Evaluation of bis-triphenylphosphano-copper(I)-butyrate (C3H7COOCu(PPh3)2) as catalyst for the synthesis of 1-glycopyranosyl-4-substituted-1,2,3-triazoles

Bokor, Éva; Koppány, Csenge; Gonda, Zsombor; Novák, Zoltán; Somsák, László
Evaluation of bis-triphenylphosphano-copper(I)-butyrate (C3H7COOCu(PPh3)2) as catalyst for the synthesis of 1-glycopyranosyl-4-substituted-1,2,3-triazoles

Author: Bokor, Éva; Koppány, Csenge; Gonda, Zsombor; Novák, Zoltán; Somsák, László
Year: 2012
Source: https://dea.lib.unideb.hu/bitstreams/6b608e32-6fa0-45d9-86b9-79986908368f/download
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G aphical abs ac
pp xxx–xxxE alua ion o bis- iphenylphosphano-coppe (I)-bu y a e (C
3
H
7
COOCu(PPh
3
)
2
) as ca alys o he syn hesis
o 1-glycopy anosyl-4-subs i u ed-1,2,3- iazoles
É a Boko , Csenge Koppány, Zsombo Gonda, Zol án No ák, László Somsák
*
Gly-N
3
RCC H
N
N
N
R
Gly
CH
2
Cl
2
,
C
3
H
7
COOCu(PPh
3
)
2
(ca .)
+
27 examples
yields: 76-99 %
CAR 6051 No. o Pages 1, Model 5G
24 Janua y 2012
1
No e
E alua ion o bis- iphenylphosphano-coppe (I)-bu y a e
(C
3
H
7
COOCu(PPh
3
)
2
) as ca alys o he syn hesis o
1-glycopy anosyl-4-subs i u ed-1,2,3- iazoles
É a Boko
a
,Csenge Koppány
a
,Zsombo Gonda
b
,Zol án No ák
b
,László Somsák
a,
⇑
a
Depa men o O ganic Chemis y, Uni e si y o Deb ecen, H-4010 Deb ecen, Hunga y
b
Depa men o O ganic Chemis y, Eö ös Lo ánd Uni e si y, H-1610 Budapes , Hunga y
10
a icle in o
A icle his o y:
Recei ed 30 No embe 2011
Recei ed in e ised o m 8 Janua y 2012
Accep ed 9 Janua y 2012
A ailable online xxxx
Keywo ds:
Azide–alkyne cycloaddi ion
20 Glycopy anosyl azide
1-Glycopy anosyl-1,2,3- iazole
abs ac
Bis- iphenylphosphano-coppe (I)-bu y a e (C
3
H
7
COOCu(PPh
3
)
2
) was applied o he syn hesis o O-pe -
acyla ed 1-glycopy anosyl-4-subs i u ed-1,2,3- iazoles om he co esponding glycosyl azides and
alkynes. This ca alys p o ed supe io o he CuSO
4
/L-asco bic acid sys em e en wi h s e ically hinde ed
and less eac i e glycosyl azides.
Ó2012 Else ie L d. All igh s ese ed.
1. In oduc ion
The egioselec i e o ma ion o 1,4-disubs i u ed-1,2,3- ia-
zoles by Cu(I) ca alysed azide–alkyne cycloaddi ion (CuAAC) is a
eliable and obus ans o ma ion cha ac e ized by high unc-
ional g oup ole ance and simple wo k-up.
1
The widesp ead use
o his eac ion is, among o he s, also ela ed o he inc easing
in e es in he 1,2,3- iazole ing as a pha macopho e.
2
The wide
a ie y o condi ions used o pe o m CuAAC include nume ous
Cu(I) sou ces such as ino ganic sal s o coppe (I) in he p esence
40
o a base and/o a ligand s abilizing he Cu(I) oxida ion s a e,
Cu(I) complexes o Cu(II) sal s coupled wi h educing agen s.
1
De elopmen o CuAAC gene a ed ema kable a en ion in he ﬁeld
o ca bohyd a e chemis y, as well. Syn hesis as well as applica ion
o 1,2,3- iazole con aining simple glycosides, oligosaccha ides,
glycomac ocycles, glycoclus e s, glycodend ime s, glycopep ides,
glycoa ays, glycopolime s and glycosyla ed biomolecules we e
su eyed in se e al e iews.
3–6
1-Glycosyl-1,2,3- iazole de i a i es we e ob ained om ela-
i ely easily a ailable glycosyl azides by using di e se Cu(I) sou ces.
50
In si u educ ion o Cu(II) sal s, usually CuSO
4
o Cu(OAc)
2
by Na-
asco ba e o
L
-asco bic acid
7–16
as well as by Cu u nings
11,17
is
one o he mos commonly used possibili ies o he ca alysis,
whe eby, wi h unp o ec ed glycosyl azides, addi ion o o-phenyl-
enediamine
18
p o ed ad an ageous. CuI is ano he o en applied
ca alys in he p esence o ei he DIPEA o E
3
N wi h TBTA (N,N,N-
is-[(1-benzyl-1H-1,2,3- iazole-4-yl)me hy]amine).
19,20
In addi-
ion, phospho ous con aining coppe complexes such as (E O)
3
P-
CuI
21
and CuB (PPh
3
)
322,23
p o ed o be also sui able ca alys s o
his pu pose.
60
We ha e epo ed on he syn heses o h ee se ies o 1-(
D
-gluco-
py anosyl)-4-subs i u ed-1,2,3- iazoles
24
4–6 (Table 1) which
we e es ed as inhibi o s o glycogen phospho ylase enzyme (GP),
a alida ed molecula a ge o he ea men o ype 2 diabe es.
Se e al b-
D
-glucopy anosyl de i a i es (O-dep o ec ed 4) p o ed
o be low mic omola inhibi o s o GP. Fu he mo e, hei inhibi ion
cons an s as well as binding modes ( e ealed by X- ay c ys allog a-
phy) showed a ema kable simila i y o hose o he co esponding
b-
D
-glucopy anosylamide ype inhibi o s,
25
he eby p o iding a
new example o he amide-1,2,3- iazole bioisos e ic ela ion-
70
ship,
26–28
and a new po en ial biological applica ion o 1-glycosyl-
1,2,3- iazoles. Regioselec i e syn heses o he O-pe acyla ed de i -
a i es 4–6 we e ca ied ou in CuAAC eac ions o he co esponding
D
-glucopy anosyl azides 1–3 wi h e minal alkynes in wa e in he
p esence o CuSO
4
and
L
-asco bic acid (Table 1, condi ions i). How-
e e , unde hese condi ions he desi ed iazoles could be ob ained
only in low yields and wi h incomple e con e sions o he s a ing
ma e ials in se e al cases. Changing he sol en o aqueous CH
3
NO
2
o DMSO, and inc easing he ca alys load up o 11 mol % did no
b ing abou signiﬁcan imp o emen s.
24
Recen ly, bis- iphenyl-
80
phosphano-coppe (I)-bu y a e (C
3
H
7
COOCu(PPh
3
)
2
) was de eloped
as a new, highly ac i e ca alys o he CuAAC eac ion. By using his
complex, se e al 1,4-disubs i u ed-1,2,3- iazoles we esyn hesised
0008-6215/$ - see on ma e Ó2012 Else ie L d. All igh s ese ed.
doi:10.1016/j.ca es.2012.01.004
⇑
Co esponding au ho . Tel.: +36 52 512 900/22348; ax: +36 52 512 744.
E-mail add ess: [email p o ec ed] (L. Somsák).
Q2
Q1
Ca bohyd a e Resea ch xxx (2012) xxx–xxx
Con en s lis s a ailable a SciVe se ScienceDi ec
Ca bohyd a e Resea ch
jou nal homepage: www.else ie .com/loca e/ca es
CAR 6051 No. o Pages 8, Model 5G
25 Janua y 2012
Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004
in excellen yields.
