1,2-Anhydrosaccharides and 1,2-cyclic sulfites as saccharide donors in convergent synthesis of glucopyranosyl-, mannopyranosyl- and ribofuranosylbenzocamalexin

Article abstract of DOI:10.1135/cccc20050487

A convergent synthesis of 1-(β-o-glucopyranosyl)-, 1-(α-D-mannopyranosyl)- and 1-(β-D-ribofuranosyl) benzocamalexin was elaborated as an alternative route to the linear approach based on the indoline-indole method. 1,2-Anhydrosaccharides and 1,2-cyclic sulfites as saccharide donors were used in the key glycosylation step. Coupling with benzocamalexin resulted in moderate to excellent yields of nucleoside analogs, depending on the saccharide donor, catalyst and solvent used.

Full text of DOI:10.1135/cccc20050487

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
487
1,2-ANHYDROSACCHARIDES AND 1,2-CYCLIC SULFITES AS
SACCHARIDE DONORS IN CONVERGENT SYNTHESIS OF
GLUCOPYRANOSYL-, MANNOPYRANOSYL- AND
RIBOFURANOSYLBENZOCAMALEXIN
b1
Martin HUMENÍKa1,*, Peter KUTSCHYa2, Vladimír KOVÁČIK and
b2
Slávka BEKEŠOVÁ
a
Institute of Chemical Sciences, Faculty of Science, P. J. Šafárik University, Moyzesova 11,
041 67 Košice, Slovak Republic; e-mail: mhumenik@kosice.upjs.sk, kutschy@kosice.upjs.sk
Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9,
1
2
b
1
2
842 38 Bratislava, Slovak Republic; e-mail: chemvkov@savba.sk, chembeke@savba.sk
Received Jan uary 14, 2005
Accepted March 1, 2005
A con vergen t syn th esis of 1-(β-D-glucopyran osyl)-, 1-(α-D-m an n opyran osyl)- an d 1-(β-D-ribo-
furan osyl)ben zocam alexin was elaborated as an altern ative route to th e lin ear approach
based on th e in dolin e–in dole m eth od. 1,2-An h ydrosacch arides an d 1,2-cyclic sulfites as
sacch aride don ors were used in th e key glycosylation step. Couplin g with ben zocam alexin
resulted in m oderate to excellen t yields of n ucleoside an alogs, depen din g on th e sacch aride
don or, catalyst an d solven t used.
Keyw ord s: In doles; Glycosides; Ph ytoalexin s; Ben zocam alexin ; 1,2-An h ydrosach arides; Cy-
clic sulfites; Nucleosides; Glycosidation s; Carboh ydrates.
In dole glycosides are a group of n ucleoside an alogs possessin g a broad spec-
trum of biological activities. Neosidom ycin 1a,1b an d SF-2140 1b,1c, kah ak-
am ides A an d B 1d an d recen tly developed glycosides of isoin digo1e an d
oxin dole1f are com poun ds with an tibacterial properties. On th e oth er h an d,
rebeccam ycin , a m icrobial m etabolite isolated from cultures of Saccharothrix
aerocolonigenes, possesses an tican cer activity2a. In ten sive structure-activity
relation sh ip studies of rebeccam ycin an alogs un covered several in terestin g
glycosylin dolocarbazoles as attractive can cer ch em oth erapy agen ts2b,2c
.
Our research aim ed at 1-glycosides derived from n atural ph ytoalexin s3
outlin ed th e structures of 1-α-D-m an n opyran osyl- (1c), 1-β-D-ribofuran osyl-
ben zocam alexin 4a (1d ) an d 1-β-D-glucopyran osyl-6-m eth oxyben zo-
cam alexin 4b (1b) with prom isin g an tiproliferative activity. Recen tly we de-
scribed th e syn th esis of com poun ds 1b–1d via th e lin ear in dolin e-in dole
m eth od5 startin g from correspon din g glycosylin dolin es4. Th e lin ear ap-
Collect. Czech. Chem. Commun. (Vol. 70) (2005)
doi:10.1135/cccc20050487

488
Humeník, Kutschy, Kováčik, Bekešová:
proach took advan tage of en h an ced n ucleoph ilicity of in dolin e in com pari-
son with th e less n ucleoph ilic in dole rin g th us allowin g utilization of eith er
un protected sacch arides1e,1f or th eir peracetylated, com m ercially an d syn -
th etically easily accessible derivatives4. On th e oth er h an d, a syn th etic
path way from glycosylated in dolin e to th e target ben zocam alexin m oiety
in evitably in fluen ces th e sacch aride due to side reaction s dim in ish in g th e
yields an d lim its th e selection of suitable reaction con dition s for m odifica-
tion of aglycon 4b. Th ese in con ven ien ces could be avoided in th e con ver-
gen t approach based on separate preparation of fin al aglycon structure an d
its subsequen t couplin g with appropriate sacch aride don or in th e glyco-
sylation step. However, in dole derivatives exh ibit low n ucleoph ilicity an d
h en ce h igh ly reactive sacch aride don ors sh ould be em ployed.
R2
1d, R2 = H
1c, R2 = H
1b, R2 = OMe
R1 =
R1 =
R1 =
S
N
OH
OH
HO
OH
O
O
O
HO
HO
HO
HO
N
R1
OH
OH OH
benzocamalexin 1a
R1, R2 = H
Our in itial attem pts at glycosylation of ben zocam alexin (1a) in cluded
widely used glycosyl don ors, n am ely tetra-O-acetyl-α-D-glucopyran osyl
brom ide un der th e Koen igs–Kn orr con dition s6,7, trich loroacetim idates7,
tetra-O-ben zyl-α-D-glucopran osyl
pyran ose in th e Mitsun obu reaction 9 an d 5-O-(tert-butyldim eth ylsilyl)-
2,3-O-isopropyliden e-α-D-ribofuran osyl ch loride in th e Robin son m eth od10
ch lorides8,
tetra-O-ben zyl-D-gluco-
.
All of th ese m eth ods failed in preparation of ben zocam alexin glycosides.
Con tin uous search for suitable glycosyl don ors fin ally led us to exam in e
th e Dan ish efsky m eth od usin g 1,2-an h ydrosach arides11 alon g with a n ew
type of glycosylation agen ts settin g as epoxide replacem en t12,13 – 1,2-cyclic
sulfites.
Applicability of 1,2-epoxides an d correspon din g 1,2-cyclic sulfites in
stereoselective syn th esis of β-D-glucopyran osyl-, β-D-ribofuran osyl- an d
α-D-m an n opran osylben zocam alexin is reported.
Th e ben zylated sacch aride don or, 1,2-an h ydro-α-D-glucopyran ose (4a),
was prepared from com m ercial pen ta-O-acetyl-β-D-glucose (2) in five steps
(Sch em e 1). Brom in ation of 2 14a, reductive elim in ation with Zn in acetic
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
489
acid14b followed by deacetylation 14c an d ben zylation 14d afforded th e de-
scribed 3,4,6-tri-O-ben zylglucal (3)14e in a good, 70% overall yield from 2
(Sch em e 1). Th is sequen ce was perform ed with out tim e-con sum in g ch ro-
m atograph ic purification s except for com poun d 3. Epoxidation of 3, effi-
cien tly perform ed with th e Cam p reagen t, 3-ch loroperoxyben zoic acid
(CPBA), an d KF afforded a m ixture of 1,2-an h ydroglucopyran ose (4a) an d
1,2-an h ydrom an n opyran ose (4b; Sch em e 1) in th e ratio 9:1, as reported in
literature14f. In stability of epoxides precluded separation of isom ers an d a
m ixture of 4a an d 4b was used in reaction with sacch aride acceptor 1a.
