Synthesis of unsaturated sulfur-linked (1→4)-disaccharides by substitution of tosyloxy group in 1,6-anhydro-3,4-dideoxy-2-O-tosyl-β-D-erythro-hex-3-enopyranose with 1-thiohexopyranoses

Article abstract of DOI:10.1135/cccc20001737

A novel method for the synthesis of unsaturated sulfur-linked (1→4)-disaccharides is described. The starting 1,6-anhydro-3,4-dideoxy-2-O-tosyl-β-D-erythro-hex-3-enopyranose (3) was reacted with potassium salt of acetylated 1-thiohexopyranoses of D-gluco-,

Full text of DOI:10.1135/cccc20001737

Sulfur-Linked Disaccharides
1737
SYNTHESIS OF UNSATURATED SULFUR-LINKED
(1→4)-DISACCHARIDES BY SUBSTITUTION OF TOSYLOXY GROUP
IN 1,6-ANHYDRO-3,4-DIDEOXY-2-O-TOSYL-β-D-erythro-
HEX-3-ENOPYRANOSE WITH 1-THIOHEXOPYRANOSES
1,
2
3
Petr BARTOŠ, Miloslav ČERNÝ *, Iva TIŠLEROVÁ and TomášT RNKA
Department of Organic Chemistry, Charles University, 128 40 Prague 2, Czech Republic;
1
2
3
e-mail: mila@mail.natur.cuni.cz, ivatis@mail.natur.cuni.cz, trnka@mail.natur.cuni.cz
Received October 20, 2000
Accepted Novem ber 20, 2000
A n ovel m eth od for th e syn th esis of un saturated sulfur-lin ked (1→4)-disacch arides is de-
scribed. Th e startin g 1,6-an h ydro-3,4-dideoxy-2-O-tosyl-β-D-erythro-h ex-3-en opyran ose (3)
was reacted with potassium salt of acetylated 1-th ioh exopyran oses of D-gluco-, D-galacto-, an d
L-galacto-con figuration to give acetylated β-glycopyran osyl-(1→4)-1,6-an h ydro-2,3-dideoxy-
4-th io-β-D-erythro-h ex-2-en opyran oses 8–10. Th eir acid m eth an olysis un der m ild con dition s
afforded th e correspon din g m eth yl glycosides 11–13. Th e structure of n ew com poun ds was
con firm ed by 1H NMR an d m ass spectra data.
Key words: Carboh ydrates; Th iosugars; Un saturated sulfur-lin ked dissacch arides; 1,6-An h ydro-
h exopyran oses; Nucleoph ilic substitution s; Allylic rearran gem en t; 1H NMR spectroscopy;
Mass spectrom etry.
Th e in h ibitor activity of sulfur-lin ked oligosacch arides again st en zym e
splittin g n atural oligosacch arides h as been con tin uously in vestigated1. In
con n ection with th ese studies, we decided to develop a m eth od for prepara-
tion of un saturated th iodisacch arides (sulfur-lin ked (1→4)). Th e syn th etic
strategy com m on ly used for preparation of saturated th iodisacch arides is
based eith er on n ucleoph ilic substitution with 1-th ioglycoses2 of a good
leavin g group (e.g. trifluorom eth an esulfon yl3) in a sugar m olecule or on
glycosylation 2b,4 of a n on -an om eric th ioglycose with glycosyl h alogen ides
or oth er glycosyl don ors5–8. Altern ative routes towards th iooligosacch arides
in volve cleavage of th e oxiran e rin g in 1,6:2,3-dian h ydro-β-D-talopyran ose9
or addition to th e con jugated double bon d in 1,6-an h ydro-3,4-dideoxy-
β-D-glycero-h ex-3-en opyran os-2-ulose10 (levoglucosen on e).
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1738
Bartoš, Černý, Tišlerová, Trnka:
RESULTS AND DISCUSSION
As a startin g com poun d for syn th eses (Sch em e 1) of un saturated
th iodisacch arides we ch ose 1,6-an h ydro-3,4-dideoxy-2-O-tosyl-β-D-erythro-
h ex-3-en opyran ose (3), th e tosyloxy group of wh ich was previously
sh own 11,12 to be a good leavin g group in SN2′ allylic rearran gem en t. Sim ilar
reactivity was observed for th e correspon din g ch loro an d brom o deriva-
tives12,13 of com poun d 3.
