Anomeric Spirocycles by Solvent Incorporation: Reactions of O-Peracylated (Glyculopyranose and Glyculopyranosyl Bromide)onamide Derivatives with Ketones
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G aphical abs ac
pp xxx–xxxAnome ic spi ocycles by sol en inco po a ion: eac ions o O-pe acyla ed (glyculopy anose and glyculopy anosyl
b omide)onamide de i a i es wi h ke ones
And ás Páhi, Ka alin Czi ák, Ka alin E. Kö é , László Somsák
*
O
B
CONH
2
(AcylO)
n
O
OH
CONH
2
(AcylO)
n
O
(AcylO)
n
O
OO
(AcylO)
n
OO
R
1
R
2
R
1
R
2
HN
NH
O
(AcylO)
n
ONH
R
1
R
2
O
R
1
R
2
O
(as sol en )
Ag(I) sal
R
1
R
2
O
(5 equi o
as sol en )
H
+
+
majo mino
con igu a ions:
D
-gluco,
D
-galac o
CAR 6720 No. o Pages 1, Model 5G
13 Ap il 2014
Highligh s
Ke one inco po a ion eac ions. P epa a ion o glycopy anosylidene-spi o-(4-imino-1,3-dioxolanes). P epa a ion o glycopy anosylidene-
spi o-(oxazolidin-4-ones).
1
Anome ic spi ocycles by sol en inco po a ion: eac ions
o O-pe acyla ed (glyculopy anose and glyculopy anosyl b omide)
onamide de i a i es wi h ke ones
And ás Páhi
a
,Ka alin Czi ák
a
,Ka alin E. Kö é
b
,László Somsák
a,
⇑
a
Depa men o O ganic Chemis y, Uni e si y o Deb ecen, POB 20, H-4010 Deb ecen, Hunga y
10
b
Depa men o Ino ganic and Analy ical Chemis y, Uni e si y o Deb ecen, POB 21, H-4010 Deb ecen, Hunga y
a icle in o
A icle his o y:
Recei ed 13 Ma ch 2014
Recei ed in e ised o m 31 Ma ch 2014
Accep ed 1 Ap il 2014
20 A ailable online xxxx
Keywo ds:
Sol en inco po a ion
Spi o compounds
Anome ic spi ocycles
4-Imino-1,3-dioxolanes
Oxazolidin-4-ones
abs ac
Reac ions o O-pe ace yla ed (
a
-D-galac o-hep ulopy anosyl b omide)onamide and O-pe benzoyla ed
(
a
-D-gluco-hep ulopy anosyl b omide)onamide wi h ke ones in he p esence o sil e (I) sal p omo e s
ga e he co esponding O-pe acyla ed 1
0
,5
0
-anhyd o-D-glyci ol-spi o-[1
0
,5]-4-imino-2,2-disubs i u ed-
1,3-dioxolanes. The D-galac o configu ed s a ing compounds u nished bo h spi o epime s, while
he D-gluco coun e pa s yielded only configu a ionally in e ed p oduc s. Unde acidic condi ions,
O-pe benzoyla ed
a
-D-gluco-hep ulopy anosonamide and ke ones yielded he p o ec ed 1
0
,5
0
-anhyd o-
D-gluci ol-spi o-[1
0
,5]-2,2-disubs i u ed-oxazolidin-4-ones, which we e O-debenzoyla ed by he Zemplén
p o ocol. These compounds had no inhibi ion agains abbi muscle glycogen phospho lyase b.
Ó2014 Published by Else ie L d.
1. In oduc ion
Spi ocyclic mo i s a e widesp ead among na u al p oduc s and
syn he ic compounds, and o en exhibi in e es ing and use ul bio-
logical ac i i ies.
1–3
Spi ocycles in ol ing he anome ic ca bon o
monosaccha ide de i a i es a e also well known, and ha e been,
among o he s, shown o possess an ipa asi ic,
4
an ibac e ial, an i-
ungal,
5
an idiabe ic,
6
he bicide,
7
glycosidase
8–10
and glycogen
phospho ylase
11
inhibi o y ac i i ies.
Syn he ic s a egies o ob ain spi ocycles we e amply
50
e iewed,
1–3
and ing closu e o geminally disubs i u ed cyclic
compounds we e highligh ed as one o se e al gene ally applied
app oaches owa ds a ious spi o de i a i es. Following his
p inciple o he p epa a ion o anome ic spi ocycles he neces-
sa y s a ing compounds can be selec ed om monosaccha ides
homo- o he e obi unc ionalized a he anome ic cen e.
1
The la -
e ype p ecu so s a e ep esen ed among o he s by de i a i es o
ulose ype suga s u ilized, o example, o he syn heses o many
so s o spi onucleosides.
12
In his line we epo ed he ans o ma-
ions o (glyculopy anosyl b omide)onic acid de i a i es
13
60 o glycopy anosylidene-spi o-( hio)hydan oins,
14,15
- hiazolidinon-
es,
16
and -oxazolines,
17
as well as ha o (glyculopy anosyl
hiocyana e)ononi iles o glycopy anosylidene-spi o- hiazolines.
18
Some yea s ago we obse ed ha on gene a ion o he co e-
sponding glycosylium ion om (glyculopy anosyl b omide)ona-
mides (e.g., 1)by Ag
2
CO
3
in ace one spi o-imino-dioxolanes 2a
and 3a (Table 1) we e o med by inco po a ion o he sol en .
19
This eac ion can be ega ded as a di ec O-glycosyla ion o a
ke one which is a e y a e ans o ma ion: o ma ion o ace al gly-
cosides in he p esence o ke ones was desc ibed om O-pe ace y-
70
la ed N-(2,4-dini ophenyl)-
a
-
D
-glucosaminyl b omide (bu no
om ace ob omoglucose),
20
TMS-glycosides
21,22
and O-pe benzy-
la ed 1- hioglycosides.
23
Fo mal glycosyla ion o ke ones by a spe-
cial in amolecula aglycon deli e y was ecen ly epo ed.
24
In his pape ull expe imen al de ails a e epo ed o he
ex ension o he abo e ke one inco po a ion in eac ions o (glycu-
lopy anosyl b omide)onamides. Fu he mo e, s udies on he eac-
ions o (glyculopy anose)onamides and ke ones as well as
de ailed s uc u al elucida ion o he compounds a e also
desc ibed.
80
2. Resul s and discussion
Following he fi s obse a ion
19
on inco po a ion o ace one
in o he p oduc s in he eac ion o 1(Table 1,en y 1) in he p es-
ence o Ag
2
CO
3
, he applicabili y o o he ke ones and p omo e s
h p://dx.doi.o g/10.1016/j.ca es.2014.04.003
0008-6215/Ó2014 Published by Else ie L d.
⇑
Co esponding au ho . Tel.: +36 52512900x22348; ax: +36 52512744.
E-mail add ess: [email p o ec ed] (L. Somsák).
1
S ic ly speaking hese compounds migh no mo e ha e a ‘ eal’ anome ic, ha is,
an ace al ype ca bon in many cases, howe e , o he sake o simplici y his e m will
be used he e.
