Anomeric spirocycles by solvent incorporation: Reactions of O-peracylated (glyculopyranose and glyculopyranosyl bromide)onamide derivatives with ketones

Article abstract of DOI:10.1016/j.carres.2014.04.003

Reactions of O-peracetylated (α-d-galacto-heptulopyranosyl bromide)onamide and O-perbenzoylated (α-d-gluco-heptulopyranosyl bromide)onamide with ketones in the presence of silver(I) salt promoters gave the corresponding O-peracylated 1′,5′-anhydro-d-glyci

Full text of DOI:10.1016/j.carres.2014.04.003

Accepted Manuscript
Anomeric spirocycles by solvent incorporation: reactions of O-peracylated (gly-
culopyranose and glyculopyranosyl bromide)onamide derivatives with ketones
András Páhi, Katalin Czifrák, Katalin E. Kövér, László Somsák
PII:
S0008-6215(14)00129-3
DOI:
http://dx.doi.org/10.1016/j.carres.2014.04.003
CAR 6720
Reference:
Carbohydrate Research
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 March 2014
31 March 2014
1 April 2014
Please cite this article as: Páhi, A., Czifrák, K., Kövér, K.E., Somsák, L., Anomeric spirocycles by solvent
incorporation: reactions of O-peracylated (glyculopyranose and glyculopyranosyl bromide)onamide derivatives
with ketones, Carbohydrate Research (2014), doi: http://dx.doi.org/10.1016/j.carres.2014.04.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Anomeric spirocycles by solvent incorporation:
reactions of O-peracylated (glyculopyranose and glyculopyranosyl
bromide)onamide derivatives with ketones
1
2
3
4
5
6
7
8
9
András Páhi,1 Katalin Czifrák,1 Katalin E. Kövér,2 László Somsák1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
1Department of Organic Chemistry,
2Department of Inorganic and Analytical Chemistry,
University of Debrecen, 1POB 20, 2POB 21, H-4010 Debrecen, Hungary
Abstract
Reactions of O-peracetylated (α-D-galacto-heptulopyranosyl bromide)onamide and O-
perbenzoylated (α-D-gluco-heptulopyranosyl bromide)onamide with ketones in the presence
of silver(I) salt promoters gave the corresponding O-peracylated 1’,5’-anhydro-D-glycitol-
spiro-[1’,5]-4-imino-2,2-disubstituted-1,3-dioxolanes. The D-galacto configured starting
compounds furnished both spiro epimers, while the D-gluco counterparts yielded only
configurationally inverted products. Under acidic conditions, O-perbenzoylated α-D-gluco-
heptulopyranosonamide and ketones yielded the protected 1’,5’-anhydro-D-glucitol-spiro-
[1’,5]-2,2-disubstituted-oxazolidin-4-ones, which were O-debenzoylated by the Zemplén
protocol. These compounds had no inhibition against rabbit muscle glycogen phosphorlyase
b.
Keywords
solvent incorporation; spiro compounds; anomeric spirocycles; 4-imino-1,3-dioxolanes;
oxazolidin-4-ones
 Corresponding author – Tel.: +3652512900 ext. 22348, Fax: +3652512744, E-mail:
somsak.laszlo@science.unideb.hu
1

1. Introduction
1
2
3
4
5
Spirocyclic motifs are widespread among natural products and synthetic compounds, and
6
7
8
9
often exhibit interesting and useful biological activities.1-3 Spirocycles involving the anomeric
carbon of monosaccharide derivatives are also well known, and have been, among others,
shown to possess antiparasitic,4 antibacterial, antifungal,5 antidiabetic,6 herbicide,7
glycosidase8-10 and glycogen phosphorylase11 inhibitory activities.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Synthetic strategies to obtain spirocycles were amply reviewed,1-3 and ring closure of
geminally disubstituted cyclic compounds were highlighted as one of several generally
applied approaches towards various spiro derivatives. Following this principle for the
preparation of anomeric spirocycles the necessary starting compounds can be selected from
monosaccharides homo- or heterobifunctionalized at the anomeric centre. The latter type
precursors are represented among others by derivatives of ulose type sugars utilized e. g. for
the syntheses of many sorts of spironucleosides.12 In this line we reported the transformations
of (glyculopyranosyl bromide)onic acid derivatives13 to glycopyranosylidene-spiro-
(thio)hydantoins,14,15 -thiazolidinones,16 and -oxazolines,17 as well as that of
(glyculopyranosyl thiocyanate)ononitriles to glycopyranosylidene-spiro-thiazolines.18
Some years ago we observed that on generation of the corresponding glycosylium ion
from (glyculopyranosyl bromide)onamides (e. g. 1) by Ag2CO3 in acetone spiro-imino-
dioxolanes 2a and 3a (Table 1) were formed by incorporation of the solvent.19 This reaction
can be regarded as a direct O-glycosylation of a ketone which is a very rare transformation:
formation of acetal glycosides in the presence of ketones was described from O-peracetylated
N-(2,4-dinitrophenyl)-α-D-glucosaminyl bromide (but not from acetobromoglucose),20 TMS-
 Strictly speaking these compounds might no more have a „real” anomeric i. e. an acetal type carbon in many
cases, however, for the sake of simplicity this term will be used here.
2

glycosides,21,22 and O-perbenzylated 1-thioglycosides.23 Formal glycosylation of ketones by a
special intramolecular aglycon delivery was recently reported.24
1
2
3
4
5
6
7
8
9
In this paper full experimental details are reported for the extension of the above ketone
incorporation in reactions of (glyculopyranosyl bromide)onamides. Furthermore, studies on
the reactions of (glyculopyranose)onamides and ketones as well as detailed structural
elucidation of the compounds are also described.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
2. Results and Discussion
Following the first observation19 on incorporation of acetone into the products in the
reaction of 1 (Table 1, Entry 1) in the presence of Ag2CO3, the applicability of other ketones
and promoters were investigated. With butanone both Ag2CO3 and AgOTf gave similar
results (Entries 2 and 3) expectedly furnishing the spiro-dioxolanes 2b and 3b as inseparable
diastereomeric mixtures. Symmetrical ketones (Entries 4-6) also gave the spiro-epimers 2c-e
as the main products whereby 3c-e could be isolated in much lower yields. From each
reaction mixture the hydrolytic product 4 could be isolated in 25-38 % yields.
3

1
2
3
Table 1. Reaction of O-peracetylated (α-D-galacto-heptulopyranosyl bromide)onamide (1) with ketones
4
5
6
7
8
O
AcO
AcO
AcO
AcO
OAc
O
OAc
O
OAc
O
OAc
O
R1
R2
NH
as solvent
promoter
(1 equiv.)
R1
R2
CONH2
O
O
CONH2
AcO
AcO
AcO
AcO
+
+
9
AcO
AcO
HN
AcO
AcO
O
Br
OH
O
10
11
12
13
14
15
16
17
18
19
20
R2
in the dark, under Ar
rt
R1
1
2
3
4
Entry
1.
R1 R2 Promoter R. time
aa Me Me Ag2CO3 1 d
Yield (%)
71
49b
43b
32
4
c
5
c
21 2.
Me Et Ag2CO3 6 d
b
22
19
14
3.
AgOTf
Et Et AgOTf
-(CH2)4- AgOTf
-(CH2)5- AgOTf
6 d
3 d
6 d
2 d
38
27
26
25
23
24
25
4.
c
d
e
26
27
5.
48
traces
8
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
6.
44
aFrom ref.19 bTwo diastereomers. cObserved but not isolated.
Similar reactions of the D-gluco configured 5 are collected in Table 2. Comparisons of
Entries 1, 3, and 5 with Entries 2, 4, and 6, respectively, show that the use of AgOTf are
superior to that of Ag2CO3 in terms of reaction times, although the higher efficiency of the
former is not always reflected in the yields. In these reactions of 5 only spiro-epimer 6 was
observed in the reaction mixtures (besides the hydrolyis product 7).
4