OBn
O
BnO
BnO
OAc
OBn
4a
O
(i)–(iv)
(v)
O
O
+
AcO
AcO
BnO
BnO
OAc
OBn
OAc
O
O
BnO
BnO
2
3
4b
(i) 33% HBr in AcOH, CH2Cl2, 0 oC–r.t., 1.5 h; (ii) Zn, 50% AcOH, –15 oC–r.t., 2.5 h; (iii) K2CO3,
MeOH, 40 min; (iv) KOH, BnBr, DMSO, 48 h, 70% based on 2; (v) CPBA, KF, CH2Cl2, N2, 17 h
SCHEME 1
Stereoselective preparation of 1,2-an h ydro-β-D-m an n opyran ose (4b) uti-
lized in tram olecular rin g closure for 2-O-acetyl-3,4,6-tri-O-ben zyl-α-D-
m an n opyran osyl ch lorid (7; Sch em e 2). Com poun d 7 was prepared from
D-m an n ose (5) peracetylated in a m ixture of pyridin e/acetic an h ydride fol-
lowed by brom in ation 14a. Th e 1,2-orth oester rin g form ation 15a furn ish ed
peracetylated 3,4,6-tri-O-acetyl-1,2-O-(1-m eth oxyeth yliden e)-α-D-m an n o-
pyran oside wh ich was tran sform ed to th e described perben zylated an alog
15b
6
in overall 75% yield based on 5 (Sch em e 2). Again , n o colum n ch ro-
m atograph y was em ployed except for 6 wh ich was subsequen tly sm ooth ly
con verted to 1,2-an h ydro-β-D-m an n opyran ose 4b by th e well-kn own cyclic
orth oester rin g open in g with trim eth ylsilyl ch loride16 (TMSCl) followed by
on e-pot h ydrolysis of ch loride17 7. Th e course of th e reaction was difficult
to m on itor sin ce 1,2-an h ydrosugar 4b com pletely decom poses wh en spot-
ted on TLC plate. However, disappearan ce of th e startin g m aterial could be
clearly in dicated. Th e reactivity of 4b allowed its structure verification after
quan titative m eth an olysis to 1-O-m eth yl-3,4,6-tri-O-ben zyl-α-D-m an n o-
pyran oside18
.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

490
Humeník, Kutschy, Kováčik, Bekešová:
O
OBn
OBn
OH
OAc
O
OH
O
O
(vi)
(i)–(v)
O
O
BnO
BnO
BnO
BnO
HO
HO
OH
Cl
6
5
7
(vii)
4b
(i) Ac2O, pyridine, 5 h; (ii) 33% HBr in AcOH, CH2Cl2, 0 oC–r.t., 2.5 h; (iii) MeOH, Bu4NBr, Et3N,
1,2-DCE, N2, 75 oC, 16 h; (iv) K2CO3, MeOH, 2 h; (v) BnBr, KOH, DMSO, 48 h, 75% based on 5;
(vi) TMSCl, CH2Cl2, 0 oC, N2, 1.5 h; (vii) t-BuOK, THF, N2, r.t.–reflux, 1 h
SCHEME 2
Th e strategy an d con dition s for preparation of th e perben zylated
orth oester 6 (Sch em e 2) were used for th e syn th esis of 1,2-an h ydro-α-D-
ribofuran ose (12; Sch em e 3). Com m ercial peracetylated β-D-ribofuran ose
(8) was ch lorin ated with a m ixture of acetyl ch loride an d m eth an ol servin g
as a m ilder source of HCl com pared with th e reported SOCl2/acetic acid
m ixture19. Th e orth oester rin g form ation was to date described for th e reac-
tion of 2,3-di-O- acetyl-5-O-ben zyl-β-D-ribofuran osyl ch loride with
(dim eth oxym eth yl)dim eth ylam in e20. Th e sam e orth oester rin g form ation
was in our case ach ieved by th e treatm en t of crude tetra-O-acetyl-β-D-ribo-
furan osyl ch loride with m eth an ol, Bu4NBr an d Et3N in dry 1,2-dich loro-
eth an e (1,2-DCE) at 70 °C. Th e required 3,5-di-O-acetyl-1,2-O-(1-m eth oxy-
eth yliden e)-α-D-ribofuran oside (9) was obtain ed from 8 in excellen t 98%
yield. An exch an ge of protectin g groups yielded com poun d 10 (77%;
Sch em e 3). In stability of n ew, as yet un described 1,2-cyclic orth oesters 9
1
an d 10 allowed con firm ation of structure on ly by H an d 13C NMR an alysis
sin ce attem pts to obtain an accurate elem en tal an alysis an d m ass spectra
were un successful. Th e reaction of 10 with TMSCl afforded ch loride 11 an d
on e-pot reaction with t-BuOK in dry THF afforded 1,2-an h ydro-α-D-ribo-
furan ose (12) after th e SN2 reaction of C-2 acetoxy group with an om eric
ch lorin e as a livin g group. Th e opposite rin g closure of C-1 acetoxy group
with C-2 tosyl livin g group was reported21. Th e rin g closure reaction ap-
peared tem perature-sen sitive. Heatin g of th e reaction m ixture, as in th e
case of m an n opyran osyl derivative (Sch em e 2), caused decom position sin ce
n o m eth yl 3,5-di-O-ben zyl-β-D-ribofuran oside was detected after alcoh olysis
in dry m eth an ol21. Am bien t tem perature appeared sufficien t for th e effec-
tive epoxide rin g form ation but som e loss could n ot by avoided sin ce cool-
in g of th e reaction produced on ly diol 17 (Sch em e 5). Due to its in stability,
th e structure of com poun d 12 was con firm ed after alcoh olysis in dry m eth -
an ol with th e form ation of expected m eth yl 3,5-di-O-ben zyl-β-D-ribo-
furan oside21 in 63% yield.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
491
AcO
AcO
BnO
OAc
O
O
(i), (ii)
(iii), (iv)
O
O
O
8
OAcOAc
O
9
AcO
O
10
BnO
O
O
(v)
BnO
BnO
Cl
(vi)
O
O
O
OAc
BnO
11
BnO
12
(i) AcCl, MeOH, CH2Cl2, 3 days; (ii) MeOH, Et3N, Bu4NBr, 1,2-DCE, N2, 70 oC,
24 h, 98% based on 8; (iii) K2CO3, MeOH, 30 min; (iv) BnBr, KOH, DMSO, 24 h,
77%; (v) TMSCl, CH2Cl2, 0 oC, N2, 5 min; (vi) t-BuOK, THF, N2, 0 oC–r.t., 1 h
SCHEME 3
Th e glycosylation step in cluded in situ gen eration of ben zocam alexin an -
ion with NaH (1 equivalen t) in appropriate solven t (DMF or CH3CN)22 an d
subsequen t con den sation with a m ixture of epoxides 4a an d 4b (prepared
from 2 to 3 equivalen ts of 3) un der N2 atm osph ere. Th e reaction m ixture
was stirred at elevated tem perature (Table I) an d products isolated by silica
gel ch rom atograph y. Two com poun ds, m ajor β-glucopyran oside 13 an d m i-
n or α-m an n opyran oside 14 (Sch em e 4) were obtain ed in good to very good
yields (60–81%). Th e ratio of com poun ds 13 an d 14 appeared to be sign ifi-
can tly solven t-depen den t (Table I). To th e best of our kn owledge, sim ilar
ch em istry of 1,2-an h ydrosach arides is n ot kn own in glycoside preparation s.
Plausibly, less polar aceton itrile discrim in ates m ore between th e reactivities
of epoxides 4a an d 4b (Sch em e 1) favorin g α-isom er 4a an d th us producin g
TABLE I
Th e effect of reaction con dition s on glucosylation of ben zocam alexin (1a) in th e reaction
with a m ixture of epoxides 4a an d 4b
Epoxides 4a an d
4b equiv.
Reaction con dition s
Yield, %
Ratio 13:14
2
NaH, DMF, 50 °C, 5 h
60
81
70
79
7:1
3
NaH, DMF, 50 °C, 5 h
2.25
2.25
NaH, CH3CN, 55 °C, 5 h
NaH, CH3CN, 18-crown -6, 60 °C, 3 h
19:1
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

492
Humeník, Kutschy, Kováčik, Bekešová:
a h igh yield of β-glycoside 13 wh ereas less reactive com poun d 4b is m ostly
con sum ed in com petitive side an d decom position reaction s.
N
BnO
S
S
OBn
O
N
(i)
(ii)
N
BnO
OH
N
O
S
OBn
N
H
N
1a
14
15
BnO
OH
(iii)
5´´
4´´
6´´
3´´a
3´´ N
7´´
OBn
7´´a
2´S´
6´
2
1
3
5´
O
1´´
BnO
BnO
2´
4´
3´
14 (minor)
+
1´
3a
N
7a
4
5
OH
7
13 (major)
6
(i) 1. 1a, NaH, N2, CH3CN, 18-crown-6 or 15-crown-5, 40 oC, 30 min, 2. 12, CH3CN, N2, 55 oC,
2 h, 35 or 41%; (ii) 1. 1a, NaH, N2, CH3CN, 18-crown-6, 40 oC, 30 min, 2. 4b, CH3CN, N2, 65 oC,
5 h, 69%; (iii) 1. 1a, NaH, N2, CH3CN, 18-crown-6, 40 oC, 30 min, 2. 4a and 4b, CH3CN, N2, 60 oC,
3 h, 79%, for other conditions, see Table I
SCHEME 4
Th e m in or α-m an n opyran osylben zocam alexin 14 (Sch em e 4) was selec-
tively prepared in a good 69% yield by an an alogous reaction of ben zo-
cam alexin sodium salt with epoxide don or 4b obtain ed in on e-pot se-
quen ce from orth oester 6 (Sch em e 2). Ribosylation of 1a was n ot as effi-
cien t as previous preparation s of glucosyl an d m an n osyl derivatives (13 an d
14, respectively). Em ployin g eith er 18-crown -6 catalysts or 15-crown -5
eth er, better fittin g Na cation , brough t n o sign ifican t im provem en t an d
ben zylated β-D-ribofuran osylben zocam alexin 15 (Sch em e 4) was prepared
in m oderate 35 or 41% yields. Lower yields of ribofuran oside 15 could be
ascribed to th e above m en tion ed h igh er in stability of epoxide 12, com -
pared with pyran osyl an alogs 4a an d 4b. Wh ile decom position an d side re-
action s com peted with glycosylation in th e case of 1,2-an h ydroglucose 4a
an d 1,2-an h ydrom an n ose 4b , th ey becam e prevalen t in rin g closure
(Sch em e 3) an d open in g (Sch em e 4) reaction s of 1,2-an h ydroribose 12 an d,
con sequen tly, m in im ized th e yield of ribofuran osylben zocam alexin 15.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
493
An h ydrosugars worked well in glycosylation of ben zocam alexin 1a as de-
scribed above; h owever, th eir in stability affected th e yields of target
glycosides. Th ese results prom pted us to study 1,2-cyclic sulfites derived
from glucose, m an n ose an d ribose as isolable, stable an d accessible substi-
tutes for epoxides 4a, 4b an d 12. Our in terest arose from th e reported fun c-
tion of 1,2-cyclic sulfites as an epoxide replacem en t in preparation of ch iral
am in o alcoh ols alon g with th eir stability12 described for glucopyran osyl-
23a–23c
24c
20
an d ribofuran osyl- 21
an alogs (Sch em e 6). Cyclic sulfites are
rarely exploited com poun ds in glycosylation ch em istry; th ey are m ain ly
used in th e syn th esis of several C-1, C-4 an d C-6 azidosacch arides24a–24d an d
in preparation of uracil derivatives23a. To th e best of our kn owledge, sim ilar
reaction s of in doles as n ucleoph iles with 1,2-cyclic sulfites h ave n ot been
described.