Q1
Ca bohyd a e Resea ch xxx (2014) xxx–xxx
Con en s lis s a ailable a ScienceDi ec
Ca bohyd a e Resea ch
jou nal homepage: www.else ie .com/loca e/ca es
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we e in es iga ed. Wi h bu anone bo h Ag
2
CO
3
and AgOT ga e
simila esul s (en ies 2 and 3) expec edly u nishing he spi o-
dioxolanes 2b and 3b as insepa able dias e eome ic mix u es.
Symme ical ke ones (en ies 4–6) also ga e he spi o-epime s
2c–e as he main p oduc s whe eby 3c–e could be isola ed in much
lowe yields. F om each eac ion mix u e he hyd oly ic p oduc 4
90
could be isola ed in 25–38% yields.
Simila eac ions o he
D
-gluco configu ed 5a e collec ed in
Table 2. Compa isons o en ies 1, 3and 5 wi h en ies 2, 4and
6, espec i ely, show ha he use o AgOT is supe io o ha o
Ag
2
CO
3
in e ms o eac ion imes, al hough he highe e ficiency
o he o me is no always eflec ed in he yields. In hese eac-
ions o 5only spi o-epime 6was obse ed in he eac ion mix-
u es (besides he hyd olyis p oduc 7).
A emp s o educe he amoun o he ke ones o 5–10 equi in
ni ome hane as he sol en p o ed unsucces ul, and he only
100
p oduc s o be obse ed we e 4and 7. T ials o use aldehydes as
he ca bonyl eagen s esul ed in mul icomponen mix u es om
which no disc e e p oduc s could be isola ed.
Reac ions o (
D
-gluco-hep -2-ulopy anose)onamide 7wi h ke-
ones we e in es iga ed nex (Table 3). As in simila cycliza ions
o non-ca bohyd a e
a
-hyd oxy-ca boxamides p- oluenesul onic
acid (pTSA) was equen ly applied o p omo e he ans o ma-
ion
25
his acid was ied fi s . Howe e , no eac ion o 7could
be obse ed wi h ace one as he sol en in he p esence o ei he
ca aly ic o s oichiome ic amoun s o pTSA. On he o he hand,
110
ca aly ic iflic acid (T OH) elici ed he eac ion (en y 1), and ais-
ing i s amoun o one equi alen significan ly inc eased he yield o
8a (en y 2). Unde he same condi ions bu anone ga e an insepa-
able dias e eome ic mix u e o 8b (en y 3). The amoun o he ke-
one could be diminished o 5 equi , and bo h THF and oluene
p o ed sui able sol en s o p epa e 8c– in good yields (en ies
4–7). In hese eac ions o ma ion o one compound was obse ed
in each case (dis ega ding dias e ome s 8b). Reac ions wi h alde-
hydes ga e only decomposi ion p oduc s.
Spi o-oxazolidinones 8we e O-debenzoyla ed by he Zempén
120
p o ocol o gi e compounds 9in e y good yields. These de i a-
i es we e es ed as possible inhibi o s o abbi muscle glycogen
phospho ylase b, howe e , showed no inhibi ion up o 625
l
M
concen a ion.
S uc u al elucida ion o he p oduc s ( ollowing he mass spec-
ome ic de e mina ion o he molecula masses) was ca ied ou
by NMR me hods as illus a ed o he compounds depic ed in
Figu e 1(see also Table 4 o selec ed NMR da a o he compounds).
P o on spec a showed spli ed esonances o a py anoid ing in
he
4
C
1
con o ma ion as well as he expec ed signals o he ali-
130
pha ic pa s and he p esence o an exchangable p o on assigned
as an NH o each compound (see de ails in Sec ion 3). The ca bon
spec a con ained (besides he expec ed esonances o he suga
ing, he acyl p o ec ing g oups and he alipha ic moie ies) signals
o h ee ca bons wi h no a ached hyd ogens. Those in he ange
o 99.9–100.7 ppm we e assigned as he C-[1
0
,5] spi o cen es.
Resonances o 112.5–122.2 and 158.2–160.9 ppm (clea ly dis inc
om he C@O esonances o he p o ec i e g oups) we e indica i e
o ace al and imida e ype ca bons, espec i ely, in compounds 2,3
and 6. On he con a y, he spec a o compounds 8exhibi ed
Table 1
Reac ion o O-pe ace yla ed (
a
-D-galac o-hep ulopy anosyl b omide)onamide (1) wi h ke ones
O
AcO
AcO
AcO OAc
B
CO
1234
NH2
O
AcO
AcO
AcO OAc
O
OO
AcO
AcO
AcO OAc
OO
O
AcO
AcO
AcO OAc
OH
CONH2
HN
NH
R1
R2
R1R2
R1R2
O
as sol en
p omo e ++
(1 equi .)
in he da k, unde A
En y R
1
R
2
P omo e R. ime (d) Yield (%)
1a
a
Me Me Ag
2
CO
3
17145
2bMe E Ag
2
CO
3
649
bc c
3 AgOT 6 43
b
19
⁄
38
4cE E AgOT 3 32 14 27
5d–(CH
2
)
4
– AgOT 6 48 T aces 26
6e–(CH
2
)
5
– AgOT 2 44 8 25
a
F om Re . 19.
b
Two dias e eome s.
c
Obse ed bu no isola ed.
Table 2
Reac ion o O-pe benzoyla ed (
a
-D-gluco-hep ulopy anosyl b omide)onamide (5) wi h ke ones
O
BzO
BzO
BzO
OBz
B
CONH
2
R
1
R
2
O
as sol en
1 equi . p omo e
in he da k, unde A
O
BzO
BzO
BzO
OBz
O
O
HN
R
1
R
2
O
BzO
BzO
BzO
OBz
OH
CONH
2
+
567
En y R
1
R
2
P omo e R. ime (d) Yield (%)
1aMe Me Ag
2
CO
3
11 17 41
2 AgOT 1 37 46
3cE E Ag
2
CO
3
20 5 34
4 AgOT 1 46 35
5d–(CH
2
)
4
–Ag
2
CO
3
13 56 18
6e–(CH
2
)
5
– AgOT 1 28 35
Q5
Q2
Q3
2A. Páhi e al. / Ca bohyd a e Resea ch xxx (2014) xxx–xxx
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140
an addi ional signal in he ange o he benzoyl ca bonyls (162.4–
166.6 ppm) and om hese ha o he highes chemical shi was
( en a i ely) assigned o amide C-4. A esonance in he ange o
92.4–100.1 ppm could be a ibu ed o an aminal ype ca bon
and his co obo a ed ha he ni ogen was in an endocyclic posi-
ion in 8. To confi m he di e ence in he cons i u ion o he he -
e ocyclic pa s o he spi ocycles, CMPG-HSQMBC expe imen s
26–
28
we e ca ied ou wi h 6a and 8e. In hese spec a c oss peaks
(indica ed by as e isks in he o mulae o he espec i e com-
pounds in Fig. 1) be ween NH and C-4 and C-5, bu no wi h C-2,
150
we e obse ed o 6a o u he p o e he imino-dioxolane s uc-
u e. On he o he hand, c oss peaks be ween NH and C-2, C-4
and C-5, as well as wi h ca bons o he alipha ic subs i uen we e
p esen o 8e o e i y he oxazolidinone ing. Fo 8e his mea-
su emen also co obo a ed he chemical shi assignmen o
amide C-4. The configu a ion o he spi o ca bons C-[1
0
,5] was
es ablished as R o 2and 6, and S o 3and 8based on he h ee
bond he e onuclea coupling cons an s be ween H-2 and C-4
shown in Figu e 1indica ing he ans diaxial e sus gauche ela-
ionships be ween he espec i e nuclei in he
4
C
1
con o ma ion
160
o he suga ing. Al hough hese couplings could no be measu ed
o each compound due o insu ficien sample quan i ies, no doub
was le abou he spi o configu a ion o he o he membe s o he
se ies. Namely, he p o on esonances had cha ac e is ic shi s
depending on he C-[1
0
,5] configu a ion (c . Fig. 1 and Table 4):
H-2
0
had a downfield shi o 0.1–0.2 ppm i he C@NH/C@O
was on he same side o he py anoid ing; simila ly, downfield
shi s we e obse ed o H-3
0
(0.7 ppm) and H-5
0
(0.4 ppm)
when hey we e in he same si ua ion. Analogous
1
H chemical shi
pa e ns we e obse ed ea lie o o he glycopy anosylidene-
170
spi o-he e ocycles.