1
2
3
Table 2. Reaction of O-perbenzoylated (α-D-gluco-heptulopyranosyl bromide)onamide (5) with ketones
4
5
6
7
8
O
OBz
O
OBz
O
OBz
O
R1
R2
BzO
BzO
BzO
BzO
BzO
as solvent
R1
R2
BzO
CONH2
CONH2
O
O
+
9
BzO
BzO
1 equiv. promoter
in the dark, under Ar
rt
BzO
HN
Br
OH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
5
6
7
Entry
1.
R1 R2 Promoter R. time
Me Me Ag2CO3 11 d
Yield (%)
17
37
5
41
46
34
35
18
35
a
c
2.
AgOTf
Et Et Ag2CO3 20 d
AgOTf 1 d
-(CH2)4- Ag2CO3 13 d
-(CH2)5- AgOTf 1 d
1 d
3.
4.
46
56
28
5.
d
e
6.
Attempts to reduce the amount of the ketones to 5-10 equivalents in nitromethane as the
solvent proved unsuccesful, and the only products to be observed were 4 and 7. Trials to use
aldehydes as the carbonyl reagents resulted in multicomponent mixtures from which no
discrete products could be isolated.
Reactions of (D-gluco-hept-2-ulopyranose)onamide 7 with ketones were investigated next
(Table 3). As in similar cyclizations of non-carbohydrate α-hydroxy-carboxamides p-
toluenesulfonic acid (pTSA) was frequently applied to promote the transformation25 this acid
was tried first. However, no reaction of 7 could be observed with acetone as the solvent in the
presence of either catalytic or stoichiometric amounts of pTSA. On the other hand, catalytic
triflic acid (TfOH) elicited the reaction (Entry 1), and raising its amount to one equivalent
significantly increased the yield of 8a (Entry 2). Under the same conditions butanone gave an
inseparable diastereomeric mixture of 8b (Entry 3). The amount of the ketone could be
diminished to 5 equivalents, and both THF and toluene proved suitable solvents to prepare 8c-
5

f in good yields (Entries 4-7). In these reactions formation of one compound was observed in
each case (disregarding diasteromers 8b). Reactions with aldehydes gave only decomposition
products.
1
2
3
4
5
6
7
8
9
Spiro-oxazolidinones 8 were O-debenzoylated by the Zempén protocol to give
compounds 9 in very good yields. These derivatives were tested as possible inhibitors of
rabbit muscle glycogen phosphorylase b, however, showed no inhibition up to 625 μM
concentration.
10
11
12
13
14
15
16
17
18
19
Table 3. Reaction of 3,4,5,7-tetra-O-benzoyl-α-D-gluco-heptulopyranosonamide (5) with ketones
20
21
22
23
24
25
26
27
28
29
30
31
32
O
OBz
O
OBz
O
OH
O
O
O
R1
2 / TfOH
R
BzO
BzO
BzO
BzO
NaOMe
HO
HO
CONH2
MeOH, rt
BzO
BzO
HO
solvent, reflux
overnight
NH
R2
NH
R2
OH
O
O
R1
R1
7
8
9
Entry
R1 R2 Ketone
equiv.
Solvent Acid
equiv.
Yield (%)
33
34
35
36
1.
Me Me as solvent
as solvent
-
0.1
1.0
1.0
1.0
1.0
58
89
92a
69
86
69
71
94
a
37
2.
-
38
39
3.
Me Et as solvent
-
96
91
91
96
77
b
c
d
e
f
40
41
4.
Et Et
-(CH2)4-
-(CH2)5-
-(CH2)6-
5
5
5
5
THF
THF
42
43
5.
44
6.
toluene 1.0
toluene 1.0
45
46
7.
47
48
49
aTwo diastereomers.
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Structural elucidation of the products (following the mass spectrometric determination of
the molecular masses) was carried out by NMR methods as illustrated for the compounds
depicted in Figure 1 (see also Table 4 for selected NMR data of the compounds). Proton
spectra showed splitted resonances for a pyranoid ring in the 4C1 conformation as well as the
6

expected signals of the aliphatic parts and the presence of an exchangable proton assigned as
an NH for each compound (see details in the Experimental section). The carbon spectra
contained (besides the expected resonances for the sugar ring, the acyl protecting groups and
the aliphatic moieties) signals for three carbons with no attached hydrogens. Those in the
range of 99.9-100.7 ppm were assigned as the C-[1’,5] spiro centres. Resonances of 112.5-
122.2 and 158.2-160.9 ppm (clearly distinct from the C=O resonances of the protective
groups) were indicative of acetal and imidate type carbons, respectively, in compounds 2, 3,
and 6. On the contrary, the spectra of compounds 8 exhibited an additional signal in the range
of the benzoyl carbonyls (162.4-166.6 ppm) and from these that of the highest chemical shift
was (tentatively) assigned to amide C-4. A resonance in the range of 92.4-100.1 ppm could be
attributed to an aminal type carbon and this corroborated that the nitrogen was in an
endocyclic position in 8. To confirm the difference in the constitution of the heterocyclic parts
of the spirocycles, CMPG-HSQMBC experiments26-28 were carried out with 6a and 8e. In
these spectra cross peaks (indicated by asterisks in the formulae of the respective compounds
in Fig. 1) between NH and C-4 and C-5, but not with C-2, were observed for 6a to further
prove the imino-dioxolane structure. On the other hand, cross peaks between NH and C-2, C-
4, and C-5, as well as with carbons of the aliphatic substituent were present for 8e to verify
the oxazolidinone ring. For 8e this measurement also corroborated the chemical shift
assignment of amide C-4. The configuration of the spiro carbons C-[1’,5] was established as
R for 2 and 6, and S for 3 and 8 based on the three bond heteronuclear coupling constants
between H-2 and C-4 shown in Fig. 1 indicating the trans diaxial vs. gauche relationships
between the respective nuclei in the 4C1 conformation of the sugar ring. Although these
couplings could not be measured for each compound due to insufficient sample quantities, no
doubt was left about the spiro configuration of the other members of the series. Namely, the
proton resonances had characteristic shifts depending on the C-[1’,5] configuration (cf. Fig. 1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
7

and Table 4): H-2’ had a downfield shift of ~0.1-0.2 ppm if the C=NH/C=O was on the same
side of the pyranoid ring; similarly, downfield shifts were observed for H-3’ (~0.7 ppm) and
H-5’ (~0.4 ppm) when they were in the same situation. Analogous 1H chemical shift patterns
were observed earlier for other glycopyranosylidene-spiro-heterocycles.14,15
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
5.60
H-2'
5.74
H-2'
3JH-2',C-4 ~ 6.1 Hz
3JH-2',C-4 ~ 2.1 Hz
AcO
AcO
AcO
AcO
100.8
NH
99.9
O
O
1'
1'
O
160.8
AcO
AcO
Et
4
5
5
H-5' OAc
H-3'
H-5' OAc
2
O
116.8
4
H-3'
O
2
Et
HN
O
5.99
5.30
Et
116.2
4.85
4.42
Et
160.4
2c
3c
5.85
H-2'
6.00
3JH-2',C-4 ~ 5.4 Hz
3JH-2',C-4 ~ 2.5 Hz
H-2'
BzO
BzO
BzO
BzO
100.3
100.1
O
O
O
4
1'
166.4
O
O
1'
Me
Me
BzO
BzO
*
5
5
H-5' OBz
H-5' OBz
*
*
*
NH
2
112.8
4
H-3'
H-3'
4.69
8e
*
O
*
HN
93.5
*
2
6.80
6.10
37.6
(39.0)
5.13
*
160.5
*
6a
39.0
(37.6)
*Cross peaks with NH in the spectra from CPMG-HSQMBC experiments.
Figure 1. Representative NMR data for the structural elucidation of the new compounds.
8

Table 4. Selected NMR data for the O-peracylated compoundsa 2, 3, 6, and 8 (δ [ppm], J
[Hz])
1
2
3
4
5
6
7
8
9
AcO
OAc
5'
4'
O
2'
R1
R2
2ab
1'
5
O
2b
2c
2d
2e
AcO
3'
2
AcO
HN
4
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
H-2’
H-3’
H-5’
5.58
6.00
5.54/5.59
6.05/5.89
4.75/4.85
100.2/100.3
114.7/114.1
160.4/160.2
4.1
5.60
5.99
4.85
99.9
116.8
160.4
6.1
5.57
5.98
5.57
6.01
4.88
4.84
4.85
C-[1’,5]
C-2
100.4
112.6
160.9
5.6
100.1
116.2
158.8
6.1
100.1
113.2
158.2
5.3
C-4
3JH-2’,C-4
AcO
OAc
NH
4
5'
4'
O
2'
1'
3ab
AcO
3b
3c
3e
AcO 5
O
3'
O
2
R2
R1
H-2’
H-3’
H-5’
5.74
5.25
5.74/5.69
5.35/5.20
4.43/4.39
100.9/100.9
114.8/113.8
160.2/160.2
n.m.c
5.74
5.30
5.75
5.26
4.41
4.42
4.41
C-[1’,5]
C-2
100.3
112.5
161.2
n.m.c
100.8
116.2
160.8
2.1
100.8
113.1
160.3
n.m.c
C-4
3JH-2’,C-4
OBz
4'
5'
O
BzO
2'
R1
R2
1'
O
2
BzO
6a
6c
6d
6e
5
3'
BzO
HN
4
O
H-2’
5.85
6.80
5.92
6.82
5.13
99.9
116.6
160.6
4.9
5.87
6.82
5.12
99.9
122.2
160.3
4.9
5.87
6.82
5.14
99.8
113.5
160.4
5.0
H-3’
H-5’
5.13
C-[1’,5]
C-2
100.3
112.8
160.5
5.4
C-4
3JH-2’,C-4
9