Syn th esis of 1,2-O-sulfin yl-α-D-glucopyran ose (20; Sch em e 6) was previ-
ously accom plish ed by treatm en t of SOCl2 or 1,1′-sulfin yldiim idazole
[SO(Im )2] with appropriately protected diol 19 (Sch em e 5), gen erated by
h ydroxylation of th e correspon din g glucal 3 (Sch em e 1)23b,23c. In our case,
we used con ven ien tly prepared orth oesters 6 an d 10 (Sch em es 2 an d 3).
Th eir acid h ydrolysis15a afforded in excellen t 95 to good 78% yields th e re-
quired diols 16 an d 17 (Sch em e 5), kn own from literature25a,25b. Prepara-
tion of diol 19 started from pen ta-O-acetyl-β-D-glucose (2; Sch em e 1) wh ich
was tran sform ed in four steps to 3,4,6-tri-O-ben zyl-1,2-O-(1-m eth oxyeth yl-
OBn
BnO
OH
O
O
(i)
(ii)
BnO
BnO
OH
6
10
OH
OH
BnO
16
17
OBn
OBn
(iii)–(vi)
O
O
(vii)
O
BnO
BnO
BnO
BnO
2
HO
OH
O
18
O
19
(i) 1.5 M H2SO4, dioxane, 110 oC, 1.5 h, 95%; (ii) 1.5 M H2SO4, dioxane, 110 oC, 1 h,
78%; (iii) 33% HBr in AcOH, CH2Cl2, 0 oC–r.t., 1.5 h; (iv) MeOH, Bu4NBr, Et3N, 1,2-DCE,
N2, 45 oC, 16 h; (v) K2CO3, MeOH, 2 h; (vi) BnBr, KOH, DMSO, 48 h, 70% from 2; (vii)
1 M H2SO4, dioxane, 110 oC, 2 h, 93%
SCHEME 5
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

494
Humeník, Kutschy, Kováčik, Bekešová:
iden e)-α-D-glucopyran ose (18) in 70% overall yield from 2 (Sch em e 6) un -
der th e sam e con dition s as used for syn th esis of orth oester 6 (Sch em e 2).
25c
25d
Th e acid h ydrolysis15a of kn own orth oester 18
gave diol 19
in 93%
yield (Sch em e 5) with out usin g colum n ch rom atograph y except for th e last
step.
Th e reaction of diols 17 an d 19 with SOCl2 in th e presen ce of pyridin e as
acid scaven ger in dry CH2Cl2 (lit.12f) proceeded sm ooth ly an d afforded
1,2-cyclic sulfites 20 an d 21 (Sch em e 6). Com poun ds 20 an d 21 were easy
to isolate in very good 83 an d 71% yields as a m ixture of endo an d exo
diastereoisom er at sulfur, as reported23 (Sch em e 6). Un expectedly, attem pts
at th ion ylation of 2,4,6-tri-O-ben zyl-D-m an n opyran ose (16) failed. Treat-
m en t of 16 eith er with SOCl2 in dry CH2Cl2 or with m ore reactive
1,1′-sulfin yldiim idazole [SO(Im )2] in THF 23b,23c did n ot produce th e re-
quired cyclic sulfite 22 (Sch em e 6). Mon itorin g th e reaction by TLC re-
vealed th e presen ce of th e un reacted startin g m aterial alon g with stron g de-
com position . 1,2-Cyclic sulfite 22 is probably h igh ly in stable due to th e
an om eric affect causin g destabilization of th e sacch aride in un favorable
β-con figuration .
16
19
(i)
17
(ii)
(iii)
OBn
BnO
O
O
OBn
O
O
S
O
O
BnO
BnO
O
BnO
BnO
O
S
O
BnO
O
S
O
O
22
20
21
(i) SOCl2, pyridine, CH2Cl2, 0 oC, N2, 15 min, 83%; (ii) SOCl2, pyridine, CH2Cl2, 0 oC, N2,
1 h, 71%; (iii) SOCl2, pyridine, CH2Cl2, 0 oC, N2, or SO(Im) 2, THF, –20 oC, N2
SCHEME 6
Th e sodium salt of ben zocam alexin 1a was glycosylated in a m odel reac-
tion em ployin g th e con dition s reported for preparation of carbocyclic ade-
n in e derivative13. Th e n ucleoph ilic open in g of sulfite 20 by 3 h h eatin g at
100 °C in dry DMF un der N2 atm osph ere proceeded with com plete stereo-
an d regioselectivity via C-1′ attack to give 1,2-tran s glycoside 13 (Sch em e 4)
albeit in m odest 19% yield (Table II, en try 1). Exch an ge of eith er th e cata-
lyst or base did n ot lead to im provem en t of th e yield (Table II). In addition ,
glycosylation carried out at am bien t tem perature revealed low reactivity of
cyclic sulfite an d substan tial am oun t of 20 was presen t in th e reaction m ix-
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
495
ture even after 48 h reaction . Th us, com pared with epoxides 4a an d 4b, th e
proposed stability of 1,2-cyclic sulfite 20 at am bien t tem peratures but, h an d
by h an d, th eir lower reactivity required elevated reaction tem peratures
(≈100 °C) led to decom position wh ich was faster th an th e rin g open in g SN2
substitution .
TABLE II
Reaction con dition s in glycosylation of ben zocam alexin (1a) with cyclic sulfite 20
En try
Reaction con dition s
Yield, %
1
2
3
NaH, DMF, 18-crown -6, 100 °C
NaH, DMF, 15-crown -6, 100 °C
DBU, DMF, 60 °C
19
20
15
Th e treatm en t of ben zocam alexin 1a with KOH (8 equivalen ts) in DMF in
th e presen ce of dryin g agen t Na2SO4 appeared to be m ore prom isin g. Th e
added 1,2-O-sulfin yl-α-D-glucopyran ose 20 was con sum ed at room tem pera-
ture in 0.5 h , providin g glycoside 13 in 44% yield (Table III, en try 1). Our
effort con tin ued by ch an gin g th e reagen t an d tem perature but com poun d
13 was on ly prepared in a lower yield (Table III, en tries 2–7) un derlin in g
th e low reactivity of 20.
TABLE III
Reaction con dition s in glycosylation of ben zocam alexin (1a) with cyclic sulfite 20
En try
Reaction con dition s
Yield, %1
1
2
3
4
5
6
7
KOH (8.0 equiv.), DMF, Na2SO4, r.t.
KOH (8.0 equiv.), DMF, Na2SO4, 0 °C
t-BuOK (8.0 equiv.), DMF, r.t.
44
24
31
24
17
28
33
KOH (8.0 equiv.), CH3CN, Na2SO4, r.t.
KOH (1.2 equiv.), DMF, Na2SO4, r.t.
KOH (1.5 equiv.), DMF, Na2SO4,100 °C
KOH (8.0 equiv.), DMF, m ol. sieves 4Å, r.t.
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496
Humeník, Kutschy, Kováčik, Bekešová:
Th e treatm en t of 3,5-di-O-ben zyl-1,2-O-sulfin yl-α-D-ribofuran oside (21;
Sch em e 6) with sacch aride acceptor 1a un der m ost appropriate reaction
con dition s (Table III, en try 1) afforded β-riboside 15 alth ough sim ilarly in a
m oderate 29% yield.
Deben zylation of com poun ds 13, 14 an d 15 (Sch em e 4) was in evitably
th e last task in developm en t of con vergen t glycosylation of in dole aglycon
1a in asm uch as deprotected com poun ds 1c, 1d an d 23 were tested an d re-
vealed an tiproliferative activities4. Th e catalytic h ydrogen ation on Pd black
was exploited for m an y in dolocarbazole derivatives2b–2e,6a. In our case we
proposed a th iazole rin g in teraction with th e catalyst sin ce sulfur acts as
a well-kn own catalytic poison of Pd. On th e oth er h an d, deprotection of
ben zyl eth er with Lewis acids BBr3 (lit.26a) an d AlCl3/Ph NMe2 (lit.26b) is de-
scribed. Th ese deben zylation s were used in th e preparation of glycosyl-
isoin digo1e an d oxin dole1f with good (60%)1e to m odest (26%)1f yields.
More efficien t deprotection usin g FeCl3 for sim ple m on o-27a,27b an d oligo-
sacch arides27c was reported as well. Previous reaction con dition s27c were ad-
justed in our case of in dole glycosides 13–15 (Sch em e 4) an d 4 equivalen ts
of FeCl3 per ben zyl group, 0 °C an d 45-m in reaction tim e were n ecessary to
deprotect th e sacch aride m oiety. Un fortun ately, th e presen ce of decom posi-
tion products com plicated ch rom atograph ic purification of glycosides 1c,
1d an d 23. Th us, before isolation , acetylation in a Py/Ac2O m ixture was
perform ed an d recen tly described peracetylated products 24 (81%), 26
(77%)4a an d th e n ew (tri-O-acetyl-β-D-ribofuran osyl)ben zocam alexin 25
(75%) were easy to isolate. Th e described deacetylation of com poun ds 24,
4a
26 an d 25 with K2CO3 in dry m eth an ol afforded target com poun d 1c, 1d
an d 23 iden tical with th ose reported in literature4a.
