Synthesis of β-D-glucopyranosides of 6-substituted 2-(indol-3-YL)benzothiazoles

Article abstract of DOI:10.1135/cccc20050072

A linear synthesis of substituted 1-(β-D-glucopyranosyl) benzocamalexins starting from indoline and penta-O-acetyl-β-D-glucopyranose was elaborated. Jacobson cyclization of corresponding 4-substituted peracetylated β-D-glucopyranosylindole-3-carbothioanil

Full text of DOI:10.1135/cccc20050072

72
Humeník et al.:
SYNTHESIS OF β-D-GLUCOPYRANOSIDES OF 6-SUBSTITUTED
2-(INDOL-3-YL)BENZOTHIAZOLES
Martin HUMENÍKa1,*, Peter KUTSCHYa2, Katarína VALKOVÁ ,
Branislav HORVÁTH , Vladimir KOVÁČIK and Slávka BEKEŠOVÁ
a
b
c1
c2
a
Institute of Chemical Sciences, Faculty of Science, P. J. Šafárik University,
1
Moyzesova 11, 041 67 Košice, Slovak Republic; e-mail: mhumenik@yahoo.com,
2
kutschy@kosice.upjs.sk
b
c
Institute of Chemistry, Faculty of Science, Comenius University,
Mlynská dolina CH-2, 842 15 Bratislava, Slovak Republic; e-mail: bhorvath@fns.uniba.sk
Institute of Chemistry, Slovak Academy of Sciences,
1
Dúbravská cesta 9, 842 38 Bratislava, Slovak Republic; e-mail: chemvkov@savba.sk,
2
chembeke@savba.sk
Received July 29, 2004
Accepted October 11, 2004
A lin ear syn th esis of substituted 1-(β-D-glucopyran osyl)ben zocam alexin s startin g from
in dolin e an d pen ta-O-acetyl-β-D-glucopyran ose was elaborated. Jacobson cyclization of corre-
spon din g 4-substituted peracetylated β-D-glucopyran osylin dole-3-carboth ioan ilides em ploy-
in g potassium ferricyan ide un der basic con dition s was a key syn th etic step.
Keyw ord s: In doles; Jacobson reaction ; Ph ytoalexin s; Ben zocam alexin ; Glycosides;
Glycosidation s; Ben zoth iazoles; Th ioam ides; Nucleosides.
Aryl ben zoth iazoles are in terestin g syn th etic targets. An early study of
2-arylben zoth iazoles described th eir an tim icrobial activity again st Mycobac-
terium tuberculosis1. More recen t studies revealed in th ese h eterocycles a
broad spectrum of an titum or activities. Polyh ydroxylated 2-ph en ylben zo-
th iazoles an d 2-(4-am in oph en yl)ben zoth iazole, design ed as a poten tial ty-
rosin e kin ase in h ibitors, exh ibited cytotoxicity again st a ran ge of h um an
can cer cell lin es2a. Subsequen t exten sive SAR studies of th is sim ple
ph arm acoph ore2b–2g resulted in developm en t of 2-(4-am in o-3-m eth yl-
ph en yl)-5-fluoroben zoth iazole as an L-lysin am ide water-soluble prodrug
wh ich was sch eduled to en ter Ph ase 1 clin ical evaluation 2h ,2i. Som e aryl-
ben zoth iazoles were syn th esized as bioisosteres of active 2-arylben zoxazoles
an d tested as in h ibitors of lysoph osph atic acid acyltran sferase-β, th e pro-
tein playin g an im portan t role in sign alin g path ways in volved in tum or cell
survival3. Moody et al.4 perform ed quite a wide ran ge of studies devoted to
Collect. Czech. Chem. Commun. (Vol. 70) (2005)
doi:10.1135/cccc20050072

Synthesis of β-D-Glucopyranosides
73
in dolylth iazoles an d th e h igh est an tiproliferative effect ach ieved again st
SKBr3 breast can cer cells with 2-(ben zoth iazol-2-yl)-1-m eth ylin dole.
2-In dol-3-ylben zoth iazole, ben zocam alexin (1), attracted our in terest due
to its structural an alogy with th e n aturally occurrin g ph ytoalexin cam a-
lexin 5a 2 wh ich exh ibited an tifun gal activity again st Alternaria brassicae
Cladosporium sp. or Alternaria brassicicola5b,5c an d sign ifican t cytotoxic activ-
4
ity again st h um an breast can cer cell lin e SKBr3 . In addition , an ti-
proliferative activity of 1-β-D-ribofuran osyl- an d 1-α-D-m an n opyran osyl-
ben zocam alexin was recen tly described by our group6. Th ese outcom es
prom pted us to study a m eth od for th e in troduction of substituen ts on th e
ben zoth iazole m oiety of 1-glycosylben zocam alexin s.
6
5
7
4
7a
S
3a
N
1
S
2
3
3
N
4
7
3a
7a
5
6
2
N
H
2
1
1
N
H
Syn th eses of ben zoth iazole rin g via th e reaction s of aldeh ydes an d
keton es with 2-am in oben zen e-1-th iol is well kn own an d 2-(in dol-3-yl)-
ben zoth iazole an d its 1-substituted derivatives were syn th esized in reac-
tion s of in dole-3-carbaldeh yde7 an d 1-glycosylin dole-3-carbaldeh yde6. Un -
fortun ately usin g of substituted 2-am in oben zen e-1-th iols does n ot seem to
be advan tageous for th e syn th esis of 2-(in dol-3-yl)ben zoth iazoles bearin g
substituen ts on ben zoth iazole m oiety. Th e m ain reason is th e poor com -
m ercial an d syn th etic availability of substituted 2-am in oben zen e-1-th iols.
On ly a few syn th eses of such derivatives h ave been reported to date8. In
addition , th is m eth od is often n ot appropriate for m an y substituted
2-arylben zoth iazoles due to th e difficulties en coun tered in th e syn th esis
caused by th e readily oxidisable 2-am in oben zen e-1-th iols bearin g sub-
stituen t groups2g. On th e oth er h an d, in troduction of substituen ts in to
ben zocam alexin was perform ed via th e cyclization of 4-substituted
in dole-3-carboth ioan ilides un der Hugesh off con dition s9. Th erefore we
decided to in vestigate applicability of th is approach to th e syn th esis of
N-glycosides of substituted ben zocam alexin s usin g D-glucose as a m odel
sacch aride.
