.1 (c 1.0 in CHCl3). For C33H34O9S (606.7) calculated: 65.32% C, 5.66% H; foun d:
65.39% C, 5.67% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-acetyl-1-th io-β-D-m an n opyran oside (23)
Preparation with trifluoroacetic acid. Com poun d 3 (8.5 g, 23.35 m m ol) was dissolved in an -
h ydrous dich lorom eth an e (150 m l) an d trityl ch loride (7.29 g, 28.0 m m ol, 1.2 equiv.) was
added. Trifluoroacetic acid (30 m l) was given in on e portion to th e reaction m ixture, wh ich
becam e brown . After 20 m in th e reaction was usually com plete. Th e m ixture was con cen -
trated un der reduced pressure. Th e residue was diluted with dich lorom eth an e an d wash ed
with water, saturated sodium h ydrogen carbon ate solution an d again with water, dried with
an h ydrous MgSO4, filtered an d th e solven t was rem oved. Th e crude product was purified by
colum n ch rom atograph y (CH/EA = 3/1). Yield 11.75 g (84%), [α ]2D0 +19.9 (c 1.0 in CHCl3).
For C33H34O9S (606.7) calculated: 65.32% C, 5.66% H; foun d: 65.37% C, 5.71% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-glucopyran oside (17)
Com poun d 16 (46.7 g, 77.1 m m ol) was deacetylated accordin g to Gen eral procedure 2. After
th at, th e crude product was ben zoylated accordin g to Gen eral procedure 1. Th e crude prod-
uct was purified by colum n ch rom atograph y (CH/EA = 6/1). Yield 63.2 g (96%), colorless
solid, m .p. 67 °C, [α ]2D0 +19.8 (c 1.0 in CHCl3). For C53H42O9S (855.0) calculated: 74.45% C,
4.96% H; foun d: 74.55% C, 4.92% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-glucopyran oside (18)
Com poun d 16 (23.9 g, 39.4 m m ol) was deacetylated accordin g to Gen eral procedure 2. After
th at, th e crude product was ben zylated accordin g to Gen eral procedure 3. Th e crude product
was purified by colum n ch rom atograph y (CH/EA = 20/1). Yield 28.3 g (90%), yellow syrup,
[α ]2D0 +21.0 (c 1.0 in CHCl3). For C53H50O5S (799.1) calculated: 79.66% C, 6.32% H; foun d:
79.55% C, 6.42% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-pivaloyl-1-th io-β-D-glucopyran oside (19)
Com poun d 16 (500 m g, 0.83 m m ol) was deacetylated accordin g to Gen eral procedure 2.
After th at, th e crude product was pivaloylated accordin g to Gen eral procedure 1. Th e crude
product was purified by colum n ch rom atograph y (CH/EA = 4/1). Yield 447 m g (70%), color-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1861
less syrup, [α ]2D0 –67.8 (c 1.0 in CHCl3). For C45H58O9S (775.1) calculated: 69.73% C, 7.56% H;
foun d: 69.91% C, 7.47% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-galactopyran oside (21)
Com poun d 20 (35.0 g, 96.15 m m ol) was deacetylated accordin g to Gen eral procedure 2.
After th at, th e crude product was ben zoylated accordin g to Gen eral procedure 1. Th e crude
product was purified by colum n ch rom atograph y (CH/EA = 3/1). Yield 53.02 g (91%), color-
less solid, m .p. 81–82 °C, [α ]D20 –10.1 (c 1.0 in CHCl3). For C53H42O9S (855.0) calculated:
74.45% C, 4.96% H; foun d: 74.50% C, 4.91% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-galactopyran oside (22)
Com poun d 20 (15.0 g, 24.8 m m ol) was deacetylated accordin g to Gen eral procedure 2. After
th at, th e crude product was ben zylated accordin g to Gen eral procedure 3. Th e crude product
was purified by colum n ch rom atograph y (CH/EA = 20/1). Yield 28.3 g (90%), yellow syrup,
[α ]2D0 –8.7 (c 1.0 in CHCl3).
Triph en ylm eth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-α-D-m an n opyran oside (24)
Com poun d 23 (6.30 g, 10.39 m m ol) was deacetylated accordin g to Gen eral procedure 2.