Com poun d 3 was prepared in about 95% yield from readily accessible
1,6-an h ydro-4-deoxy-2-O-tosyl-β-D-xylo-h exopyran ose14 (1) via trifluoro-
m eth an esulfon ate 2 followed by elim in ation of trifluorom eth an esulfon ic
O
O
(ii)
O
O
RO
OTs
OTs
3
1, R = H
2, R = CF3SO2
(i)
(iii)
(iv)
O
OH
O
O
R
S
H
OMe
R
S
11, R = A
12, R = B
13, R = C
4, R = Ph
8, R = A
9, R = B
10, R = C
AcO
In formulae 8-13: R =
OAc
OAc
O
H3C
AcO
O
O
AcO
AcO
OAc
AcO
OAc
OAc
AcO
OAc
C
A
B
OAc
OAc
O
SH
OAc
H3C
O
O
AcO
AcO
OAc
SH
AcO
SH
OAc
AcO
OAc
5
6
7
(i) (CF3SO2)2O, pyridine;(ii) DBU; (iii) RSH, K2CO3/Me2CO; (iv) pyridinium tosylate/MeOH
SCHEME 1
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Sulfur-Linked Disaccharides
1739
acid usin g dich lorom eth an e solution of 1,8-diazabicyclo[5.4.0]un dec-7-en e
(DBU) at room tem perature in a procedure with out isolation of 2. Treat-
m en t of 3 with an aceton e solution of ben zen eth iol in th e presen ce of po-
tassium carbon ate gave ph en ylth io derivative 4 in alm ost quan titative
yield. Un der sim ilar con dition s, en opyran ose
3 was reacted with
2,3,4,6-tetra-O-acetyl-1-th io-β-D-glucopyran ose (5) or with th e correspon d-
in g acetates of 1-th io-β-D-galactopyran ose 6 an d 1-th io-β-L-fucopyran ose 7
to give un saturated an h ydrodisacch arides 8–10 in about 90% yield.
As m en tion ed above, th e tosyloxy group in com poun d 3 was readily re-
placed by sulfur n ucleoph iles at room tem perature to give 4-substituted
4-th iolevoglucosen es 4, 8–10. Th is reaction in volves stereoselective allylic
rearran gem en t in keepin g with previous observation s wh en ben zyl alcoh ol
was used as a n ucleoph ile11a. However, several products were isolated wh en
sodium m eth oxide in stead of ben zyl oxide was used11b. Th e reaction of 3
with n ucleoph iles can th eoretically yield four stereoisom ers, but on ly on e
of th em – th e syn-product resultin g from th e allylic rearran gem en t – sh ould
be preferred due to favoured in teraction of syn-orien ted orbitals of th e
n ucleoph ile an d leavin g group in th e tran sition state15. In addition , steric
in teraction s of th e 1,6-an h ydro bon d m ay h in der th e access of th e
n ucleoph ile toward C-2 an d C-4 from th e endo side, an d th is effect sh ould
be m ore eviden t with bulky n ucleoph iles. Substitution at C-2 with reten -
tion of con figuration is disfavoured by repulsive in teraction between th e
n ucleoph ile an d th e O-5 rin g oxygen .
Th e 1,6-an h ydro bon d in com poun ds 8–10 was cleaved by m eth an olysis
catalyzed with pyridin ium tosylate (cf. ref.16) to give very good yields of ac-
etylated m eth yl α-D-glycosides 11–13. Neverth eless, sm all am oun ts of th e
correspon din g β-glycosides were presen t in th e reaction m ixture as fol-
lowed from NMR spectra of crude products.
Th e structure of all com poun ds described h ere was proved by NMR m ea-
surem en ts. Expectably, th e 1,6-an h ydroh ex-3-en ose m oiety adopts a 5HO
con form ation an d th e correspon din g 1-th ioh exopyran ose m oieties adopt
1
th e com m on 4C1(D) con form ation s for com poun ds 8 an d 9, an d C4(L) con -
form ation for com poun d 10. Th e ch em ical sh ifts an d couplin g con stan ts
for H-2, H-3, an d H-4 sign als of com poun ds 4, 8–10 in dicate th e position of
th e double bon d between carbon atom s C-2 an d C-3 of th e 1,6-an h ydro-
h exopyran ose un it. Th e con figuration at C-4 was deduced from th e low
value of th e couplin g con stan t J(H-4,H-5) = 1.3 Hz wh ich is in agreem en t
with th e correspon din g data publish ed for l,6-an h ydro-2,3,4-trideoxy-
β-D-glycero-h ex-2-en opyran ose17 an d its derivatives18. Addition ally, th e
proxim ity of H-4 to H-6 endo of th e 1,6-an h ydro group was proved by
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Bartoš, Černý, Tišlerová, Trnka:
2D-NOESY spectra of com poun ds 4 an d 8. Th e latter tech n ique was used to
establish th e α-an om er con figuration of m eth yl glycosides 11, 12, an d 13.