29
In iew o he e ﬁciency o his ca alys , he aim
o ou p esen wo k has been o in es iga e i s applicabili y o he
syn hesis o he abo e and o he 1-glycosyl-1,2,3- iazoles.
2. Resul s and discussion
Fi s , he e ﬁciency o C
3
H
7
COOCu(PPh
3
)
2
was p obed in eac-
ions be ween pe acyla ed glycopy anosyl azides 1–3 and e minal
alkynes a–d bea ing ee hyd oxyl, es e ,as well as a oma ic g oups.
90
The expe imen s we e pe o med acco ding o he li e a u e p oce-
du e
29
in dichlo ome hane a oom empe a u e (Table 1, condi-
ions ii). In he eac ions wi h p opa gyl alcohol (a) he coppe (I)-
bu y a e p o ed o be e ﬁcien in 2 and 5 mol % a io o he syn he-
ses o 4a and 5a, espec i ely, while e en8 mol % o he ca alys was
insu ﬁcien o ob ain 6a. Alkynes b–d wi h b-
D
-glucopy anosyl
azides 1and 2 equi ed 1 mol % ca alys load. Gene ally, syn heses
o compounds 5 equi ed longe eac ion ime as compa ed o hose
o de i a i es 4, p esumably because o he s e ically mo e c owded
en i onmen o he azido g oup in 2. Howe e , i has o be no ed,
100
ha in aqueous medium in he p esence o CuSO
4
/
L
-asco bic acid
(condi ions i) ans o ma ion o he O-pe benzoyla ed (b-
D
-gluco-
hep -2-ulopy anosylazide)onamide (2) occu ed only wi h e hyl
p opiola e, and unde modiﬁed eac ion condi ions in DMSO he
con e sions we e also no comple e.
24
Somewha highe amoun
o he ca alys and longe eac ion ime we e needed o ob ain
a
-
D
-glucopy anosyl-1,2,3- iazole de i a i es 6b,c (2 mol %) and 6d
(5 mol %) om he less eac i e azide
8,11,24
3. Yields we e a ound
o abo e 90% in almos each case demons a ing he supe io pe -
o mance o C
3
H
7
COOCu(PPh
3
)
2
o e he CuSO
4
/
L
-asco bic acid sys-
110
em (compa e yields unde headings iand ii in Table 1).
The Cu(I)-bu y a e complex was also applied o he syn heses
o u he O-pe ace yla ed 1-glycopy anosyl-4-subs i u ed-1,2,3-
iazoles om he co esponding glycosyl azides 7–13 (Table 2).
Fo he o ma ion o b-
D
-xylopy anosyl- and 2
0
-ace amido-2
0
-
deoxy-b-
D
-glucopy anosyl-1,2,3- iazoles 14 and 15 1mol % o
he ca alys was as e ec i e as in he b-
D
-glucopy anosyl se ies
4. In a simila manne , eac ion o 2-deoxy-2-ph alimido-b-
D
-glu-
copy anosyl azide 9wi h phenylace ylene wo ked well in he p es-
ence o 1 mol % ca alys o gi e 16d in excellen yield, while
120
cycloaddi ion wi h he bulky 2-e hynylnaph alene ep oceeded
only wi h highe ca alys load (2 mol %). Syn hesis o (2
0
-deoxy-
2
0
-ph alimido-
a
-
D
-glucopy anosyl)-4-phenyl-1,2,3- iazole 17d
equi ed highe ca alys concen a ion and longe eac ion ime
compa ed o i s bcoun e pa 16d, simila ly o obse a ions wi h
a
–bpai s ea lie (4 e sus 6). The obse ed di e ences in he eac-
i i y o he anome ic pai s o glycosyl azides a e in acco d wi h
li e a u e expe iences, and may be explained by he highe s e ic
hind ance o he azido g oup in
a
-posi ion o by he di e en dipo-
la cha ac e o he anome ic azides a ising om he anome ic
130
e ec .
8,11,24
The beha iou o glycopy anosyl azides 11–13 wi h an axial
subs i uen in posi ion 4 was di e en om ha o he p e iously
s udied 1,2- ans glycopy anosyl azides (1,7–9). Con a y o o he
bazides, ans o ma ion o he b-
D
-galac o conﬁgu ed 11 in o he
co esponding iazoles 18 needed longe eac ion ime. The
a
-
L
-
a abinopy anosyl azide 12 p o ided simila esul s, howe e ,
1 mol % ca alys load was su ﬁcien o he syn hesis o 19b and
19d. Resul s wi h he b-
L
- ucopy anosyl de i a i es 20 a e simila
o expe iences in he
a
-
D
-glycopy anosyl cases 6,17 ha is, o
140
achie e o al consump ion o he s a ing ma e ial 13 he ca alys
concen a ion had o be inc eased o 2–5 mol %. These obse a-
ions a e in line wi h li e a u e expe iences whe e b-
D
-manno
and b-
D
-galac o conﬁgu ed glycopy anosyl azides wi h axial sub-
s i uen s ga e he 1,2,3- iazoles unde longe eac ion imes
Table 1
Compa ison o ca alys s in eac ions o D-glucopy anosyl azides and alkynes
RCC H
i
o
ii
a-d
Glc-N
3
N
N
N
R
Glc
1-3 4-6
i24) CuSO4, L-asco bic acid,a H2O, 70 ºC, 8 h; ii) C3H7COOCu(PPh3)2, CH2Cl2,
Glc Alkyne R P oduc Condi ions
iii
Yield (%) Ca alys (mol %) Reac ion ime
b
Yield (%)
1
O
OAc
AcO
AcO
OAc
a–CH
2
OH 4a 65 2 1 day 90
b–CH
2
OAc 4b No in es iga ed 1 1 h 96
c–CO
2
E 4c 89 1 1 h 92
dPhenyl 4d 58 1 10 min 95
2
O
BzO
BzO
BzO
O
Bz
CONH
2
a–CH
2
OH 5a No eac ion 5 1 day 89
b–CH
2
OAc 5b No in es iga ed 1 8 h 97
c–CO
2
E 5c 56
c
14h90
dPhenyl 5d No eac ion 1 4 h 92
3
O
AcO
AcO
AcO
O
Ac
a–CH
2
OH 6a 36 8 1 day T aces
d
b–CH
2
OAc 6b No in es iga ed 2 5 h 87
c–CO
2
E 6c 72 2 1 day 91
dPhenyl 6d 39 5 1 day 76
e
a
1.5 mol % CuSO
4
, 20 mol %
L
-asco bic acid o 4, 7.5 mol % CuSO
4
, 20 mol %
L
-asco bic acid o 5and 6we e used.
24
b
Necessa y o comple e consump ion o he s a ing ma e ials 1–3.
c
Con e sion: 63%.
24
d
Repo ed yield by a di e en me hod: 60%.
11
e
Repo ed yield by a di e en me hod: 63%.
11
2É. Boko e al./Ca bohyd a e Resea ch xxx (2012) xxx–xxx
CAR 6051 No. o Pages 8, Model 5G
25 Janua y 2012
Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004
and/o in lowe yields as compa ed o he b-
D
-glucopy anosyl
coun e pa s.
13,17
3. Conclusion
Applica ion o he C
3
H
7
COOCu(PPh
3
)
2
complex as a highly ac i e
ca alys in CuAAC eac ions wi h a a ie y o glycosyl azides ga e
150
he co esponding 1,2,3- iazoles in excellen yields. The p esence
o a ee hyd oxyl g oup in he alkyne, inc easing s e ic hind ance
o diminished eac i i y as well as he p esence o an axial subs i u-
en in he py anoid ing o he glycosyl azide equi ed highe ca a-
lys load and/o ex ended eac ion imes. Gene ally, his ca alys
has b oade applicabili y wi h glycosyl azides han he commonly
used CuSO
4
/
L
-asco bic acid sys em.