AcO
OAc
O
AcO
AcO
N
S
N
R
N
S
S
26
O
R
R
AcO
N
R
N
O
N
23, R = OH
24, R = OAc
25
AcO
OAc
We recen tly reported detailed NMR study of acetylated glycoside 26. Its
β-coun terpart adopted un doubtedly com m on 4C1 con form ation as de-
picted. Th is con clusion arose from com parison of h ydrogen couplin g con -
stan ts of α-D-m an n opyran osyl rin g: J(3′,4′) = 8.4 an d J(4′,5′) = 8.3 Hz, th at
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1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
497
represen t a clear vicin al trans-diaxial in teraction of h ydrogen H-3′, H-4′ an d
H-5′ (lit.4a). Th e ben zylated an alog 14 (Sch em e 4) revealed con siderably
lower trans-diequatorial couplin g con stan ts J(4′,5′) = 5.3 an d J(3′,4′) =
5.8 Hz th us con firm in g a tran sform ation in to 1C4 con form ation . Th is un -
usual con form ation can be attributed to th e bulkin ess of th e in dole m oiety
wh ich prefers th e less h in dered equatorial con form ation in spite of pre-
sen ted an om eric affect. Th is stereoelectron ic factor is n ot as dom in an t in
N-glycosides as in O-glycosides; th us steric h in dran ce of th e in dole m oiety
an d ben zylated m an n opyran osyl rin g becam e prevalen t in 14. Th e ex-
ch an ge of bulky ben zyl protectin g groups for sm all acetyls in 26 dim in -
ish ed th e m en tion ed in teraction s an d caused th e an om eric effect to becom e
m ore im portan t for th e m an n opyran osyl rin g th an steric factors: th e con -
4
form ation of 26 flipped back to C1.
1,2-An h ydrosach arides derived from glucose (4a) an d m an n ose (4b) are
reactive sacch aride don ors in th e syn th esis of 1-glycosylben zocam alexin s.
Th is route is m ore efficien t th an th e altern ative in dolin e-in dole lin ear ap-
proach 4. Alth ough 1,2-an h ydroribofuran ose 12 due to its h igh in stability
an d 1,2-cyclic sulfites 20 an d 21 due to low reactivity coupled with
ben zocam alexin with lover efficien cy, both types of sacch aride don ors can
be used in th e reaction s with in dole aglycon s wh ich are n ot suitable for th e
use of th e lin ear m eth od startin g from 1-glycosylin dolin e.
EXPERIMENTAL
1H an d 13C NMR spectra were m easured on a Varian Mercury Plus spectrom eter operatin g
at 400 MHz for 1H an d at 100 MHz for 13C. Ch em ical sh ifts (δ) 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 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 ). Th e ion acce-
leration 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 atogra-
ph y (flash ch rom atograph y) was perform ed on Kieselgel Merck Type 9385, 230–400 m esh .
Ben zocam alexin (1a)
Solution of com m ercial in dole-3-carbaldeh yde (1.0 g, 6.88 m m ol) in m eth an ol (10 m l) was
treated with 2-am in oben zen e-1-th iol (0.86 g, 0.73 m l, 6.88 m l) an d 3 drops of con cen trated
HCl were added. Th e reaction m ixture was h eated for 30 m in , cooled to room tem perature
an d n eutralized with few drops of NH4OH. Th e solution was poured in to a crush ed ice–
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

498
Humeník, Kutschy, Kováčik, Bekešová:
water m ixture (50 m l) an d th e precipitated product was filtered off. Yield 0.930 g (54%),
lit.28 54%; C15H10N2S (250.3); yellow-grey crystals; m .p. 155–157 °C (m eth an ol), lit.28
169.5–170.5 °C.
3,4,6-Tri-O-ben zylglucal (3)
Pen ta-O-acetyl-β-D-glucopyran ose (2; 2.0 g, 5.12 m m ol) was dissolved in dry CH2Cl2 (2 m l),
cooled to 0 °C an d a com m ercial 33% solution of HBr in AcOH (1.97 m l) was added drop-
wise in to a vigorously stirred solution of 2. Th e reaction m ixture was stirred at room tem -
perature for 1.5 h , diluted with CH2Cl2 (20 m l), wash ed with ice-cold water (2×) an d n eu-
tralized with cooled saturated solution of NaHCO3. Th e organ ic layer was wash ed with
brin e, dried over an h ydrous Na2SO4, filtered off an d con cen trated. Well powdered crude
brom ide was added in several portion s in to a m ixture of Zn (3.15 g, 48.3 m m ol) in 50%
AcOH at –15 °C durin g 10 m in . Dark grey slurry was stirred at 0 °C for an oth er 2.5 h , th en
filtered th rough Celite , diluted with CH2Cl2, wash ed with cold water an d saturated solu-
tion of NaHCO3. Th e organ ic layer was dried over an h ydrous Na2SO4 an d filtered. Th e
filtrate was con cen trated an d crude 3,4,6-tri-O-acetylglucal was deacetylated with K2CO3
(0.06 g, 0.468 m m ol) in dry m eth an ol (25 m l) durin g 40 m in Th e reaction m ixture was con -
cen trated un der reduced pressure an d th e residue was dissolved in DMSO (40 m l). Th e solu-
tion was treated with fin e powdered KOH (2.57 g, 45.90 m m ol), cooled to 0 °C an d ben zyl
brom ide (4.37 g, 3.03 m l, 26.6 m m ol) was added dropwise. Th e reaction m ixture was stirred
vigorously at am bien t tem perature for 48 h , poured in to a crush ed ice an d extracted with
two portion s of dieth yl eth er. Organ ic extracts were dried with an h ydrous Na2SO4, an d th e
solven t was evaporated un der reduced pressure. Flash colum n ch rom atograph y afforded
3,4,6-tri-O-ben zylglucal (3; 1.49 g, 70% based on 2); C27H28O4 (416.5); colorless oil. Spectral
data were in accordan ce with th ose reported in lit.14e
.
1,2-An h ydro-3,4,6-tri-O-ben zyl-α-D-glucopyran ose (4a) an d
1,2-an h ydro-3,4,6-tri-O-ben zyl-β-D-m an n opyran ose (4b)
KF (0.746 g, 12.84 m m ol) was added to 3-ch loroperoxyben zoic acid (1.10 g, 6.42 m m ol) in
dry CH2Cl2 (20 m l) an d th e suspen sion was kept un der N2 at room tem perature with stir-
rin g. After 30 m in glucal 3 was added (1.07 g, 2.57 m m ol) in CH2Cl2 (8 m l) an d th e m ixture
was stirred for 17 h . In soluble com plexes were filtered off th rough Florisil, an d th e solven t
was rem oved un der reduced pressure. Wh ite solid residue was used im m ediately in th e n ext
glycosylation step.
3,4,6-Tri-O-ben zyl-1,2-O-(1-m eth oxyeth yliden e)-β-D-m an n opyran oside (6)
D-Man n ose (5; 1.44 g, 7.99 m m ol) was dissolved in dry pyridin e (5 m l), cooled to 0 °C an d
acetic an h ydride (3 m l) was added dropwise. Th e reaction m ixture was stirred at room tem -
perature for 5 h an d crush ed ice was added. After stirrin g for an oth er 30 m in , th e m ixture
was wash ed with dieth yl eth er (2×). Eth er extracts were wash ed with cold water (2×), satu-
rated NaHCO3 solution (2×), aqueous 1 M HCl (2×), dried (an h ydrous Na2SO4), filtered an d
evaporated. Th e residue was dissolved in dry CH2Cl2 (4 m l) an d ice-cold solution was treated
with 33% HBr solution in AcOH. Th e reaction m ixture was kept for 2.5 h at am bien t tem -
perature, th en diluted with CH2Cl2, wash ed with cold water (2×) an d n eutralized with satu-
rated NaHCO3 solution . Th e organ ic layer was wash ed with brin e, dried (an h ydrous Na2SO4),
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1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
499
filtered an d con cen trated. Th e crude brom ide was dissolved in dry 1,2-dich loroeth an e (20 m l)
an d Et3N (1.62 g, 2.23 m l, 15.9 m m ol), m eth an ol (0.28 g, 0.356 m l, 8.79 m m ol) an d Bu4NBr
(1.28 g, 3.99 m m ol) were added un der N2 atm osph ere. Th e reaction m ixture was stirred at
75 °C overn igh t, cooled to room tem perature an d con cen trated. Th e dark residue was dis-
solved in dieth yl eth er an d th e precipitated salt was rem oved by filtration trough a pad of
silica gel. Th e filtrate was con cen trated an d th e pale yellow residue was dissolved in dry
m eth an ol. Fin e powdered K2CO3 (0.110 g, 0.80 m m ol) was added an d th e reaction m ixture
was stirred for 2 h . Th e deacetylated product was con cen trated an d th e residue was dissolved
in DMSO (40 m l). Th e solution was cooled to 0 °C an d powdered KOH (4.34 g, 77.5 m m ol)
was added followed by ben zyl brom ide (7.34 g, 5.15 m l, 43.0 m m ol). Th e reaction m ixture
was stirred for 48 h , poured in to a crush ed ice–water m ixture, extracted with cold dieth yl
eth er (2×), dried (an h ydrous Na2SO4), an d filtered. Th e residue was purified by flash colum n
ch rom atograph y (cycloh exan e–eth yl acetate 5:1). Yield 3.03 g (75%); C30H34O7 (506.6);
wh ite solid; m .p. 83–87 °C (dieth yl eth er–h exan e); lit.15b 74–76 °C. Spectral data were in ac-
cordan ce with th ose reported in lit.15b
.