After th at, th e crude product was ben zoylated accordin g to Gen eral procedure 1. Th e crude
product was purified by colum n ch rom atograph y (CH/EA = 6/1). Yield 8.26 g (93%), color-
less solid, m .p. 78–80 °C, [α ]D20 –6.5 (c 1.0 in CHCl3). For C53H42O9S (855.0) calculated:
74.45% C, 4.96% H; foun d: 74.55% C, 4.92% H.
Triph en ylm eth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-α-D-m an n opyran oside (25)
Com poun d 23 (2.30 g, 3.79 m m ol) was deacetylated accordin g to Gen eral procedure 2. After
th at, th e crude product was ben zylated accordin g to Gen eral procedure 3. Th e crude product
was purified by colum n ch rom atograph y (CH/EA = 20/1). Yield 2.30 g (76%), yellow syrup,
[α ]2D0 +9.2 (c 1.0 in CHCl3).
2,3,4,6-Tetra-O-ben zoyl-1-th io-α-D-glucopyran ose (26α) an d
2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-glucopyran ose (26β)
Com poun d 17 (15.5 g, 18.15 m m ol) was detritylated accordin g to Gen eral procedure 8. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 3/1). Two substan ces
could be iden tified.
Compound 26α: yield 3.34 g (30%), colorless solid, m .p. 87–88 °C, [α ]2D0 +83.5 (c 1.0 in
CHCl3). For C34H28O9S (612.7) calculated: 66.65% C, 4.62% H; foun d: 66.61% C, 4.56% H.
Compound 26β: yield 6.56 g (59%), colorless solid, m .p. 104–106 °C, [α ]2D0 +20.6 (c 1.0 in
CHCl3); reported13 [α ]2D3 +62.1 (c 2.0 in CHCl3). For C34H28O9S (612.7) calculated: 66.65% C,
4.62% H; foun d: 66.60% C, 4.66% H.
2,3,4,6-Tetra-O-pivaloyl-1-th io-β-D-glucopyran ose (27)
Com poun d 18 (500 m g, 0.65 m m ol) was detritylated accordin g to Gen eral procedure 8. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 5/1). Yield 316 m g (92%),
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1862
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
colorless syrup, [α ]2D0 +13.2 (c 1.0 in CHCl3); reported26 m .p. 115–116 °C, [α ]2D0 +18.8 (c 1.18
in CHCl3). For C26H44O9S (532.8) calculated: 58.61% C, 8.34% H; foun d: 58.74% C, 8.46% H.
2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-glucopyran ose (28)
Com poun d 19 (12.5 g, 15.66 m m ol) was detritylated accordin g to Gen eral procedure 8. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 10/1). Yield 7.49 g (86%),
colorless syrup, [α ]2D0 –18.2 (c 1.0 in CHCl3); reported27 m .p. 83.5–84 °C, [α ]2D0 –18.1 (c 1.0 in
CHCl3). For C34H36O5S (556.8) calculated: 73.34% C, 6.53% H; foun d: 73.24% C, 6.61% H.
2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-galactopyran ose (29)
Com poun d 21 (11.00 g, 12.88 m m ol) was detritylated accordin g to Gen eral procedure 8.
Th e crude product was purified by colum n ch rom atograph y (CH/EA = 8/1). Yield 6.94 g
(88%), colorless crystals, m .p. 89–90 °C, [α ]2D0 –24.3 (c 1.0 in CHCl3). For C34H28O9S (612.7)
calculated: 66.65% C, 4.62% H; foun d: 66.62% C, 4.66% H.
2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-galactopyran ose (30)
Com poun d 22 (1.25 g, 1.56 m m ol) was detritylated accordin g to Gen eral procedure 8. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 763 m g
(88%), colorless syrup, [α ]2D0 –13.7 (c 1.0 in CHCl3).
2,3,4,6-Tetra-O-ben zoyl-1-th io-α-D-m an n opyran ose (31)
Com poun d 24 (6.50 g, 7.61 m m ol) was detritylated accordin g to Gen eral procedure 8. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 4/1). Yield 4.05 g (87%),
colorless syrup, [α ]2D0 –30.5 (c 1.0 in CHCl3). For C34H28O9S (612.7) calculated: 66.65% C,
4.62% H; foun d: 66.58% C, 4.73% H.