4. Expe imen al
4.1. Gene al me hods
Mel ing poin s we e measu ed in open capilla y ubes o on a
160
Koﬂe ho -s age and a e unco ec ed. Op ical o a ions we e de e -
mined wi h a Pe kin–Elme 241 pola ime e a . NMR spec a
we e eco ded wi h B uke 360 (360/90 MHz o
1
H/
13
C) spec om-
e e . Chemical shi s a e e e enced o Me4Si (
1
H), o o he esidual
sol en signals (
13
C). TLC was pe o med on DC-Alu olle Kieselgel
60 F
254
(Me ck), and he pla es we e isualised unde UV ligh
and by gen le hea ing. Fo column ch oma og aphy Kieselgel 60
(Me ck, pa icle size 0.063–0.200 mm) was used. Dichlo ome hane
was dis iled om P
4
O
10
and s o ed o e 4Åmolecula sie es. P op-
a gyl alcohol (a), p opa gyl ace a e (b), e hyl p opiola e (c) and
170
phenylace ylene (d) we e pu chased om Ald ich. 2-E hynylnaph-
halene
30
(e) and he pe -O-acyla ed glycopy anosyl azides
31–35
1–3 and 7–13 as well as he complex
29
C
3
H
7
COOCu(PPh
3
)
2
we e
syn hesized acco ding o published p ocedu es.
4.2. Gene al p ocedu e o he syn hesis o pe acyla ed 1-glyco
py anosyl-4-subs i u ed-1,2,3- iazoles in he p esence o C
3
H
7
COOCu(PPh
3
)
2
ca alys
An azide (1–3 o 7–13,0.1 g) and an equimola amoun o an al-
kyne (a–e) we e dissol ed in anhyd ous CH
2
Cl
2
(2 mL), C
3
H
7
COOC-
u(PPh
3
)
2
(1–5 mol %, Tables 1 and 2) ca alys was added, he
180
mix u e was s i ed a and moni o ed by TLC (1:1 E OAc–hex-
ane). A e comple ion o he eac ion (Tables 1 and 2), he sol en
was e apo a ed and he esidue was pu iﬁed by column
ch oma og aphy.
4.2.1. 4-Hyd oxyme hyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-b-
D
-gluco
py anosyl)-1,2,3- iazole (4a)
F om 1(0.1 g, 0.27 mmol), p opa gyl alcohol (16
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(3.6 mg, 5.4
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (2:1 E OAc–hexane) o yield
0.10 g (90%) o whi e solid.
1
H and
13
C NMR da a co espond o
190
he epo ed spec a.
8,11
4.2.2. 4-Ace oxyme hyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-b-
D
-gluco
py anosyl)-1,2,3- iazole (4b)
F om 1(0.1 g, 0.27 mmol), p opa gyl ace a e (27
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.8 mg, 2.7
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (1:1 E OAc–hexane) o yield
0.12 g (96%) o whi e solid. Mp: 151–153 °C (li .
8
mp: 143–144 °C);
[
a
]
D
24 (c0.57, CHCl
3
);
1
H and
13
C NMR da a co espond o he
epo ed spec a.
8
4.2.3. E hyl 1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-b-
D
-glucopy anosyl)-
200
1,2,3- iazole-4-ca boxyla e (4c)
F om 1(0.1 g, 0.27 mmol), e hyl p opiola e (28
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.8 mg, 2.7
l
mol) acco ding o Sec ion
4.2. Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o
yield 0.12 g (92%) o whi e solid.
1
H and
13
C NMR da a co espond
o he epo ed spec a.
24
4.2.4. 4-Phenyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-b-
D
-glucopy anosyl)-
1,2,3- iazole (4d)
F om 1(0.1 g, 0.27 mmol), phenylace ylene (29
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.8 mg, 2.7
l
mol) acco ding o Sec ion 4.2.
210
Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o yield
0.12 g (95%) o whi e solid.
1
H and
13
C NMR da a co espond o
he epo ed spec a.
7,11,19
4.2.5. [4-Hyd oxyme hyl-1-(3
0
,4
0
,5
0
,7
0
- e a-O-benzoyl-b-
D
-gluco-
hep -2-ulopy anosyl)-1,2,3- iazole]onamide (5a)
F om 2(0.1 g, 0.15 mmol), p opa gyl alcohol (9
l
L, 0.15 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(5.1 mg, 7.6
l
mol) acco ding o Sec ion
4.2. Pu iﬁed by column ch oma og aphy (2:1 E OAc–hexane) o
yield 0.10 g (89%) o whi e solid.
1
H and
13
C NMR da a co espond
o he epo ed spec a.
24
220
4.2.6. [4-Ace oxyme hyl-1-(3
0
,4
0
,5
0
,7
0
- e a-O-benzoyl-b-
D
-gluco-
hep -2-ulopy anosyl)-1,2,3- iazole]onamide (5b)
F om 2(0.1 g, 0.15 mmol), p opa gyl ace a e (15
l
L, 0.15 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.0 mg, 1.5
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (1:1 E OAc–hexane) o yield
0.11 g (97%) o colou less oil. R
: 0.51 (5:4 E OAc–hexane); [
a
]
D
9(c0.56, CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 8.10–7.23 (21H, m,
a oma ics, iazole CH), 6.97 (1H, s, CONH
2
), 6.56 (1H, s, CONH
2
),
6.33 (1H, pseudo , J= 8.0, 8.0 Hz, H-4
0
o H-5
0
), 6.17 (1H, d,
J= 8.0 Hz, H-3
0
), 5.89 (1H, pseudo , J= 9.2, 8.6 Hz, H-4
0
o H-5
0
),
230
5.23 (1H, ddd, J= 9.9, 3.7, <1 Hz, H-6
0
), 5.10 (2H, s, CH
2
), 4.89
(1H, dd, J= 12.3, <1 Hz, H-7
0
a), 4.57 (1H, dd, J= 12.3, 3.7 Hz, H-
7
0
b), 2.00 (3H, s, CH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.5, 166.2,
166.1, 165.0, 164.9, 164.2 (CO), 142.9 ( iazole C-4), 133.7–128.2
(a oma ics), 122.5 ( iazole C-5), 89.4 (C-2
0
), 73.9, 72.2, 71.0, 68.1
(C-3
0
–C-6
0
), 62.3 (C-7
0
), 57.1 (CH
2
), 20.6 (CH
3
). Anal. Calcd o
C
40
H
34
N
4
O
12
(762.74): C, 62.99; H, 4.49; N, 7.35. Found: C, 63.11;
H, 4.63; N, 7.24.
4.2.7. [4-E hoxyca bonyl-1-(3
0
,4
0
,5
0
,7
0
- e a-O-benzoyl-b-
D
-
gluco-hep -2-ulopy anosyl)-1,2,3- iazole]onamide (5c)
240
F om 2(0.1 g, 0.15 mmol), e hyl p opiola e (15
l
L, 0.15 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.0 mg, 1.5
l
mol) acco ding o Sec ion
4.2. Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o
yield 0.10 g (90%) o colou less oil.
1
H and
13
C NMR da a co espond
o he epo ed spec a.
24
4.2.8. [4-Phenyl-1-(3
0
,4
0
,5
0
,7
0
- e a-O-benzoyl-b-
D
-gluco-hep -2-
ulopy anosyl)-1,2,3- iazole]onamide (5d)
F om 2(0.1 g, 0.15 mmol), phenylace ylene (17
l
L, 0.15 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.0, 1.5
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o yield
250
0.11 g (92%) o whi e solid.