Th e syn th esis of 1-(β-D-glucopyran osyl)in dole-3-carboth ioam ides as a key
scaffold for th e Hugesh off reaction started from 1-(2,3,4,6-tetra-O-acetyl-
β-D-glucopyran osyl)in dole-3-carbaldeh yde6,10f (5; Sch em e 1) prepared from
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

74
Humeník et al.:
in dolin e (3) an d peracetylated β-D-glucose (4) applyin g th e in dolin e–in dole
protocol10. Aldeh yde 5 was efficien tly oxidized at room tem perature with
11
NaClO2 in a m ixture of tert-butyl alcoh ol, dioxan e an d water in th e pres-
en ce of 2-m eth ylbut-2-en e an d NaH2PO4·2H2O. Th us carboxylic acid 6 was
prepared in an excellen t of 95% yield (Sch em e 1).
Th e reaction of 6 with PCl3 in a m ixture of toluen e an d aceton itrile at
50 °C gave ch loride 7 (Sch em e 1). Th e reaction m ixture was con cen trated
un der reduced pressure to 1/6 of th e in itial volum e an d un stable crude
product 7 was used with out furth er purification in th e subsequen t reaction .
OAc
O
AcO
AcO
OAc
N
H
OAc
4
3
3 steps
OAc
OAc
O
O
NaClO2,
NaH2PO4·2H2O
O
O
AcO
AcO
OH
AcO
AcO
N
N
t-BuOH, H2O
2-methylbut-2-ene,
dioxane, 4 h, 95%
OAc
OAc
6
5
H2N
R
OAc
O
O
PCl3
8a-8d
AcO
Cl
N
AcO
toluene, CH3CN
50 °C, 30 min
OAc
7
S
O
OAc
OAc
6´
Lawesson
reagent
NH
NH
2
1
3
2
3
4´
6´
4´
1´´
1´´
5´
6´´
5´´
5´
6´´
5´´
O
O
1
AcO
AcO
3a
2´´
3a
2´´
4
1´
1´
N
7a
N
7a
AcO
toluene, ∆,
64-91%
AcO
2´
4
5
2´
3´
3´
OAc
4´´
OAc
4´´
3´´
3´´
5
7
7
9a-9d
R
10a-10d
R
6
6
R
a
b
c
d
CH3
OCH3
Cl
NO2
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Synthesis of β-D-Glucopyranosides
75
Th e in corporation of differen t substituen ts in to th e aglycon m oiety was
perform ed th rough th e reaction s of crude ch loride 7 with 4-substituted an i-
lin es 8a–8d in toluen e (Sch em e 1). Th e acylation of 4-m eth yl- 8a an d
4-m eth oxyan ilin e 8b possessin g electron -don atin g substituen ts proceeded
readily an d afforded an ilides 9a an d 9b in 99 an d 85% yield durin g 24 h
(Sch em e 1). In 8c, th e electron -with drawin g ch lorin e sligh tly decreased
n ucleoph ilicity of n itrogen an d reaction with ch loride 7 required pro-
lon ged reaction tim e (48 h ) at room tem perature affordin g product 9c in a
very good 88% yield. Th e least reactive 4-n itroan ilin e 8d afforded n o prod-
uct at room tem perature even after stirrin g for 5 days. It was foun d: th at
th e reaction can be successfully perform ed at th e reflux tem perature in th e
presen ce of a catalytic am oun t of 4-(dim eth ylam in o)pyridin e (DMAP), af-
fordin g com poun d 9d in 75% yield with in 2 h (Sch em e 1). Con version of
an ilides 9a–9c to th ioan ilides 10a–10c (Sch em e 1) proceeded readily with
th e Lawesson reagen t in boilin g toluen e12 durin g 0.5 h an d gave very good
yields of com poun ds 10a (91%), 10b (94%) an d 10c (83%). Less reactive 9d
required 24-h h eatin g an d afforded th ioan ilide 10d in 64% yield.
Th e m ost com m on m eth od for preparation of ben zoth iazoles is th e
Hugersh off reaction of arylth ioureas13. Usin g th e recen tly described con di-
tion s9, we tried to ach ieve th e Hugersh off rin g closure by th e reaction of
1-glucosylth ioan ilides 10a–10d with Br2 in CHCl3 (Table I, en try 1). TLC
m on itorin g of th e reaction s revealed th e con sum ption of th e startin g m ate-
rial an d form ation of an un stable product alon g with an ilides 9a–9d in
15 m in . Attem pts to work up th e reaction by wash in g with saturated solu-
tion of NaHCO3 led on ly to isolation of an ilides 9a–9d . Sim ple evaporation
of th e solven t un der reduced pressure gave a m ixture of th ioan ilides an d
TABLE I
Attem pts at cyclization of N-(4-substituted ph en yl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyran osyl)-
in dole-3-carboth ioam ides 10a–10d
Reagen t (equiv.)
Solven t
CHCl313, dioxan e, CH3COOH
14
Br2 (1.1–3)
15
SOCl2 (5)
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
N-Brom osuccin im ide (2)
Br2 + tetrabutylam m on ium brom ide16 (1.2 + 1.2)
Pyridin ium tribrom ide (2)
m-Ch loroperoxyben zoic acid17 (2)
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

76
Humeník et al.:
an ilides in th e ratio ca. 1:1. Usin g of strictly an h ydrous con dition s un der
n itrogen atm osph ere afforded th e sam e result. On th e basis of th ese obser-
vation s it seem s plausible th at a h igh ly un stable in term ediate, arisin g in th e
reaction m ixture, quickly h ydrolyzed in con tact with air m oisture or aque-
ous work up. Several m odification s of reaction con dition s (Table I, en tries
2–6) gave th e sam e result: fast con sum ption of th e startin g m aterial an d iso-
lation of am ides 9a–9d as m ain products (Sch em e 2). Sin ce th e rin g closure
of in dole-3-carboth ioam ides substituted on in dole n itrogen proceeded
sm ooth ly9, th e failure of th e Hugersh off cyclization with th ioam ides
10a–10d can be attributed to electron ic an d/or steric effects of th e
sacch aride m oiety. Study of th is problem will be th e subject of our future
in vestigation .