2,3,4,6-Tetra-O-ben zyl-1-th io-α-D-m an n opyran ose (32)
Com poun d 25 (2.50 g, 3.13 m m ol) was detritylated accordin g to Gen eral procedure 8. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 1.45 g (83%),
colorless syrup, [α ]2D0 +54.7 (c 1.0 in CHCl3).
2-Ch loroeth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-glucopyran oside (33)
Com poun d 26 (650 m g, 1.06 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 8/1). Yield 680 m g (95%),
colorless crystals, m .p. 134 °C, [α ]2D0 +67.4 (c 1.0 in CHCl3). For C36H39ClO5S (619.3) calcu-
lated: 69.82% C, 6.36% H; foun d: 69.86% C, 6.30% H.
2-Brom oeth yl 2,3,4,6-Tetra-O-pivaloyl-1-th io-β-D-glucopyran oside (34)
Com poun d 27 (450 m g, 0.85 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 6/1). Yield 497 m g (92%),
colorless syrup, [α ]2D0 –42.9 (c 1.0 in CHCl3). For C28H47BrO9S (639.7) calculated: 52.57% C,
7.42% H; foun d: 52.48% C, 7.50% H.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1863
2-Ch loroeth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-glucopyran oside (35)
Com poun d 28 (800 m g, 1.44 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 801 m g
(90%), colorless solid, m .p. 96–97 °C, [α ]2D0 +39.2 (c 1.0 in CHCl3). For C36H39ClO5S (619.3)
calculated: 69.82% C, 6.36% H; foun d: 69.86% C, 6.30% H.
2-Brom oeth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-β-D-galactopyran oside (36)
Com poun d 29 (6.00 g, 9.8 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 8/1). Yield 6.48 g (92%),
colorless solid, m .p. 112–114 °C, [α ]2D0 –39.9 (c 1.0 in CHCl3). For C36H31BrO9S (719.6) calcu-
lated: 60.08% C, 4.35% H; foun d: 60.15% C, 4.33% H.
2-Brom oeth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-β-D-galactopyran oside (37)
Com poun d 30 (130 m g, 0.23 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 132 m g
(85%), colorless solid, m .p. 61–63 °C, [α ]2D0 –14.5 (c 1.0 in CHCl3). For C36H39BrO5S (663.7)
calculated: 65.14% C, 5.93% H; foun d: 65.27% C, 6.10% H.
2-Brom oeth yl 2,3,4,6-Tetra-O-ben zoyl-1-th io-α-D-m an n opyran oside (38)
Com poun d 31 (2.00 g, 3.27 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 6/1). Yield 2.09 g (89%),
colorless solid, m .p. 79–81 °C, [α ]D20 –17.0 (c 1.0 in CHCl3). For C36H31BrO9S (719.6) calcu-
lated: 60.08% C, 4.35% H; foun d: 59.94% C, 4.26% H.
2-Brom oeth yl 2,3,4,6-Tetra-O-ben zyl-1-th io-α-D-m an n opyran oside (39)
Com poun d 32 (650 m g, 1.17 m m ol) was alkylated accordin g to Gen eral procedure 4. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 620 m g
(80%), colorless syrup, [α ]2D0 +39.8 (c 1.0 in CHCl3).
Triph en ylm eth yl 4,6-O-Ben zyliden e-1-th io-β-D-glucopyran oside (40)
Com poun d 16 (10.0 g, 16.5 m m ol) was deacetylated accordin g to Gen eral procedure 2. Th e
residue was codistilled several tim es with toluen e. Un der argon atm osph ere th e dry com -
poun d was dissolved in an h ydrous N,N-dim eth ylform am ide (35 m l), an d distilled ben z-
aldeh yde (10 m l, 98.4 m m ol) an d con cen trated sulfuric acid (12 drops) were added an d
stirred for th ree days. Th e reaction m ixture was n eutralized with con cen trated am m on ia, th e
residue con cen trated in h igh vacuo an d purified by colum n ch rom atograph y (CH/EA = 3/1).
Yield 7.03 g (81%), colorless solid, m .p. 123–125 °C, [α ]2D0 +10.9 (c 1.0 in MeOH). For
C
32H30O5S (526.7) calculated: 72.97% C, 5.75% H; foun d: 72.90% C, 5.69% H.