1
H and
13
C NMR da a co espond o
he epo ed spec a.
24
4.2.9. 4-Ace oxyme hyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-
a
-
D
-gluco
py anosyl)-1,2,3- iazole (6b)
F om 3(0.1 g, 0.27 mmol), p opa gyl ace a e (27
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(3.6 mg, 5.4
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (1:1 E OAc–hexane) o yield
0.11 g (87%) o whi e solid. Mp: 139–141 °C; [
a
]
D
+92 (c0.51,
CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 7.74 (1H, s, iazole CH), 6.37
É. Boko e al./Ca bohyd a e Resea ch xxx (2012) xxx–xxx 3
CAR 6051 No. o Pages 8, Model 5G
25 Janua y 2012
Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004

(1H, d, J= 6.2 Hz, H-1
0
), 6.25 (1H, pseudo , J= 9.9, 9.2 Hz, H-3
0
o H-
260
4
0
), 5.33 (1H, dd, J= 9.9, 6.2 Hz, H-2
0
), 5.27–5.21 (3H, m, H-3
0
o H-
4
0
,CH
2
), 4.39 (1H, ddd, J= 10.5, 3.7, <1 Hz, H-5
0
), 4.27 (1H, dd,
J= 12.3, 3.7 Hz, H-6
0
a), 4.04 (1H, dd, J= 12.3, <1 Hz, H-6
0
b), 2.10,
2.07 (2), 2.04, 1.88 (5 3H, 5s, OCOCH
3
);
13
CNMR (CDCl
3
): d
(ppm) 170.6, 170.3, 170.0, 169.5 (2) (COCH
3
), 142.4 ( iazole C-4),
125.8 ( iazole C-5), 81.3 (C-1
0
), 71.1, 70.2, 69.6, 67.8 (C-2
0
–C-5
0
),
61.1 (C-6
0
), 57.2 (CH
2
), 20.7, 20.5 (3), 20.1 (COCH
3
). Anal. Calcd
o C
19
H
25
N
3
O
11
(471.42): C, 48.41; H, 5.35; N, 8.91. Found: C,
48.56; H, 5.44; N, 8.78.
4.2.10. E hyl 1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-
a
-
D
-glucopy anosyl)-
270
1,2,3- iazole-4-ca boxyla e (6c)
F om 3(0.1 g, 0.27 mmol), e hyl p opiola e (28
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(3.6 mg, 5.4
l
mol) acco ding o Sec ion
4.2. Pu iﬁed by column ch oma og aphy (4:5 E OAc–hexane) o
yield 0.12 g (91%) o whi e solid.
1
H and
13
C NMR da a co espond
o he epo ed spec a.
24
4.2.11. 4-Phenyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-
a
-
D
-glucopy ano
syl)-1,2,3- iazole (6d)
F om 3(0.1 g, 0.27 mmol), phenylace ylene (29
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(9 mg, 14
l
mol) acco ding o Sec ion 4.2.
280
Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o yield
0.10 g (76%) o whi e solid.
1
H and
13
C NMR da a co espond o
he epo ed spec a.
11,24
4.2.12. 4-Ace oxyme hyl-1-(2
0
,3
0
,4
0
- i-O-ace yl-b-
D
-xylopy ano
syl)-1,2,3- iazole (14b)
F om 7(0.1 g, 0.33 mmol), p opa gyl ace a e (33
l
L, 0.33 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(2.2 mg, 3.3
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o yield
0.13 g (96%) o whi e solid. Mp: 160–161 °C; [
a
]
D
55 (c0.50,
CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 7.87 (1H, s, iazole CH), 5.83
290
(1H, d, J= 8.0 Hz, H-1
0
), 5.47–5.38 (2H, m, H-2
0
, H-3
0
), 5.25–5.14
(3H, m, H-4
0
,CH
2
), 4.31 (1H, dd, J= 11.1, 5.5 Hz, H-5
0
a), 3.64 (1H,
pseudo , J= 11.1, 11.1 Hz, H-5
0
b), 2.08 (2), 2.06, 1.89 (4 3H, 4s,
OCOCH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.6, 169.7, 169.6, 168.8
(OCOCH
3
), 143.5 ( iazole C-4), 122.0 ( iazole C-5), 86.1 (C-1
0
),
71.9, 70.4, 68.2 (C-2
0
–C-4
0
), 65.4 (C-5
0
), 57.3 (CH
2
), 20.6, 20.5,
20.4, 20.0 (OCOCH
3
). Anal. Calcd o C
16
H
21
N
3
O
9
(399.35): C,
48.12; H, 5.30; N, 10.52. Found: C, 48.24; H, 5.17; N, 11.02.
4.2.13. 4-Phenyl-1-(2
0
,3
0
,4
0
- i-O-ace yl-b-
D
-xylopy anosyl)-
1,2,3- iazole (14d)
300
F om 7(0.2 g, 0.66 mmol), phenylace ylene (73
l
L, 0.66 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(4.5 mg, 6.6
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by ec ys allisa ion om E OH o yield 0.25 g (93%) o
Table 2
Syn hesis o 1-glycopy anosyl-4-subs i u ed-1,2,3- iazoles
Gly-N
3
RCC H
C
3
H
7
COOCu(PPh
3
)
2
CH
2
Cl
2
,
N
N
N
R
Gly
02-4131-7
b, d, e
Gly Alkyne R Condi ions
P oduc Ca alys (mol %) Reac ion ime Yield (%)
7
O
OAc
AcO
A
cO
b–CH
2
OAc 14b 12h96
dPhenyl 14d 1 10 min 93
e2-Naph hyl 14e 1 10 min 86
8
O
N
H
A
c
AcO
AcO
O
Ac
b–CH
2
OAc 15b 11h88
dPhenyl 15d 1 30 min 94
a
e2-Naph hyl 15e 1 30 min 85
9
O
N
P
h
AcO
AcO
O
Ac
dPhenyl 16d 1 10 min 99
e2-Naph hyl 16e 26h96
10
O
Ph N
AcO
AcO
O
Ac
dPhenyl 17d 5 1 day 98
11
O
OAc
A
cO
OAc
AcO
b–CH
2
OAc 18b 16h92
dPhenyl 18d 28h90
b
12
O
OAc
A
cO
AcO
b–CH
2
OAc 19b 12h96
dPhenyl 19d 15h98
13
O
Me
O
Ac
OAc OAc
b–CH
2
OAc 20b 24h96
dPhenyl 20d 52h97
a
Repo ed yield by a di e en me hod: 90%.
12
b
Repo ed yield by di e en me hods: 74%;
19
91%.
16
4É. Boko e al./Ca bohyd a e Resea ch xxx (2012) xxx–xxx
CAR 6051 No. o Pages 8, Model 5G
25 Janua y 2012
Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004
whi e solid. Mp: 271–272 °C; [
a
]
D
104 (c0.50, DMSO);
1
H NMR
(DMSO-d
6
): d(ppm) 8.95 (1H, s, iazole CH), 7.84–7.34 (5H, m,
a oma ics), 6.29 (1H, d, J= 8.6 Hz, H-1
0
), 5.64, 5.56 (2 1H, 2 pseu-
do , J= 9.2, 9.2 Hz in each, H-2
0
, H-3
0
), 5.12 (1H, ddd, J= 10.5, 9.2,
5.5 Hz, H-4
0
), 4.13 (1H, dd, J= 11.1, 5.5 Hz, H-5
0
a), 3.90 (1H, pseudo
, J= 11.1, 10.5 Hz, H-5
0
b), 2.03, 2.01, 1.81 (3 3H, 3s, OCOCH
3
);
13
C
NMR (DMSO-d
6
): d(ppm) 169.5 (2), 168.6 (OCOCH
3
), 146.8 ( ia-
310
zole C-4), 130.1, 129.0 (2), 128.2, 125.1 (2) (a oma ics), 120.2 ( i-
azole C-5), 84.7 (C-1
0
), 71.7, 70.4, 68.0 (C-2
0
–C-4
0
), 64.0 (C-5
0
), 20.4,
20.3, 19.9 (OCOCH
3
). Anal. Calcd o C
19
H
21
N
3
O
7
(403.39): C, 56.57;
H, 5.25; N, 10.42. Found: C, 56.44; H, 5.37; N, 10.30.