1,2-An h ydro-3,4,6-tri-O-ben zyl-β-D-m an n opyran oside (4b)
Th e ben zylated orth oester 6 (0.182 g, 0.36 m m ol) was dissolved in dry CH2Cl2 (3.5 m l)
un der N2 atm osph ere an d th e solution was cooled to 0 °C. TMSCl (0.047 g, 0.055 m l,
0.432 m m ol) was added with a syrin ge an d th e reaction m ixture was stirred at room tem per-
ature for 1.5 h , th en diluted with CH2Cl2, filtered th rough Florisil, an d evaporated. Crude
colorless ch loride 7 was im m ediately dissolved in dry THF (3.5 m l) un der N2 atm osph ere
an d th e solution was treated with t-BuOK (0.060 g, 0.534 m m ol) at room tem perature. Th e
reaction m ixture was h eated for 1 h , cooled to room tem perature, diluted with CH2Cl2 an d
wash ed with brin e (2×). Th e aqueous layer was extracted with an oth er portion of CH2Cl2,
com bin ed organ ic extracts were dried (an h ydrous Na2SO4), filtered an d evaporated un der
reduced pressure affordin g crude wh ite solid epoxide 4a im m ediately used in glycosylation
reaction s.
3,5-Di-O-acetyl-1,2-O-(1-m eth oxyeth yliden e)-α-D-ribofuran oside (9)
Com m ercial peracetylated β-D-ribose 8 (3.215 g, 10.1 m m ol) was dissolved in dry CH2Cl2
(70 m l). Acetyl ch loride (7.9 g, 7.18 m l, 101 m m ol) an d dry m eth an ol (0.642 g, 0.82 m l,
20.2 m m ol) were added and the reaction m ixture was kept without stirring at room tem perature
for 3 days. The reaction m ixture was concentrated and residue was coevaporated several tim es
with toluene until the sm ell of acetic acid disappeared. The crude chloride (colorless oil) was dis-
solved in dry 1,2-dichloroethane (80 m l), and Et3N (5.71 g, 7.86 m l, 56.4 m m ol), dry m eth an ol
(0.903 g, 1.14 m l, 28.19 m m ol) an d Bu4NBr (1.52 g, 4.7 m m ol) were added to th e stirred so-
lution . Th e reaction m ixture was h eated at 75 °C un der N2 atm osph ere for 24 h , cooled to
room tem perature an d con cen trated. Dieth yl eth er was added to th e dark brown residue an d
in soluble salt was rem oved by filtration th rough a pad of silica gel. Th e pale yellow solution
was con cen trated an d th e residue was subjected to colum n ch rom atograph y (cycloh exan e–
eth yl acetate 3:1). Yield 2.87g (98%); m ixture of two diastereoisom ers of orth oester in th e ra-
tio 10:1; m ajor diastereoisom er C12H18O8 (290.3); colorless oil. 1H NMR (CDCl3): 1.69 s, 3 H
(CH3, orth oester); 2.10 s, 3 H (CH3, acetyl); 2.16 s, 3 H (CH3, acetyl); 3.21 s, 3 H (OCH3,
orth oester); 4.15 dd, 1 H, J(5a,5b) = 12.3, J(4,5a) = 5.1 (H-5a); 4.23 ddd, 1 H, J(3,4) = 9.2,
J(4,5a) = 5.1, J(4,5b) = 2.5 (H-4); 4.38 dd, 1 H, J(5a,5b) = 12.3, J(4,5b) = 2.5 (H-5b); 4.66 dd,
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500
Humeník, Kutschy, Kováčik, Bekešová:
1 H, J(3,4) = 9.2, J(2,3) = 5.2 (H-3); 4.95 dd, 1 H, J(2,3) = 5.2, J(1,2) = 4.0 (H-2); 5.95 d, 1 H,
J(1,2) = 4.0 (H-1). 13C NMR (CDCl3): 20.53 an d 20.76 (CH3, acetyl); 22.80 (CH3, orth oester);
49.55 (OCH3, orth oester); 62.24 (C-5); 72.23, 76.00 an d 77.75 (C-2–C-4); 104.18 (C-1);
124.96 (Cq-orth oester); 170.08 an d 170.64 (CO acetyl).
3,5-Di-O-ben zyl-1,2-O-(1-m eth oxyeth yliden e)-α-D-ribofuran oside (10)
K2CO3 (0.220 g, 1.59 m m ol) was added to a solution of peracetylated orth oester 9 (2.315 g,
7.98 m m ol) in dry m eth an ol (50 m l). Th e m ixture was stirred at room tem perature for
30 m in , evaporated to dryn ess an d th e residue was dissolved in DMSO (25 m l). Th e solution
was cooled to 0 °C an d fin ely powdered KOH (2.68 g, 47.9 m m ol) was added followed by
dropwise addition of ben zyl brom ide (4.36 g, 3.03 m l, 25.5 m m ol). Th e reaction m ixture
was stirred at room tem perature for 24 h an d partition ed between dieth yl eth er an d cold wa-
ter. Th e aqueous layer was extracted with dieth yl eth er, com bin ed organ ic layers were dried
(an h ydrous Na2SO4), filtered an d evaporated. Th e residue was purified by silica gel colum n
ch rom atograph y (cycloh exan e–eth yl acetate 3:1). Yield 2.37 g (77%); C22H26O6 (386.4); pale
yellow oil. 1H NMR (CDCl3): 1.72 s, 3 H (CH3); 3.23 s, 3 H (OCH3); 3.57 dd, 1 H, J(5a,5b) =
11.2, J(4,5a) = 4.0 (H-5a); 3.77 dd, 1 H, J(5a,5b) = 11.2, J(4,5b) = 2.1 (H-5b); 3.86 dd, 1 H,
J(3,4) = 9.0, J(2,3) = 4.7 (H-3); 4.08 ddd, 1 H, J(3,4) = 9.0, J(4,5a) = 4.0, J(4,5b) = 2.1 (H-4);
4.50 d, 1 H, J = 12.2 (CH2); 4.54 d, 1 H, J = 12.4 (CH2); 4.57 d, 1 H, J = 13.3 (CH2); 4.64 dd,
1 H, J(2,3) = 4.7, J(1,2) = 4.0 (H-2); 4.72 d, 1 H, J(1,2) = 4.0 (H-1); 7.26–7.35 bm , 10 H
(H arom .). 13C NMR (CDCl3): 22.74 (CH3); 49.05 (OCH3); 68.05 (C-5); 72.56 an d 73.73 (2 ×
CH2Bn ); 77.41, 78.18 an d 78.85 (C-2–C-4); 104.47 (C-1); 124.97 (Cq-orth oesth er); 127.91,
127.96, 128.29, 128.60, 128.59, 137.57 an d 138.14 (C arom .).
1,2-An h ydro-3,5-O-ben zyl-α-D-ribofuran oside (12)
Trim eth ylsilyl ch loride (0.092 g, 0.108 m l, 0.854 m m ol) was added in to a solution of
ben zylated orth oester 10 (0.3 g, 0.776 m m ol) in dry CH2Cl2 (6 m l) cooled to 0 °C un der N2
atm osph ere. Th e reaction m ixture was stirred at decreased tem perature for 5 m in before con -
cen tration un der reduced pressure. Crude ch loride 11 (colorless oil) was im m ediately dis-
solved in dry THF (6 m l) un der N2 atm osph ere. Th e solution was cooled to 0 °C an d treated
with t-BuOK (0.13 g, 1.16 m ol). Th e reaction m ixture was stirred at 0 °C for 15 m in an d at
am bien t tem perature for an oth er 45 m in , filtered th rough Florisil, wash ed with dry THF an d
evaporated un der reduced pressure. Th e residue (pale yellow oil) was subjected im m ediately
to glycosylation reaction .