Proton s of th e m eth oxy groups at C-1 in teract with th e proton at C-5. Opti-
m ization of th e geom etry of m eth yl glycosides 11–13 by th e MM+ m eth od
usin g program Hypercube Hyperch em ™ 5.02 was in good agreem en t with
NMR spectral data.
Th e described procedure for preparation of un saturated th iodisacch arides
utilizin g versatile 1,6-an h ydro-3,4-dideoxy-2-O-tosyl-β-D-erythro-h ex-3-en o-
pyran ose (3) is applicable n ot on ly to various 1-th iosugars but also to oth er
sulfur an d am in o n ucleoph iles. Hydroxym eth yl group in th e h ex-3-en o-
pyran ose m oiety of m eth yl glycosides 11–13 offers excellen t possibility of
addition al m odification s.
EXPERIMENTAL
Th e m eltin g poin ts were determ in ed with a Boëtius m icrom eltin g-poin t apparatus an d are
un corrected. Optical rotation s were m easured with a polarim eter AUTOPOL III (Rudolph Re-
.
search , Flan ders (NJ)) at 25 °C, [α]D values are given in 10–1 deg cm 2 g–1 1H NMR spectra
were m easured with Varian UNITY 400 INOVA apparatus (1H at 400 MHz ) in CDCl3, ch em i-
cal sh ifts in ppm (δ-scale) were referen ced to tetram eth ylsilan e as in tern al stan dard; cou-
plin g con stan ts (J) are given in Hz. Mass spectrom etry m easurem en ts were perform ed with a
Jeol MS D 100 spectrom eter (70 eV, direct in let at 100–120 °C). Positive FAB m ass spectra
were m easured usin g a ZAB-EQ spectrom eter (VG An alytical, Man ch ester, U.K.) with BEqG
geom etry. Sam ples were dissolved in ch loroform an d a m ixture of glycerol an d th ioglycerol
or 3-n itroben zyl alcoh ol was used as a m atrix. Th in -layer ch rom atograph y (TLC) was per-
form ed on DC Alufolien plates (Merck, type 5554) coated with Kieselgel 60 F254; detection
with 50% sulfuric acid or 3% eth an ol solution of an isaldeh yde acidified with con cen trated
sulfuric acid, an d h eatin g. For preparative colum n ch rom atograph y, silica gel Kieselgel 60
(Merck, 60–230 m esh ) was used. Reaction s were perform ed in an argon atm osph ere. Solu-
tion s were evaporated un der dim in ish ed pressure at tem peratures below 40 °C. An alytical
sam ples were dried over ph osph orus pen toxide at room tem perature un der dim in ish ed pres-
sure.
1,6-An h ydro-4-deoxy-2-O-tosyl-3-O-(trifluorom eth an esulfon yl)-β-D-xylo-h exopyran ose (2)
Pyridin e (107 µl, 1.3 m m ol) was added to a solution of deoxy com poun d14 1 (100 m g, 0.33
m m ol) in an h ydrous dich lorom eth an e (7.5 m l) an d th e solution was cooled to –16 °C. Th en
trifluorom eth an esulfon ic an h ydride (65 µl, 0.4 m m ol) was added dropwise un der stirrin g
an d th e reaction m ixture was stirred at –16 °C for 1 h . After warm in g to room tem perature,
th e solution was extracted with saturated aqueous solution of sodium h ydrogen carbon ate
(5 m l) an d th e water layer was extracted twice with dich lorom eth an e (2 m l). Com bin ed or-
gan ic extracts were dried an d evaporated th ree tim es to dryn ess with toluen e (2 m l) to give
140 m g (99%) of a syrup, wh ich was crystallized from eth er–ligh t petroleum to obtain 102 m g
(72%) of 2, m .p. 87–89 °C, [α]D –15 (c 0.25, CHCl3). 1H NMR: 1.98 dm , 1 H, J(4β,4α) = 16.1
(H-4β); 2.47 s, 3 H (CH3); 2.57 dddd, 1 H, J(4α,4β) = 16.1, J(4α,3) = 5.6, J(4α,5) = 3.9,
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Sulfur-Linked Disaccharides
1741
J(4α,6ex) = 1.7 (H-4α); 3.76 ddd, 1 H, J(6ex,6en ) = 7.3, J(5,6ex) = 5.1, J(6ex,4α) = 1.5 (H-6ex);
4.06 d, 1 H, J(6en ,6ex) = 7.3 (H-6en ); 4.31 q, 1 H, J(2,1) = 1.7, J(2,3) = 1.7, J(2,4β) = 1.7
(H-2); 4.59 bt, 1 H, J(5,6ex) = 4.5, J(5,4α) = 4.5 (H-5); 5.00 bdm , 1 H, J(3,4α) = 5.1 (H-3);
5.36 bs, 1 H (H-1); 7.37–7.41 m , 2 H, 7.80–7.85 m , 2 H (4 × H arom ). MS (FAB), m/z (%): 283
([MH – CF3SO3H]+, 10). For C14H15F3O8S2 (432.4) calculated: 38.89% C, 3.50% H, 13.18% F,