14,15
Fo ma ion o spi ocycles 2,3and 6can be unde s ood by
ollowing he mechanis ic p oposal in Scheme 1. The sil e sal
p omo e acili a es he gene a ion o he co esponding glycosyli-
umion B1 om 1o 5. Nucleophilic a ack o a ke one wi h anchi-
me ic assis ance o he 2-O-acyl g oup (D1) may lead o
ca boca ion A1 while wi hou neighbou ing g oup pa icipa ion
he epime ic ca ion, ep esen ed by esonance o ms E1 and F1,
can be o med. In amolecula a ack o he amide oxygen (illus-
a ed in de ails o F1 only), he ha de pa o his unc ional g oup,
H-5'
O
O
O
AcO
AcO
OAc
HN
E
E
H-3'
H-2'
AcO
H-5'
O
O
O
AcO
AcO
OAc
H-3'
H-2'
AcO NH
E
E
3JH-2',C-4 ~6.1Hz 3JH-2',C-4 ~2.1Hz
160.4
160.8
116.8
99.9 100.8
116.2
5.99 4.85
5.60
5.30 4.42
5.74
H-5'
O
O
O
BzO
BzO
OBz
HN
Me
Me
H-3'
H-2'
BzO
3JH-2',C-4 ~5.4Hz
160.5
112.8
100.3
6.80 5.13
5.85
H-5'
O
O
NH
BzO
BzO
OBz
H-3'
H-2'
BzO O
3JH-2',C-4 ~2.5Hz
166.4
6.10 4.69
6.00
**
**
*
*
*
**
*
C oss peaks wi h NH in he spec a om CPMG-HSQMBC expe imen s.
100.1
93.5
37.6
(39.0)
39.0
(37.6)
2c 3c
6a 8e
2
4
4
2
2
4
4
2
1'
55
1'
1'
5
1'
5
Figu e 1. Rep esen a i e NMR da a o he s uc u al elucida ion o he new compounds.
Table 3
Reac ion o 3,4,5,7- e a-O-benzoyl-
a
-D-gluco-hep ulopy anosonamide (5) wi h ke ones
O
BzO
BzO
BzO
OBz
OH
CONH
2
R
1
R
2
O
O
BzO
BzO
BzO
OBz
ONH
/T OH
sol en , e lux
o e nigh
O
R
2
R
1
O
HO
HO
HO
OH
ONH
O
R
2
R
1
NaOMe
MeOH,
78
9
En y R
1
R
2
Ke one (equi .) Sol en Acid (equi .) Yield (%)
1aMe Me As sol en — 0.1 58 94
2 As sol en — 1.0 89
3bMe E As sol en — 1.0 92
a
96
4cE E 5 THF 1.0 69 91
5d–(CH
2
)
4
– 5 THF 1.0 86 91
6e–(CH
2
)
5
– 5 Toluene 1.0 69 96
7 –(CH
2
)
6
– 5 Toluene 1.0 71 77
a
Two dias e eome s.
A. Páhi e al. / Ca bohyd a e Resea ch xxx (2014) xxx–xxx 3
CAR 6720 No. o Pages 11, Model 5G
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180
may gi e he cyclized iminium ion C1. Dep o ona ion o his in e -
media e and ha o he analogous one (no shown) de i ed om
A1 gi e hen he isola ed p oduc s o e ained (3) and in e ed con-
figu a ion (2), espec i ely. Fo ma ion o he by-p oduc s 4and 7
a e o be explained by he wa e con en o he sol en s a acking
on glycosyliumion B1. The finding ha om he
D
-gluco configu ed
5only he o ma ion o 6was obse ed,
2
while 1o he D-galac o con-
figu a ion ga e bo h epime s 2and 3, may be indica i e o a emo e
pa icipa ion
29
o he axial 4-O-ace yl g oup o 1 acili a ing he o -
ma ion o 3.
190
A mechanis ic p oposal o he o ma ion o spi ocycles 8
(Scheme 2) can be mo e complex since, due o he p esence o se -
e al unc ional g oups whose p o ona ion may s a he eac ion,
al e na i e pa hways may occu simul aneously. The fi s (mos
emp ing) possibili y is he p o ona ion o he glycosidic OH in 7
ollowed by loss o wa e o gi e glycosyliumion C2 which is he
same in e media e as B1 in Scheme 1. A ack o a ke one on C2
would gi e A2 (equal o in e media e F1 in Scheme 1), howe e ,
he o ma ion o he epime ic in e media e A1 (shown in Scheme 1)
mus also be aken in o accoun . This possibili y ende s his pa h-
200
way less p obable since only he configu a ionally e ained epime
8was obse ed in he eac ions. Fo ma ion o A2 (wi hou epime -
iza ion) should also be possible ia p o ona ion and subsequen
dehyd a ion o a mixed hemike al E2 which can de elop om 7
by nucleophilic addi ion o he glycosidic OH o he ke one o i s
p o ona ed o m D2. Ring closu e o A2 (=F1) occu ed by he
nucleophilic a ack o he amide oxygen unde condi ions o
Scheme 1 (c . F1?C1) o gi e he imino-dioxolanes 3, howe e ,
hese compounds we e no p esen in he eac ions o 7(Scheme
2). Conside ing he di e en eac ion condi ions his may aise
210
wo possibili ies: (i) imino-dioxolanes may be o med as p ima y
Table 4
Selec ed NMR da a o he O-pe acyla ed compounds
a
2,3,6and 8(d[ppm], J[Hz])
O
AcO
AcO
AcO OAc
O
O
HN
R
1
R
2
1'
2'
3'
4' 5'
2
4
5
2a
b
2b 2c 2d 2e
H-2
0
5.58 5.54/5.59 5.60 5.57 5.57
H-3
0
6.00 6.05/5.89 5.99 5.98 6.01
H-5
0
4.88 4.75/4.85 4.85 4.84 4.85
C-[1
0
,5] 100.4 100.2/100.3 99.9 100.1 100.1
C-2 112.6 114.7/114.1 116.8 116.2 113.2
C-4 160.9 160.4/160.2 160.4 158.8 158.2
3
J
H-2
0
,C-4
5.6 4.1 6.1 6.1 5.3
O
AcO
AcO
AcO OAc
OO
NH
R1R2
1'
2'
3'
4' 5'
2
4
5
3a
b
3b 3c 3e
H-2
0
5.74 5.74/5.69 5.74 5.75
H-3
0
5.25 5.35/5.20 5.30 5.26
H-5
0
4.41 4.43/4.39 4.42 4.41
C-[1
0
,5] 100.3 100.9/100.9 100.8 100.8
C-2 112.5 114.8/113.8 116.2 113.1
C-4 161.2 160.2/160.2 160.8 160.3
3
J
H-2
0
,C-4
n.m.