3,4,6-Tri-O-ben zyl-D-m an n opyran ose (16)
1.5 M aqueous solution of H2SO4 (10.8 m l) was added to a stirred solution of ben zylated
orth oester 6 (3.06 g, 6.04 m ol) in dioxan e (30 m l). Th e reaction m ixture was stirred at
110 °C for 1.5 h , cooled to room tem perature an d carefully n eutralized with powdered
NaHCO3 wh ile stirrin g. Precipitated in organ ic salts were filtered off an d th e filtrate was con -
cen trated un der reduced pressure. Th e resultin g residue was partition ed between CH2Cl2 an d
water, th e organ ic layer was wash ed with brin e, dried (an h ydrous Na2SO4), filtered an d con -
cen trated in vacuo to afford 2.59 g (95%). Com poun d 16: C27H30O6 (450.5); wh ite solid;
m .p. 92–95 °C (h exan e–eth yl acetate), lit.25a 96–98 °C. Spectral data were in accordan ce with
th ose reported in lit.25a
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1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
501
3,5-di-O-ben zyl-D-ribofuran ose (17)
Diol 17 was prepared accordin g to th e procedure for syn th esis of 16 after 1-h h eatin g. Yield
78%; C19H22O5 (330.4); wh ite solid; m .p. 85–87 °C, lit.25b 79.8 °C. Spectral data were in ac-
cordan ce with th ose reported in lit.25b
3,4,6-Tri-O-ben zyl-1,2-O-(1-m eth oxyeth yliden e)-α-D-glucopyran oside (18)
Perben zylated orth oester 18 was prepared accordin g to th e procedure for syn th esis of
m an n opyran osyl orth oester 6 in overall yield 70% from com m ercial pen ta-O-acetyl-β-D-
glucopyran ose (2). C30H34O7 (506.6); pale-yellow oil. Spectral data were in accordan ce with
th ose reported in lit.25c
3,4,6-Tri-O-ben zyl-D-glucopyran ose (19)
Diol 19 was prepared accordin g to th e procedure for syn th esis of 16. 1 M aqueous solution
of H2SO4 was used an d th e reaction m ixture was stirred for 2 h . Yield 1.93 g (93%);
C
27H30O6 (450.5); wh ite solid; m .p. 85–87 °C (h exan e–eth yl acetate), lit.25d 80–82 °C. Spec-
tral data were in accordan ce with th ose reported in lit.25d
3,4,6-Tri-O-ben zyl-1,2-O-sulfin yl-α-D-glucopyran oside (20)
Diol 19 (0.250 g, 0.555 m m ol) was dissolved in dry CH2Cl2 (2 m l) under N2 atm osphere at 0 °C,
an d pyridin e (0.219 g, 0.222 m l, 2.77 m m ol) an d SOCl2 (0.092 g, 0.056 m l, 0.777 m m ol)
were added to th e cooled solution . Th e reaction m ixture was stirred for 15 m in , dissolved in
CH2Cl2 an d th e solution was wash ed with ice-cold water (2×). Th e organ ic layer was dried
over an h ydrous Na2SO4, filtered th rough a pad of Florisil an d evaporated. Pure product 20
was obtain ed in th e yield 0.229 g (83%). C27H28O7S (496.6); colorless oil. It was used in
glycosylation reaction . Its ph ysical data were iden tical with th ose reported in lit.23b
3,5-Di-O-ben zyl-1,2-O-sulfin yl-α-D-ribofuran oside (21)
Sulfite 21 was prepared accordin g to procedure for syn th esis of 20 durin g 1 h . Yield 71%;
C19H20O6S (376.4); colorless oil. It was used in glycosylation reaction . Its ph ysical data were
iden tical with th ose reported in lit.24c
3-(Ben zoth iazol-2-yl)-1-(3,4,6-tri-O-ben zyl-β-D-glucopyran osyl)-1H-in dole (13)
Method A: A solution of ben zocam alexin 1a (0.04 g, 0.159 m m ol) in dry CH3CN (1 m l)
was treated with 18-crown -6 (0.021 g, 0.0799 m m ol) an d NaH (8.3 m g, 0.208 m m ol), an d
th e reaction was stirred at 40 °C for 30 m in . Th e m ixture of epoxides 4a an d 4b (fresh ly pre-
pared from 0.360 m m ol of glucal 3) in dry CH3CN (1 m l) was added in to a previously pre-
pared solution of ben zocam alexin salt. Th e reaction m ixture was stirred un der N2 atm o-
sph ere at 60 °C for 3 h , cooled to room tem perature an d con cen trated. Th e residue was dis-
solved in eth yl acetate, wash ed with 1 M aqueous solution of HCl an d brin e. Th e organ ic
layer was dried (an h ydrous Na2SO4), filtered an d con cen trated. Colum n ch rom atograph y
(cycloh exan e–eth yl acetate 5:1) afforded com poun ds 13 an d 14 (0.086 g, 79% overall yield)
in th e ratio 19:1 an d ben zocam alexin 1a (6.7 m g, 17%) was recovered. Glycosides 13 an d 14
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

502
Humeník, Kutschy, Kováčik, Bekešová:
were separated by colum n ch rom atograph y (cycloh exan e–eth yl acetate 5:1), wh ich afforded
com poun ds 13 (0.081 g, 75%) an d 14 (4.0 m g 4%).
Method B: An h ydrous Na2SO4 (1.16 g, 8.15 m m ol) an d KOH (0.203 g, 3.62 m m ol) were
added to a solution of ben zocam alexin 1a (0.113 g, 0.453 m m ol) in dry DMF (5 m l). Th e re-
action m ixture was vigorously stirred at room tem perature for 30 m in an d a solution of sul-
fite 20 (0.449 g, 0.906 m m ol) in DMF (5 m l) was added. Stirrin g was con tin ued for an oth er
30 m in an d th e reaction m ixture was partition ed between eth yl acetate an d ice-cold water.
Th e organ ic layer was wash ed with brin e, dried (an h ydrous Na2SO4), filtered an d con cen -
trated. Th e residue was subjected to colum n ch rom atograph y (cycloh exan e–eth yl acetate
5:1) an d com poun d 13 (0.136 g) was obtain ed in 44% yield alon g with th e startin g com -
poun d 1a (0.06 g, 53%).
Com poun d 13: For C42H38N2O5S (682.8) calculated: 73.88% C, 5.61% H, 4.10% N; foun d:
73.63% C, 5.77% H, 3.96% N; pale yellow crystals; m .p. 165–168 °C (eth yl acetate–petroleum
eth er). 1H NMR (CDCl3): 3.73–3.81 bm , 3 H (H-5′, H-6′a an d H-6′b); 3.84 dd, 1 H, J(2′,3′) =
8.1, J(3′,4′) = 9.2 (H-3′); 3.92 dd, 1 H, J(3′,4′) ≈ J(4′,5′) = 9.2 (H-4′); 4.12 bs, 1 H (OH,
CH3COOD exch an geable); 4.33 dd, 1 H, J(1′,2′) = 8.9, J(2′,3′) = 8.1 (H-2′); 4.47 d, 1 H, J =
12.1 (CH2); 4.56 d, 1 H, J = 12.1 (CH2); 4.68 d, 1 H, J = 10.7 (CH2); 4.94 d, 1 H, J = 10.7
(CH2); 4.98 d, 1 H, J = 11.3 (CH2); 5.03 d, 1 H, J = 11.3 (CH2); 5.38 d, 1 H, J(1′,2′) = 8.9
(H-1′); 7.04 t, 1 H, J = 7.5; 7.14 t, 1 H, J = 7.5; 7.25–7.41 bm , 17 H (H arom .); 7.45 d, 1 H, J =
8.2; 7.78 d, 1 H, J = 7.8; 7.87 d, 1 H, J = 8.0; 8.04 s, 1 H; 8.26 d, 1 H, J = 7.9 (H arom ).
13C NMR (CDCl3): 68.77 (C-6′); 73.11 (C-2′); 73.72 an d 75.42 (3 × CH2Bn ); 75.84, 78.16 an d
85.60 (C-3′–C-5′); 87.87 (C-1′); 111.97, 112.08, 121.05, 121.38, 122.01, 122.23, 123.20,
124.25 an d 126.27 (C aglycon ); 127.84, 127.91, 128.10, 128.12, 128.19, 128.21, 128.59,
128.72 an d 128.80 (Bn ); 133.71 an d 136.11 (C aglycon ); 138.23, 138.27, 138.72 (Bn ); 153.16
an d 162.78 (C aglycon ). MS MALDI-TOF, m/z (%): 683 (100) [M + H]+, 705 (6) [M + Na]+,
721 (10) [M + K]+.