OH
6´
5´
4´
HO
HO
R
7´´
1´´
S
6´´
5´´
O
7´´a
3´
Jacobson conditions:
1. 1 M NaOH, 0 °C, 5 min
2. aq. K3Fe(CN)6
2
2´
HO
1
N
7a
3
1´
4´´
2´´
3´´a
N
3a
3´´
11a-11c
R
7
4
MeOH,
51-64%
a
CH3
OCH3
Cl
5
6
b
c
d
10a-10d
OAc
NO2
AcO
AcO
O
Hugershoff conditions:
Br2, different solvents
O
R
AcO
N
N
H
9a-9d
SCHEME 2
Th e un expected failure of cyclization of 1-glucosylin dole-3-carboth io-
am ides 10a–10d m ade us apply an oth er m eth od to obtain desired
1-glucosylben zocam alexin s. Syn th esis of ben zoth iazole rin g is also possible
usin g th e Jacobson oxidative cyclization 2b,2g,18 of arylth ioan ilides un sub-
stituted in ortho-position 18e. Rin g closure proceeded in th e presen ce of po-
tassium ferricyan ide in basic m edium , usually in aqueous 1 M NaOH. Th e
solubility of tetraacetylated 1-glucosylth ioan ilides 10a–10b in aqueous
m edium was very poor, th erefore th ey were dissolved in m eth an ol an d 1 M
aqueous solution of NaOH was added. Im m ediate deacetylation of th e
sacch aride m oiety was observed by TLC (fast disappearan ce of th e startin g
m aterial) an d occurren ce of a n ew spot on th e start lin e (in cycloh exan e–
eth yl acetate 3:1). Deacetylated products were n ot isolated an d subsequen t
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Synthesis of β-D-Glucopyranosides
77
addition of 15% aqueous solution of K3[Fe(CN)6] resulted in th e form ation
of target com poun ds 11a–11c (Sch em e 2). Th e best result was ach ieved
with 6 equivalen ts of NaOH an d 3 equivalen ts of K3[Fe(CN)6]. Th e reaction
tim e was in fluen ced by substituen ts on th e an ilide m oiety of 10a–10d .
Electron -don atin g CH3 an d CH3O groups facilitated electroph ilic substitu-
tion . Reaction proceeded at room tem perature an d after 2–2.5 h gave cyclic
product 11a (64%) or 11b (61%). Sligh tly-electron with drawin g ch lorin e
atom caused prolon gation of reaction tim e an d th e reaction with
K3[Fe(CN)6] gave 11c in 51% yield after 4.5 h . In all cases un iden tified de-
com position products were presen t in th e reaction m ixture. In 10d , th e
stron g electron -with drawin g n itrogroup deactivates th e ben zen e rin g of
th ioan ilide m akin g electroph ilic substitution difficult. No progress was ob-
served perform in g th e reaction un der con dition s used with 10a–10c.
Heatin g at 60 °C, stron ger basic con dition (8 equivalen ts of NaOH) an d
h igh er excess of K3[Fe(CN)6] (5 equivalen ts) resulted after 18 h in com plete
decom position of startin g com poun d with out form ation of com poun d 11d .
As a prim ary in vitro screen in g for growth in h ibition an d cytotoxicity,
com poun ds 11a–11c were subm itted to th e Nation al Can cer In stitute,
Beth esda, U.S.A.) for testin g. Th eir cytotoxic poten cy on th ree h um an cell
lin es NCI-H460 lun g can cer, MCF7 breast can cer an d SF-268 gliom a was
evaluated. A com poun d is con sidered active wh en it reduces th e growth of
an y of th e cell lin es to 32% or less an d it is passed on for evaluation in th e
full pan el of sixty cell lin es. Com poun d 11b was active in th is test. Th e
pan el of sixty h um an tum or cell lin es is organ ized in to subpan els represen t-
in g leukem ia, m elan om a an d can cers of lun g, colon , kidn ey, ovary, breast,
prostate an d cen tral n ervous system . Th e test com poun ds were dissolved in
DMSO an d evaluated usin g five con cen tration s at ten -fold dilution s, th e
h igh est bein g 10–4 m ol l–1 an d th e oth ers 10–5–10–8 m ol l–1. Com poun d 11b
did n ot sh ow a level of activity sufficien t to en ter th e subsequen t in vivo
step.
Th e syn th esis of th ree n ovel derivatives of 1-glucosylben zocam alexin was
perform ed by applyin g th e in dolin e–in dole m eth od an d Jacobson cyc-
lization . In troduction of substituen ts in to th e ben zoth iazole m oiety al-
lowed evaluatin g th eir in fluen ce on th e an tican cer effect. In term s of m ean
GI50 values across th e cell pan el, 11b sh owed th e best activity again st ovar-
ian can cer cell lin e IGROV1 (13.4 µm ol l–1). Th is en h an cem en t of an ti-
proliferative activity is un doubtedly attributed to th e presen ce of m eth oxy
group in its structure com pared to recen tly syn th esized in active un sub-
stituted 1-glucosylben zocam alexin 6.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

78
Humeník et al.:
EXPERIMENTAL
1H an d 13C NMR spectra were m easured on a Varian Gem in i 2000 NMR spectrom eter operat-
in g at 300 MHz for 1H an d at 75 MHz for 13C. Ch em ical sh ifts (δ-scale) are reported in ppm ,
down field from tetram eth ylsilan e used as an in tern al stan dard; couplin g con stan ts (J) in Hz.
Microan alyses were perform ed with a Perkin –Elm er, Model 2400 an alyzer. Th e EI m ass spec-
tra were recorded on a Fin igan SSQ 700 spectrom eter at ion ization en ergy 70 eV, wh ereas
MALDI-TOF m ass spectra were m easured on a MALDI IV (Sh im adzu, Kratos An alytical) in -
strum en t. For MALDI m easurem en ts th e an alyzed sam ples were dissolved in an aceton itrile–
water m ixture (1:1). Th e m atrix, 2,5-dih ydroxyben zoic acid, was dissolved in th e sam e
m ixture. Solution s of a sam ple an d th e m atrix were m ixed in th e ratio 1:10. After dryin g
on target, th e sam ples were bom barded with a 3-n s dose (100 doses) of a n itrogen laser
(λ = 337 n m ). Ion acceleration voltage was 5 kV. Th e reaction course was m on itored by th in
layer ch rom atograph y, usin g plates Mach erey–Nagel Alugram Sil G/UV254. Th e preparative
colum n ch rom atograph y (flash ch rom atograph y) was perform ed on Kieselgel Merck Type 9385,
230–400 m esh .