4.2.14. 4-(2-Naph hyl)-1-(2
0
,3
0
,4
0
- i-O-ace yl-b-
D
-xylopy anosyl)
-1,2,3- iazole (14e)
F om 7(0.1 g, 0.33 mmol), 2-e hynylnaph halene (0.05 g,
0.33 mmol) and C
3
H
7
COOCu(PPh
3
)
2
(2.2 mg, 3.3
l
mol) acco ding
o Sec ion 4.2. Pu iﬁed by ec ys allisa ion om E OH o yield
0.13 g (86%) o whi e solid. Mp: 285–286 °C;
1
H NMR (DMSO-d
6
):
320
d(ppm) 9.08 (1H, s, iazole CH), 8.41–7.54 (7H, m, a oma ics),
6.33 (1H, d, J= 8.6 Hz, H-1
0
), 5.67, 5.58 (2 1H, 2 pseudo ,
J= 9.2, 9.2 Hz in each, H-2
0
, H-3
0
), 5.14 (1H, ddd, J= 10.5, 9.2,
4.9 Hz, H-4
0
), 4.15 (1H, dd, J= 11.1, 4.9 Hz, H-5
0
a), 3.92 (1H, pseudo
, J= 11.1, 10.5 Hz, H-5
0
b), 2.05, 2.02, 1.83 (3 3H, 3s, OCOCH
3
);
13
C
NMR (DMSO-d
6
): d(ppm) 169.5 (2), 168.6 (OCOCH
3
), 146.8 ( ia-
zole C-4), 132.9, 132.6, 128.6, 127.9, 127.6, 127.5, 126.6, 126.2,
123.6, 123.4 (a oma ics), 120.5 ( iazole C-5), 84.7 (C-1
0
), 71.7,
70.4, 67.9 (C-2
0
–C-4
0
), 64.0 (C-5
0
), 20.4, 20.2, 19.8 (OCOCH
3
). Anal.
Calcd o C
23
H
23
N
3
O
7
(453.44): C, 60.92; H, 5.11; N, 9.27. Found:
330
C, 61.01; H, 5.25; N, 9.18.
4.2.15. 1-(2
0
-Ace amido-2
0
-deoxy-3
0
,4
0
,6
0
- i-O-ace yl-b-
D
-gluco
py anosyl)-4-ace oxy-me hyl-1,2,3- iazole (15b)
F om 8(0.2 g, 0.54 mmol), p opa gyl ace a e (53
l
L, 0.54 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(3.6 mg, 5.4
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (4:1 E OAc–hexane, hen
E OAc) o yield 0.22 g (88%) o whi e solid. Mp: 240–241 °C; [
a
]
D
30 (c0.51, CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 7.98 (1H, s, iazole
CH), 6.75 (1H, d, J= 8.8 Hz, NHAc), 6.15 (1H, d, J= 9.6 Hz, H-1
0
),
5.55 (1H, pseudo , J= 9.6, 9.6 Hz, H-3
0
o H-4
0
), 5.27–5.22 (3H, m,
340
H-3
0
o H-4
0
,CH
2
) 4.61 (1H, ddd, J= 9.6, 9.6, 8.7 Hz H-2
0
), 4.30 (1H,
dd, J= 12.3, 4.4 Hz, H-6
0
a), 4.16 (1H, dd, J= 12.3, <1 Hz, H-6
0
b),
4.09 (1H, ddd, J= 8.8, 4.4, <1 Hz, H-5
0
), 2.07 (12H, s, 4 OCOCH
3
),
1.77 (3H, s, NHCOCH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.6 (4),
169.3, (COCH
3
), 143.2 ( iazole C-4), 123.0 ( iazole C-5), 85.7 (C-
1
0
), 74.8, 72.1, 68.0 (C-3
0
–C-5
0
), 61.7 (C-6
0
), 57.3 (CH
2
), 53.3 (C-2
0
),
22.7, 20.8, 20.6, 20.5 (2) (COCH
3
). Anal. Calcd o C
19
H
26
N
4
O
10
(470.43): C, 48.51; H, 5.57; N, 11.91. Found: C, 48.66; H, 5.65; N,
11.74.
4.2.16. 1-(2
0
-Ace amido-2
0
-deoxy-3
0
,4
0
,6
0
- i-O-ace yl-b-
D
-gluco
350
py anosyl)-4-phenyl-1,2,3- iazole (15d)
F om 8(0.1 g, 0.27 mmol), phenylace ylene (29
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.8 mg, 2.7
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (7:3 E OAc–hexane, hen
MeOH) o yield 0.12 g (94%) o whi e solid. Mp: 282–284 °C; [
a
]
D
71 (c0.58, DMSO);
1
H and
13
C NMR da a co espond o he e-
po ed spec a.
12
4.2.17. 1-(2
0
-Ace amido-2
0
-deoxy-3
0
,4
0
,6
0
- i-O-ace yl-b-
D
-gluco
py anosyl)-4-(2-naph hyl)-1,2,3- iazole (15e)
F om 8(0.2 g, 0.54 mmol), 2-e hynylnaph halene (0.08 g,
360
0.54 mmol) and C
3
H
7
COOCu(PPh
3
)
2
(3.6 mg, 5.4
l
mol) acco ding
o Sec ion 4.2. Pu iﬁed by column ch oma og aphy (7:3 E OAc–
hexane, hen MeOH) o yield 0.24 g (85%) o whi e solid. Mp:
298–300 °C; [
a
]
D
70 (c0.51, DMSO);
1
H NMR (DMSO-d
6
): d
(ppm) 9.00 (1H, s, iazole CH), 8.42 (1H, s, a oma ic), 8.17–7.54
(7H, m, a oma ics, NHAc), 6.19 (1H, d, J= 9.6 Hz, H-1
0
), 5.42, 5.14
(2 1H, 2 pseudo , J= 9.6 Hz in each, H-3
0
, H-4
0
), 4.69 (1H, ddd,
J= 9.6, 9.6, 8.8 Hz, H-2
0
), 4.31 (1H, ddd, J= 8.8, 4.4, <1 Hz, H-5
0
),
4.20 (1H, dd, J= 12.3, 4.4 Hz, H-6
0
a), 4.10 (1H, dd, J= 12.3, <1 Hz,
H-6
0
b), 2.03, 2.01, 1.97 (3 3H, 3s, OCOCH
3
), 1.60 (3H, s, NHCOCH
3
);
370
13
C NMR (DMSO-d
6
): d(ppm) 170.0, 169.6 169.5, 169.4, (COCH
3
),
146.5 ( iazole C-4), 133.0, 132.6, 128.6, 128.0, 127.7, 127.6,
126.7, 126.3, 123.6, 123.4 (a oma ics), 120.6 ( iazole C-5), 84.9
(C-1
0
), 73.3, 72.2, 68.0 (C-3
0
–C-5
0
), 61.7 (C-6
0
), 52.3 (C-2
0
), 22.3,
20.5, 20.4, 20.3 (COCH
3
). Anal. Calcd o C
26
H
28
N
4
O
8
(524.52): C,
59.54; H, 5.38; N, 10.68. Found: C, 59.70; H, 5.29; N, 10.81.