14.83 S; foun d: 39.12% C, 3.55% H, 13.12% F, 14.76% S.
1,6-An h ydro-3,4-dideoxy-2-O-tosyl-β-D-erythro-h ex-3-en opyran ose (3)
To a solution of deoxy com poun d14 1 (1.0 g, 3.3 m m ol) in a m ixture of an h ydrous dich loro-
m eth an e (10 m l) an d pyridin e (0.66 m l, 8.2 m m ol) cooled to –16 °C was added dropwise
trifluorom eth an esulfon ic an h ydride (0.67 m l, 3.7 m m ol) un der stirrin g an d th e reaction
m ixture was stirred at –16 °C for 2 h . 1,8-Diazabicyclo[5.4.0]un dec-7-en e (1.64 m l, 11.0 m m ol)
was added dropwise an d th e reaction m ixture was stirred for 1 h at room tem perature. Th en
th e reaction m ixture was wash ed with 5% aqueous HCl (20 m l), th e organ ic layer was sepa-
rated an d th e water solution was extracted th ree tim es with 10 m l portion s of dich loro-
m eth an e. Th e com bin ed extracts were dried with an h ydrous MgSO4 an d filtered th rough a
sh ort colum n of silica gel. Evaporation of th e solven t gave 0.9 g (95%) crystallin e com poun d
3 wh ich after recrystallization from eth er–ligh t petroleum gave 0.75 g (80%), m .p. 80–81 °C
(dec.), [α]D –154 (c 0.25, CHCl3); refs11,19 m .p. 85–86 °C (dec.), [α]D –161 (c 0.5, CHCl3) an d
85 °C, [α]D –159 (CHCl3), respectively. 1H NMR: 2.46 s, 3 H (CH3); 3.62–3.68 m , 2 H (H-6en ,
H-6ex); 4.39 dt, 1 H, J(2,3) = 3.9, J(2,1) = 1.5, J(2,4) = 1.2 (H-2); 4.74 m , 1 H (H-5); 5.50 t, 1 H,
J(1,2) = 1.6, J(1,3) = 1.6 (H-1); 5.62 ddd, 1 H, J(2,3) = 3.9, J(3,4) = 9.8, J(1,3) = 2.0 (H-3);
6.31 ddd, 1 H, J(4,3) = 9.8, J(4,5) = 4.9, J(4,2) = 1.2 (H-4); 7.34–7.38 m , 2 H, 7.81–7.85 m , 2 H
(4 × H arom ).
1,6-An h ydro-2,3-dideoxy-4-S-ph en yl-4-th io-β-D-erythro-h ex-2-en opyran ose (4)
Ben zen eth iol (0.71 m l, 6.9 m m ol) was added dropwise to a solution of en opyran ose 3 (1.3 g,
4.6 m m ol) in an h ydrous aceton e (20 m l) con tain in g a suspen sion of an h ydrous K2CO3 (0.95 g,
6.9 m m ol) at room tem perature an d th e reaction m ixture was stirred for 1 h . Th en th e reac-
tion m ixture was diluted with water (20 m l) an d extracted th ree tim es with th e total
am oun t of 50 m l ch loroform . Ch loroform solution was dried (MgSO4) an d purified by
colum n ch rom atograph y in dich lorom eth an e to give 1.0 g (99%) of 4, m .p. 52–53 °C,
[α]D +195 (c 0.25, CHCl3). Literature13 describes an altern ative preparation of 4 from
1,6-an h ydro-2-ch loro-2-deoxy-β-D-erythro-h ex-3-en opyran ose with out givin g ph ysical con -
stan ts. 1H NMR: 3.49 dt, 1 H, J(3,4) = 4.4, J(2,4) = 1.3, J(4,5) = 1.3 (H-4); 3.62 dd, 1 H,
J(6ex,6en ) = 7.8, J(5,6en ) = 2.0 (H-6en ); 3.97 dd, 1 H, J(6en ,6ex) = 7.8, J(5,6ex) = 6.3 (H-6ex);
4.69 dm , 1 H, J(6ex,5) = 6.3 (H-5); 5.55 d, 1 H, J(2,1) = 3.4 (H-1); 5.85 dddd, 1 H, J(2,3) =
9.5, J(4,3) = 4.3, J(5,3) = 1.8, J(1,3) = 0.8 (H-3); 6.01 ddd, 1 H, J(3,2) = 9.5, J(1,2) = 3.3, J(4,2) =
1.5 (H-2). MS (EI), m/z (%): 220 (M+, 49.3). For C12H12O2S2 (220.3) calculated: 65.43% C,
5.49% H, 14.56% S; foun d: 65.69% C, 5.52% H, 14.41% S.