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyran osyl)in dole-3-carboxylic Acid (6)
Aldeh yde
5 (6.50 g, 13.67 m m ol) was dissolved in tert-butyl alkoh ol (146 m l) an d
2-m eth ybut-2-en e (146 m l). Th e solution was cooled to 0 °C an d sodium ch lorite (24.6 g,
271.6 m m ol) was added followed by a solution of NaH2PO4·2H2O (31.9 g, 204.6 m m ol) in
146 m l of water. Fin ally dioxan e (169 m l) was added an d th e reaction m ixture was stirred at
room tem perature for 4 h . After addition of water (130 m l), th e reaction m ixture was ex-
tracted with CHCl3 (2 × 150 m l) an d th e organ ic layer was wash ed with brin e an d dried over
an h ydrous Na2SO4. Solven ts were evaporated un der reduced pressure an d th e crude product
was recrystallized from a m ixture of eth yl acetate–h exan e. Yield 6.37 g (95%) of wh ite crys-
tals, m .p. 224–226 °C (eth yl acetate–h exan e). For C23H25NO11 (491.4) calculated: 56.21% C,
5.13% H, 2.85% N; foun d: 56.56% C, 5.38% H, 2.69% N. 1H NMR (CDCl3): 1.71 s, 3 H
(CH3); 2.05 s, 3 H (CH3); 2.11 s, 3 H (CH3); 2.12 s, 3 H (CH3); 4.04 m , 1 H (H-5′); 4.21 d,
1 H, J(6′a,6′b) = 12.3 (H-6′b); 4.34 dd, J(6′a,6′b) = 12.6, J(6′a,5′) = 4.8 (H-6′a); 5.34 m , 1 H
(H-4′); 5.51 m , 2 H (H-3′, H-2′); 5.68 d, J = 8.63 (H-1′); 7.35 m , 2 H; 7.49 m , 1 H; 8.25 m ,
1 H an d 8.09 s, 1 H (H-arom .). 13C NMR (CDCl3): 20.06, 20.61, 20.75 (CH3CO); 61.77 (C-6′);
67.94 (C-4′); 70.77 (C-2′); 73.02 (C-3′); 75.12 (C-5′); 83.76 (C-1′); 109.19, 110.42, 122.27,
123.09, 123.72, 126.93, 132.54, 136.32 (C arom .); 168.57, 169.40, 169.60, 170.21, 170.65
(C=O). MS MALDI-TOF, m/z (%): 530 [M + K]+ (36); 514 [M + Na]+ (76); 492 [M + H]+ (30).
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyran osyl)in dole-3-carbon yl Ch loride (7)
To stirred solution of carboxylic acid 6 (1.50 g, 3.05 m m ol) in a m ixture of toluen e (18 m l)
an d aceton itrile (3 m l) was added PCl3 (0.836 g, 0.53 m l, 6.10 m m ol) at 50 °C. Th e reaction
m ixture was stirred at 50 °C un til th e wh ole am oun t of th e acid was dissolved, an d stirrin g
con tin ued for 20 m in . Th e reaction m ixture was cooled to room tem perature, poured in to
an oth er flask an d residue of ph osph oric acid was wash ed with 15 m l of toluen e. Solven ts
were evaporated un der reduced pressure to 1/6 of th e in itial volum e. Th e obtain ed solution
of crude ch loride 7 was used for subsequen t reaction .
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Synthesis of β-D-Glucopyranosides
79
N-(4-Substituted ph en yl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyran osyl)in dole-
3-carboxam ides 9a–9d . Gen eral Procedure
Con cen trated solution of crude ch loride 7 (approx. 3.05 m m ol) was diluted with 20 m l of
dry toluen e an d 4-substituted an ilin e 8a–8d (7.63 m m ol) was added to th e obtain ed solu-
tion . Th e reaction m ixture was stirred at room tem perature for 24 h (48 h required for 8c),
diluted with eth yl acetate an d wash ed with aqueous 1 M HCl (2×), saturated aqueous solu-
tion of NaHCO3 an d water. Th e organ ic layer was dried over an h ydrous Na2SO4 an d th e
crude product was recrystallized from an eth yl acetate–h exan e m ixture.
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-N-p-tolylindole-3-carboxamide (9a). Yield 99% of
wh ite crystals, m .p. 190–194 °C (eth yl acetate–h exan e). For C30H32N2O10 (580.6) calculated:
62.06% C, 5.56% H, 4.83% N; foun d: 62.31% C, 5.27% H, 4.51% N. 1H NMR (CDCl3): 1.68 s,
3 H (CH3); 2.03 s, 3 H (CH3); 2.09 s, 6 H (2 × CH3); 2.34 s, 3 H (Ph -CH3); 4.01 ddd, 1 H,
J(5′,6′b) = 2.0, J(5′,6′a) = 5.0, J(4′,5′) = 10.2 (H-5′); 4.15 dd, 1 H, J(6′a,6′b) = 12.6, J(5′,6′b) =
2.0 (H-6′b); 4.32 dd, 1 H, J(6′a,6′b) = 12.6, J(5′,6′a) = 5.0 (H-6′a); 5.26 t, 1 H, J = 10.2 (H-4′);
5.42–5.53 bm , 2 H (H-2′, H-3′); 5.66 d, 1 H, J(1′,2′) = 8.6 (H-1′); 7.17 d, 2 H, J = 8.4 (H-3′′,
H-5′′); 7.29–7.37 bm , 2 H (H-6, H-5); 7.47–7.49 m , 1 H (H-7); 7.53 d, 2 H, J = 8.4 (H-2′′,
H-6′′); 7.67 s, 1 H (NH); 7.87 s, 1 H (H-2); 8.12–8.14 m , 1 H (H-4). 13C NMR (CDCl3): 20.35,
20.81, 20.85, 20.98 (CH3CO); 21.16 (Ph -CH3); 62.02 (C-6′); 68.18 (C-4′); 70.45 (C-2′); 73.20
(C-3′); 75.22 (C-5′); 83.56 (C-1′); 110.49 (H-7); 114.33 (C-3); 120.36 (C-2′′, C-6′′); 121.42
(C-4); 122.83 (C-5); 123.79 (C-6); 126.33 (C-3a); 127.31 (C-2); 129.71 (C-3′′, C-5′′); 133.87
(C-4′′); 135.74 (C-1′′); 136.48 (C-7a); 162.63 (CONH); 168.86, 169.49, 170.21, 170.71
(CH3CO). MS MALDI-TOF, m/z (%): 619 [M + K]+ (15); 603 [M + Na]+ (77); 581 [M + H]+
(100).