c
n.m.
c
2.1 n.m.
c
O
BzO
BzO
BzO
OBz
O
O
HN
R
1
R
2
1'
2'
3'
4' 5'
2
4
5
6a 6c 6d 6e
H-2
0
5.85 5.92 5.87 5.87
H-3
0
6.80 6.82 6.82 6.82
H-5
0
5.13 5.13 5.12 5.14
C-[1
0
,5] 100.3 99.9 99.9 99.8
C-2 112.8 116.6 122.2 113.5
C-4 160.5 160.6 160.3 160.4
3
J
H-2
0
,C-4
5.4 4.9 4.9 5.0
O
BzO
BzO
BzO
OBz
ONH
O
R2
R1
1'
2'
3'
4' 5'
2
5
4
8a 8b 8c 8d 8e 8
H-2
0
5.96 5.99/5.97 6.00 5.97 6.00 5.98
H-3
0
6.09 6.10/6.09 6.10 6.08 6.10 6.08
H-5
0
4.66 4.63/4.63 4.64 4.63 4.69 4.66
H-4
0
5.73 5.72/5.71 5.70 5.73 5.71 5.70
C-[1
0
,5] 100.5 100.3/100.35 100.2 100.7 100.1 100.1
C-2 92.4 94.9, 94.5 97.1 100.1 93.5 97.2
C-4 166.0 166.4/166.1 166.6 166.1 166.4 166.1
3
J
H-2
0
,C-4
n.m.
c
n.m
c
n.m
c
n.m.
c
2.5 n.m.
c
a
Fo subs i uen s R
1
and R
2
see he espec i e ables (Table 1 o 2and 3,Table 2 o 6, and Table 3 o 8).
b
Da a aken om Re . 19.
c
No measu ed because o insu ficien sample quan i y.
2
I is o be no ed ha om he ace yla ed coun e pa o 5 o ma ion o a e y
mino amoun (6%) o he in e ed p oduc was epo ed.
19
4A. Páhi e al. / Ca bohyd a e Resea ch xxx (2014) xxx–xxx
CAR 6720 No. o Pages 11, Model 5G
15 Ap il 2014
Please ci e his a icle in p ess as: Páhi, A.; e al. Ca bohyd . Res. (2014), h p://dx.doi.o g/10.1016/j.ca es.2014.04.003
p oduc s which hen gi e oxazolidinones 8in a p o on ca alysed
equilib a ion; (ii) ing closu e akes place by a N-nucleophilic a -
ack o he hyd oximide au ome o he amide moie y. The fi s
possibili y was uled ou by an expe imen in which an imino-
dioxolane 6was subjec ed o he condi ions o he o ma ion o
8. Thus, 6a was boiled in ace one in he p esence o T OH (1 equi )
o 24 h, howe e , no change could be de ec ed by TLC. The second
possibili y can be easonable since au ome iza ion o amides un-
de acidic condi ions (c . 7?F2?I2) is a known phenomenon.
30
220
Thus, A2 may ing-close o p o ona ed hyd oxy-oxazoline B2
which, a e dep o ona ion and au ome iza ion can gi e he
isola ed 8.
OCONH2
B
RCO
O
O
CONH2
RCO
O
OCONH2
RCO
O
O
CONH2
O
O
R
O
CONH2
RCO
O
O
RCO
O
NH2
O
C1
B1A1
D1 E1 F1
Ag -AgB
R1R2
O
O
R1R2
O
R1R2
O
RCOOO
NH
R1R2
O
O
RCOOO
NH2
R1R2
O
-H
R2
R1
O
R2
R1
O
O
ROCO
O
O
HN
R1
R2
R1R2
O
R1R2
O
Ag / Ag /
1o 5
2o 63
OCONH2
OH
RCO
O
4o 7
H2O
Ag
H2O
Scheme 1. P oposed mechanism o he o ma ion o 1
0
,5
0
-anhyd o-
D
-glyci ol-spi o-[1
0
,5]-4-imino-1,3-dioxolanes 2,3, and 6.
O
CONH2
RCO
O
C2 (= B1 in
Scheme 1)
OCONH2
OH
RCO
O
H
O
RCOONH
O
R1R2
O
R1R2
OH
O
OH
RCO
O
OH
NH2
O
OH
RCO
O
OH
NH
R1R2
O
O
OH
RCO
O
OH
N
H-H2O
HO R2
R1
-H
O
RCOO
HO N
OH
R1R2
-H au ome-
isa ion
78
F2 H2
I2 J2
O
RCO
O
OH
N
HO R2
R1
G2
O
OH
RCO
O
OH
N
R2
R1
K2
H
-H2O
+
H
-H2O
OCONH2
O
RCO
O
R1R2
OH
OH
R1R2
-H
R1R2
O
H
-H2O
O
RCO
O
OH
NH
A2 (= F1 in
Scheme 1,
c A1 also)
O
R1R2
O
RCOONH
OH
R1R2
O
-H
au ome-
isa ion
B2
E2
D2
Scheme 2. Possible mechanis ic pa hways o he o ma ion o 1
0
,5
0
-anhyd o-
D
-gluci ol-spi o-[1
0
,5]-oxazolidin-4-ones 8.
A. Páhi e al. / Ca bohyd a e Resea ch xxx (2014) xxx–xxx 5
CAR 6720 No. o Pages 11, Model 5G
15 Ap il 2014
Please ci e his a icle in p ess as: Páhi, A.; e al. Ca bohyd . Res. (2014), h p://dx.doi.o g/10.1016/j.ca es.2014.04.003
Since
a
-hyd oxy-ca boxamides and ca bonyl compounds a e
known o u nish oxazoles unde acidic condi ions, he gene ally ac-
cep ed mechanism o he Fische oxazole syn hesis
25
should also be
conside ed in he p esen ans o ma ion. P o ona ion o he amide
oxygen o 7as shown in F2 may esul in a au ome iza ion
30
o gi e
a leas a mino p opo ion o I2 which can a ack he ke one (o i s
p o ona ed o mD2) as a N-nucleophile o gi ein e media e J2.P o-
230
ona iono ahyd oxylg oupinJ2 maylead oelimina iono wa e o
p oduce ei he ca boca ion G2 o K2, bo h o which can ing close o
H2 by he nucleophilic a ack o he emaining OH on he posi i ely
cha ged ca bon. Due o he p esence o h ee elec on eleasing sub-
s i uen s, ca boca ion K2 migh be mo e s able han glycosyliumion
G2, he e o e, o ma ion o H2 ia K2 migh be p e e ed. This is also
madelikely by he o ma iono a single isome o 8 ha would p ob-
ably no be he case in ou e J2?G2?H2. Final dep o ona ion and
au ome iza ion o H2 may hen yield he isolable p oduc 8.