Preparation of An h ydro Derivatives of Th iodisacch arides 8–10. Gen eral Procedure
To a solution of en opyran ose 3 (141 m g, 0.5 m m ol) an d 1-th ioh exose 5 (ref.20), 6 (ref.21) or
7 (ref.22) (0.55 m m ol) in an h ydrous aceton e (5 m l) fin ely powdered an h ydrous K2CO3
(207 m g, 1.5 m m ol) was added an d th e reaction m ixture was stirred at room tem perature for
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

1742
Bartoš, Černý, Tišlerová, Trnka:
3 h . Th en th e reaction m ixture was poured in to water (50 m l), n eutralized with h ydroch lo-
ric acid to pH ≈ 7, an d extracted th ree tim es with 20 m l portion s of dich lorom eth an e. Th e
com bin ed organ ic extracts were dried with an h ydrous MgSO4, filtered an d evaporated to
dryn ess. Th e products were purified by colum n ch rom atograph y.
2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl-(1→4)-1,6-anhydro-2,3-dideoxy-4-thio-β-D-erythro-hex-
2-enopyranose (8). Th e crude product obtain ed from th e reaction of 3 with 1-th ioglucose 5
was ch rom atograph ed in a m ixture of toluen e–eth yl acetate (5 : 1) to obtain 8 (216 m g,
91%), m .p. 131–132 °C (m eth an ol), [α]D +103 (c 0.25, CHCl3). 1H NMR: 2.01 s, 3 H, 2.03 s,
3 H, 2.05 s, 3 H, 2.07 s, 3 H (4 × OAc); 3.20 bd, 1 H, J(3,4) = 4.2 (H-4); 3.62 dd, 1 H,
J(6ex,6en ) = 7.8, J(5,6en ) = 2.0 (H-6en ); 3.73 ddd, 1 H, J(4′,5′) = 10.0, J(6b′,5′) = 4.9, J(6a′,5′)
= 2.6 (H-5′); 3.98 dd, 1 H, J(6en ,6ex) = 7.8, J(5,6ex) = 6.2 (H-6ex); 4.17 dd, 1 H, J(6b′,6a′) =
12.3, J(5′,6a′) = 2.6 (H-6a′); 4.22 dd, 1 H, J(6a′,6b′) = 12.5, J(5′,6b′) = 5.0 (H-6b′); 4.63 d, 1 H,
J(2′,l′) = 10.3 (H-1′); 4.90 dm , 1 H, J(6ex,5) = 6.2 (H-5); 5.05 dd, 1 H, J(1′,2′) = 10.4, J(3′,2′) =
9.2 (H-2′); 5.08 dd, 1 H, J(5′,4′) = 10.0, J(3′,4′) = 9.4 (H-4′); 5.24 t, 1 H, J(2′,3′) = 9.3, J(4′,3′) =
9.3 (H-3′); 5.50 bd, 1 H, J(1,2) = 3.3 (H-1); 5.64 bddd, 1 H, J(2,3) = 9.2, J(4,3) = 4.3, J(5,3) =
1.8 (H-3); 6.07 ddd, 1 H, J(3,2) = 9.5, J(1,2) = 3.4, J(4,2) = 1.7 (H-2). MS (EI), m/z (%): 474
(M+, 8.1). For C20H26O11S (474.5) calculated: 50.63% C, 5.52% H, 6.76% S; foun d: 50.52% C,
5.58% H, 6.70% S.