OBz
4'
O
4
5'
O
BzO
BzO
1
2
3
4
5
2'
1'
5
3'
8a
8b
8c
8d
8e
8f
BzO
NH
2
O
R1
R2
6
7
8
9
H-2’
H-3’
H-5’
H-4’
5.96
6.09
5.99/5.97
6.10/6.09
4.63/4.63
5.72/5.71
100.3/100.35
94.9, 94.5
166.4/166.1
n.mc
6.00
6.10
4.64
5.70
100.2
97.1
166.6
n.mc
5.97
6.08
6.00
6.10
4.69
5.71
100.1
93.5
166.4
2.5
5.98
6.08
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
4.66
4.63
4.66
5.73
5.73
5.70
C-[1’,5]
C-2
100.5
92.4
100.7
100.1
166.1
n.m.c
100.1
97.2
C-4
3JH-2’,C-4
166.0
n.m.c
166.1
n.m.c
aFor substituents R1 and R2 see the respective Tables (Table 1 for 2 and 3, Table 2 for 6, and Table 3 for 8).
bData taken from ref.19 cNot measured because of insufficient sample quantity.
Formation of spirocycles 2, 3, and 6 can be understood by following the mechanistic
proposal in Scheme 1. The silver salt promoter facilitates the generation of the corresponding
glycosyliumion B1 from 1 or 5. Nucleophilic attack of a ketone with anchimeric assistance of
the 2-O-acyl group (D1) may lead to carbocation A1 while without neighbouring group
participation the epimeric cation, represented by resonance forms E1 and F1, can be formed.
Intramolecular attack of the amide oxygen (illustrated in details for F1 only), the harder part
of this functional group, may give the cyclized iminium ion C1. Deprotonation of this
intermediate and that of the analogous one (not shown) derived from A1 give then the isolated
products of retained (3) and inverted configuration (2), respectively. Formation of the by-
products 4 and 7 are to be explained by the water content of the solvents attacking on
glycosyliumion B1. The finding that from the D-gluco configured 5 only the formation of 6
was observed, while 1 of the D-galacto configuration gave both epimers 2 and 3, may be
 It is to be noted that from the acetylated counterpart of 5 formation of a very minor amount (6 %) of the
inverted product was reported.19
10

indicative of a remote participation29 of the axial 4-O-acetyl group of 1 facilitating the
formation of 3.
1
2
3
4
5
6
7
O
O
8
9
NH
1
1
Ag /
R2
Ag /
R
R2
O
O
O
R
CONH2
R1
R2
O
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
ROCO
HN
RCO
O
RCO
O
O
Br
Ag
H2O
O
R2
R1
O
1 or 5
CONH2
OH
2 or 6
3
RCO
O
-AgBr
Ag
-H
4 or 7
H2O
R1
NH2
O
O
O
O
R2
RCO
O
RCO
O
RCO
O
CONH2
O
CONH2
A1
O
R2
R1
B1
C1
O
R1
R1
R2
NH2
O
R2
O
O
O
CONH2
O
CONH2
RCO
O
R1
O
R
RCO
O
O
O
O
R1
R2
D1
R2
F1
E1
Scheme 1. Proposed mechanism for the formation of 1’,5’-anhydro-D-glycitol-spiro-[1’,5]-4-
imino-1,3-dioxolanes 2, 3, and 6.
A mechanistic proposal for the formation of spirocycles 8 (Scheme 2) can be more
complex since, due to the presence of several functional groups whose protonation may start
the reaction, alternative pathways may occur simultaneously. The first (most tempting)
possibility is the protonation of the glycosidic OH in 7 followed by loss of water to give
glycosyliumion C2 which is the same intermediate as B1 in Scheme 1. Attack of a ketone on
C2 would give A2 (equal to intermediate F1 in Scheme1), however, the formation of the
epimeric intermediate A1 (shown in Scheme 1) must also be taken into account. This
11

possibility renders this pathway less probable since only the configurationally retained epimer
8 was observed in the reactions. Formation of A2 (without epimerization) should also be
possible via protonation and subsequent dehydration of a mixed hemiketal E2 which can
develop from 7 by nucleophilic addition of the glycosidic OH to the ketone or its protonated
form D2. Ring closure of A2 (= F1) occurred by the nucleophilic attack of the amide oxygen
under conditions of Scheme 1 (cf F1→C1) to give the imino-dioxolanes 3, however, these
compounds were not present in the reactions of 7 (Scheme 2). Considering the different
reaction conditions this may raise two possibilities: i) imino-dioxolanes may be formed as
primary products which then give oxazolidinones 8 in a proton catalysed equilibration; ii) ring
closure takes place by a N-nucleophilic attack of the hydroximide tautomer of the amide
moiety. The first possibility was ruled out by an experiment in which an imino-dioxolane 6
was subjected to the conditions of the formation of 8. Thus, 6a was boiled in acetone in the
presence of TfOH (1 equiv) for 24 h, however, no change could be detected by TLC. The
second possibility can be reasonable since tautomerisation of amides under acidic conditions
(cf 7→F2→I2) is a known phenomenon.30 Thus, A2 may ring-close to protonated hydroxy-
oxazoline B2 which, after deprotonation and tautomerization can give the isolated 8.
Since α-hydroxy-carboxamides and carbonyl compounds are known to furnish oxazoles
under acidic conditions, the generally accepted mechanism of the Fischer oxazole synthesis25
should also be considered in the present transformation. Protonation of the amide oxygen of 7
as shown in F2 may result in a tautomerisation30 to give at least a minor proportion of I2
which can attack the ketone (or its protonated form D2) as a N-nucleophile to give
intermediate J2. Protonation of a hydroxyl group in J2 may lead to elimination of water to
produce either carbocation G2 or K2, both of which can ring close to H2 by the nucleophilic
attack of the remaining OH on the positively charged carbon. Due to the presence of three
electron releasing substituents, carbocation K2 might be more stable than glycosyliumion G2,
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
12

therefore, formation of H2 via K2 might be preferred. This is also made likely by the
formation of a single isomer of 8 that would probably not be the case in route J2→G2→H2.
Final deprotonation and tautomerisation of H2 may then yield the isolable product 8.
1
2
3
4
5
6
7
8
9
OH
NH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
OH
O
O
RCO
RCO
NH
R2
O
O
O
O
O
R1
R1
R2
H
R1
R2
-H2O
A2 (= F1 in
Scheme 1,
cf A1 also)
B2
O
O
CONH2
OH
-H
RCO
O
CONH2
RCO
O
O
tautome-
risation
OH
R1 R2
C2 (= B1 in
Scheme 1)
D2
E2
H
R1
R2
-H2O
-H
O
O
O
O
H
CONH2
OH
+
R1
R2
RCO
O
RCO
NH
O
O
R2
R1
7
8
H
tautome-
risation
-H
OH
NH2
F2
OH
OH
O
O
O
N
RCOO
RCO
O
RCO
O
N
OH
HO
R2
R1
HO
R2
G2
H2
R1
-H
OH
NH
I2
H
O
-H2O
OH
OH
R1
R2
O
O
H
N
N
O
RCO
O
RCO
O
RCO
O
-H2O
OH
OH
HO
OH
R2
R2
R1
R1
J2
K2
Scheme 2. Possible mechanistic pathways for the formation of 1’,5’-anhydro-D-glucitol-spiro-
[1’,5]-oxazolidin-4-ones 8.
13

In conclusion, the reactions of (glyculopyranose and glyculopyranosyl bromide)onamides
with ketones gave access to the preparation of new anomeric spirocycles, namely, 1’,5’-
anhydro-D-glycitol-spiro-[1’,5]-4-imino-2,2-disubstituted-dioxolanes and 1’,5’-anhydro-D-
glycitol-spiro-[1’,5]-2,2-disubstituted-oxazolidin-4-ones. The structures were unambigously
assigned by NMR methods. Detailed mechanisms were proposed to explain the formation of
both constitutional isomers as well as the stereoselectivities of the ring forming reactions. The
spiro-oxazolidinones were tested against rabbit muscle glycogen phosphorlyase b, however,
had no inhibitory effect.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3. Experimental
3.1. General methods
Melting points were measured in open capillary tubes or on a Kofler hot-stage and are
uncorrected. Optical rotations were determined with a Perkin-Elmer 241 polarimeter at room
temperature. NMR spectra were recorded with Bruker 200 (200/50 MHz for 1H/13C), Bruker
DRX 360 (360/90 MHz for 1H/13C) or Avance II 500 (500/125 MHz for 1H/13C)
spectrometers. Chemical shifts are referenced to Me4Si (1H), or to the solvent signals or DSS
in D2O (13C). Mass spectra were recorded by a Bruker micrOTOF-Q instrument. TLC was
performed on DC-Alurolle Kieselgel 60 F254 (Merck), and the plates were visualised under
UV light and by gentle heating. For column chromatography Kieselgel 60 (Merck, particle
size 0.063-0.200 mm) was used. Dichloromethane was distilled from P4O10 and acetone from
CaSO4) and stored over 4Å molecular sieves. Organic solutions were dried over anhydrous
MgSO4 and concentrated under diminished pressure at 40-50 ºC (water bath).
14