4.2.18. 1-(2
0
-Deoxy-2
0
-ph alimido-3
0
,4
0
,6
0
- i-O-ace yl-b-
D
-
glucopy anosyl)-4-phenyl-1,2,3- iazole (16d)
F om 9(0.3 g, 0.65 mmol), phenylace ylene (71
l
L, 0.65 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(4.4 mg, 6.5
l
mol) acco ding o Sec ion
380
4.2. Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o
yield 0.37 g (99%) o whi e solid. Mp: 194–196 °C; [
a
]
D
107 (c
0.55, CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 8.05 (1H, s, iazole CH),
7.83–7.28 (9H, m, a oma ics, Ph ), 6.85 (1H, d, J= 10.5 Hz, H-1
0
),
6.06 (1H, J= 10.5, 9.2 Hz), 5.39 (1H, J= 9.9, 9.2 Hz), 4.94 (1H,
J= 10.5, 9.9 Hz) (3 pseudo , H-2
0
, H-3
0
, H-4
0
), 4.40 (1H, dd,
J= 12.3, 4.3 Hz, H-6
0
a), 4.24–4.20 (2H, m, H-5
0
, H-6
0
b), 2.12, 2.09,
1.89 (3 3H, 3s, OCOCH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.5,
169.8, 169.3 (COCH
3
), 167.5, 166.4 (NPh CO), 148.2 ( iazole C-4),
134.6, 134.4, 131.0, 130.5, 129.7, 128.7, 128.4, 125.7, 123.8 (a o-
390
ma ics, Ph ), 117.7 ( iazole C-5), 83.0 (C-1
0
), 75.0, 70.4, 68.1 (C-
3
0
–C-5
0
), 61.6 (C-6
0
), 53.9 (C-2
0
), 20.6, 20.5, 20.3 (COCH
3
). Anal. Calcd
o C
28
H
26
N
4
O
9
(562.53): C, 59.78; H, 4.66; N, 9.96. Found: C, 59.89;
H, 4.81; N, 9.90.
4.2.19. 1-(2
0
-Deoxy-2
0
-ph alimido-3
0
,4
0
,6
0
- i-O-ace yl-b-
D
-gluco
py anosyl)-4-(2-naph hyl)-1,2,3- iazole (16e)
F om 9(0.3 g, 0.65 mmol), 2-e hynylnaph halene (0.1 g,
0.65 mmol) and C
3
H
7
COOCu(PPh
3
)
2
(8.8 mg, 6.5
l
mol) acco ding
o Sec ion 4.2. Pu iﬁed by column ch oma og aphy (2:3 E OAc–
hexane) o yield 0.38 g (96%) o whi e solid. Mp: 194–196 °C; [
a
]
D
400
164 (c0.54, CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 8.30–7.45 (12H,
m, a oma ics, Ph , iazole CH), 6.88 (1H, d, J= 10.5 Hz, H-1
0
), 6.08
(1H, J= 10.5, 9.2 Hz), 5.40 (1H, J= 9.9, 9.2 Hz), 4.97 (1H, J= 10.5,
9.9 Hz) (3 pseudo , H-2
0
, H-3
0
, H-4
0
), 4.42 (1H, dd, J= 12.3, 4.9 Hz,
H-6
0
a), 4.26–4.21 (2H, m, H-5
0
, H-6
0
b), 2.13, 2.10, 1.90 (3 3H, 3s,
OCOCH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.5, 169.9, 169.4 (COCH
3
),
167.6, 166.5 (NPh CO), 148.3 ( iazole C-4), 134.6–123.8 (a oma -
ics, Ph ), 118.0 ( iazole C-5), 83.1 (C-1
0
), 75.1, 70.4, 68.2 (C-3
0
–C-
5
0
), 61.6 (C-6
0
), 54.0 (C-2
0
), 20.7, 20.6, 20.3 (COCH
3
). Anal. Calcd o
C
32
H
28
N
4
O
9
(612.59): C, 62.74; H, 4.61; N, 9.15. Found: C, 62.60;
410
H, 4.70; N, 9.04.
4.2.20. 1-(2
0
-Deoxy-2
0
-ph alimido-3
0
,4
0
,6
0
- i-O-ace yl-
a
-
D
-gluco
py anosyl)-4-phenyl-1,2,3- iazole (17d)
F om 10 (0.1 g, 0.22 mmol), phenylace ylene (24
l
L, 0.22 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(7.3 mg, 11
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (4:5 E OAc–hexane) o yield
0.12 g (98%) o whi e solid. Mp: 161–163 °C; [
a
]
D
+182 (c0.54,
CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 7.91 (1H, s, iazole CH), 7.79–
7.29 (9H, m, a oma ics, Ph ), 7.17 (1H, pseudo , J= 10.5, 10.5 Hz,
H-3
0
), 6.44 (1H, d, J= 5.5 Hz, H-1
0
), 5.30 (1H, pseudo , J= 9.9,
420
9.2 Hz, H-4
0
), 5.07 (1H, dd, J= 10.5, 5.5 Hz, H-2
0
), 4.70 (1H, ddd,
J= 10.5, 3.1, <1 Hz, H-5
0
), 4.37 (1H, dd, J= 12.3, 3.1 Hz, H-6
0
a), 4.12
(1H, dd, J= 12.3, <1 Hz, H-6
0
b), 2.10, 1.90 (9H, 2s, 3 OCOCH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.4, 170.1, 168.9 (COCH
3
), 166.8 (2)
(NPh CO), 147.3 ( iazole C-4), 134.5 (2), 130.7 (2), 129.6, 128.7
(2), 128.4, 125.8 (2), 123.7 (2) (a oma ics, Ph ), 121.0 ( iazole C-
5), 82.8 (C-1
0
), 71.9, 69.6, 67.2 (C-3
0
–C-5
0
), 61.4 (C-6
0
), 53.3 (C-2
0
),
É. Boko e al./Ca bohyd a e Resea ch xxx (2012) xxx–xxx 5
CAR 6051 No. o Pages 8, Model 5G
25 Janua y 2012
Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004
20.6 (3) (COCH
3
). Anal. Calcd o C
28
H
26
N
4
O
9
(562.53): C, 59.78; H,
4.66; N, 9.96. Found: C, 59.68; H, 4.77; N, 10.05.
4.2.21. 4-Ace oxyme hyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-b-
D
-galac
430
opy anosyl)-1,2,3- iazole (18b)
F om 11 (0.1 g, 0.27 mmol), p opa gyl ace a e (27
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(1.8 mg, 2.7
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (1:1 E OAc–hexane) o yield
0.12 g (92%) o whi e solid. Mp: 110–112 °C; [
a
]
D
7(c0.50, CHCl
3
);
1
HNMR(CDCl
3
): d(ppm) 7.93 (1H, s, iazole CH), 5.92 (1H, d,
J=9.2Hz,H-1
0
), 5.57–5.52 (2H, m, H-2
0
,H-4
0
), 5.33–5.19 (3H, m, H-
3
0
,CH
2
), 4.32 (1H, pseudo , J= 6.2, 6.2, H-5
0
), 4.25–4.13 (2H, m, H-
6
0
a, H-6
0
b), 2.24, 2.10, 2.05, 2.02, 1.89 (5 3H, 5s, OCOCH
3
);
13
C
NMR (CDCl
3
): d(ppm) 170.6, 170.1, 169.8, 169.6, 168.8 (OCOCH
3
),
440
143.3 ( iazole C-4), 122.1 ( iazole C-5), 85.9 (C-1
0
), 73.8, 70.5, 67.7,
66.7 (C-2
0
–C-5
0
), 61.1 (C-6
0
), 57.2 (CH
2
), 20.6, 20.4 (2), 20.3, 20.0
(OCOCH
3
). Anal. Calcd o C
19
H
25
N
3
O
11
(471.42): C, 48.41; H, 5.35; N,
8.91. Found: C, 48.52; H, 5.26; N, 8.78.
4.2.22. 4-Phenyl-1-(2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-b-
D
-galac opy an
osyl)-1,2,3- iazole (18d)
F om 11 (0.1 g, 0.27 mmol), phenylace ylene (29
l
L, 0.27 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(3.6 mg, 5.4
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (4:5 E OAc–hexane) o yield
0.12 g (90%) o whi e solid. Mp: 197–199 °C (li .