Diacetate 1H NMR (300 MHz, CDCl3): 7.19–7.44 m , 20
(arom . H); 5.36 s, 1
H
H
(ben zyliden e-H); 5.10 m , 2 H (H-2, H-3); 4.13 d, 1 H, J(1,2) = 9.0 (H-1); 3.85 dd, 1 H, J(5,6′) =
4.8, J(6,6′) = 9.0 (H-6′); 3.52 m , 1 H (H-4); 3.47 dd, 1 H, J(5,6′) = 9.8, J(6,6′) = 9.0 (H-6′);
2.75 ddd, 1 H, J(4,5) = 9.0, J(5,6) = 9.0, J(5,6′) = 4.8 (H-5); 2.16, 2.01 2 s, 2 × 3 H (OAc).
13C NMR (75 MHz, CDCl3): 170.02, 169.36 (OAc), 144.29 (CPh 3), 136.76 (Ci), 120.03–129.80
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1864
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
(arom . H), 101.29 (ben zyliden e-C), 84.17 (C-1), 78.11, 73.16, 70.67, 70.13 (C-5, C-4, C-3,
C-2), 68.17 (C-6), 20.79, 20.69 (OCOCH3).
Triph en ylm eth yl 2,3-Di-O-ben zyl-4,6-O-ben zyliden e-1-th io-β-D-glucopyran oside (41)
Com poun d 40 (600 m g, 1.14 m m ol) was ben zylated accordin g to Gen eral procedure 3. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 15/1). Yield 765 m g
(95%), colorless solid, m .p. 89 °C, [α ]2D0 +34.9 (c 1.0 in CHCl3). For C46H42O5S (706.9) calcu-
lated: 78.16% C, 5.99% H; foun d: 78.29% C, 6.12% H. 1H NMR (300 MHz, CDCl3):
7.14–7.48 m , 30 H (arom . H); 5.42 s, 1 H (ben zyliden e-H); 5.08 d, 1 H, J = 9.8 (Ph CH2);
4.95 d, 1 H, J = 9.8 (Ph CH2); 4.89 d, 1 H, J = 10.2 (Ph CH2); 4.76 d, 1 H, J = 10.2 (Ph CH2);
4.16 d, 1 H, J(1,2) = 9.4 (H-1); 3.75 dd, 1 H, J(5,6′) = 4.8, J(6,6′) = 9.8 (H-6′); 3.66 dd, 1 H,
J(3,4) = 7.6, J(4,5) = 9.0 (H-4); 3.36–3.56 m , 3 H (H-6, H-3, H-2); 2.61 ddd, 1 H, J(4,5) = 9.0,
J(5,6) = 9.0, J(5,6′) = 4.8 (H-5). 13C NMR (75 MHz, CDCl3): 144.54 (CPh 3), 138.36, 138.14,
137.28 (Ci), 129.89–125.86 (arom . H), 100.86 (ben zyliden e-C), 85.73 (C-1), 83.20, 81.32,
81.18 (C-2, C-3, C-4), 76.21, 75.14 (Ph CH2), 69.62 (C-5), 68.34 (C-6).
2-Ch loroeth yl 4,6-O-Isopropyliden e-1-th io-β-D-glucopyran oside (42)
Com poun d 7 (5.07 g, 11.9 m m ol) was deacetylated accordin g to Gen eral procedure 2. Th e
residue was dissolved in an h ydrous aceton e (400 m l), an d 2,2-dim eth oxypropan e (6 m l,
48.8 m m ol) an d catalytic am oun t of 4-toluen esulfon ic acid were added. After stirrin g over-
n igh t, th e reaction m ixture was n eutralized with con cen trated am m on ia an d th e solution
was con cen trated in vacuo. Th e resultin g residue was extracted with h ot dich lorom eth an e.
After reducin g th e solven t, th e crude product was purified by colum n ch rom atograph y
(CH/EA = 1/1). Yield 2.56 g (72%), colorless syrup, [α ]2D0 –42.6 (c 1.0 in MeOH). For
C
16H23ClO7S (394.9) calculated: 48.67% C, 5.87% H; foun d: 48.52% C, 5.90% H.