3.2. General procedure I for the preparation of O-peracylated 1’,5’-anhydro-D-glycitol-
spiro-[1’,5]-4-imino-2,2-disubstituted-1,3-dioxolanes 2, 3, and 6
1
2
3
4
5
6
7
8
9
To a solution of an O-peracylated (glyculopyranosyl bromide)onamide 131 or 532 (0.50 g)
in a dry ketone (5 mL) containing molecular sieves (3 Å) Ag2CO3 (1 equiv) or AgOTf/Et3N (1
equiv) were added. The mixture was stirred at rt in the dark under Ar atmosphere until TLC
(1:1 or 1:2 EtOAc-hexane) showed complete transformation of the starting material. Then the
mixture was filtered on a Celite pad and the solvent removed under diminished pressure. The
crude product was purified by column chromatography.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.2.1. (1’R,2RS)- and (1’S,2RS)-2’,3’,4’,6’-Tetra-O-acetyl-1’,5’-anhydro-D-galactitol-
spiro-[1’,5]-2-ethyl-4-imino-2-methyl-1,3-dioxolanes (2b and 3b)
Prepared from 1 (0.50 g, 1.10 mmol) and butanone in the presence of AgOTf according
to General procedure I (section 3.2). Column chromatography (1:1 EtOAc-hexane) gave three
fractions.
Fraction I: 0.21 g (43%) of an inseparable diastereomeric mixture of 2b as a colourless oil; Rf
= 0.71 (1:1 EtOAc-hexane).
Characterisation of diastereomer A: 1H NMR (CDCl3, 360 MHz): δ (ppm) 7.40 (s, 1H, NH),
6.05 (dd, 1H, J2’,3’ 11.1 Hz, J3’,4’ 3.2 Hz, H-3’), 5.54 (d, 1H, J2’,3’ 11.1 Hz, H-2’), 5.51 (dd, 1H,
J3’,4’ 3.2 Hz, J4’,5’ 1.0 Hz, H-4’), 4.75 (ddd, 1H, J5’,6’a 6.8 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.0 Hz, H-5’),
4.20-4.02 (m, 2H, H-6’a, H-6’b), 2.15, 2.05, 1.95, 1.93 (4s, 12H, OCOCH3), 1.70 (q, 2H, J
7.3 Hz, CH2CH3), 1.35 (s, 3H, CH3), 0.88 (t, 3H, J 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 90
MHz): δ (ppm) 170.3, 170.0, 169.6, 169.3 (CO), 160.4 (C-4, 3JH-2’,C-4 = ~4.1 Hz), 114.7 (C-2),
15

100.2 (C-1’), 69.8, 68.8, 67.5, 66.9 (C-2’ - C-5’), 61.3 (C-6’), 33.4 (CH2CH3), 25.6 (CH3),
20.7, 20.5, 20.3, 20.2 (COCH3); 6.9 (CH2CH3).
1
2
3
4
5
6
7
8
9
Characterisation of diastereomer B: 1H NMR (CDCl3, 360 MHz): δ (ppm) 7.40 (s, 1H, NH),
5.89 (dd, 1H, J2’,3’ 11.1 Hz, J3’,4’ 3.2 Hz, H-3’), 5.59 (1H, d, J2’,3’ 11.1 Hz, H-2’), 5.48 (dd, 1H,
J3’,4’ 3.2 Hz, J4’,5’ 1.0 Hz, H-4’), 4.85 (ddd, 1H, J5’,6’a 6.8 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.0 Hz, H-5’),
4.20-4.02 (m, 2H, H-6’a, H-6’b), 2.16, 2.04, 1.98, 1.94 (4s, 12H, OCOCH3), 1.85 (q, 2H, J
7.3 Hz, CH2CH3), 1.55 (s, 3H, CH3), 0.96 (t, 3H, J 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 90
MHz): δ (ppm) 170.2, 170.0, 169.8, 169.1 (CO), 160.2 (C-4), 114.1 (C-2), 100.3 (C-1’), 69.9,
68.8, 67.2 (2) (C-2’ - C-5’), 61.3 (C-6’), 32.4 (CH2CH3), 25.6 (CH3), 20.8, 20.5, 20.3, 20.1
(OCOCH3), 6.9 (CH2CH3). Calcd for C19H27NO11 (Mol. Wt.: 445.42, Ex. Mass.: 445.16);
ESI-MS (positive mode) m/z: 468.148 [M+Na]+, 913.305 [2M+Na]+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Fraction II: 0.10 g (19%) of an inseparable diastereomeric mixture of 3b as a yellowish oil; Rf
= 0.36 (1:1 EtOAc-hexane).
Characterisation of diastereomer C: 1H NMR (CDCl3, 360 MHz): δ (ppm) 7.48 (s, 1H, NH),
5.74 (d, 1H, J2’,3’ 11.1 Hz, H-2’), 5.51 (dd, 1H, J3’,4’ 3.2 Hz, J4’,5’ 1.0 Hz, H-4’), 5.35 (dd, 1H,
J2’,3’ 11.1 Hz, J3’,4’ 3.2 Hz, H-3’), 4.43 (ddd, 1H, J5’,6’a 6.8, J5’,6’b 6.3 Hz, J4’,5’ 1.0 Hz, H-5’),
4.20-4.03 (m, 2H, H-6’a, H-6’b), 2.10, 2.08, 2.01, 1.98 (4s, 12H, OCOCH3), 1.88 (q, 2H, J
7.3 Hz, CH2CH3), 1.54 (s, 3H, CH3), 1.00 (t, 3H, J 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 90
MHz): δ (ppm) 170.4, 170.2, 169.8, 169.1 (CO), 160.2 (C-4), 114.8 (C-2), 100.9 (C-1’), 69.7,
68.6, 67.7, 66.5 (C-2’ - C-5’), 61.7 (C-6’), 32.4 (CH2CH3), 25.8 (CH3), 20.7, 20.5, 20.2, 20.1
(COCH3); 6.8 (CH2CH3).
Characterisation of diastereomer D: 1H NMR (CDCl3, 360 MHz): δ (ppm) 7.48 (s, 1H, NH),
5.69 (d, 1H, J2’,3’ 11.1 Hz, H-2’), 5.49 (dd, 1H, J3’,4’ 3.2 Hz, J4’,5’ 1.0 Hz, H-4’), 5.20 (dd, 1H,
J2’,3’ 11.1 Hz, J3’,4’ 3.2 Hz, H-3’), 4.39 (ddd, 1H, J5’,6’a 6.8 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.0 Hz, H-
5’), 4.18-4.02 (m, 2H, H-6’a, H-6’b), 2.11, 2.09, 1.99, 1.97 (4s, 12H, OCOCH3), 1.86 (2H, q,
16

J 7.3 Hz, CH2CH3), 1.61 (s, 3H, CH3), 1.26 (t, 3H, J 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 90
MHz) δ (ppm): 170.4, 170.0, 169.9, 169.6 (CO), 160.2 (C-4), 113.8 (C-2), 100.9 (C-1’), 69.7,
67.6, 66.2 (2) (C-2’ - C-5’), 60.3 (C-6’), 33.5 (CH2CH3), 24.2 (CH3), 20.7, 20.6, 20.2, 20.1
(COCH3); 7.9 (CH2CH3). Calcd for C19H27NO11 (Mol. Wt.: 445.42, Ex. Mass.: 445.16); ESI-
MS (positive mode) m/z: 468.147 [M+Na]+, 913.304 [2M+Na]+.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Fraction III: 0.16 g (38%) of 414 as a white solid.
3.2.2. (1’R)- and (1’S)-2’,3’,4’,6’-Tetra-O-acetyl-1’,5’-anhydro-D-galactitol-spiro-[1’,5]-
2,2-diethyl-4-imino-1,3-dioxolanes (2c and 3c)
Prepared from 1 (0.50 g, 1.10 mmol) and pentan-3-one with AgOTf according to General
procedure I (section 3.2). Column chromatography (1:1 EtOAc-hexane) gave three fractions.
Fraction I: 0.16 g (32 %) of 2c as white crystals; mp: 100-102 C; []D +37 (c 0.90, CHCl3);
1H NMR (CDCl3, 360 MHz): δ (ppm) 7.45 (s, 1H, NH), 5.99 (dd, 1H, J2’,3’ 11.1 Hz, J3’,4’ 3.7
Hz, H-3’), 5.60 (d, 1H, J2’,3’ 11.1 Hz, H-2’), 5.50 (dd, 1H, J3’,4’ 3.7 Hz, J4’,5’ 1.2 Hz, H-4’),
4.85 (ddd, 1H, J5’,6’a 6.8 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.2 Hz, H-5’), 4.17 (dd, 1H, J6’a,6’b 11.6 Hz,
J5’,6’a 6.8 Hz, H-6’a), 4.09 (dd, 1H, J6’a,6’b 11.6 Hz, J5’,6’b 6.3 Hz, H-6’b), 2.17, 2.06, 2.02, 1.96
(4s, 12H, OCOCH3), 1.87 (q, 2H, J 7.3 Hz, CH2CH3), 1.72 (q, 2H, J 7.3 Hz, CH2CH3), 0.96
(t, 3H, J 7.3 Hz, CH2CH3), 0.88 (t, 3H, J 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 90 MHz): δ
(ppm) 170.1 (2), 169.6, 169.2 (CO), 160.4 (C-4, 3JH-2’,C-4 =~6.1 Hz from HSQMBC at 125
MHz), 116.8 (C-2), 99.9 (C-1’), 69.7, 68.9, 67.3 (2) (C-2’ - C-5’), 61.3 (C-6’), 31.2, 29.4
(CH2CH3), 20.5, 20.4 (2), 20.2 (COCH3); 7.8, 6.7 (CH2CH3).
Fraction II: 0.07 g (14%) of 3c as a white crystals, mp: 61-63 C; []D +59 (c 1.00, CHCl3);
1H NMR (CDCl3, 360 MHz): δ (ppm) 7.42 (s, 1H, NH), 5.74 (d, 1H, J2’,3’ 11.1 Hz, H-2’),
5.51 (dd, 1H, J3’,4’ 3.2 Hz, J4’,5’ 1.1 Hz, H-4’), 5.30 (dd, 1H, J2’,3’ 11.1 Hz, J3’,4’ 3.2 Hz, H-3’),
17