3-(Ben zoth iazol-2-yl)-1-(3,4,6-tri-O-ben zyl-α-D-m an n opyran osyl)-1H-in dole (14)
Com poun d 14 was prepared accordin g to th e procedure for syn th esis of 13 (m eth od A),
startin g from epoxide 4b (fresh ly prepared from orth oester 6). Colum n ch rom atograph y
(cycloh exan e–eth yl acetate 5:1) afforded th e title com poun d 14 (69%) an d th e startin g
ben zocam alexin 1a (28%). Com poun d 14: For C42H38N2O5S (682.8) calculated: 73.88% C,
5.61% H, 4.10% N; foun d: 73.96% C, 5.43% H, 4.28%N; pale yellow oil. 1H NMR (CDCl3):
2.83 bs, 1 H (OH, CH3COOD exch an geable); 3.66 dd, 1 H, J(6′a,6′b) = 10.3, J(5′,6′a) = 4.2
(H-6′a); 3.86 dd, 1 H, J(6′a,6′b) = 10.3, J(5′,6′b) = 5.7 (H-6′b); 3.92 ddd, 1 H, J(5′,6′b) = 5.7,
J(5′,6′a) = 4.2, J(4′,5′) = 5.3 (H-5′); 3.99 dd, 1 H, J(3′,4′) = 5.8, J(4′,5′) = 5.3 (H-4′); 4.13 dd,
1 H, J(3′,4′) = 5.8, J(2′,3′) = 3.6 (H-3′); 4.47 d, 1 H, J = 12.0 (CH2); 4.52 dd, 1 H, J(1′,2′) = 5.6,
J(2′,3′) = 3.6 (H-2′); 4.57 d, 1 H, J = 12.0 (CH2); 4.62 d, 1 H, J = 11.6 (CH2); 4.68 d, 1 H, J =
4.8 (CH2); 4.69 d, 1 H, J = 6.4 (CH2); 4.76 d, 1 H, J = 11.6 (CH2); 5.91 d, 1 H, J(1′,2′) = 5.6
(H-1′);7.24–7.40 bm , 18 H (H arom .); 7.45 m , 1 H; 7.63 d, 1 H, J = 8.4; 7.87 s, 1 H; 7.88 d, 1 H,
J = 6.0; 8.03 d, 1 H, J = 7.6; 8.39 d, 1 H, J = 8.0 (H arom .). 13C NMR (CDCl3): 67.31 (C-2′);
67.72 (C-6′); 73.31, 73.33 an d 73.38 (3 × CH2Bn ); 73.40 (C-4′); 74.11 (C-3′); 78.51 (C-5′);
82.11 (C-1′); 111.98, 112.49, 121.18, 121.27, 122.21, 122.30, 123.55, 124.20, 125.93, 126.00
an d 126.99 (C aglycon ); 127.73, 127.80, 127.90, 127.94, 128.21, 128.40, 128.50, 128.54 an d
128.89 (Bn ); 133.92 (C aglycon ); 137.09, 137.23 an d 137.67 (Bn ); 137.84, 153.76 an d 162.32
(C aglycon ). MS MALDI-TOF, m/z (%): 683 (100) [M + H]+.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
503
3-(Ben zoth iazol-2-yl)-1-(3,5-di-O-ben zyl-β-D-ribofuran osyl)-1H-in dole (15)
Com poun d 15 was prepared accordin g to th e procedure for syn th esis of 13 (m eth od A),
startin g from epoxide 12 (fresh ly prepared form orth oester 10) an d em ployin g 15-crown -5 as
catalyst in stead of 18-crown -6 eth er. Colum n ch rom atograph y (cycloh exan e–eth yl acetate
5:1) afforded th e required com poun d 15 (41%) an d ben zocam alexin 1 (54%). Meth od B af-
forded ribofuran osylben zocam alexin 15 in 29% yield an d startin g com poun d 1a (67%) after
colum n ch rom atograph y (cycloh exan e–eth yl acetate 5:1). Com poun d 15: For C34H30N2O4S
(562.7) calculated: 72.58% C, 5.37% H, 4.98% N; foun d: 72.39% C, 5.55% H, 5.08% N; pale
yellow oil. 1H NMR (CDCl3): 3.73 bs, 1 H (OH, CH3COOD exch an geable); 3.63 dd, 1 H,
J(5′a,5′b) = 10.6, J(4′,5′a) = 2.3 (H-5′a); 3.84 dd, 1 H, J(5′a,5′b) = 10.8, J(4′,5′b) = 2.5 (H-5′b);
4.32 m , 2 H (H-3′, H-4′); 4.47 dd, 1 H, J(2′,3′) = 4.6, J(1′,2′) = 4.5 (H-2′); 4.59 d, 1 H, J = 11.9
(CH2); 4.63 s, 2 H (2 × CH2); 4.72 d, 1 H, J = 11.9 (CH2); 6.05 d, 1 H, J(1′,2′) = 4.5 (H-1′);
7.28–7.38 bm , 13 H (H arom .); 7.45 dt, 1 H, J = 8.2, 7.1, 1.2; 7.56 d, 1 H, J = 8.1; 7.84 dd,
1 H, J = 7.7, 0.9; 8.02 d, 1 H, J = 8.19; 8.26 s, 1 H; 8.46 td, 1 H, J = 7.7, 0.9 (H arom .).
13C NMR (CDCl3): 69.02 (C-5′); 73.00 an d 73.71 (2 × CH2Bn ); 74.15, 77.49 an d 81.15
(C-2′–C-4′); 90.60 (C-1′); 110.53, 112.25, 121.19, 121.52, 122.15, 122.20, 123.35, 124.12,
125.90, 126.19 an d 126.91 (C aglycon ); 127.91, 127.94, 128.15, 128.50, 128.56 an d 128.74
(2 × Bn ); 133.87 (C aglycon ); 136.38 (Bn ); 136.73 (C aglycon ); 137.56 (Bn ); 154.00 an d
162.86 (C aglycon ). MS MALDI-TOF, m/z (%): 563 (100) [M + H]+.
Deben zylation /Acetylation of Com poun ds 13–15. Gen eral Procedure
FeCl3 (4 equivalen ts per ben zyl group) was added to a solution of com poun ds 13, 14 an d 15
(0.058 m m ol) dissolved in dry CH2Cl2 (2 m l) un der N2 atm osph ere at 0 °C. Th e reaction
m ixture was stirred for 45 m in an d 0.1 m l of water was added to quen ch th e reaction . Th e
reaction m ixture was diluted with m eth an ol (10 m l) an d filtered th rough a pad of silica gel.
Th e filtrate was con cen trated an d rest of water was coevaporated with toluen e (2×). Th e resi-
due was dissolved in dry pyridin e (0.8 m l) an d Ac2O (0.5 m l) was added dropwise. Th e reac-
tion m ixture was stirred overn igh t an d partition ed between eth yl acetate an d water. Th e or-
gan ic layer was wash ed with saturated NaHCO3 solution (2×), aqueous 1 M HCl an d brin e,
dried over an h ydrous Na2SO4, filtered an d con cen trated. Colum n ch rom atograph y (cyclo-
h exan e–eth yl acetate 5:1) afforded acetylated com poun ds 24 (81%), 25 (75%) an d 26 (77%).
3-(Benzothiazol-2-yl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1H-indole (24): C29H28N2O9S
(580.6); wh ite crystals; m .p. 224–226 °C (m eth an ol), lit.4a 228–230 °C. Spectral data were
iden tical with th ose reported in lit.4a
3-(Benzothiazol-2-yl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-indole (25): For C26H24N2O7S
(508.5) calculated: 61.41% C, 4.76% H, 5.51% N; foun d: 61.21% C, 4.92% H, 5.38% N; pale
yellow am orph ous solid. 1H NMR (CDCl3): 2.09 s, 3 H (CH3); 2.17 s, 3 H (CH3); 2.29 s, 3 H
(CH3); 4.44–4.48 bm , 3 H (H-4′, H-5′a, H-5′b); 5.51 dd, 1 H, J(2′,3′) = 5.4, J(3′,4′) = 4.2 (H-3′);
5.61 dd, 1 H, J(1′,2′) = 5.7, J(2′,3′) = 5.4 (H-2′); 6.24 s, 1 H (H-1′); 7.33–7.38 m , 3 H; 7.47 dt,
1 H, J = 7.7, 1.2; 7.57 m , 1 H; 7.89 d, 1 H, J = 7.6; 8.03 d, 1 H, J = 7.6; 8.15 s, 1 H; 8.47 m ,
1 H (H arom .). 13C NMR (CDCl3): 20.43, 20.60 an d 20.71 (CH3CO); 63.05 (C-5′); 70.46,
73.80 an d 80.00 (C-2′–C-4′); 87.34 (C-1′); 110.28, 113.48, 121.33, 121.67, 122.36, 122.51,
123.73, 124.40, 125.74, 126.11, 126.22, 133.90, 136.48, 153.82 an d 162.00 (C arom .);
169.34, 169.61 an d 170.52 (CH3CO). MS MALDI-TOF, m/z (%): 509 (100) [M + H]+, 531 (23)
[M + Na]+, 547 (7) [M + K]+.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

504
Humeník, Kutschy, Kováčik, Bekešová:
3-(Benzothiazol-2-yl)-1-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-1H-indole (26): C29H28N2O9S
(580.6); wh ite crystals; m .p. 135–137 °C (m eth an ol), lit.4a 133–135 °C. Spectral data were
iden tical with th ose reported in lit.4a
We thank the Grant Agency for Science, Slovak Republic for financial support of this work (grants
No. 1/9246/02 and No. 1/2472/05).
REFERENCES
1. a) Furuta R., Naruto S., Tamura A., Yokogawa K.: Tetrahedron Lett. 1979, 20, 1701;
b) Buchanan J. G., Stoddard J., Wightman R. H.: J. Chem. Soc., Perkin Trans. 1 1994,
1417; c) Ito T., Ohbai K., Koyama M., Sezaki M., Tohyama H., Shomura T., Fukuyasu H.,
Kazuno Y., Niwa T., Kojima M., Niida T.: J. Antibiot. 1984, 37, 931; d) Schumacher
R. W., Harrigan B. L., Davidson B. S.: Tetrahedron Lett. 2001, 42, 5133; e) Sassatelli M.,
Saab E., Anizon F., Prudhomme M., Moreau P.: Tetrahedron Lett. 2004, 45, 4827;
f) Messaoudi S., Sancelme M., Polard-Housset V., Aboab B., Moreau P., Prudhomme M.:
Eur. J. Med. Chem. 2004, 39, 453.
2. a) Nettleton D. E., Doyle T. W., Kirshnan B., Matsumoto G. K., Clardy J.: Tetrahedron Lett.
1985, 26, 4011; b) Prudhomme M.: Eur. J. Med. Chem. 2003, 38, 123; c) Balasubramanian
N. B., St. Laurent D. R. S., Saulnier M. G., Long B. H., Bachand C., Beaulieu F., Clarke W.,
Deshpande M., Eummer J., Fairchild C. R., Frennesson D. B., Kramer R., Lee F. Y., Mahler M.,
Martel A., Naidu B. N., Rose W. C., Russell J., Ruediger E., Solomon C., Stoffan K. M.,
Wong H., Zimmermann K., Vyas D. M.: J. Med. Chem. 2004, 47, 1609.