N-(4-Methoxyphenyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carboxamide (9b ).
Yield 85% of wh ite crystals, m .p. 202–204 °C (eth yl acetate–h exan e). For C30H32N2O11
(596.6) calculated: 60.40% C, 5.41% H, 4.70% N; foun d: 60.23% C, 5.10% H, 4.37% N.
1H NMR (CDCl3): 1.68 s, 3 H (CH3); 2.03 s, 3 H (CH3); 2.09 s, 6 H (2 × CH3); 3.82 s, 3 H
(Ph -OCH3); 4.02 ddd, 1 H, J(5′,6′b) = 2.2, J(5′,6′a) = 5.0, J(4′,5′) = 10.2 (H-5′); 4.13 dd, 1 H,
J(6′a,6′b) = 12.5, J(5′,6′b) = 2.2 (H-6′b); 4.33 dd, 1 H, J(6′a,6′b) = 12.5, J(5′,6′a) = 5.0 (H-6′a);
5.26 t, 1 H, J = 10.2 (H-4′); 5.42–5.53 bm , 2 H (H-2′, H-3′); 5.65 d, 1 H, J(1′,2′) = 8.8 (H-1′);
6.91 d, 2 H, J = 9.1 (H-3′′, H-5′′); 7.26–7.37 bm , 2 H (H-6, H-5); 7.47–7.50 m , 1 H (H-7);
7.55 d, 2 H, J = 9.1 (H-2′′, H-6′′); 7.64 s, 1 H (NH); 7.86 s, 1 H (H-2); 8.12–8.15 m , 1 H (H-4).
13C NMR (CDCl3): 20.36, 20.82, 20.85, 20.98 (CH3CO); 55.75 (Ph -OCH3); 62.03 (C-6′); 68.17
(C-3′); 70.95 (C-2′); 73.20 (C-4′); 75.22 (C-5′); 83.52 (C-1′); 110.45 (H-7); 114.27 (C-3);
114.40 (C-3′′, C-5′′); 121.45 (C-4); 122.23 (C-2′′, C-6′′); 122.80 (C-5); 123.78 (C-6); 123.35
(C-3a); 127.21 (C-2); 131.38 (C-1′′); 136.57 (C-7a); 156.48 (C-4′′); 162.66 (CONH); 168.86,
169.51, 170.21, 170.71 (CH3CO). MS MALDI-TOF, m/z (%): 635 [M + K]+ (13); 619 [M + Na]+
(89); 597 [M + H]+ (100).
N-(4-Chlorophenyl)1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carboxamide (9c). Yield
88% of wh ite crystals, m .p. 201–202 °C (eth yl acetate–h exan e). For C29H29ClN2O10 (601.0)
calculated: 57.96% C, 4.86% H, 4.66% N; foun d: 58.14% C, 4.75% H, 4.95% N. 1H NMR
(CDCl3): 1.67 s, 3 H (CH3); 2.03 s, 3 H (CH3); 2.08 s, 3 H (CH3); 2.09 s, 3 H (CH3); 4.02 ddd,
1 H, J(5′,6′b) = 2.2, J(5′,6′a) = 5.2, J(4′,5′) = 9.9 (H-5′); 4.14 dd, 1 H, J(6′a,6′b) = 12.5, J(5′,6′b) =
2.2 (H-6′b); 4.33 dd, 1 H, J(6′a,6′b) = 12.5, J(5′,6′a) = 5.2 (H-6′a); 5.24 t, 1 H, J = 9.9 (H-4′);
5.43–5.51 bm , 2 H (H-2′, H-3′); 5.67 d, 1 H, J(1′,2′) = 9.1 (H-1′); 7.30–7.38 bm , 4 H (H-3′′,
H-5′′, H-6, H-5); 7.46–7.49 m , 1 H (H-7); 7.60 d, 2 H, J = 8.8 (H-2′′, H-6′′); 7.76 s, 1 H (NH);
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7.88 s, 1 H (H-2); 8.12–8.15 m , 1 H (H-4). 13C NMR (CDCl3): 20.33, 20.81, 20.84, 20.98
(CH3CO); 62.03 (C-6′); 68.17 (C-4′); 71.03 (C-2′); 73.12 (C-3′); 75.28 (C-5′); 83.41 (C-1′);
110.44 (H-7); 113.96 (C-3); 121.46 (C-2′′, C-6′′, C-4); 122.98 (C-5); 123.94 (C-6); 126.26
(C-3a); 127.34 (C-2); 129.12 (C-4′′); 129.19 (C-3′′, C-5′′); 136.60 (C-7a); 136.95(C-1′′); 162.68
(CONH); 168.88, 169.50, 170.17, 170.70 (CH3CO). MS MALDI-TOF, m/z (%): 639 [M + K]+
(10); 623 [M + Na]+ (100); 601 [M + H]+ (48).
N-(4-Nitrophenyl)1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carboxamide (9d ). Con -
cen trated solution of crude ch loride 7 (ca. 3.05 m m ol) was diluted with 40 m l of dry tolu-
en e, 4-n itroan ilin e (1.053 g, 7.63 m m ol) an d DMAP (37 m g, 0.305 m m ol) were added to th e
solution . Th e reaction m ixture was refluxed for 2 h , cooled to room tem perature, diluted
with eth yl acetate an d wash ed with aqueous 6 M HCl (2×), saturated aqueous solution of
NaHCO3 an d water. Th e organ ic layer was dried over an h ydrous Na2SO4, filtered th rough
Celite an d con cen trated un der reduced pressure. Th e crude product was recrystallized from
a m ixture of solven ts eth yl acetate–h exan e. Yield 1.40 g (75%) of pale oran ge crystals, m .p.