4.42 (ddd, 1H, J5’,6’a 6.8 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.1 Hz, H-5’), 4.16 (dd, 1H, J6’a,6’b 11.6 Hz,
J5’,6’a 6.8 Hz, H-6’a), 4.11 (dd, 1H, J6’a,6’b 11.6 Hz, J5’,6’b 6.3 Hz, H-6’b), 2.19, 2.03, 2.01, 1.98
(4s, 12H, OCOCH3), 1.88 (q, 2H, J 7.3 Hz, CH2CH3), 1.84 (q, 2H, J 7.3 Hz, CH2CH3), 0.99
(t, 3H, J 7.3 Hz, CH2CH3), 0.95 (t, 3H, J 7.3 Hz, CH2CH3); 13C NMR (CDCl3, 90 MHz): δ
(ppm) 170.3 (2), 170.1, 168.6 (CO), 160.8 (C-4, 3JH-2’,C-4 = ~2.1 Hz from HSQMBC at 125
MHz), 116.2 (C-2), 100.8 (C-1’), 69.6, 69.2, 67.7, 66.1 (C-2’ - C-5’), 61.8 (C-6’), 31.6, 29.0
(CH2CH3), 20.8, 20.5, 20.3 (2) (COCH3); 8.0, 6.6 (CH2CH3); Calcd for C20H29NO11 (Mol.
Wt.: 459.44, Ex. Mass.: 459.17); ESI-MS (positive mode) m/z: 482.163 [M+Na]+, 941.337
[2M+Na]+.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Fraction III: 0.12 g (27%) of 414 as a white solid.
3.2.3. (1’R)- and (1’S)-2’,3’,4’,6’-Tetra-O-acetyl-1’,5’-anhydro-D-galactitol-spiro-[1’,5]-
4-imino-1,3-dioxolane-spiro-[2,1’’]-cyclopentanes (2d and 3d)
Prepared from 1 (0.20 g, 0.44 mmol) and cyclopentanone with AgOTf according to
General procedure I (section 3.2). Column chromatography (1:1 EtOAc-hexane) gave three
fractions.
Fraction I: 0.10 g (48%) of 2d as white crystals; mp: 148-150 C; []D +28 (c 0.20, CHCl3);
1H NMR (CDCl3, 360 MHz): δ (ppm) 7.40 (s, 1H, NH), 5.98 (dd, 1H, J2’,3’ 11.1 Hz, J3’,4’ 3.6
Hz, H-3’), 5.57 (d, 1H, J2’,3’ 11.1 Hz, H-2’), 5.50 (dd, 1H, J3’,4’ 3.6 Hz, J4’,5’ 1.1 Hz, H-4’),
4.85 (ddd, 1H, J5’,6’a 6.8 Hz, J5’6’b 6.3 Hz, J4’,5’ 1.1 Hz, H-5’), 4.15 (dd, 1H, J6’a,6’b 11.6 Hz,
J5’,6’a 6.8 Hz, H-6’a) 4.09 (dd, 1H, J6’a,6’b 11.6 Hz, J5’,6’b 6.3 Hz, H-6’b), 2.16, 2.05, 2.03, 1.97
(4s, 12H, OCOCH3), 1.92-1.84 (m, 4H, 2  CH2), 1.82-1.68 (m, 4H, 2  CH2); 13C NMR
(CDCl3, 90 MHz): δ (ppm): 170.0 (2), 169.6, 169.0 (CO), 158.8 (C-4, 3JH-2’,C-4 = ~6.1 Hz),
116.2 (C-2), 100.1 (C-1’), 69.9, 68.6, 67.3, 67.2 (C-2’ - C-5’), 61.2 (C-6’), 38.2, 36.6, 23.6,
18

22.6 (4  CH2), 20.6, 20.5 (2), 20.4 (COCH3); Calcd for C20H27NO11 (Mol. Wt.: 457.43, Ex.
Mass.: 457.16); ESI-MS (positive mode) m/z: 480.149 [M+Na]+, 937.306 [2M+Na]+.
Fraction II: traces of 3d insufficient for NMR characterization. Calcd for C20H27NO11 (Mol.
Wt.: 457.43, Ex. Mass.: 457.16); ESI-MS (positive mode) m/z: 480.147 [M+Na]+, 937.306
[2M+Na]+.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Fraction III: 0.045 g (26%) of 414 as a white solid.
3.2.4. (1’R)- and (1’S)-2’,3’,4’,6’-Tetra-O-acetyl-1’,5’-anhydro-D-galactitol-spiro-[1’,5]-
4-imino-1,3-dioxolane-spiro-[2,1]-cyclohexanes (2e and 3e)
Prepared from 1 (0.50 g, 1.10 mmol) and cyclohexane with AgOTf according to General
procedure I (section 3.2). Column chromatography (1:1 EtOAc-hexane) gave three fractions.
Fraction I: 0.23 g (44%) of 2e as white crystals; mp: 124-126 C; []D +14 (c 0.22, CHCl3);
1H NMR (CDCl3, 360 MHz): δ (ppm) 7.40 (s, 1H, NH), 6.01 (dd, 1H, J2’,3’ 10.5 Hz, J3’,4’ 3.2
Hz, H-3’), 5.57 (d, 1H, J2’,3’ 10.5 Hz, H-2’), 5.51 (dd, 1H, J3’,4’ 3.2 Hz, J4’,5’ 1.0 Hz, H-4’),
4.85 (ddd, 1H, J5’,6’a 7.3 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.0 Hz, H-5’), 4.10-4.08 (m, 2H, H-6’a, H-
6’b), 2.18, 2.08, 2.04, 1.97 (4s, 12H, OCOCH3), 1.87-1.81 (m, 2H, CH2), 1.77-1.56 (m, 4H, 2
 CH2), 1.53-1.33 (m, 2H, CH2), 1.30-1.23 (m, 2H, CH2); 13C NMR (CDCl3, 90 MHz): δ
(ppm) 170.8 (2), 169.2, 169.8 (CO), 158.2 (C-4, 3JH-2’,C-4 = ~5.3 Hz), 113.2 (C-2), 100.1 (C-
1’), 69.9, 68.9, 67.5 (2) (C-2’ - C-5’), 61.3 (C-6’), 37.2, 36.4, 24.4, 23.1 (2) (5  CH2), 20.8,
20.6 (2), 20.3 (COCH3); Calcd for C21H29NO11 (Mol. Wt.: 471.46, Ex. Mass.: 471.17); ESI-
MS (positive mode) m/z: 494.164 [M+Na]+, 965.339 [2M+Na]+.
Fraction II: 0.04 g (8 %) of 3e as white crystals; mp: 112-114 C; []D +23 (c 0.20, CHCl3);
1H NMR (CDCl3, 360 MHz): δ (ppm) 7.40 (s, 1H, NH), 5.75 (d, 1H, J2’,3’ 10.5 Hz, H-2’),
5.50 (dd, 1H, J3’,4’ 3.2 Hz, J4’,5’ 1.0 Hz, H-4’), 5.26 (dd, 1H, J2’,3’ 10.5 Hz, J3’,4’ 3.2 Hz, H-3’),
19

4.41 (ddd, 1H, J5’,6’a 7.3 Hz, J5’,6’b 6.3 Hz, J4’,5’ 1.0 Hz, H-5’), 4.16 (dd, 1H, J6’a,6’b 11.6 Hz,
J5’,6’a 7.3 Hz, H-6’a), 4.07 (dd, 1H, J6’a,6’b 11.6 Hz, J5’,6’b 6.3 Hz, H-6’b), 2.20, 2.06, 2.01, 1.95
(4s, 12H, OCOCH3), 1.88-1.81 (m, 2H, CH2), 1.79-1.60 (m, 6H, 3  CH2), 1.52-1.41 (m, 2H,
CH2); 13C NMR (CDCl3, 90 MHz): δ (ppm) 170.3 (2), 168.9, 168.8 (CO), 160.3 (C-4), 113.1
(C-2), 100.8 (C-1’), 69.7, 69.3, 67.7, 66.0 (C-2’ - C-5’), 61.8 (C-6’), 37.0, 36.0, 24.3, 23.3 (2)
(5  CH2), 20.6 (2), 20.5 (2) (COCH3); Calcd for C21H29NO11 (Mol. Wt.: 471.46, Ex. Mass.:
471.17); ESI-MS (positive mode) m/z: 494.164 [M+Na]+, 965.336 [2M+Na]+.
Fraction III: 0.11 g (25%) of 414 as a white solid.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.2.5. (1’R)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-2,2-
dimethyl-4-imino-1,3-dioxolane (6a)
Prepared from 5 (0.50 g, 0.71 mmol) and acetone with AgOTf according to General
procedure I (section 3.2). Column chromatography (1:2 EtOAc-hexane than EtOAc) gave two
fractions.
Fraction I: 0.18 g (37%) of 6a as a colourless oil; Rf = 0.51 (1:2 EtOAc-hexane); []D +63 (c
0.52, CHCl3); 1H NMR (CDCl3, 360 MHz): δ (ppm) 8.04-7.24 (m, 20H, ArH), 7.73 (s, 1H,
NH), 6.80 (pseudo t, 1H, J2’,3’ 10.2 Hz, J3’,4’ 9.7 Hz, H-3’), 5.85 (d, 1H, J2’,3’ 10.2 Hz, H-2’),
5.76 (pseudo t, 1H, J4’,5’ 9.9 Hz, J3’,4’ 9.7 Hz, H-4’), 5.13 (ddd, 1H, J4’,5’ 9.9 Hz, J5’,6’b 4.5 Hz,
J5’,6’a 1.2 Hz, H-5’), 4.63 (dd, 1H, J6’a,6’b 12.0 Hz, J5’,6’a 1.2 Hz, H-6’a), 4.47 (dd, 1H, J6’a,6’b
12.0 Hz, J5’,6’b 4.5 Hz, H-6’b), 1.61, 1.29 (2s, 6H, CH3); 13C NMR (CDCl3, 90 MHz): δ (ppm)
166.0, 165.4, 165.3, 164.8 (CO), 160.5 (C-4, 3JH-2’,C-4 =~5.4 Hz, from HSQMBC at 125
MHz), 112.8 (C-2), 100.3 (C-1’), 70.8, 70.7, 70.5, 69.4 (C-2’ - C-5’), 63.1 (C-6’), 27.6, 26.7
(CH3); Calcd for C38H33 NO11 (Mol. Wt.: 679.67, Ex. Mass.: 679.21); ESI-MS (positive mode)
m/z: 702.190 [M+Na]+, 1381.399 [2M+Na]+.
20