Inconclusion, he eac ions o (glyculopy anoseandglyculopy ano-
240
syl b omide)onamides wi h ke ones ga e access o he p epa a ion o
new anome ic spi ocycles, namely, 1
0
,5
0
-anhyd o-
D
-glyci ol-
spi o-[1
0
,5]-4-imino-2,2-disubs i u ed-dioxolanes and 1
0
,5
0
-anhyd o-
D
-glyci ol-spi o-[1
0
,5]-2,2-disubs i u ed-oxazolidin-4-ones. The
s uc u es we e unambiguously assigned by NMR me hods. De ailed
mechanisms we e p oposed o explain he o ma ion o bo h cons i u-
ional isome s as well as he s e eoselec i i ies o he ing o ming
eac ions. The spi o-oxazolidinones we e es ed agains abbi muscle
glycogen phospho lyase b, howe e , had no inhibi o y e ec .
3. Expe imen al
250
3.1. Gene al me hods
Mel ing poin s we e measu ed in open capilla y ubes o on a
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 oom empe a u e.
NMR spec a we e eco ded wi h B uke 200 (200:50 MHz o
1
H/
13
C), B uke DRX 360 (360:90 MHz o
1
H/
13
C) o A ance II
500 (500:125 MHz o
1
H/
13
C) spec ome e s. Chemical shi s a e
e e enced o Me
4
Si (
1
H), o o he sol en signals o DSS in D
2
O
(
13
C). Mass spec a we e eco ded by a B uke mic OTOF-Q ins u-
men . TLC was pe o med on DC-Alu olle Kieselgel 60 F
254
(Me ck),
260
and he pla es we e isualized 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 illed om
P
4
O
10
and ace one om CaSO
4
) and s o ed o e 4Å molecula
sie es. O ganic solu ions we e d ied o e anhyd ous MgSO
4
and
concen a ed unde diminished p essu e a 40–50 °C (wa e ba h).
3.2. Gene al p ocedu e I o he p epa a ion o O-pe acyla ed
1
0
,5
0
-anhyd o-
D
-glyci ol-spi o-[1
0
,5]-4-imino-2,2-disubs i u ed-
1,3-dioxolanes 2, 3 and 6
To a solu ion o an O-pe acyla ed (glyculopy anosyl b o-
270
mide)onamide 1
31
o 5
32
(0.50 g) in a d y ke one (5 mL) con aining
molecula sie es (3 Å) Ag
2
CO
3
(1 equi ) o AgOT /E
3
N (1 equi )
was added. The mix u e was s i ed a in he da k unde A a mo-
sphe e un il TLC (1:1 o 1:2 E OAc–hexane) showed comple e ans-
o ma iono hes a ingma e ial.Then hemix u ewasfil e edona
Celi e pad and he sol en emo ed unde diminished p essu e. The
c ude p oduc was pu ified by column ch oma og aphy.
3.2.1. (1
0
R,2RS)- and (1
0
S,2RS)-2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-1
0
,5
0
-
anhyd o-
D
-galac i ol-spi o-[1
0
,5]-2-e hyl-4-imino-2-me hyl-
1,3-dioxolanes (2b and 3b)
280
P epa ed om 1(0.50 g, 1.10 mmol) and bu anone in he
p esence o AgOT acco ding o Gene al p ocedu e I (Sec ion 3.2).
Column ch oma og aphy (1:1 E OAc–hexane) ga e h ee ac ions.
F ac ion I: 0.21 g (43%) o an insepa able dias e eome ic mix u e
o 2b as a colou less oil; R
= 0.71 (1:1 E OAc–hexane).
Cha ac e iza ion o dias e eome A:
1
H NMR (CDCl
3
, 360 MHz):
d(ppm) 7.40 (s, 1H, NH), 6.05 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.2 Hz,
H-3
0
), 5.54 (d, 1H, J
2
0
,3
0
11.1 Hz, H-2
0
), 5.51 (dd, 1H, J
3
0
,4
0
3.2 Hz,
J
4
0
,5
0
1.0 Hz, H-4
0
), 4.75 (ddd, 1H, J
5
0
,6
0
a
6.8 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.0 Hz, H-5
0
), 4.20–4.02 (m, 2H, H-6
0
a, H-6
0
b), 2.15, 2.05, 1.95,
290
1.93 (4s, 12H, OCOCH
3
), 1.70 (q, 2H, J7.3 Hz, CH
2
CH
3
), 1.35 (s,
3H, CH
3
), 0.88 ( , 3H, J7.3 Hz, CH
2
CH
3
);
13
C NMR (CDCl
3
,
90 MHz): d(ppm) 170.3, 170.0, 169.6, 169.3 (CO), 160.4 (C-4,
3
J
H-
2
0
,C-4
=4.1 Hz), 114.7 (C-2), 100.2 (C-1
0
), 69.8, 68.8, 67.5, 66.9 (C-
2
0
–C-5
0
), 61.3 (C-6
0
), 33.4 (CH
2
CH
3
), 25.6 (CH
3
), 20.7, 20.5, 20.3,
20.2 (COCH
3
); 6.9 (CH
2
CH
3
).
Cha ac e iza ion o dias e eome B:
1
H NMR (CDCl
3
, 360 MHz):
d(ppm) 7.40 (s, 1H, NH), 5.89 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.2 Hz,
H-3
0
), 5.59 (1H, d, J
2
0
,3
0
11.1 Hz, H-2
0
), 5.48 (dd, 1H, J
3
0
,4
0
3.2 Hz,
J
4
0
,5
0
1.0 Hz, H-4
0
), 4.85 (ddd, 1H, J
5
0
,6
0
a
6.8 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
300
1.0 Hz, H-5
0
), 4.20–4.02 (m, 2H, H-6
0
a, H-6
0
b), 2.16, 2.04, 1.98,
1.94 (4s, 12H, OCOCH
3
), 1.85 (q, 2H, J7.3 Hz, CH
2
CH
3
), 1.55 (s,
3H, CH
3
), 0.96 ( , 3H, J7.3 Hz, CH
2
CH
3
);
13
C NMR (CDCl
3
,
90 MHz): d(ppm) 170.2, 170.0, 169.8, 169.1 (CO), 160.2 (C-4),
114.1 (C-2), 100.3 (C-1
0
), 69.9, 68.8, 67.2 (2) (C-2
0
–C-5
0
), 61.3 (C-
6
0
), 32.4 (CH
2
CH
3
), 25.6 (CH
3
), 20.8, 20.5, 20.3, 20.1 (OCOCH
3
), 6.9
(CH
2
CH
3
). Calcd o C
19
H
27
NO
11
(Mol. W .: 445.42, Ex. Mass.:
445.16); ESI-MS (posi i e mode) m/z:468.148 [M+Na]
+
, 913.305
[2M+Na]
+
.
F ac ion II: 0.10 g (19%) o an insepa able dias e eome ic mix-
310
u e o 3b as a yellowish oil; R
= 0.36 (1:1 E OAc–hexane).