Diacetate 1H NMR (300 MHz, CDCl3): 5.12 dd, 1 H, J(1,2) = 10.2, J(2,3) = 9.2 (H-2);
4.93 dd, 1 H, J(2,3) = 9.6, J(3,4) = 9.2 (H-3); 4.52 d, 1 H, J(1,2) = 10.2 (H-1); 3.93 dd, J(5,6) =
5.4, J(6,6′) = 10.9 (H-6); 3.77–3.57 m , 4 H (CH2Cl, H-6′, H-4); 3.37 ddd, J(4,5) = 10.0, J(5,6) =
5.4, J(5,6′) = 10.2 (H-5); 2.96 m , 2 H (SCH2); 2.03, 2.01 2 s, 2 × 3 H (2 × OAc); 1.44, 1.35 2 s,
2 × 3 H (2 × isoprop.-CH3).
Vin yl 2,3-Di-O-ben zyl-4,6-O-isopropyliden e-1-th io-β-D-glucopyran oside (43)
Com poun d 42 (2.56 g, 8.57 m m ol) was ben zylated accordin g to Gen eral procedure 3. Th e
crude product was purified by colum n ch rom atograph y (CH/EA = 10/1). Yield 2.11 g (82%),
colorless crystals, m .p. 61 °C, [α ]D20 +3.5 (c 1.0 in MeOH). For C25H30O5S (442.6) calculated:
67.85% C, 6.83% H; foun d: 67.54% C, 7.11% H. 1H NMR (300 MHz, CDCl3): 7.36–7.25 m ,
10 H (arom . H); 6.47 dd, 1 H, J = 10.0 (=CH2); 5.39 d, 1 H, J = 16.9 (=CH2); 5.34 d, 1 H, J =
10.0 (=CH2); 4.87, 4.74 2 d, 2 × 1 H (Ph CH2); 4.78 s, 2 H (Ph CH2); 4.63 d, 1 H, J(1,2) = 9.7
(H-1); 3.94 dd, 1 H, J(5,6) = 5.4, J(6,6′) = 10.9 (H-6); 3.75 dd, 1 H, J(5,6′) = 9.6, J(6,6′) = 10.9
(H-6′); 3.72 dd, 1 H, J(3,4) = 9.1, J(4,5) = 9.5 (H-4); 3.64 dd, 1 H, J(2,3) = 8.2, J(3,4) = 9.1
(H-3); 3.49 dd, 1 H, J(1,2) = 9.7, J(2,3) = 8.2 (H-2); 3.30 ddd, 1 H, J(4,5) = 9.5, J(5,6) = 5.4,
J(5,6′) = 9.6 (H-5); 1.49, 1.41 2 s, 2 × 3 H (2 × isoprop.-CH3).
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1865
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1866
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1867
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1868
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1869
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1870
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

2-Haloethyl 1-Thioglycosides
1871
2-Hydroxyeth yl 2,3-Di-O-ben zyl-4,6-O-isopropyliden e-1-th io-β-D-glucopyran oside (44)
Com poun d 43 (940 m g, 2.21 m m ol) was dissolved in an h ydrous tetrah ydrofuran e (6 m l)
an d un der argon atm osph ere an d ice coolin g 2 M boran e–dim eth yl sulfide com plex in THF
(1.2 m l) was added durin g 30 m in . After stirrin g at room tem perature for 3 h , 3 M sodium
h ydroxide solution (0.3 m l) was added an d th e reaction m ixture was cooled to 0 °C. Hydro-
gen peroxide solution (30%, 0.28 m l) was dropped to th e m ixture (tem perature sh ould n ot
reach m ore th an 5 °C), after th at th e solution was h eated up to 40–50 °C. After 2-h stirrin g
at th is tem perature, th e m ixture was poured in to ice water (15 m l) an d extracted several
tim es with dieth yl eth er. Th e organ ic layer was dried with an h ydrous MgSO4 an d th e crude
product was purified by colum n ch rom atograph y (CH/EA = 2/1). Yield 722 m g (72%), color-
less syrup, [α ]2D0 –7.3 (c 1.0 in MeOH). For C27H34O7S (502.6) calculated: 64.52% C, 6.82% H;
foun d: 64.40% C, 6.88% H.