Fraction II: 0.21 g (46%) of 732 as a white solid.
1
2
3
4
5
3.2.6. (1’R)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-2,2-diethyl-
6
7
8
4-imino-1,3-dioxolane (6c)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Prepared from 5 (0.50 g, 0.71 mmol) and pentan-3-one with AgOTf according to General
procedure I (section 3.2). Column chromatography (1:2 EtOAc-hexane than EtOAc) gave two
fractions.
Fraction I: 0.23 g (46 %) of 6c as a white foam; Rf = 0.49 (1:2 EtOAc-hexane); []D +60 (c
0.40, CHCl3); 1H NMR (CDCl3, 360 MHz): δ (ppm) 8.05-7.20 (m, 20H, ArH), 7.71 (s, 1H,
NH), 6.82 (pseudo t, 1H, J2’,3’ 10.2 Hz, J3’,4’ 9.8 Hz, H-3’), 5.92 (d, 1H, J2’,3’ 10.2 Hz, H-2’),
5.76 (pseudo t, 1H, J3’,4’ 9.8 Hz, J4’,5’ 9.7 Hz, H-4’), 5.13 (ddd, 1H, J4’,5’ 9.7 Hz, J5’,6’b 5.6 Hz,
J5’,6’a 2.2 Hz, H-5’), 4.64 (dd, 1H, J6’a,6’b 12.0 Hz, J5’,6’a 2.2 Hz, H-6’a), 4.50 (dd, 1H, J6’a,6’b
12.0 Hz, J5’,6’b 5.6 Hz, H-6’b), 1.87 (q, 2H, J 7.2 Hz, CH2CH3), 1.57 (q, 2H, J 7.4 Hz,
CH2CH3), 0.90 (t, 3H, J 7.4 Hz, CH2CH3), 0.63 (t, 3H, J 7.4 Hz, CH2CH3); 13C NMR (CDCl3,
90 MHz): δ (ppm) 165.9, 165.4 (2), 164.8 (CO), 160.6 (C-4, 3JH-2’,C-4 =~4.9 Hz), 116.6 (C-2),
99.9 (C-1’), 70.9, 70.7, 70.5, 69.5 (C-2’ - C-5’), 63.0 (C-6’), 31.2, 29.1 (CH2CH3), 7.8, 6.6
(CH2CH3); Calcd for C40H37NO11 (Mol. Wt.: 707.72, Ex. Mass.: 707.24); ESI-MS (positive
mode) m/z: 730.223 [M+Na]+, 1437.468 [2M+Na]+.
Fraction II: 0.16 g (35%) of 732 as a white solid.
21

3.2.7. (1’R)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-4-imino-1,3-
dioxolane-spiro-[2,1’’]-cyclopentane (6d)
1
2
3
4
5
6
7
8
9
Prepared from 5 (0.50 g, 0.71 mmol) and cyclopentanone with Ag2CO3 according to
General procedure I (section 3.2). Column chromatography (1:2 EtOAc-hexane than EtOAc)
gave two fractions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
Fraction I: 0.28 g (56 %) of 6d as a white foam; Rf = 0.55 (1:2 EtOAc-hexane); []D +62 (c
0.46, CHCl3); 1H NMR (CDCl3, 360 MHz): δ (ppm) 8.05-7.22 (m, 20H, ArH), 7.75 (s, 1H,
NH), 6.82 (pseudo t, 1H, J2’,3’ 10.2 Hz, J3’,4’ 9.8 Hz, H-3’), 5.87 (d, 1H, J2’,3’ 10.2 Hz, H-2’),
5.79 (pseudo t, 1H, J4’,5’ 9.9 Hz, J3’,4’ 9.8 Hz, H-4’), 5.12 (ddd, 1H, J4’,5’ 9.9 Hz, J5’,6’b 4.6 Hz,
J5’,6’a 2.8 Hz, H-5’), 4.63 (dd, 1H, J6’a,6’b 12.1 Hz, J5’,6’a 2.8 Hz, H-6’a), 4.49 (dd, 1H, J6’a,6’b
12.1 Hz, J5’6’b 4.6 Hz, H-6’b), 2.15-2.07 (m, 2H, CH2), 1.91-1.86 (m, 2H, CH2), 1.75-1.54 (m,
4H, 2  CH2); 13C NMR (CDCl3, 90 MHz): δ (ppm) 165.9, 165.3, 165.2, 164.8 (CO), 160.3
(C-4, 3JH-2’,C-4 =~4.9 Hz), 122.2 (C-2), 99.9 (C-1’), 70.8, 70.6, 70.5, 69.4 (C-2’ - C-5’), 62.9
(C-6’), 38.0, 36.3, 23.3, 22.4 (4  CH2); Calcd for C40H35NO11 (Mol. Wt.: 705.71, Ex. Mass.:
705.22); ESI-MS (positive mode) m/z: 728.207 [M+Na]+, 1433.434 [2M+Na]+
Fraction II: 0.08 g (18%) of 732 as a white solid.
3.2.8. (1’R)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-4-imino-1,3-
dioxolane-spiro-[2,1’’]-cyclohexane (6e)
Prepared from 5 (0.50 g, 0.71 mmol) and cyclohexanone with AgOTf according to
General procedure I (section 3.2). Column chromatography (1:2 EtOAc-hexane than EtOAc)
gave two fractions.
22

Fraction I: 0.14 g (28%) of 6e as a white foam; Rf = 0.61 (1:2 EtOAc-hexane than EtOAc);
1
2
3
[] +53 (c 0.40, CHCl3); 1H NMR (CDCl3, 360 MHz): δ (ppm) 8.04-7.24 (m, 20H, ArH),
D
4
5
6
7
8
7.75 (s, 1H, NH), 6.82 (pseudo t, 1H, J2’,3’ 10.2 Hz, J3’,4’ 9.9 Hz, H-3’), 5.87 (d, 1H, J2’,3’ 10.2
Hz, H-2’), 5.77 (pseudo t, 1H, J3’,4’ 9.9 Hz, J4’,5’ 9.7 Hz, H-4’), 5.14 (ddd, 1H, J4’,5’ 9.7 Hz,
J5’,6’b 5.0 Hz, J5’,6’a 2.4 Hz, H-5’), 4.61 (dd, 1H, J6’a,6’b 12.2 Hz, J5’,6’a 2.4 Hz, H-6’a), 4.49 (dd,
1H, J6’a,6’b 12.2 Hz, J5’,6’b 5.0 Hz, H-6’b), 1.86-1.83 (m, 2H, CH2), 1.55-1.26 (m, 8H, 4 
CH2); 13C NMR (CDCl3, 90 MHz): δ (ppm) 165.9, 165.3, 165.2, 164.8 (CO), 160.4 (C-4, 3JH-
2’,C-4 =~5.0 Hz), 113.5 (C-2), 99.8 (C-1’), 70.7 (2), 70.5, 69.5 (C-2’ - C-5’), 63.0 (C-6’), 37.0,
36.0, 24.1, 22.9, 22.8 (5  CH2); Calcd for C41H37NO11 (Mol. Wt.: 719.73, Ex. Mass.:
719.24); ESI-MS (positive mode) m/z: 742.224 [M+Na]+, 1461.462 [2M+Na]+
Fraction II: 0.16 g (35%) of 732 as a white solid.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.3. General procedure II for the preparation of O-perbenzoylated 1’,5’-anhydro-D-
glucitol-spiro-[1’,5]-2,2-disubstituted-oxazolidin-4-ones 8
Ulosonamide 732 was dissolved in a ketone or in a mixture of dry THF or toluene and 5
equiv of a ketone, then TfOH (1 equiv) was added. The mixture was stirred at reflux temp
until TLC (9:1 CHCl3–acetone) showed complete transformation of the starting material.
Then the mixture was diluted with chloroform, washed with satd aq NaHCO3, and with water,
dried, and the solvent was evaporated. The remaining syrup was purified by column
chromatography (18:1 CHCl3–acetone).
23