19
mp: 197–
450
199 °C);[
a
]
D
44 (c0.50, CHCl
3
);
1
H and
13
C NMR da a co espond
o he epo ed spec a.
19
4.2.23. 4-Ace oxyme hyl-1-(2
0
,3
0
,4
0
- i-O-ace yl-
a
-
L
-a abinopy
anosyl)-1,2,3- iazole (19b)
F om 12 (0.1 g, 0.33 mmol), p opa gyl ace a e (33
l
L,
0.33 mmol) and C
3
H
7
COOCu(PPh
3
)
2
(2.2 mg, 3.3
l
mol) acco ding
o Sec ion 4.2. Pu iﬁed by column ch oma og aphy (1:1 E OAc–hex-
ane) o yield 0.13 g (96%) o whi e solid. Mp: 183–184 °C; [
a
]
D
+2 (c
0.50, CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 7.93 (1H, s, iazole CH), 5.81
(1H, d, J= 9.2 Hz, H-1
0
), 5.58 (1H, pseudo , J= 9.9, 9.2 Hz, H-2
0
), 5.45
460
(1H, b s, H-4
0
), 5.29 (1H, dd, J= 9.9, 3.1 Hz, H-3
0
), 5.21, 5.19 (2 1H,
2d, J= 12.9 Hz in each, CH
2
a, CH
2
b), 4.20(1H, d, J= 13.6 Hz, H-5
0
a),
4.00 (1H, d, J= 13.6 Hz, H-5
0
b), 2.23, 2.09, 2.04, 1.90 (4 3H, 4s,
OCOCH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.6, 169.9, 169.6, 168.8
(OCOCH
3
), 143.3 ( iazole C-4), 122.1 ( iazole C-5), 86.4 (C-1
0
),
70.2, 68.0, 67.5 (C-2
0
–C-4
0
), 67.1 (C-5
0
), 57.2 (CH
2
), 20.7, 20.6, 20.3,
20.0 (OCOCH
3
). Anal. Calcd o C
16
H
21
N
3
O
9
(399.35): C, 48.12; H,
5.30; N, 10.52. Found: C, 48.17; H, 5.46; N, 10.41.
4.2.24. 4-Phenyl-1-(2
0
,3
0
,4
0
- i-O-ace yl-
a
-
L
-a abinopy anosyl)-
1,2,3- iazole (19d)
470
F om 12 (0.1 g, 0.33 mmol), phenylace ylene (37
l
L, 0.33 mmol)
and C
3
H
7
COOCu(PPh
3
)
2
(2.2 mg, 3.3
l
mol) acco ding o Sec ion 4.2.
Pu iﬁed by column ch oma og aphy (2:3 E OAc–hexane) o yield
0.13 g (98%) o whi e solid. Mp: 217–219 °C; [
a
]
D
55 (c0.51,
CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 8.07 (1H, s, iazole CH), 7.87–
7.33 (5H, m, a oma ics), 5.83 (1H, d, J= 9.2 Hz, H-1
0
), 5.68 (1H,
pseudo , J= 9.9, 9.2 Hz, H-2
0
), 5.47 (1H, b s, H-4
0
), 5.29 (1H, dd,
J= 9.9, 2.5 Hz, H-3
0
), 4.20 (1H, d, J= 13.6 Hz, H-5
0
a), 3.99 (1H, d,
J= 13.6 Hz, H-5
0
b), 2.24, 2.04, 1.90 (3 3H, 3s, OCOCH
3
);
13
C
NMR (CDCl
3
): d(ppm) 170.0, 169.8, 169.1 (OCOCH
3
), 148.2 ( ia-
480
zole C-4), 130.0, 128.8 (2), 128.4, 125.8 (2) (a oma ics), 117.7 ( i-
azole C-5), 86.6 (C-1
0
), 70.5, 68.0, 67.7 (C-2
0
–C-4
0
), 67.2 (C-5
0
), 20.9,
20.5, 20.2 (OCOCH
3
). Anal. Calcd o C
19
H
21
N
3
O
7
(403.39): C, 56.57;
H, 5.25; N, 10.42. Found: C, 56.64; H, 5.11; N, 10.27.
4.2.25. 4-Ace oxyme hyl-1-(2
0
,3
0
,4
0
- i-O-ace yl-b-
L
- ucopy ano
syl)-1,2,3- iazole (20b)
F om 13 (0.1 g, 0.32 mmol), p opa gyl ace a e (32
l
L,
0.32 mmol) and C
3
H
7
COOCu(PPh
3
)
2
(4.3 mg, 6.4
l
mol) acco ding
o Sec ion 4.2. Pu iﬁed by column ch oma og aphy (1:1 E OAc–
hexane) o yield 0.13 g (96%) o colou less oil. R
: 0.37 (1:1
490
E OAc–hexane); [
a
]
D
+13 (c0.52, CHCl
3
);
1
H NMR (CDCl
3
): d
(ppm) 7.94 (1H, s, iazole CH), 5.89 (1H, d, J= 9.2 Hz, H-1
0
), 5.52
(1H, pseudo , J= 9.9, 9.9 Hz, H-2
0
), 5.42 (1H, d, J= 2.5 Hz, H-4
0
),
5.32 (1H, dd, J= 9.9, 2.5 Hz, H-3
0
), 5.25, 5.20 (2 1H, 2d,
J= 12.9 Hz in each, CH
2
a, CH
2
b), 4.20 (1H, q, J= 6.2 Hz, H-5
0
), 2.26,
2.09, 2.02, 1.89 (4 3H, 4s, OCOCH
3
), 1.28 (3H, d, J= 6.2 Hz, CH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.4, 170.1, 169.5, 168.8 (OCOCH
3
),
143.0 ( iazole C-4), 122.0 ( iazole C-5), 85.9 (C-1
0
), 72.3, 70.8,
69.6, 67.8 (C-2
0
–C-5
0
), 57.1 (CH
2
), 20.5, 20.3, 20.2, 19.9 (OCOCH
3
),
15.7 (CH
3
). Anal. Calcd o C
17
H
23
N
3
O
9
(413.38): C, 49.39; H, 5.61;
500
N, 10.17. Found: C, 49.32; H, 5.75; N, 10.11.