Acetate 1H NMR (300 MHz, CDCl3): 7.35–7.25 m , 10 H (arom . H); 4.84, 4.73 d, 2 × 1 H,
J = 11.4 (Ph CH2); 4.79 s, 2 H (Ph CH2); 4.51 d, 1 H, J(1,2) = 9.8 (H-1); 4.23 td, 2 H, J = 1.8,
J(1,2) = 6.8 (CH2OAc); 3.91 dd, 1 H, J(5,6) = 5.4, J(6,6′) = 10.9 (H-6); 3.74 dd, 1 H, J(5,6′) =
9.6, J(6,6′) = 10.9 (H-6′); 3.71 dd, 1 H, J(3,4) = 9.1, J(4,5) = 9.5 (H-4); 3.61 dd, 1 H, J(2,3) =
8.2, J(3,4) = 9.8 (H-3); 3.37 dd, 1 H, J(2,1) = 9.8, J(2,3) = 8.2 (H-2); 3.26 ddd, 1 H, J(4,5) =
9.5, J(5,6) = 5.4, J(5,6′) = 9.6 (H-5); 2.90 m , 2 H (SCH2); 2.02 s, 3 H (OAc); 1.48, 1.40 2 s, 2 ×
3 H (2 × isoprop.-CH3).
2-Brom oeth yl 2,3-Di-O-ben zyl-4,6-O-isopropyliden e-1-th io-β-D-glucopyran oside (45)
Com poun d 44 (3.19 g, 6.94 m m ol) was dissolved in an h ydrous toluen e (100 m l), an d
ch lorodiph en ylph osph an e (1.98 g, 8.97 m m ol) an d brom in e (1.05 g, 15.42 m m ol) were
added. Th e reaction m ixture was cooled in an ice-bath , an d brom in e (ca. 1.1 g) was dropped
slowly to th e solution un til th e m ixture stayed ligh t brown . After th e reaction was com plete
(10 m in ), it was wash ed with saturated sodium h ydrogen carbon ate solution , saturated so-
dium ch loride solution an d water. Th e organ ic layer was dried with an h ydrous MgSO4 an d
con cen trated un der reduced pressure. Th e crude product was purified by colum n ch rom atog-
raph y (CH/EA = 3/1). Yield 3.10 g (85%), colorless syrup, [α ]2D0 –3.8 (c 1.0 in CHCl3). For
C
25H31BrO5S (523.5) calculated: 57.36% C, 5.97% H; foun d: 57.03% C, 5.81% H. 1H NMR
(300 MHz, CDCl3): 7.35–7.25 m , 10 H (arom . H); 4.87, 4.73 d, 2 × 1 H, J = 11.2 (Ph CH2);
4.78 s, 2 H (Ph CH2); 4.49 d, 1 H, J(1,2) = 10.0 (H-1); 3.92 dd, 1 H, J(5,6) = 5.4, J(6,6′) = 10.9
(H-6); 3.74 dd, 1 H, J(5,6′) = 9.6, J(6,6′) = 10.9 (H-6′); 3.71 dd, 1 H, J(3,4) = 9.4, J(4,5) = 9.5
(H-4); 3.62 dd, 1 H, J(2,3) = 8.2, J(3,4) = 9.4 (H-3); 3.49 m , 2 H (CH2Br); 3.37 dd, 1 H,
J(2,1) = 10.0, J(2,3) = 8.2 (H-2); 3.26 ddd, 1 H, J(4,5) = 9.5, J(5,6) = 5.4, J(5,6′) = 9.6 (H-5);
3.20–2.95 m , 2 H (SCH2); 1.48, 1.41 2 s, 2 × 3 H (2 × isoprop.-CH3).
Cycloh exyl 2,3,4,6-Tetra-O-acetyl-α-D-glucopyran oside16 (46)
Com poun d 4 (100 m g, 0.23 m m ol) an d cycloh exan ol (1.2 equiv.) were glycosylated accord-
in g to Gen eral procedure 5. Tem perature 0 °C, solven t n itrom eth an e. Yield 39.6 m g (40%)
of 46, th e substitution product 47 was n ot furth er ch aracterized.