3. Pedras M. S. C., Okanga F. I., Zaharia I. L., Khan A. Q.: Phytochemistry 2000, 53, 161.
4. a) Humeník M., Dzurilla M., Kutschy P., Solčániová E., Kováčik V., Bekešová S.: Collect.
Czech. Chem. Commun. 2004, 69, 1657; b) Humeník M., Kutschy P., Valková K., Horváth B.,
Kováčik V., Bekešová S.: Collect. Czech. Chem. Commun. 2005, 70, 72.
5. a) Suvorov N. N., Preobrazhenskaya M. N.: Zh. Obshch. Khim. 1961, 2839; b) Walton E.,
Holly F. W., Jenkins S. R.: J. Org. Chem. 1968, 33, 192; c) Magnin A. A., Stephen A. M.,
Davis R. J. H.: Tetrahedron 1972, 28, 3069; d) Preobrazhenskaya M. N., Suvorov N. N.:
Zh. Obshch. Khim. 1965, 893; e) Preobrazhenskaya M. N., Korbukh I. A. in: Chemistry of
Nucleosides and Nucleotides (L. B. Townsend, Ed.), Vol. 3, p. 1. Plenum Press, New York
1994; f) Preobrazhenskaya M. N., Tolkachev V. N., Geling O. N., Kostyuchenko P. P.: Zh.
Org. Khim. 1974, 10, 1764.
6. a) Tanaka S., Ohkubo M., Kojiri K., Suda H.: J. Antibiot. 1992, 45, 1797; b) Kaneko T.,
Wong H., Okamoto T. K., Clardy J.: Tetrahedron Lett. 1985, 26, 4015.
7. a) El-Desoky E. I., Abel-Rahman A. H.: Liebigs Ann. Chem. 1990, 877; b) Sokolova T. N.,
Shevchenko V. E., Preobrazhenskaya M. N.: Carbohydr. Res. 1980, 83, 249; c) Buchanan
J. G., Stoddart J., Wightman R. H.: J. Chem. Soc., Perkin Trans. 1 1994, 1417.
8. a) Ohkubo M., Kawamoto H., Ohno T., Nakano M., Morishima H.: Tetrahedron 1997,
53, 585; b) Akao A., Hiraga S., Iida T., Kamatani A., Kawasaki M., Mase T., Nemoto T.,
Satake N., Weissman A. S., Tschaen M. D., Rossen K., Petrillo D., Reamer A. R., Volante
R. P.: Tetrahedron 2001, 57, 8917.
9. a) Ohkubo M., Nishimura T., Honma T., Nishimura I., Ito S., Yoshinari T., Arakawa H.,
Suda H., Morishima H., Nishimura S.: Bioorg. Med. Chem. Lett. 1999, 9, 3307; b) Ohkubo M.,
Nishimura T., Kawamoto H., Nakano M., Honma T., Yoshinari T., Arakawa H., Suda H.,
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

1,2-Anhydrosaccharides and 1,2-Cyclic Sulfites as Saccharide Donors
505
Morishima H., Nishimura S.: Bioorg. Med. Chem. Lett. 2000, 10, 419; c) Ohkubo M.,
Nishimura T., Jona H., Honma T., Ito S., Morishima H.: Tetrahedron 1997, 53, 5937;
d) Zembower D. E., Zhang H., Lineswala J. P., Kuffel M. J., Aytes S. A., Ames M. M.:
Bioorg. Med. Chem. Lett. 1999, 9, 145; e) Voldoire A., Sancelme M., Prudhomme M.,
Colsom P., Houssier C., Bailly C., Léonce S., Lambel S.: Bioorg. Med. Chem. 2001, 9, 357.
10. Chen J. J., Wei Y., Drach C. J., Townsend B. L.: J. Med. Chem. 2000, 43, 2449.
11. a) Gallant M., Link J. T., Danishefsky S. J.: J. Org. Chem. 1993, 58, 343; b) Link J. T.,
Gallant M., Danishefsky S. J., Huber S.: J. Am. Chem. Soc. 1993, 115, 3782; c) Link J. T.,
Subharekha R., Danishefsky S. J.: J. Am. Chem. Soc. 1995, 117, 552; d) Eils S., Winterfeld E.:
Synthesis 1998, 2, 275.
12. a) Lohray B. B., Ahuja J. R.: J. Chem. Soc., Chem. Commun. 1991, 95; b) Kim B. M.,
Sharpless K. B.: Tetrahedron Lett. 1990, 31, 4317; c) Gao Y., Zepp C. M.: Tetrahedron Lett.
1991, 32, 3155; d) Guiller A., Gagnieu C. H., Pacheco H.: Tetrahedron Lett. 1985, 26,
6343; e) Nymann K., Svendsen J. S.: Acta Chem. Scand. 1994, 48, 183; f) Lohray B. B.:
Synthesis 1992, 1035; g) Nymann K., Mylvaganam S., Svendsen J. S.: Acta Chem. Scand.
1998, 52, 1060.
13. a) Jeong L. S., Marquez V. E.: Tetrahedron Lett. 1996, 37, 2353; b) Moon H. R., Kim H. O.,
Chun M. W., Jeong L. S.: J. Org. Chem. 1999, 64, 4733.
14. a) Draghetti V., Poletti L., Prosperi D., Lay L.: J. Carbohydr. Chem. 2001, 20, 813;
b) Kozikowski P. A., Lee. J.: J. Org Chem. 1990, 55, 863; c) Perrin C. L., Fabian A. M.,
Brunckova J., Brian K. O.: J. Am. Chem. Soc. 1999, 121, 6911; d) Chmielewski M., Kaluza Z.,
Abramski W., Grodner J., Belzecki C., Sedmera P.: Tetrahedron 1989, 45, 227; e) Fischer S.,
Hamann C. H.: J. Carbohydr. Chem. 1995, 14, 327; f) Bellucci G., Catelani G., Chiappe C.,
D’Andrea F.: Tetrahedron. Lett. 1994, 35, 8433.
15. a) Asai N., Fusetani N., Matsunaga S.: J. Nat. Prod. 2001, 64, 1210; b) Zhong-Jun L., Hui L.,
Meng-Shen C.: Carbohydr. Res. 1999, 320, 1.
16. Kolb C. H., Sharpless B. K.: Tetrahedron 1992, 48, 10515.
17. a) Du Y., Kong F.: J. Carbohydr. Chem. 1995, 14, 341; b) Xianglan D., Kong F.:
J. Carbohydr. Chem. 1998, 17, 915; c) Manabe S., Marui Y., Ito Y.: Chem. Eur. J. 2003, 9,
1435; d) Xue J., Shao N., Guo Z.: J. Org. Chem. 2003, 68, 4020.
18. Ogawa T., Katano K., Sasajima K., Matsui M.: Tetrahedron 1981, 37, 2779.
19. a) Chittenden G. J. F.: Carbohydr. Res. 1993, 242, 297; b) Dini C., Collette P., Drochon N.,
Guillot J. C., Lemoine G., Mauvais P., Aszodi J.: Bioorg. Med. Chem. Lett. 2000, 10, 1839.
20. Chan L., Just G.: Tetrahedron Lett. 1988, 29, 4049.
21. Ning J., Kong F.: Carbohydr. Res. 1997, 300, 355.
22. Faul M. M., Winneroski L. L., Krumrich A. C.: J. Org. Chem. 1999, 64, 2465.
23. a) Gagnieu C. H., Guiller A., Pacheco H.: Carbohydr. Res. 1988, 180, 223; b) Sanders W. J.,
Kiessling L. L.: Tetrahedron Lett. 1994, 35, 7335; c) Sanders W. J., Manning D. D., Koeller
K. M., Kiessling L. L.: Tetrahedron 1997, 53, 16391.
24. a) Tewson T. J.: J. Org. Chem. 1983, 48, 3507; b) Guiller A., Gagnieu C. H., Pacheco H.:
J. Carbohydr. Chem. 1986, 5, 153; c) Guiller A., Gagnieu C. H., Pacheco H.: J. Carbohydr.
Chem. 1986, 5, 161; d) El Meslouti A., Beaupere D., Deamailly G., Uzan R.: Tetrahedron
Lett. 1994, 35, 3913.
25. a) Ponpipom M. M.: Carbohydr. Res. 1977, 59, 311; b) Bachir-Lesage S., Gode P., Goethals G.,
Villa P., Martin P.: J. Carbohydr. Chem. 2003, 22, 35; c) Ogawa T., Nozachi M., Matsui M.:
Tetrahedron 1980, 36, 2641; d) Carpintero M., Nieto I., Fernandez-Mayoralas A.: J. Org.
Chem. 2001, 66, 1768.
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506
Humeník, Kutschy, Kováčik, Bekešová:
26. a) Ward D. E., Gai Y., Kaller B. F.: J. Org. Chem. 1995, 60, 7830; b) Akiyama T., Hirofuji H.,
Ozaki S.: Tetrahedron Lett. 1991, 32, 1321.
27. a) Kartha K. P. R., Dasgupta F., Singh P. P., Srivastava H. C.: J. Carbohydr. Chem. 1986,
5, 437; b) Park M. H., Takeda R., Nakanishi K.: Tetrahedron Lett. 1987, 28, 3823;
c) Rodebaugh R., Debenham J. S., Fraser-Reid B.: Tetrahedron Lett. 1996, 37, 5477.
28. Palmer P. J., Trigg R. B., Warrington J. V.: J. Med. Chem. 1971, 14, 248.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)