3.3.1. (1’S)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-2,2-
1
2
3
dimethyl-oxazolidin-4-one (8a)
4
5
6
7
8
9
Prepared from 7 (0.1 g, 0.15 mmol) and acetone (5 ml) according to General procedure II
(section 3.3) to give 0.09 g (89 %) of 8a as a white solid. Mp.: 104-107C; Rf = 0.74 (9:1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
CHCl3–acetone); []D +45 (c 0.40, CHCl3); 1H NMR (CDCl3, 360 MHz):  (ppm) 8.70 (s,
1H, NH), 7.99-7.20 (m, 20H, ArH), 6.09 (t, 1H, J2’,3’ 9.8 Hz, J3’,4’ 9.8 Hz, H-3’), 5.96 (d, 1H,
J2’,3’ 9.8 Hz, H-2’), 5.73 (t, 1H, J4’,5’ 9.8 Hz, J3’,4’ 9.8 Hz, H-4’), 4.66 (ddd, 1H, J4’,5’ 9.8 Hz,
J5’,6’b 5.5 Hz, J5’,6’a 2.4 Hz, H-5’), 4.58 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’a 2.4 Hz, H-6’a), 4.47 (dd,
1H, J6’a,6’b 12.3 Hz, J5’,6’b 5.5 Hz, H-6’b), 1.64 (s, 3H, CH3), 1.57 (s, 3H, CH3); 13C NMR
(CDCl3, 90 MHz):  (ppm) 166.0 (C-4), 165.8, 165.7, 165.1, 164.3 (CO), 133.4-128.1 (ArC),
100.5 (C-1’), 92.4 (C-2), 71.8, 70.1, 69.4, 68.3 (C-2’ - C-5’), 63.2 (C-6’), 29.5 (CH3), 28.3
(CH3); Calcd for C38H33NO11 (Mol. Wt.: 679.67, Ex. Mass.: 679.21); ESI-MS (positive mode)
m/z: 702.192 [M+Na]+, 1381.402 [2M+Na]+.
3.3.2. (1’S,2RS)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-2-ethyl-
2-methyl-oxazolidin-4-ones (8b)
Prepared from 7 (0.1 g, 0.15 mmol) and butanone (5 ml) according to General procedure
II (section 3.3) to give 0.1 g (92 %) an inseparable mixture of 8b as a white solid. Rf = 0.58
(9:1 CHCl3–acetone); []D +22 (c 0.42, CHCl3); 1H NMR (CDCl3, 360 MHz):  (ppm) 8.89
(s, 1H, NH), 8.05-7.24 (m, 20H, ArH), 6.10, 6.09 (t, 1H, J2’,3’ 10.4 Hz, J3’,4’ 9.8 Hz, H-3’),
5.99, 5.97 (d, 1H, J2’,3’ 10.4 Hz, H-2’), 5.72, 5.71 (t, 1H, J4’,5’ 9.8 Hz, J3’,4’ 9.8 Hz, H-4’), 4.63
(ddd, 1H, J4’,5’ 9.8 Hz, J5’,6’b 5.5 Hz, J5’,6’a 2.4 Hz, H-5’), 4.59 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’a
2.4 Hz, H-6’a), 4.45 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’b 5.5 Hz, H-6’b), 1.89, 1.85 (2q, 2H, J 7.5
24

Hz, CH2), 1.65, 1.56 (2s, 3H, CH3), 0.98, 0.95 (2t, 3H, J 7.5 Hz CH3); 13C NMR (CDCl3, 90
MHz):  (ppm) 166.4, 166.1 (C-4), 165.9, 165.6, 165.1, 164.3 (CO), 133.4-128.1 (ArC), 100.3
(C-1’), 94.9, 94.5 (C-2), 71.7, 70.3, 69.9, 69.4, 69.3, 68.6, 68.4 (C-2’ - C-5’), 63.2 (C-6’),
34.9, 33.7 (CH2), 27.3, 26.1 (CH3), 8.0, 7.5 (CH3); Calcd for C39H35NO11 (Mol. Wt.: 693.70,
Ex. Mass.: 693.22); ESI-MS (positive mode) m/z: 716.209 [M+Na]+, 1409.435 [2M+Na]+.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.3.3. (1’S)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-2,2-diethyl-
oxazolidin-4-one (8c)
Prepared from 7 (0.1 g, 0.15 mmol) and pentan-3-one (82 l, 0.75 mmol) in dry THF (5
ml) according to General procedure II (section 3.3) to give 0.07 g (69 %) of 8c as a white
solid. Mp.: 101-103C; Rf = 0.66 (9:1 CHCl3–acetone); []D +27 (c 0.32, CHCl3); 1H NMR
(CDCl3, 360 MHz):  (ppm) 9.07 (s, 1H, NH), 8.00-7.17 (m, 20H, ArH), 6.10 (t, 1H, J2,’3’ 9.8
Hz, J3’,4’ 9.8 Hz, H-3’), 6.00 (d, 1H, J2’,3’ 9.8 Hz, H-2’), 5.70 (t, 1H, J4’,5’ 9.8 Hz, J3’,4’ 9.8 Hz,
H-4’), 4.64 (ddd, 1H, J4’,5’ 9.8 Hz, J5’,6’b 6.7 Hz, J5’,6’a 2.4 Hz, H-5’), 4.60 (dd, 1H, J6’a,6’b 12.3
Hz, J5’,6’a 2.4 Hz, H-6’a), 4.45 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’b 6.7 Hz, H-6’b), 1.86, 1.75 (2q,
4H, J 7.0 Hz, CH2), 0.89, 0.85 (2t, 6H, J 7.0 Hz, CH3); 13C NMR (CDCl3, 90 MHz):  (ppm)
166.6 (C-4), 165.9, 165.6, 165.1, 164.3 (CO), 133.4-128.1 (ArC), 100.2 (C-1’), 97.1 (C-2),
71.6, 70.2, 69.4, 68.6 (C-2’ - C-5’), 63.3 (C-6’), 32.2 (CH2), 30.9 (CH2), 7.8 (CH3), 7.3 (CH3);
Calcd for C40H37NO11 (Mol. Wt.: 707.72, Ex. Mass.: 707.24); ESI-MS (positive mode) m/z:
730.225 [M+Na]+, 1437.464 [2M+Na]+.
25

3.3.4. (1’S)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-4-oxo-
oxazolidine-spiro-[2,1’’]-cyclopentane (8d)
1
2
3
4
5
6
7
8
9
Prepared from 7 (0.1 g, 0.15 mmol) and cyclopentanone (70 l, 0.75 mmol) in dry THF
(5 ml) according to General procedure II (section 3.3) to give 0.08 g (78 %) of 8d as a white
solid. Mp.: 180-182C; Rf = 0.72 (9:1 CHCl3–acetone); []D +49 (c 0.62, CHCl3); 1H NMR
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
(CDCl3, 360 MHz):  (ppm) 8.84 (s, 1H, NH), 8.04-7.28 (m, 20H, ArH), 6.08 (t, 1H, J2’,3’ 9.8
Hz, J3’,4’ 9.8 Hz, H-3’), 5.97 (d, 1H, J2’,3’ 9.8 Hz, H-2’), 5.73 (t, 1H, J4’,5’ 9.2 Hz, J3’,4’ 9.8 Hz,
H-4’), 4.63 (ddd, 1H, J4’,5’ 9.2 Hz, J5’,6’b 6.1 Hz, J5’,6’a 3.1 Hz, H-5’), 4.58 (dd, 1H, J6’a,6’b 12.3
Hz, J5’,6’a 3.1 Hz, H-6’a), 4.47 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’b 6.1 Hz, H-6’b), 2.08-1.71 (m,
8H, 4  CH2); 13C NMR (CDCl3, 90 MHz):  (ppm) 166.1 (C-4), 165.9, 165.7, 165.1, 164.3
(CO), 133.4-128.1 (ArC), 100.7 (C-1’), 100.1 (C-2), 71.8, 70.2, 69.4, 68.3 (C-2’ - C-5’), 63.2
(C-6’), 39.9, 37.7, 23.1, 22.6 (CH2); Calcd for C40H35NO11 (Mol. Wt.: 705.71, Ex. Mass.:
705.22); ESI-MS (positive mode) m/z: 728.210 [M+Na]+, 1433.435 [2M+Na]+.
3.3.5. (1’S)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-4-oxo-
oxazolidine-spiro-[2,1’’]-cyclohexane (8e)
Prepared from 7 (0.1 g, 0.15 mmol) and cyclohexanone (80 l, 0.75 mmol) in dry toluene
(5 ml) according to General procedure II (section 3.3) to give 0.07 g (69 %) of 8e as a white
solid. Mp.: 178-181C; Rf = 0.78 (9:1 CHCl3–acetone); []D +52 (c 0.46, CHCl3); 1H NMR
(CDCl3, 360 MHz):  (ppm) 9.00 (s, 1H, NH), 8.12-7.30 (m, 20H, ArH), 6.10 (t, 1H, J2’,3’ 9.8
Hz, J3’,4’ 9.8 Hz, H-3’), 6.00 (d, 1H, J2’,3’ 9.8 Hz, H-2’), 5.71 (t, 1H, J4’,5’ 9.8 Hz, J3’,4’ 9.8 Hz,
H-4’), 4.69 (ddd, 1H, J4’,5’ 9.8 Hz, J5’,6’b 6.7 Hz, J5’,6’a 3.1 Hz, H-5’), 4.63 (dd, 1H, J6’a,6’b 12.3
Hz, J5’,6’a 3.1 Hz, H-6’a), 4.45 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’b 6.7 Hz, H-6’b), 1.92-1.32 (m,
26