Com poun d 46, colorless syrup. 1H NMR (300 MHz, CDCl3): 5.47 dd, 1 H, J(2,3) = 10.4,
J(3,4) = 9.6 (H-3); 5.20 d, 1 H, J(1,2) = 3.8 (H-1); 5.01 dd, 1 H, J(3,4) = 9.6, J(4,5) = 9.8 (H-4);
4.78 dd, 1 H, J(1,2) = 3.8, J(2,3) = 10.4 (H-2); 4.22 dd, 1 H, J(5,6) = 4.8, J(6,6′) = 12.4 (H-6);
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1872
Krüger, Pyplo-Schnieders, Redlich, Winkelmann:
4.14–4.04 m , 2 H (H-5, H-6′); 3.59–3.54 m , 1 H (cycloh exyl-H); 2.06, 2.03, 2.01, 1.99 4 s, 4 ×
3 H (4 × OAc); 1.86–1.22 m , 10 H (cycloh exyl-H). 13C NMR (75 MHz, CDCl3): 94.1 (C-1α).
Meth yl 2,3,4,6-Tetra-O-ben zoyl-α/β-D-glucopyran osyl-(1→6)-2,3,4-tri-O-acetyl-
α-D-glucopyran oside21 (51αβ)
a) Com poun d 14 (100 m g, 0.139 m m ol) an d th e h ydroxy com poun d 48 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 5. Solven t n itrom eth an e, colum n ch rom atogra-
ph y (CH/EA = 3/1). Yield 92 m g (78%), colorless crystals. For C47H46O18 (898.9) calculated:
62.79% C, 5.17% H; foun d: 62.83% C, 5.20% H.
b) Com poun d 14 (100 m g, 0.139 m m ol) an d th e h ydroxy com poun d 48 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 6. Solven t dich lorom eth an e, colum n ch rom a-
tograph y (CH/EA = 3/1). Yield 86 m g (83%), colorless crystals.
Meth yl 2,3,4,6-Tetra-O-ben zoyl-α/β-D-glucopyran osyl-(1→6)-2,3,4-tri-O-ben zyl-
α-D-glucopyran oside22 (52αβ)
Com poun d 14 (100 m g, 0.139 m m ol) an d th e h ydroxy com poun d 49 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 5. Solven t n itrom eth an e, colum n ch rom atog-
raph y (CH/EA = 6/1). Yield 116 m g (80%), colorless crystals.
Meth yl 2,3,4,6-Tetra-O-ben zyl-α/β-D-glucopyran osyl-(1→6)-2,3,4-tri-O-ben zyl-
α-D-glucopyran oside24 (53αβ)
a) Com poun d 15 (100 m g, 0.151 m m ol) an d th e h ydroxy com poun d 49 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 5. Solven t dioxan e, colum n ch rom atograph y
(CH/EA = 6/1). Yield 115 m g (81%), colorless syrup.
b) Com poun d 15 (100 m g, 0.151 m m ol) an d th e h ydroxy com poun d 49 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 5. Solven t aceton itrile, colum n ch rom atogra-
ph y (CH/EA = 6/1). Yield 130 m g (92%), colorless syrup.
c) Com poun d 15 (100 m g, 0.151 m m ol) an d th e h ydroxy com poun d 49 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 6. Solven t dich lorom eth an e, colum n ch rom a-
tograph y (CH/EA = 6/1). Yield 119 m g (84%), colorless syrup.
Meth yl 2,3,4,6-Tetra-O-ben zoyl-α/β-D-glucopyran osyl-(1→4)-2,3,6-tri-O-ben zyl-
α-D-glucopyran oside23 (54αβ)
Com poun d 14 (100 m g, 0.139 m m ol) an d th e h ydroxy com poun d 50 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 5. Solven t n itrom eth an e, colum n ch rom atogra-
ph y (CH/EA = 6/1). Yield 40 m g (71%), colorless crystals.
Meth yl 2,3,4,6-Tetra-O-ben zyl-α/β-D-glucopyran osyl-(1→4)-2,3,6-tri-O-ben zyl-
α/β-D-glucopyran oside25 (55αβ)
Com poun d 15 (100 m g, 0.151 m m ol) an d th e h ydroxy com poun d 50 (1.2 equiv.) were
glycosylated accordin g to Gen eral procedure 5. Solven t dioxan e, colum n ch rom atograph y
(CH/EA = 8/1). Yield 110 m g (74%), colorless syrup.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)