Cha ac e iza ion o dias e eome C:
1
H NMR (CDCl
3
, 360 MHz):
d(ppm) 7.48 (s, 1H, NH), 5.74 (d, 1H, J
2
0
,3
0
11.1 Hz, H-2
0
), 5.51 (dd,
1H, J
3
0
,4
0
3.2 Hz, J
4
0
,5
0
1.0 Hz, H-4
0
), 5.35 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.2 Hz, H-3
0
), 4.43 (ddd, 1H, J
5
0
,6
0
a
6.8, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.0 Hz,
H-5
0
), 4.20–4.03 (m, 2H, H-6
0
a, H-6
0
b), 2.10, 2.08, 2.01, 1.98 (4s,
12H, OCOCH
3
), 1.88 (q, 2H, J7.3 Hz, CH
2
CH
3
), 1.54 (s, 3H, CH
3
),
1.00 ( , 3H, J7.3 Hz, CH
2
CH
3
);
13
C NMR (CDCl
3
, 90 MHz): d(ppm)
170.4, 170.2, 169.8, 169.1 (CO), 160.2 (C-4), 114.8 (C-2), 100.9
(C-1
0
), 69.7, 68.6, 67.7, 66.5 (C-2
0
–C-5
0
), 61.7 (C-6
0
), 32.4 (CH
2
CH
3
),
320
25.8 (CH
3
), 20.7, 20.5, 20.2, 20.1 (COCH
3
); 6.8 (CH
2
CH
3
).
Cha ac e iza ion o dias e eome D:
1
H NMR (CDCl
3
, 360 MHz):
d(ppm) 7.48 (s, 1H, NH), 5.69 (d, 1H, J
2
0
,3
0
11.1 Hz, H-2
0
), 5.49 (dd,
1H, J
3
0
,4
0
3.2 Hz, J
4
0
,5
0
1.0 Hz, H-4
0
), 5.20 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.2 Hz, H-3
0
), 4.39 (ddd, 1H, J
5
0
,6
0
a
6.8 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.0 Hz,
H-5
0
), 4.18–4.02 (m, 2H, H-6
0
a, H-6
0
b), 2.11, 2.09, 1.99, 1.97 (4s,
12H, OCOCH
3
), 1.86 (2H, q, J7.3 Hz, CH
2
CH
3
), 1.61 (s, 3H, CH
3
),
1.26 ( , 3H, J7.3 Hz, CH
2
CH
3
);
13
C NMR (CDCl
3
, 90 MHz) d(ppm):
170.4, 170.0, 169.9, 169.6 (CO), 160.2 (C-4), 113.8 (C-2), 100.9
(C-1
0
), 69.7, 67.6, 66.2 (2) (C-2
0
–C-5
0
), 60.3 (C-6
0
), 33.5 (CH
2
CH
3
),
330
24.2 (CH
3
), 20.7, 20.6, 20.2, 20.1 (COCH
3
); 7.9 (CH
2
CH
3
). Calcd o
C
19
H
27
NO
11
(Mol. W .: 445.42, Ex. Mass.: 445.16); ESI-MS (posi i e
mode) m/z:468.147 [M+Na]
+
, 913.304 [2M+Na]
+
.
F ac ion III: 0.16 g (38%) o 4
14
as a whi e solid.
3.2.2. (1
0
R)- and (1
0
S)-2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-1
0
,5
0
-anhyd o-
D
-
galac i ol-spi o-[1
0
,5]-2,2-die hyl-4-imino-1,3-dioxolanes (2c
and 3c)
P epa ed om 1(0.50 g, 1.10 mmol) and pen an-3-one wi h
AgOT acco ding o Gene al p ocedu e I (Sec ion 3.2). Column ch o-
ma og aphy (1:1 E OAc–hexane) ga e h ee ac ions.
340
F ac ion I: 0.16 g (32%) o 2c as whi e c ys als; mp: 100–102 °C;
[
a
]
D
+37 (c0.90, CHCl
3
);
1
H NMR (CDCl
3
, 360 MHz): d(ppm) 7.45
(s, 1H, NH), 5.99 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.7 Hz, H-3
0
), 5.60
(d, 1H, J
2
0
,3
0
11.1 Hz, H-2
0
), 5.50 (dd, 1H, J
3
0
,4
0
3.7 Hz, J
4
0
,5
0
1.2 Hz,
H-4
0
), 4.85 (ddd, 1H, J
5
0
,6
0
a
6.8 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.2 Hz, H-5
0
),
4.17 (dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
a
6.8 Hz, H-6
0
a), 4.09 (dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
b
6.3 Hz, H-6
0
b), 2.17, 2.06, 2.02, 1.96 (4s, 12H,
OCOCH
3
), 1.87 (q, 2H, J7.3 Hz, CH
2
CH
3
), 1.72 (q, 2H, J7.3 Hz, CH
2-
6A. Páhi e al. / Ca bohyd a e Resea ch xxx (2014) xxx–xxx
CAR 6720 No. o Pages 11, Model 5G
15 Ap il 2014
Please ci e his a icle in p ess as: Páhi, A.; e al. Ca bohyd . Res. (2014), h p://dx.doi.o g/10.1016/j.ca es.2014.04.003
CH
3
), 0.96 ( , 3H, J7.3 Hz, CH
2
CH
3
), 0.88 ( , 3H, J7.3 Hz, CH
2
CH
3
);
13
C NMR (CDCl
3
, 90 MHz): d(ppm) 170.1 (2), 169.6, 169.2 (CO),
350
160.4 (C-4,
3
J
H-2
0
,C-4
=6.1 Hz om HSQMBC a 125 MHz), 116.8
(C-2), 99.9 (C-1
0
), 69.7, 68.9, 67.3 (2) (C-2
0
–C-5
0
), 61.3 (C-6
0
), 31.2,
29.4 (CH
2
CH
3
), 20.5, 20.4 (2), 20.2 (COCH
3
); 7.8, 6.7 (CH
2
CH
3
).
F ac ion II: 0.07 g (14%) o 3c as a whi e c ys als, mp: 61–63 °C;
[
a
]
D
+59 (c1.00, CHCl
3
);
1
H NMR (CDCl
3
, 360 MHz): d(ppm) 7.42
(s, 1H, NH), 5.74 (d, 1H, J
2
0
,3
0
11.1 Hz, H-2
0
), 5.51 (dd, 1H, J
3
0
,4
0
3.2 Hz, J
4
0
,5
0
1.1 Hz, H-4
0
), 5.30 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.2 Hz,
H-3
0
), 4.42 (ddd, 1H, J
5
0
,6
0
a
6.8 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.1 Hz, H-5
0
),
4.16 (dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
a
6.8 Hz, H-6
0
a), 4.11 (dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
b
6.3 Hz, H-6
0
b), 2.19, 2.03, 2.01, 1.98 (4s, 12H,
360
OCOCH
3
), 1.88 (q, 2H, J7.3 Hz, CH
2
CH
3
), 1.84 (q, 2H, J7.3 Hz,
CH
2
CH
3
), 0.99 ( , 3H, J7.3 Hz, CH
2
CH
3
), 0.95 ( , 3H, J7.3 Hz, CH
2-
CH
3
);
13
C NMR (CDCl
3
, 90 MHz): d(ppm) 170.3 (2), 170.1, 168.6
(CO), 160.8 (C-4,
3
J
H-2
0
,C-4
=2.1 Hz om HSQMBC a 125 MHz),
116.2 (C-2), 100.8 (C-1
0
), 69.6, 69.2, 67.7, 66.1 (C-2
0
–C-5
0
), 61.8
(C-6
0
), 31.6, 29.0 (CH
2
CH
3
), 20.8, 20.5, 20.3 (2) (COCH
3
); 8.0, 6.6
(CH
2
CH
3
); Calcd o C
20
H
29
NO
11
(Mol. W .: 459.44, Ex. Mass.:
459.17); ESI-MS (posi i e mode) m/z:482.163 [M+Na]
+
, 941.337
[2M+Na]
+
.