10H, 5  CH2); 13C NMR (CDCl3, 90 MHz):  (ppm) 166.4 (C-4, 3JH-2’,C-4 = 2.5 Hz from
HSQMBC at 125 MHz), 166.0, 165.7, 165.2, 164.3 (C’O), 133.4-128.2 (ArC), 100.1 (C-1’),
93.5 (C-2), 71.8, 70.3, 69.4, 68.3 (C-2’ - C-5’), 63.3 (C-6’), 39.0, 37.6, 24.3, 22.9, 22.6 (CH2);
Calcd for C41H37NO11 (Mol. Wt.: 719.73, Ex. Mass.: 719.24); ESI-MS (positive mode) m/z:
742.222 [M+Na]+, 1462.462 [2M+Na]+.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.3.6. (1’S)-2’,3’,4’,6’-Tetra-O-benzoyl-1’,5’-anhydro-D-glucitol-spiro-[1’,5]-4-oxo-
oxazolidine-spiro-[2,1’’]-cycloheptane (8f)
Prepared from 7 (0.1 g, 0.15 mmol) and cycloheptanone (81 l, 0.75 mmol) in dry
toluene (5 ml) according to General procedure II (section 3.3) to give 0.08 g (71 %) of 8f as a
white solid. Mp.: 124-126C; Rf = 0.55 (9:1 CHCl3–acetone); []D +59 (c 0.36, CHCl3); 1H
NMR (CDCl3, 360 MHz):  (ppm) 9.31 (s, 1H, NH), 8.00-7.18 (m, 20H, ArH), 6.08 (t, 1H,
J2’,3’ 9.8 Hz, J3’,4’ 9.8 Hz, H-3’), 5.98 (d, 1H, J2’,3’ 9.8 Hz, H-2’), 5.70 (t, 1H, J4’,5’ 9.8 Hz, J3’,4’
9.8 Hz, H-4’), 4.66 (ddd, 1H, J4’,5’ 9.8 Hz, J5’,6’b 6.8 Hz, J5’,6’a 3.1 Hz, H-5’), 4.61 (dd, 1H,
J6’a,6’b 12.3 Hz, J5’,6’a 3.1 Hz, H-6’a), 4.44 (dd, 1H, J6’a,6’b 12.3 Hz, J5’,6’b 6.8 Hz, H-6’b), 2.12-
1.45 (m, 12H, 6  CH2); 13C NMR (CDCl3, 90 MHz):  (ppm) 166.1 (C-4), 165.9, 165.6,
165.1, 164.2 (CO), 133.3-128.1 (ArC), 100.1 (C-1’), 97.2 (C-2), 71.8, 70.1, 69.4, 68.3 (C-2’ -
C-5’), 63.2 (C-6’), 42.4, 41.2, 28.2, 28.1, 21.4, 21.1 (CH2); Calcd for C42H39NO11 (Mol. Wt.:
733.76, Ex. Mass.: 733.25); ESI-MS (positive mode) m/z: 756.240 [M+Na]+, 1490.498
[2M+Na]+.
27

3.4. General procedure III for the removal of O-acyl protecting groups
1
2
3
4
5
6
7
8
9
An O-acylated compound was dissolved in the minimum volume of abs MeOH and a few
drops of NaOMe in MeOH (~1 M) were added. The mixture was stirred at rt until TLC (9:1
CHCl3–MeOH) showed complete transformation of the starting material. It was then
neutralized with a cation exchange resin Amberlyst 15 (H+ form). Filtration and solvent
removal left a syrup which was purified by column chromatography (CHCl3–MeOH).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.4.1. (1’S)-1’,5’-Anhydro-D-glucitol-spiro-[1’,5]-2,2-dimethyl-oxazolidin-4-one (9a)
Prepared from 8a (0.14 g, 0.20 mmol) according to General procedure III (section 3.4) to
give 0.05 g (94 %) of 9a as a white solid. Mp.: 97-99C; Rf = 0.3 (8:2 CHCl3–MeOH); []D
+50 (c 0.28, MeOH); 1H NMR (D2O 360 MHz):  (ppm) 3.90-3.67 (m, 5H, H-2’, H-3’ or H-
4’, H-5’, H-6’ab), 3.51 (pseudo t, 1H, J= 8.7 Hz, 7.7 Hz, H-3’ or H-4’), 1.61 (s, 3H, CH3),
1.58 (s, 3H, CH3); 13C NMR (D2O, 90 MHz):  (ppm) 168.4 (C-4), 102.3 (C-1’), 92.6 (C-2),
74.1, 73.6, 69.7, 69.4 (C-2’ - C-5’), 60.6 (C-6’), 28.6 (CH3), 27.1 (CH3); Calcd for C10H17NO7
(Mol. Wt.: 263.24, Ex. Mass.: 263.10); ESI-MS (positive mode) m/z: 286.088 [M+Na]+,
549.192 [2M+Na]+, 812.290 [3M+Na]+.
3.4.2. (1’S,2RS)-1’,5’-Anhydro-D-glucitol-spiro-[1’,5]-2-ethyl-2-methyl-oxazolidin-4-ones
(9b)
Prepared from 8b (0.17 g, 0.25 mmol) according to General procedure III (section 3.4) to
give 0.06 g (96 %) of 9b as a white solid. Rf = 0.3 (8:2 CHCl3–MeOH); []D +53 (c 0.46,
MeOH); 1H NMR (D2O 360 MHz):  (ppm) 3.82-3.44 (m, 6H, H-2’, H-3’, H-4’, H-5’, H-
28

6’ab), 1.79-1.75 (m, 2H, CH2), 1.51, 1.48 (2s, 3H, CH3), 0.90, 0.86 (2t, 3H, J 7.5 Hz CH3);
13C NMR (D2O, 90 MHz):  (ppm) 168.9, 168.6 (C-4), 102.2, 101.9 (C-1’), 95.2, 94.7 (C-2),
74.3, 73.9, 73.5, 69.8, 69.7, 69.5, 69.3 (C-2’ - C-5’), 60.5 (C-6’), 34.1, 33.0 (CH2), 26.4, 25.3
(CH3), 7.3, 6.9 (CH3); Calcd for: C11H19NO7 (Mol. Wt.: 277.27, Ex. Mass.: 277.12); ESI-MS
(positive mode) m/z: 300.104 [M+Na]+, 577.225 [2M+Na]+, 854.342 [3M+Na]+.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
3.4.3. (1’S)-1’,5’-Anhydro-D-glucitol-spiro-[1’,5]-2,2-diethyl-oxazolidin-4-one (9c)
Prepared from 8c (0.14 g, 0.20 mmol) according to General procedure III (section 3.4) to
give 0.05 g (91 %) of 9c as a white solid. Mp.: 70-72C; Rf = 0.3 (8:2 CHCl3–MeOH); []D
+48 (c 0.44, MeOH); 1H NMR (D2O 360 MHz):  (ppm) 3.82-3.61 (m, 5H, H-2’, H-3’ or H-
4’, H-5’, H-6’ab), 3.44 (t, 1H, J= 7.6 Hz, 7.6 Hz, H-3’ or H-4’) 1.82-1.75 (m, 4H, 2  CH2),
0.89, 0.87 (2t, 6H, J 7.5 Hz, 2  CH3); 13C NMR (D2O, 90 MHz):  (ppm) 168.9, (C-4), 101.9
(C-1’), 97.3 (C-2), 74.1, 73.5, 69.9, 69.4, (C-2’ - C-5’), 60.5 (C-6’), 31.4, 30.7 (CH2), 7.1, 6.9
(CH3); Calcd for C12H21NO7 (Mol. Wt.: 291.30, Ex. Mass.: 291.13); ESI-MS (positive mode)
m/z: 314.120 [M+Na]+, 605.255 [2M+Na]+, 896.387 [3M+Na]+.
3.4.4. (1’S)-1’,5’-Anhydro-D-glucitol-spiro-[1’,5]-oxazolidin-4-one-spiro-[2,1’’]-
cyclopentane (9d)
Prepared from 8d (0.19 g, 0.27 mmol) according to General procedure III (section 3.4) to
give 0.07 g (91 %) of 9d as a white solid. Mp.: 112-115C; Rf = 0.3 (8:2 CHCl3–MeOH); []D
+46 (c 0.43, MeOH); 1H NMR (D2O 360 MHz):  (ppm) 3.82-3.62 (m, 5H, H-2’, H-3’ or H-
4’, H-5’, H-6’ab), 3.44 (pseudo t, 1H, J = 7.8 Hz, 7.3 Hz, H-3’ or H-4’) 1.94-1.69 (m, 8H, 4 
CH2); 13C NMR (D2O, 90 MHz):  (ppm) 168.6, (C-4), 101.9, 101.8 (C-1’, C-2), 74.2, 73.6,
29