4.2.26. 4-Phenyl-1-(2
0
,3
0
,4
0
- i-O-ace yl-b-
L
- ucopy anosyl)-
1,2,3- iazole (20d)
F om 13 (0.1 g, 0.32 mmol), phenylace ylene (35
l
L,
0.32 mmol) and C
3
H
7
COOCu(PPh
3
)
2
(10.7 mg, 16
l
mol) acco ding
o Sec ion 4.2. Pu iﬁed by column ch oma og aphy (2:3 E OAc–
hexane) o yield 0.13 g (97%) o whi e solid. Mp: 237–239 °C;
[
a
]
D
+67 (c0.51, CHCl
3
);
1
H NMR (CDCl
3
): d(ppm) 8.08 (1H, s, i-
azole CH), 7.87–7.29 (5H, m, a oma ics), 5.89 (1H, d, J= 9.2 Hz, H-
1
0
), 5.62 (1H, pseudo , J= 9.9, 9.9 Hz, H-2
0
), 5.42 (1H, d, J= 2.5 Hz,
510
H-4
0
), 5.29 (1H, dd, J= 9.9, 2.5 Hz, H-3
0
), 4.16 (1H, q, J= 6.2 Hz, H-
5
0
), 2.26, 2.02, 1.89 (3 3H, 3s, OCOCH
3
), 1.28 (3H, d, J= 6.2 Hz,
CH
3
);
13
C NMR (CDCl
3
): d(ppm) 170.2, 169.7, 169.1 (OCOCH
3
),
148.1 ( iazole C-4), 130.0, 128.7 (2), 128.3, 125.8 (2) (a oma ics),
117.7 ( iazole C-5), 86.2 (C-1
0
), 72.6, 71.1, 69.8, 67.8 (C-2
0
–C-5
0
),
20.6, 20.4, 20.2 (OCOCH
3
), 15.9 (CH
3
). Anal. Calcd o C
20
H
23
N
3
O
7
(417.41): C, 57.55; H, 5.55; N, 10.07. Found: C, 57.64; H, 5.69; N,
9.98.
Acknowledgemen s
This wo k was suppo ed by he Hunga ian Scien iﬁc Resea ch
520
Fund (OTKA CK 77712 and CK 80763) and by he TÁMOP 4.2.1/B-
09/1/KONV-2010–0007 P ojec co-ﬁnanced by he Eu opean Union
and he Eu opean Social Fund.
Re e ences
1. Meldal, M.; To noe, C. W. Chem. Re . 2008,108, 2952–3015.
2. Agala e, S. G.; Maujan, S. R.; Po e, V. S. Chem. Asian J. 2011,6, 2696–2718.
3. Dedola, S.; Nepogodie , S. A.; Field, R. A. O g. Biomol. Chem. 2007,5, 1006–1017.
4. Dondoni, A. Chem. Asian J. 2007,2, 700–708.
5. San oyo Gonzalez, F.; He nandez-Ma eo, F. Top. He e ocycl. Chem. 2007,7, 133–
177.
5306. A agao-Leone i, V.; Campo, V. L.; Gomes, A. S.; Field, R. A.; Ca alho, I.
Te ahed on 2010,66, 9475–9492.
7. Akula, R. A.; Temelko , D. P.; A is, N. D.; No is, P. He e ocycles 2004,63, 2719–
2725.
8. Wilkinson, B. L.; Bo naghi, L. F.; Poulsen, S.-A.; Hous on, T. A. Te ahed on 2006,
62, 8115–8125.
9. Kube an, B.; E hi ajan, M.; Vic o , X. V.; T an, V.; Nguyen, K.; Do, A.
Chembiochem 2008,9, 198–200.
10. Ca alho, I.; And ade, P.; Campo, V. L.; Guedes, P. M. M.; Ses i-Cos a, R.; Sil a, J.
S.; Schenkman, S.; Dedola, S.; Hill, L.; Rejzek, M.; Nepogodie , S. A.; Field, R. A.
540Bioo g. Med. Chem. 2010,18, 2412–2427.
11. Dedola, S.; Hughes, D. L.; Nepogodie , S. A.; Rejzek, M.; Field, R. A. Ca bohyd .
Res. 2010,345, 1123–1134.
12. Li, T. H.; Guo, L. N.; Zhang, Y.; Wang, J. J.; Li, Z. H.; Lin, L.; Zhang, Z. X.; Li, L.; Lin,
J. P.; Zhao, W.; Li, J.; Wang, P. G. Ca bohyd . Res. 2011,346, 1083–1092.
13. Paul, K. J. V.; Logana han, D. Te ahed on Le . 2008,49, 6356–6359.
14. Kuijpe s, B. H. M.; G oo huys, S.; Kee ewee , A. B. R.; Quaedﬂieg, P. J. L. M.;
Blaauw, R. H.; Del , F. L. .; Ru jes, F. P. J. T. O g. Le . 2004,6, 3123–3126.
15. dos Anjos, J. V.; Sinou, D.; de Melo, S. J.; S i as a a, R. M. Syn hesis 2007, 2647–
2652.
55016. Chi aboina, S.; Xie, F.; Wang, Q. Te ahed on Le . 2005,46, 2331–2336.
17. E mola ’e , D.; Dehaen, W.; Van de Eycken, E. QSAR Comb. Sci. 2004,23, 915–
918.
18. Ba on, A.; Ble io , Y.; Sollogoub, M.; Vauzeilles, B. O g. Biomol. Chem. 2008,6,
1898–1901.
19. Rossi, L. L.; Basu, A. Bioo g. Med. Chem. Le . 2005,15, 3596–3599.
6É. Boko e al./Ca bohyd a e Resea ch xxx (2012) xxx–xxx
CAR 6051 No. o Pages 8, Model 5G
25 Janua y 2012
Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004
20. G oo huys, S.; Kuijpe s, B. H. M.; Quaedﬂieg, P. J. L. M.; Roelen, H. C. P. F.;
Wie z, R. W.; Blaauw, R. H.; Del , F. L. .; Ru jes, F. P. J. T. Syn hesis 2006,
3146–3152.
21. Pie zik, N.; Schips, C.; Ziegle , T. Syn hesis 2008, 519–526.
560 22. Nepogodie , S. A.; Dedola, S.; Ma muse, L.; Oli ei a, M. T. d.; Field, R. A.
Ca bohyd . Res. 2007,342, 529–540.
23. Lal, S.; Diez-Gonzalez, S. J. O g. Chem. 2011,76, 2367–2373.
24. Boko , É.; Docsa, T.; Ge gely, P.; Somsák, L. Bioo g. Med. Chem. 2010,18, 1171–
1180.
25. Ch ysina, E. D.; Boko , É.; Alexacou, K.-M.; Cha a gi, M.-D.; Oikonomakos, G.
N.; Zog aphos, S. E.; Leonidas, D. D.; Oikonomakos, N. G.; Somsák, L.
Te ahed on: Asymme y 2009,20, 733–740.
26. Ho ne, W. S.; Yada , M. K.; S ou , C. D.; Ghadi i, M. R. J. Am. Chem. Soc. 2004,
126, 15366–15367.
57027. Appendino, G.; Bacchiega, S.; Minassi, A.; Cascio, M. G.; De Pe ocellis, L.; Di
Ma zo, V. Angew. Chem., In . Ed. 2007,46, 9312–9315.
28. Angell, Y. L.; Bu gess, K. Chem. Soc. Re . 2007,36, 1674–1689.
29. Gonda, Z.; No ák, Z. Dal on T ans. 2010,39, 726–729.
30. Gangjee, A.; Yu, J. M.; Kisliuk, R. L. J. He e ocycl. Chem. 2002,39, 833–840.
31. Szilágyi, L.; Gyö gydeák, Z. Ca bohyd . Res. 1985,143, 21–41.
32. Czi ák, K.; Ko ács, L.; Kö é , K. E.; Somsák, L. Ca bohyd . Res. 2005,340, 2328–
2334.
33. Paulsen, H.; Gyö gydeák, Z.; F iedmann, M. Chem. Be . 1974,107, 1568–1578.
34. Gyö gydeák, Z.; Thiem, J. Ad . Ca bohyd . Chem. Biochem. 2006,60, 103–
580182.
35. Gyö gydeák, Z.; Szilágyi, L. Liebigs Ann. 1987, 235–241.
É. Boko e al./Ca bohyd a e Resea ch xxx (2012) xxx–xxx 7
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Please ci e his a icle in p ess as: Boko ,É.; e al. Ca bohyd . Res. (2012), doi:10.1016/j.ca es.2012.01.004