F ac ion III: 0.12 g (27%) o 4
14
as a whi e solid.
370
3.2.3. (1
0
R)- and (1
0
S)-2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-1
0
,5
0
-anhyd o-
D
-
galac i ol-spi o-[1
0
,5]-4-imino-1,3-dioxolane-spi o-[2,1
00
]-
cyclopen anes (2d and 3d)
P epa ed om 1(0.20 g, 0.44 mmol) and cyclopen anone wi h
AgOT acco ding o Gene al p ocedu e I (Sec ion 3.2). Column ch o-
ma og aphy (1:1 E OAc–hexane) ga e h ee ac ions.
F ac ion I: 0.10 g (48%) o 2d as whi e c ys als; mp: 148–150 °C;
[
a
]
D
+28 (c0.20, CHCl
3
);
1
H NMR (CDCl
3
, 360 MHz): d(ppm) 7.40 (s,
1H, NH), 5.98 (dd, 1H, J
2
0
,3
0
11.1 Hz, J
3
0
,4
0
3.6 Hz, H-3
0
), 5.57 (d, 1H,
J
2
0
,3
0
11.1 Hz, H-2
0
), 5.50 (dd, 1H, J
3
0
,4
0
3.6 Hz, J
4
0
,5
0
1.1 Hz, H-4
0
),
380
4.85 (ddd, 1H, J
5
0
,6
0
a
6.8 Hz, J
5
0
6
0
b
6.3 Hz, J
4
0
,5
0
1.1 Hz, H-5
0
), 4.15
(dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
a
6.8 Hz, H-6
0
a) 4.09 (dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
b
6.3 Hz, H-6
0
b), 2.16, 2.05, 2.03, 1.97 (4s, 12H,
OCOCH
3
), 1.92–1.84 (m, 4H, 2CH
2
), 1.82–1.68 (m, 4H, 2CH
2
);
13
C NMR (CDCl
3
, 90 MHz): d(ppm): 170.0 (2), 169.6, 169.0 (CO),
158.8 (C-4,
3
J
H-2
0
,C-4
=6.1 Hz), 116.2 (C-2), 100.1 (C-1
0
), 69.9,
68.6, 67.3, 67.2 (C-2
0
–C-5
0
), 61.2 (C-6
0
), 38.2, 36.6, 23.6, 22.6
(4CH
2
), 20.6, 20.5 (2), 20.4 (COCH
3
); Calcd o C
20
H
27
NO
11
(Mol. W .: 457.43, Ex. Mass.: 457.16); ESI-MS (posi i e mode)
m/z:480.149 [M+Na]
+
, 937.306 [2M+Na]
+
.
390
F ac ion II: T aces o 3d insu ficien o NMR cha ac e iza ion.
Calcd o C
20
H
27
NO
11
(Mol. W .: 457.43, Ex. Mass.: 457.16); ESI-
MS (posi i e mode) m/z:480.147 [M+Na]
+
, 937.306 [2M+Na]
+
.
F ac ion III: 0.045 g (26%) o 4
14
as a whi e solid.
3.2.4. (1
0
R)- and (1
0
S)-2
0
,3
0
,4
0
,6
0
- e a-O-ace yl-1
0
,5
0
-anhyd o-
D
-
galac i ol-spi o-[1
0
,5]-4-imino-1,3-dioxolane-spi o-[2,1]-
cyclohexanes (2e and 3e)
P epa ed om 1(0.50 g, 1.10 mmol) and cyclohexane wi h
AgOT acco ding o Gene al p ocedu e I (Sec ion 3.2). Column ch o-
ma og aphy (1:1 E OAc–hexane) ga e h ee ac ions.
400
F ac ion I: 0.23 g (44%) o 2e as whi e c ys als; mp: 124–126 °C;
[
a
]
D
+14 (c0.22, CHCl
3
);
1
H NMR (CDCl
3
, 360 MHz): d(ppm) 7.40
(s, 1H, NH), 6.01 (dd, 1H, J
2
0
,3
0
10.5 Hz, J
3
0
,4
0
3.2 Hz, H-3
0
), 5.57 (d,
1H, J
2
0
,3
0
10.5 Hz, H-2
0
), 5.51 (dd, 1H, J
3
0
,4
0
3.2 Hz, J
4
0
,5
0
1.0 Hz, H-4
0
),
4.85 (ddd, 1H, J
5
0
,6
0
a
7.3 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.0 Hz, H-5
0
),
4.10–4.08 (m, 2H, H-6
0
a, H-6
0
b), 2.18, 2.08, 2.04, 1.97 (4s, 12H,
OCOCH
3
), 1.87–1.81 (m, 2H, CH
2
), 1.77–1.56 (m, 4H, 2CH
2
),
1.53–1.33 (m, 2H, CH
2
), 1.30–1.23 (m, 2H, CH
2
);
13
C NMR (CDCl
3
,
90 MHz): d(ppm) 170.8 (2), 169.2, 169.8 (CO), 158.2 (C-4,
3
J
H-2
0
,C-
4
=5.3 Hz), 113.2 (C-2), 100.1 (C-1
0
), 69.9, 68.9, 67.5 (2) (C-2
0
–C-
410
5
0
), 61.3 (C-6
0
), 37.2, 36.4, 24.4, 23.1 (2) (5CH
2
), 20.8, 20.6 (2),
20.3 (COCH
3
); Calcd o C
21
H
29
NO
11
(Mol. W .: 471.46, Ex. Mass.:
471.17); ESI-MS (posi i e mode) m/z:494.164 [M+Na]
+
, 965.339
[2M+Na]
+
.
F ac ion II: 0.04 g (8%) o 3e as whi e c ys als; mp: 112–114 °C;
[
a
]
D
+23 (c0.20, CHCl
3
);
1
H NMR (CDCl
3
, 360 MHz): d(ppm) 7.40 (s,
1H, NH), 5.75 (d, 1H, J
2
0
,3
0
10.5 Hz, H-2
0
), 5.50 (dd, 1H, J
3
0
,4
0
3.2 Hz,
J
4
0
,5
0
1.0 Hz, H-4
0
), 5.26 (dd, 1H, J
2
0
,3
0
10.5 Hz, J
3
0
,4
0
3.2 Hz, H-3
0
),
4.41 (ddd, 1H, J
5
0
,6
0
a
7.3 Hz, J
5
0
,6
0
b
6.3 Hz, J
4
0
,5
0
1.0 Hz, H-5
0
), 4.16
(dd, 1H, J
6
0
a,6
0
b
11.6 Hz, J
5
0
,6
0
a
7.3 Hz, H-6
0
a), 4.07 (dd, 1H, J
6
0
a,6
0
b
420
11.6 Hz, J
5
0
,6
0
b
6.3 Hz, H-6
0
b), 2.20, 2.06, 2.01, 1.95 (4s, 12H,
OCOCH
3
), 1.88–1.81 (m, 2H, CH
2
), 1.79–1.60 (m, 6H, 3CH
2
),
1.52–1.41 (m, 2H, CH
2
);
13
C NMR (CDCl
3
, 90 MHz): d(ppm) 170.3
(2), 168.9, 168.8 (CO), 160.3 (C-4), 113.1 (C-2), 100.8 (C-1
0
), 69.7,
69.3, 67.7, 66.0 (C-2
0
–C-5
0
), 61.8 (C-6
0
), 37.0, 36.0, 24.3, 23.3 (2)
(5CH
2
), 20.6 (2), 20.5 (2) (COCH
3
); Calcd o C
21
H
29
NO
11
(Mol.