120–124 °C (eth yl acetate–h exan e). For C29H29N3O12 (611.6) calculated: 56.96% C, 4.78% H,
6.87% N; foun d: 57.11% C, 4.81% H, 6.59% N. 1H NMR (CDCl3): 1.66 s, 3 H (CH3); 2.02 s,
3 H (CH3); 2.07 s, 3 H (CH3); 2.09 s, 3 H (CH3); 4.02 ddd, 1 H, J(5′,6′b) = 2.2, J(5′,6′a) = 5.2,
J(4′,5′) = 10.2 (H-5′); 4.12 dd, 1 H, J(6′a,6′b) = 12.4, J(5′,6′b) = 2.2 (H-6′b); 4.33 dd, 1 H,
J(6′a,6′b) = 12.4, J(5′,6′a) = 5.2 (H-6′a); 5.16 t, 1 H, J = 10.2 (H-4′); 5.39–5.49 bm , 2 H (H-2′,
H-3′); 5.69 d, 1 H, J(1′,2′) = 8.8 (H-1′); 7.32–7.40 bm , 2 H (H-6, H-5); 7.45–7.49 m , 1 H (H-7);
7.82 d, 2 H, J = 9.1 (H-2′′, H-6′′); 7.96 s, 1 H (H-2); 8.15–8.18 m , 1 H (H-4); 8.22 d, 2 H, J =
9.1 (H-3′′, H-5′′); 8.25 bs, 1 H (NH). 13C NMR (CDCl3): 20.31, 20.78, 20.84, 20.98 (CH3CO);
62.08 (C-6′); 68.19 (C-4′); 71.13 (C-2′); 73.98 (C-3′); 75.36 (C-5′); 83.20 (C-1′); 110.37 (C-7);
113.40 (C-3); 119.33 (C-2′′, C-6′′); 121.55 (C-4); 123.29 (C-5); 124.20 (C-6); 125.30 (C-3′′,
C-5′′); 126.23 (C-3a); 127.59 (C-2); 136.64 (C-7a); 143.36 (C-4′′); 144.46(C-1′′); 162.82
(CONH); 168.93, 169.52, 170.12, 170.75 (CH3CO). MS MALDI-TOF, m/z (%): 651 [M + K]+
(6); 635 [M + Na]+ (46); 612 [M + H]+ (33).
N-(4-Substituted ph en yl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyran osyl)in dole-
3-carboth ioam ides 10a–10d . Gen eral Procedure
Th e correspon din g am ide 9a–9d (3.01 m m ol) was dissolved in dry toluen e (30 m l) an d th e
Lawesson reagen t (0.61 g, 1.51 m m ol) was added to th e solution . Th e reaction m ixture was
refluxed for 30 m in (9a–9c) or 24 h (9d ), cooled to room tem perature an d toluen e was evap-
orated un der reduced pressure. Th e obtain ed residue was subjected to colum n ch rom atogra-
ph y (cycloh exan e–eth yl acetate 2:1).
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-N-p-tolylindole-3-carbothioamide (10a). Yield
1.63 g (91%) of yellow crystals, m .p. 103–104 °C (eth yl acetate–h exan e). For C30H32N2O9S
(596.7) calculated: 60.39% C, 5.41% H, 4.70% N; foun d: 60.45% C, 5.32% H, 4.99% N.
1H NMR (CDCl3): 1.74 s, 3 H (CH3); 2.03 s, 3 H (CH3); 2.08 s, 3 H (CH3); 2.09 s, 3 H (CH3);
2.38 s, 3 H (Ph -CH3); 4.02 ddd, 1 H, J(5′,6′b) = 2.2, J(5′,6′a) = 4.9, J(4′,5′) = 9.9 (H-5′);
4.18 dd, 1 H, J(6′a,6′b) = 12.6, J(5,6′b) = 2.2 (H-6′b); 4.32 dd, 1 H, J(6′a,6′b) = 12.6, J(5′,6′a) =
4.9 (H-6′a); 5.9 t, 1 H, J = 9.9 (H-4′); 5.42 t, 1 H, J = 9.3 (H-3′); 5.53 t, 1 H, J = 9.3 (H-2′);
5.63 d, 1 H, J(1′,2′) = 8.8 (H-1′); 7.23 d, 2 H, J = 8.4 (H-3′′, H-5′′); 7.27–7.36 bm , 2 H (H-6,
H-5); 7.51–7.53 m , 1 H (H-7); 7.59 d, 2 H, J = 8.0 (H-2′′, H6′′); 8.03 s, 1 H (H-2); 8.7 bd, 1 H,
J = 8.0 (H-4); 8.97 s, 1 H (NH). 13C NMR (CDCl3): 20.41, 20.79, 20.81, 20.96 (CH3CO); 21.39
(Ph -CH3); 61.99 (C-6′); 68.15 (C-4′); 70.86 (C-2′); 73.17 (C-3′); 75.29 (C-5′); 84.14 (C-1′);
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Synthesis of β-D-Glucopyranosides
81
111.26 (H-7); 120.79 (C-4); 122.18 (C-3); 123.07 (C-5); 123.87 (C-6); 124.30 (C-2′′, C-6′′);
124.81 (C-3a); 129.78 (C-3′′, C-5′′, C-2); 136.53 (C-4′′); 136.69 (C-7a); 136.79 (C-1′′); 168.91,
169.52, 170.27, 170.75 (CH3CO); 191.33 (CSNH). MS MALTI-TOF, m/z (%): 635 [M + K]+
(16); 619 [M + Na]+ (44); 597 [M + H]+ (65); 563 [M – H2S]+ (100).
N-(4-Methoxyphenyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carbothioamide
(10b). Yield 94% of yellow crystals, m .p. 95–98 °C (eth yl acetate–h exan e). For C30H32N2O10
S
(612.7) calculated: 58.81% C, 5.26% H, 4.57% N; foun d: 58.68% C, 5.41% H, 4.62% N.