2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl-(1→4)-1,6-anhydro-2,3-dideoxy-4-thio-β-D-erythro-
hex-2-enopyranose (9). Th e crude product obtain ed from th e reaction of
3 with
1-th iogalactose 6 was ch rom atograph ed in a m ixture of toluen e–eth yl acetate (5 : 1) to ob-
tain 9 (221 m g, 93%), m .p. 132–133 °C (aceton e–eth er–ligh t petroleum ), [α]D +128 (c 0.25,
CHCl3). 1H NMR: 1.99 s, 3 H, 2.03 s, 3 H, 2.06 s, 3 H, 2.16 s, 3 H (4 × OAc); 3.22 dt, 1 H,
J(3,4) = 4.3, J(5,4) = 1.3, J(2,4) = 1.3 (H-4); 3.62 dd, 1 H, J(6ex,6en ) = 7.8, J(5,6en ) = 2.0
(H-6en ); 3.73 td, 1 H, J1 = 6.6, J2 = 1.2 (H-5′); 3.99 dd, 1 H, J(6en ,6ex) = 7.8, J(5,6ex) = 6.2
(H-6ex); 4.13 d, 2 H, J = 6.6 (H-6a′, H-6b′); 4.63 d, 1 H, J(2′,l′) = 10.1 (H-1′); 4.88 dm , 1 H,
J(6ex,5) = 6.3 (H-5); 5.07 dd, 1 H, J(2′,3′) = 10.0, J(4′,3′) = 3.4 (H-3′); 5.25 t, 1 H, J(1′,2′) =
10.0, J(3′,2′) = 10.0 (H-2′); 5.44 dd, 1 H, J(5′,4′) = 1.2, J(3′,4′) = 3.4 (H-4′); 5.51 bd, 1 H, J(1,2) =
3.4 (H-1); 5.66 dddd, 1 H, J(2,3) = 9.5, J(4,3) = 4.3, J(5,3) = 1.8, J(1,3) = 0.6 (H-3); 6.07 ddd,
1 H, J(3,2) = 9.5, J(1,2) = 3.4, J(4,2) = 1.7 (H-2). MS (EI), m/z (%): 474 (M+, 8.1). For
C
20H26O11S (474.5) calculated: 50.63% C, 5.52% H, 6.76% S; foun d: 50.91% C, 5.59% H,
6.70% S.
2,3,4-Tri-O-acetyl-6-deoxy-β-L-galactopyranosyl-(1→4)-1,6-anhydro-2,3-dideoxy-4-thio-β-D-erythro-
hex-2-enopyranose (10). Th e crude product obtain ed from th e reaction of 3 with 1-th iofucose
7 was ch rom atograph ed in a m ixture of toluen e–eth yl acetate (10 : 1) to obtain 10 (183 m g,
88%), m .p. 133–134 °C (aceton e–eth er–ligh t petroleum ), [α]D +166 (c 0.25, CHCl3). 1H NMR:
1.20 d, 3 H, J(5′,6′) = 6.5 (H-6′); 1.99 s, 3 H, 2.08 s, 3 H, 2.18 s, 3 H (3 × OAc); 3.25 dt, 1 H,
J(3,4) = 4.3, J(5,4) = 1.2, J(2,4) = 1.2 (H-4); 3.65 dd, 1 H, J(6ex,6en ) = 7.8, J(5,6en ) = 2.1
(H-6en ); 3.80 qd, 1 H, J(6′,5′) = 6.5, J(4′,5′) = 1.1 (H-5′); 4.01 dd, 1 H, J(6en ,6ex) = 7.9,
J(5,6ex) = 6.2 (H-6ex); 4.78 d, 1 H, J(2′,l′) = 10.0 (H-1′); 4.78 m , 1 H (H-5); 5.06 dd, 1 H,
J(2′,3′) = 10.0, J(4′,3′) = 3.4 (H-3′); 5.22 t, 1 H, J(1′,2′) = 10.0, J(3′,2′) = 10.0 (H-2′); 5.28 dd, 1 H,
J(5′,4′) = 1.1, J(3′,4′) = 3.4 (H-4′); 5.54 bd, 1 H, J(1,2) = 3.4 (H-1); 5.86 dddd, 1 H, J(2,3) = 9.4,
J(4,3) = 4.4, J(5,3) = 1.8, J(1,3) = 0.7 (H-3); 5.96 ddd, 1 H, J(3,2) = 9.5, J(1,2) = 3.4, J(4,2) =
1.5 (H-2). MS (FAB), m/z (%): 417 (MH+, 2.8). For C18H24O9S (416.4) calculated: 51.92% C,
5.81% H, 7.70% S; foun d: 52.19% C, 5.88% H, 7.64% S.
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Sulfur-Linked Disaccharides
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Preparation of Meth yl Th iodisacch arides 11–13. Gen eral Procedure
1,6-An h ydrodisacch arides 8, 9 or 10 (0.3 m m ol) were dissolved in m eth an ol (6 m l),
pyridin ium tosylate (8 m g, 0.03 m m ol ) was added an d th e solution was refluxed for 1 h . Af-
ter evaporation of m eth an ol, th e residue was purified by colum n ch rom atograph y.
Methyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-(1→4)-2,3-dideoxy-4-thio-α-D-erythro-hex-
2-enopyranoside (11). Th e crude product obtain ed by m eth an olysis of 8 was ch rom ato-
graph ed in a m ixture of ligh t petroleum –eth yl acetate (1 : 1) to give 11 (139 m g, 91%), m .p.
133–135 °C, [α]D +92 (c 0.25, CHCl3). 1H NMR: 2.01 s, 3 H, 2.02 s, 3 H, 2.06 s, 3 H, 2.10 s,
3 H (4 × OAc); 3.43 s, 3 H (OMe); 3.58 bdd, 1 H, J(5,4) = 10.4, J(3,4) = 1.4 (H-4); 3.71 dt,
1 H, J(4′,5′) = 10.1, J(6a′,5′) = 3.5, J(6b′,5′) = 3.5 (H-5′); 3.93 m , 2 H (H-6a, H-6b); 3.99 m , 1 H
(H-5); 4.20 m , 2 H (H-6a′, H-6b′); 4.65 d, 1 H, J(2′,1′) = 10.2 (H-1′); 4.91 bs, 1 H (H-1); 5.00 t,
1 H, J(1′,2′) = 9.2, J(3′,2′) = 9.2 (H-2′); 5.07 t, 1 H, J(5′,4′) = 9.8, J(3′,4′) = 9.8 (H-4′); 5.22 t,
1 H, J(2′,3′) = 9.3, J(4′,3′) = 9.3 (H-3′); 5.89 m , 2 H (H-2, H-3). MS (FAB), m/z (%): 475 ([MH –
MeOH]+, 2.8). For C21H30O12S (506.5) calculated: 49.80% C, 5.97% H, 6.33% S; foun d:
49.84% C, 6.00% H, 6.27% S.
Methyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1→4)-2,3-dideoxy-4-thio-α-D-erythro-hex-
2-enopyranoside (12). Th e crude product obtain ed by m eth an olysis of 9 was ch rom ato-
graph ed in a m ixture of ligh t petroleum –eth yl acetate (1 : 1) to give 12 (122 m g, 80%),
m .p. 135–136 °C, [α]D +92 (c 0.25, CHCl3). 1H NMR: 1.99 s, 3 H, 2.06 s, 3 H, 2.08 s, 3 H, 2.16 s,
3 H (4 × OAc); 3.43 s, 3 H (OMe); 3.62 bd, 1 H, J(5,4) = 9.2 (H-4); 3.90–4.00 m , 4 H (H-5′,
H-6a, H-6b, H-5); 4.06–4.20 m , 2 H (H-6a′, H-6b′); 4.63 d, 1 H, J(2′,1′) = 10.1 (H-1′); 4.90 bs,
1 H (H-1); 5.05 dd, 1 H, J(2′,3′) = 9.9, J(4′,3′) = 3.4 (H-3′); 5.22 t, 1 H, J(1′,2′) = 10.1, J(3′,2′) =
10.1 (H-2′); 5.43 bd, 1 H, J(3′,4′) = 3.4 (H-4′); 5.86–5.94 m , 2 H (H-2, H-3). MS (FAB), m/z
(%): 475 ([MH – MeOH]+, 3.6). For C21H30O12S (506.5) calculated: 49.80% C, 5.97% H,
6.33% S; foun d: 49.85% C, 6.01% H, 6.25% S.
Methyl 2,3,4-tri-O-acetyl-6-deoxy-β-L-galactopyranosyl-(1→4)-2,3-dideoxy-4-thio-α-D-erythro-
hex-2-enopyranoside (13). Th e crude product obtain ed by m eth an olysis of 10 was
ch rom atograph ed in a m ixture of ligh t petroleum –eth yl acetate (2 : 1) to give syrupy 13
(134 m g, 95%), [α]D +82 (c 0.25, CHCl3). 1H NMR: 1.21 d, 3 H, J(5′,6′) = 6.4 (H-6′); 1.99 s,
3 H, 2.08 s, 3 H, 2.18 s, 3 H (3 × OAc); 3.44 s, 3 H (OMe); 3.61 dm , 1 H, J(5,4) = 10.4 (H-4);
3.75–3.80 m , 1 H (H-5); 3.80 qd, 1 H, J(6′,5′) = 6.4, J(4′,5′) = 1.2 (H-5′); 3.87 dd, 1 H, J(6a,6b) =
12.0, J(5,6a) = 2.8 (H-6a); 3.93 dd, 1 H, J(6a,6b) = 12.0, J(5,6b) = 4.4 (H-6b); 4.57 d, 1 H,
J(2′,l′) = 10.1 (H-1′); 4.90 m , 1 H (H-1); 5.05 dd, 1 H, J(2′,3′) = 9.9, J(4′,3′) = 3.4 (H-3′); 5.20 t,
1 H, J(1′,2′) = 9.9, J(3′,2′) = 9.9 (H-2′); 5.26 dd, 1 H, J(5′,4′) = 1.2, J(3′,4′) = 3.4 (H-4′); 5.80
ddd, 1 H, J(3,2) = 10.1, J(1,2) = 3.1, J(4,2) = 2.4 (H-2); 6.10 ddd, 1 H, J(2,3) = 10.1, J(4,3) =
2.1, J(1,3) = 1.1 (H-3). MS (FAB), m/z (%): 417 ([MH – MeOH]+, 2.2). For C19H28O10S (448.5)
calculated: 50.88% C, 6.29% H, 7.15% S; foun d: 51.07% C, 6.44% H, 6.79% S.