W .: 471.46, Ex. Mass.: 471.17); ESI-MS (posi i e mode) m/z:
494.164 [M+Na]
+
, 965.336 [2M+Na]
+
.
F ac ion III: 0.11 g (25%) o 4
14
as a whi e solid.
3.2.5. (1
0
R)-2
0
,3
0
,4
0
,6
0
-Te a-O-benzoyl-1
0
,5
0
-anhyd o-
D
-gluci ol-
430
spi o-[1
0
,5]-2,2-dime hyl-4-imino-1,3-dioxolane (6a)
P epa ed om 5(0.50 g, 0.71 mmol) and ace one wi h AgOT
acco ding o Gene al p ocedu e I (Sec ion 3.2). Column ch oma og-
aphy (1:2 E OAc–hexane han E OAc) ga e wo ac ions.
F ac ion I: 0.18 g (37%) o 6a as a colou less oil; R
= 0.51 (1:2
E OAc–hexane); [
a
]
D
+63 (c0.52, CHCl
3
);
1
H NMR (CDCl
3
,
360 MHz): d(ppm) 8.04–7.24 (m, 20H, A H), 7.73 (s, 1H, NH),
6.80 (pseudo , 1H, J
2
0
,3
0
10.2 Hz, J
3
0
,4
0
9.7 Hz, H-3
0
), 5.85 (d, 1H,
J
2
0
,3
0
10.2 Hz, H-2
0
), 5.76 (pseudo , 1H, J
4
0
,5
0
9.9 Hz, J
3
0
,4
0
9.7 Hz,
H-4
0
), 5.13 (ddd, 1H, J
4
0
,5
0
9.9 Hz, J
5
0
,6
0
b
4.5 Hz, J
5
0
,6
0
a
1.2 Hz, H-5
0
),
440
4.63 (dd, 1H, J
6
0
a,6
0
b
12.0 Hz, J
5
0
,6
0
a
1.2 Hz, H-6
0
a), 4.47 (dd, 1H, J
6
0
a,6
0
b
12.0 Hz, J
5
0
,6
0
b
4.5 Hz, H-6
0
b), 1.61, 1.29 (2s, 6H, CH
3
);
13
CNMR
(CDCl
3
, 90 MHz): d(ppm) 166.0, 165.4, 165.3, 164.8 (CO), 160.5
(C-4,
3
J
H-2
0
,C-4
=5.4 Hz, om HSQMBC a 125 MHz), 112.8 (C-2),
100.3 (C-1
0
), 70.8, 70.7, 70.5, 69.4 (C-2
0
–C-5
0
), 63.1 (C-6
0
), 27.6,
26.7 (CH
3
); Calcd o C
38
H
33
NO
11
(Mol. W .: 679.67, Ex. Mass.:
679.21); ESI-MS (posi i e mode) m/z:702.190 [M+Na]
+
, 1381.399
[2M+Na]
+
.
F ac ion II: 0.21 g (46%) o 7
32
as a whi e solid.
3.2.6. (1
0
R)-2
0
,3
0
,4
0
,6
0
-Te a-O-benzoyl-1
0
,5
0
-anhyd o-
D
-gluci ol-
450
spi o-[1
0
,5]-2,2-die hyl-4-imino-1,3-dioxolane (6c)
P epa ed om 5(0.50 g, 0.71 mmol) and pen an-3-one wi h
AgOT acco ding o Gene al p ocedu e I (Sec ion 3.2). Column ch o-
ma og aphy (1:2 E OAc–hexane han E OAc) ga e wo ac ions.
F ac ion I: 0.23 g (46%) o 6c as a whi e oam; R
= 0.49 (1:2
E OAc–hexane); [
a
]
D
+60 (c0.40, CHCl
3
);
1
H NMR (CDCl
3
,
360 MHz): d(ppm) 8.05–7.20 (m, 20H, A H), 7.71 (s, 1H, NH),
6.82 (pseudo , 1H, J
2
0
,3
0
10.2 Hz, J
3
0
,4
0
9.8 Hz, H-3
0
), 5.92 (d, 1H,
J
2
0
,3
0
10.2 Hz, H-2
0
), 5.76 (pseudo , 1H, J
3
0
,4
0
9.8 Hz, J
4
0
,5
0
9.7 Hz,
H-4
0
), 5.13 (ddd, 1H, J
4
0
,5
0
9.7 Hz, J
5
0
,6
0
b
5.6 Hz, J
5
0
,6
0
a
2.2 Hz, H-5
0
),
460
4.64 (dd, 1H, J
6
0
a,6
0
b
12.0 Hz, J
5
0
,6
0
a
2.2 Hz, H-6
0
a), 4.50 (dd, 1H, J
6
0
a,6
0
b
12.0 Hz, J
5
0
,6
0
b
5.6 Hz, H-6
0
b), 1.87 (q, 2H, J7.2 Hz, CH
2
CH
3
), 1.57 (q,
2H, J7.4 Hz, CH
2
CH
3
), 0.90 ( , 3H, J7.4 Hz, CH
2
CH
3
), 0.63 ( , 3H, J
7.4 Hz, CH
2
CH
3
);
13
C NMR (CDCl
3
, 90 MHz): d(ppm) 165.9, 165.4
(2), 164.8 (CO), 160.6 (C-4,
3
J
H-2
0
,C-4
=4.9 Hz), 116.6 (C-2), 99.9
(C-1
0
), 70.9, 70.7, 70.5, 69.5 (C-2
0
–C-5
0
), 63.0 (C-6
0
), 31.2, 29.1 (CH
2-
CH
3
), 7.8, 6.6 (CH
2
CH
3
); Calcd o C
40
H
37
NO
11
(Mol. W .: 707.72, Ex.
Mass.: 707.24); ESI-MS (posi i e mode) m/z:730.223 [M+Na]
+
,
1437.468 [2M+Na]
+
.
F ac ion II: 0.16 g (35%) o 7
32
as a whi e solid.
470
3.2.7. (1
0
R)-2
0
,3
0
,4
0
,6
0
-Te a-O-benzoyl-1
0
,5
0
-anhyd o-
D
-gluci ol-
spi o-[1
0
,5]-4-imino-1,3-dioxolane-spi o-[2,1
00
]-cyclopen ane
(6d)
P epa ed om 5(0.50 g, 0.71 mmol) and cyclopen anone wi h
Ag
2
CO
3
acco ding o Gene al p ocedu e I (Sec ion 3.2). Column
A. Páhi e al. / Ca bohyd a e Resea ch xxx (2014) xxx–xxx 7
CAR 6720 No. o Pages 11, Model 5G
15 Ap il 2014
Please ci e his a icle in p ess as: Páhi, A.; e al. Ca bohyd . Res. (2014), h p://dx.doi.o g/10.1016/j.ca es.2014.04.003