1H NMR (CDCl3): 1.73 s, 3 H (CH3); 2.03 s, 3 H (CH3); 2.08 s, 3 H (CH3); 2.09 s, 3 H (CH3);
3.84 s, 3 H (Ph -OCH3); 4.02 ddd, 1 H, J(5′,6′b) = 2.2, J(5′,6′a) = 5.0, J(4′,5′) =10.2 (H-5′);
4.17 dd, 1 H, J(6′a,6′b) = 12.4, J(5′,6′b) = 2.2 (H-6′b); 4.32 dd, 1 H, J(6′a,6′b) = 12.4, J(5′,6′a) =
5.0 (H-6′a); 5.28 t, 1 H, J = 10.2 (H-4′); 5.46 t, 1 H, J = 9.2 (H-3′); 5.51 t, 1 H, J = 9.2 (H-2′);
5.64 d, 1 H, J(1′,2′) = 8.8 (H-1′); 6.96 d, 2 H, J = 9.1 (H-3′′, H-5′′); 7.27–7.36 bm , 2 H (H-6,
H-5); 7.50–7.54 m , 1 H (H-7); 7.60 d, 2 H, J = 9.1 (H-2′′, H-6′′); 8.03 s, 1 H (H-2); 8.08 bd, 1 H,
J = 6.31 (H-4); 8.95 bs, 1 H (NH). 13C NMR (CDCl3): 20.42, 20.79, 20.82, 20.96 (CH3CO);
55.72 (Ph -OCH3); 62.00 (C-6′); 68.16 (C-4′); 70.87 (C-2′); 73.18 (C-3′); 75.26 (C-5′); 84.11
(C-1′); 111.45 (H-7′); 114.37 (C-3, C-3′′, C-5′′); 120.80 (C-4); 123.03 (C-5); 123.85 (C-6);
126.85 (C-3a); 126.12 (C-2′′, C-6′′); 129.68 (C-2); 132.03 (C-1′′); 136.68 (C-7a); 158.24 (C-4′′);
168.88, 169.50, 170.23, 170.72 (CH3CO); 191.40 (CSNH). MS MALDI-TOF, m/z (%): 652 [M +
K]+ (74); 636 [M + Na]+ (76); 613 [M + H]+ (80); 579 [M – H2S]+ (100).
N-(4-Chlorophenyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carbothioamide (10c).
Yield 83% of yellow crystals, m .p. 165–170 °C (eth yl acetate–h exan e). For C29H29ClN2O9S
(617.1) calculated: 56.45% C, 4.74% H, 4.54% N; foun d: 56.71% C, 4.56% H, 4.78% N.
1H NMR (CDCl3): 1.73 s, 3 H (CH3); 2.03 s, 3 H (CH3); 2.08 s, 3 H (CH3); 2.09 s, 3 H (CH3);
4.03 ddd, 1 H, J(5′,6′b) = 2.0, J(5′,6′a) = 5.0, J(4′,5′) = 10.0 (H-5′); 4.17 dd, 1 H, J(6′a,6′b) =
12.7, J(5′,6′b) = 2.0 (H-6′b); 4.32 dd, 1 H, J(6′a,6′b) = 12.6, J(5′,6′a) = 5.2 (H-6′a); 5.28 t, 1 H,
J = 10.0 (H-4′); 5.42–5.56 m , 2 H (H-3′, H-2′); 5.65 d, 1 H, J(1′,2′) = 9.0 (H-1′); 7.31–7.40 bm ,
4 H (H-3′′, H-5′′, H-5, H-6); 7.50–7.55 m , 1 H (H-7); 7.69 d, 2 H, J = 8.8 (H-2′′, H-6′′); 8.03 s,
1 H (H-2); 8.06–8.10 m , 1 H (H-4); 9.03 bs, 1 H (NH). 13C NMR (CDCl3): 20.13, 20.54, 20.69
(CH3CO); 61.72 (C-6′); 67.93 (C-4′); 70.72(C-2′); 72.89 (C-3′); 75.04 (C-5′); 83.77 (C-1′);
110.95, 120.66, 121.93, 122.97, 123.80, 124.58, 125.23, 129.04, 129.33, 131.61, 136.56,
137.40 (C arom .); 168.74, 169.35, 170.04, 170.55 (CH3CO); 191.31 (CSNH). MS MALDI-TOF,
m/z (%): 655 [M + K]+ (12); 639 [M + Na]+ (89); 617 [M + H]+ (77); 583 [M – H2S]+ (100).
N-(4-Nitrophenyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carbothioamide (10d ).
Yield 64% of oran ge crystals, m .p. 118–121 °C (eth yl acetate–h exan e). For C29H29N3O11
S
(627.6) calculated: 55.50% C, 4.66% H, 6.70% N; foun d: 55.89% C, 4.53% H, 6.49% N.
1H NMR (CDCl3): 1.72 s, 3 H (CH3); 2.03 s, 3 H (CH3); 2.08 s, 3 H (CH3); 2.09 s, 3 H (CH3);
4.05 ddd, 1 H, J(5′,6′b) = 1.8, J(5′,6′a) = 4.9, J(4′,5′) = 10.2 (H-5′); 4.18 dd, 1 H, J(6′a,6′b) =
12.1, J(5′,6′b) = 1.7 (H-6′b); 4.34 dd, 1 H, J(6′a,6′b) = 12.1, J(5′,6′a) = 4.9 (H-6′a); 5.28 t, 1 H,
J = 10.2 (H-4′); 5.33–5.55 m , 2 H (H-3′, H-2′); 5.66 d, 1 H, J(1′,2′) = 9.2 (H-1′); 7.33–7.40 bm ,
2 H (H-6, H-5); 7.45–7.54 m , 1 H (H-7); 8.01–8.10 bm , 4 H; 8.24–8.23, bd, 2 H, J = 8.8 (H-4);
9.24 bs, 1 H (NH). 13C NMR (CDCl3): 20.12, 20.50, 20.53, 20.69 (CH3CO); 61.73 (C-6′);
67.91 (C-4′); 70.82 (C-2′); 72.78 (C-3′); 75.14 (C-5′); 83.60 (C-1′); 110.91, 120.71, 122.38,
122.49, 123.26, 124.06, 124.52, 124.72, 129.28, 136.64, 144.52, 144.60 (C arom .); 168.84,
169.33, 169.99, 170.52 (CH3CO); 191.55 (CSNH). MS MALDI-TOF, m/z (%): 665 [M + K]+ (3);
650 [M + Na]+ (32); 628 [M + H]+ (41); 594 [M – H2S]+ (100).
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Humeník et al.:
6-Substituted 2-(1-(β-D-Glucopyran osyl)in dol-3-yl)ben zoth iazoles 11a–11c.