This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic
(grant No. VS 96 140).
REFERENCES
1. a) Defaye J., Gelas J. in: Studies in Natural Product Chemistry (Atta-ur-Rahman Ed.), Vol. 8,
p. 315. Elsevier, Amsterdam 1991; b) Driguez H.: Top. Curr. Chem. 1997, 187, 85.
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Bartoš, Černý, Tišlerová, Trnka:
2. a) Blanc-Muesser M., Defaye J., Driguez H.: J. Chem. Soc., Perkin Trans. 1 1982, 15;
b) Contour-Galcera M.-O., Guillot J.-M., Ortiz-Mellet C., Pflieger-Carrara F., Defaye J.,
Gelas J.: Carbohydr. Res. 1996, 281, 99.
3. Auzanneau F.-I., Bennis K., Fanton E., Promé D., Defaye J., Gelas J.: J. Chem. Soc., Perkin
Trans. 1 1998, 3629.
4. Blanc-Muesser M., Defaye J., Driguez H.: Carbohydr. Res. 1978, 67, 305.
5. Wang L.-X., Sakairi N., Kuzuhara H.: J. Chem. Soc., Perkin Trans. 1 1990, 1677.
6. Defaye J., Driguez H., Poncet S., Chambert R., Petit-Glatron M.-F.: Carbohydr. Res. 1984,
130, 299.
7. Mehta S., Andrews J. S., Johnston B. D., Svensson B., Pinto M. B.: J. Am. Chem. Soc.
1995, 117, 9783.
8. Calvo-Asín J. A., Calvo-Flores F. G., Exposito-López J. M., Hernández-Mateo F.,
García-López J. J., Isac-García J., Santoyo-González F., Vargas-Berenguel A.: J. Chem. Soc.,
Perkin Trans. 1 1997, 1079; and references therein.
9. Hashimoto H., Shimada K., Horito S.: Tetrahedron: Asymmetry 1994, 5, 2351.
10. Witczak Z. J., Sun J. M., Mielguj R.: Bioorg. Med. Chem. Lett. 1995, 5, 2169; and
references therein.
11. a) Pecka J., Staněk J., Jr., Černý M.: Collect. Czech. Chem. Commun. 1974, 39, 1192;
b) Nosková D.: M.S. Thesis. Charles University, Prague 1983.
12. Ranganayakulu K., Brown R. K.: J. Org. Chem. 1974, 39, 3941.
13. Matsumoto M., Ishikawa H., Soya Y., Ozawa T.: Heterocycles 1994, 38, 2377.
14. Trnka T., Buděšínský M., Černý M.: Carbohydr. Res. 1994, 259, 131.
15. Yates R. L., Epiotis N. D., Bernardi F.: J. Am. Chem. Soc. 1975, 97, 6615.
16. Miyashita N., Yoshikoshi A., Grieco P. A.: J. Org. Chem. 1977, 42, 3772.
17. Pecka J., Černý M.: Collect. Czech. Chem. Commun. 1973, 38, 132.
18. Mereyala H. B., Venkataramanaiah K. C., Dalvoy V. S.: Carbohydr. Res. 1992, 225, 151.
19. Paulsen H., Heiker F. R., Feldmann J., Heyns K.: Synthesis 1980, 636.
20. Černý M., Pacák J.: Collect. Czech. Chem. Commun. 1961, 26, 2084.
21. Černý M., Staněk J., Pacák J.: Monatsh. Chem. 1963, 94, 290.
22. Matta K. L., Girotra R. N., Barlow J. J.: Carbohydr. Res. 1975, 43, 101.
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