Gen eral Procedure
Th ioam ide 10a–10c (0.754 m m ol) was dissolved in m eth an ol (27 m l), th e solution was
cooled to 0 °C an d aqueous 1 M NaOH (4.52 m l, 4.52 m m ol) was added. After 5 m in , con -
sum ption of th e startin g m aterial was detected (TLC). A 15% aqueous solution of K3Fe(CN)6
(4 m l, 2.26 m m ol) was added to th e reaction m ixture, an d th e yellow slurry was stirred at
room tem perature for 2.5 h . Th e reaction m ixture was diluted with THF (30 m l) an d in or-
gan ic salts were filtered off. Th e filtrate was con cen trated un der reduced pressure an d th e
residue was subjected to colum n ch rom atograph y (dich lorom eth an e–m eth an ol–NH4OH
100:10:1).
6-Methyl-2-(1-(β-D-glucopyranosyl)indol-3-yl)benzothiazole (11a). Yield 64% of pale yellow
solid, m .p. 192–194 °C. For C22H22N2O5S (426.5) calculated: 61.96% C, 5.20% H, 6.57% N;
foun d: 62.14% C, 5.36% H, 6.38% N. 1H NMR (DMSO-d6): 2.46 s, 3 H (Ph -CH3); 3.39 t, 1 H,
J = 8.7; 3.47–3.57 bm , 3 H; 3.75 d, 1 H, J = 10.2 an d 3.88 t, 1 H, J = 8.7 (H sacch aride,
H-2′–H-6′); 4.59 bs, 1 H (CD3COOD exch an geable, OH); 5.18 bs, 1 H (CD3COOD exch an ge-
able, OH); 5.24 bs, 1 H (CD3COOD exch an geable, OH); 5.38 bs, 1 H (CD3COOD exch an ge-
able, OH); 5.58 d, 1 H, J = 8.4 (H-1′); 7.25–7.43 bm , 3 H; 7.73 m , 1 H; 7.85–7.89 m , 2 H;
8.33 s, 1 H an d 8.43 m , 1 H (H arom .). 13C NMR (CDCl3): 20.90 (Ph -CH3); 60.78 (C-6′);
69.54, 71.72, 77.18, 79.54 (C-2′–C-5′); 85.02 (C-1′); 110.64, 111.81, 120.89, 121.26, 121.37,
121.65, 122.88, 124.81, 127.45, 129.09, 133.15, 133.96, 136.78, 151.65, 161.19 (C arom .).
MS MALDI-TOF, m/z (%): 465 [M + K]+ (3); 449 [M + Na]+ (24); 427 [M + H]+ (100).
6-Methoxy-2-(1-(β-D-glucopyranosyl)indol-3-yl)benzothiazole (11b). Yield 61% of pale yellow
solid, m .p. 195–197 °C. For C22H22N2O6S (442.5) calculated: 59.72% C, 5.01% H, 6.33% N;
foun d: 60.05% C, 5.21% H, 6.55% N. 1H NMR (DMSO-d6): 3.41 t, 1 H, J = 9.3; 3.46–3.62 bm ,
3 H; 3.74 d, 1 H, J = 9.6 an d 3.72–3.90 m , 1 H (H sacch aride, H-2′–H-6′); 3.86 s, 3 H (OCH3);
4.57 bs, 1 H (CD3COOD exch an geable, OH); 5.16 d, 1 H, J = 4.2 (CD3COOD exch an geable,
OH); 5.22 bs, 1 H (CD3COOD exch an geable, OH); 5.36 d, 1 H, J = 5.4 (CD3COOD exch an ge-
able, OH); 5.57 d, 1 H, J = 9.3 (H-1′); 7.07 dd, 1 H, J = 2.6, 8.9; 7.27–7.34 bm , 2 H; 7.67 d,
1 H, J = 2.7; 7.72 m , 1 H; 7.88 d, 1 H, J = 8.7; 8.29 s, 1 H an d 8.41 m , 1 H (H arom .).
13C NMR (CDCl3): 55.60 (OCH3); 60.77 (C-6′); 69.57, 71.66, 77.19, 79.53 (C-2′–C-5′); 84.97
(C-1′); 104.74, 110.69, 114.96, 120.91, 121.56, 122.16, 122.84, 124.80, 125.06, 128.70,
134.41, 136.75, 147.92, 156.74, 159.84 (C arom .). MS MALTI-TOF, m/z (%): 481 [M + K]+ (4);
465 [M + Na]+ (5); 443 [M + H]+ (100).
6-Chloro-2-(1-(β-D-glucopyranosyl)indol-3-yl)benzothiazole (11c). Yield 51% of pale yellow
solid, m .p. 205–208 °C. For C21H19ClN2O5S (446.9) calculated: 56.44% C, 4.29% H, 6.27% N;
foun d: 56.54% C, 4.51% H, 6.44% N. 1H NMR (DMSO-d6): 3.35 t, 1 H, J = 9.0; 3.46–3.62 bm ,
3 H; 3.74 d, 1 H, J = 8.4 an d 3.88 t, 1 H, J = 9.0 (H sacch aride, H-2′–H-6′); 4.58 bs, 1 H
(CD3COOD exch an geable, OH); 5.17 bs, 1 H (CD3COOD exch an geable, OH); 5.32 bs, 2 H
(CD3COOD exch an geable, 2 × OH); 5.53 d, 1 H, J = 9.3 (H-1′); 7.30–7.35 m , 2 H; 7.51 dd,
1 H, J = 2.1, 8.7; 7.68–7.71 m , 1 H; 7.98 d, 1 H, J = 9.0; 8.02–8.05 m , 1 H; 8.18 s, 1 H an d
8.21 d, 1 H, J = 1.8 (H arom .). 13C NMR (CDCl3): 60.74 (C-6); 69.48, 71.78, 77.04, 79.55
(C-2′–C-5′); 85.21 (C-1′); 106.33, 110.25, 112.06, 120.45, 121.83, 122.51, 123.03, 126.07,
133.06, 136.32, 152.39, 163.28, 164.34 (C arom .). MS MALDI-TOF, m/z (%): 485 [M + K]+
(3); 469 [M + Na]+ (12); 447 [M + H]+ (100).
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Synthesis of β-D-Glucopyranosides
83
We thank the Grant Agency for Science, Slovak Republic for financial support of this work (grant
No. 1/9246/02). We are grateful to the National Cancer Institute, Bethesda (MD), U.S.A. for evalua-
tion of cytotoxic potency of our compounds on human cell lines.
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