Influence of Steric Crowding on Diastereoselective Arabinofuranosylations

Article abstract of DOI:10.1021/acs.joc.5b00964

The occurrence of arabinofuranosides on the cell surface of Mycobacterium tuberculosis (Mtb) and their significance in controlling disease spurred interest in developing strategies for their diastereoselective synthesis. Mtb uses enzymes to achieve diastereoselectivity through noncovalent interactions. Of the two possible glycosidic linkages, chemically, 1,2-trans linkage is relatively easy to synthesize by taking advantage of neighboring group participation, whereas synthesis of the 1,2-cis linkage is notoriously difficult. In this article, stereochemical effects on the diastereoselectivity of arabinofuranosidation are investigated with thiopyridyl, imidate, and thiotolyl donors as well as differently crowded glycosyl acceptors; subtle differences in the stereochemical environment of the acceptors were observed to alter the diastereoselectivity of the furanoside formation. Results from this endeavor suggest that 1,2-cis arabinofuranosides can be synthesized conveniently by conducting the reaction at lower temperature on sterically demanding and less reactive substrates.

Full text of DOI:10.1021/acs.joc.5b00964

Page 1 of 26
The Journal of Organic Chemistry
Influence of Steric Crowding on the Diastereoselective Arabinofuranosylations
Maidul Islam,a Gaddamanugu Gayatrib and Srinivas Hothaa*
1
2
3
4
5
6
7
a Department of Chemistry, Indian Institute of Science Education and Research, Pune – 411 008, India
b Molecular Modelling Group, Indian Institute of Chemical Technology, Hyderabad 500 008, India
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
s.hotha@iiserpune.ac.in
Abstract:
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
Occurrence of arabinofuranosides in the cell surface of Mycobacterium tuberculosis (Mtb) and their
significance in controlling the disease spurred interest in developing strategies for their diastereoselective
synthesis. Mtb uses enzymes to achieve the diastereoselectivity through nonꢀcovalent interactions. Of the
two possible glycosidic linkages, chemically, 1,2ꢀtrans linkage is relatively easy to synthesize by taking
advantage of the neighbouring group participation whereas synthesis of the 1,2ꢀcis linkage is notoriously
difficult. In this article, stereochemical effects on the diastereoselectivity of arabinofuranosidation are
investigated with thiopyridyl, imidate and thiotolyl donors and differently crowded glycosyl acceptors;
subtle differences in the stereochemical environment of the acceptors were observed to alter the
diastereoselectivity of the furanoside formation.
Results from this endeavour suggest 1,2ꢀcis
arabinofuranosides can be synthesized conveniently by conducting the reaction at lower temperature on
sterically demanding and less reactive substrates.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 26
INTRODUCTION
1
2
3
4
5
6
7
8
9
Tuberculosis has plagued mankind for a long time and it has been continuing to show its socioeconomic
impact even now.1 Mycobacterium tuberculosis, the causative agent of tuberculosis is established to have a
thick cell wall which makes the small molecules difficult to enter for eventual killing.2 Fine structural
details of mycobacterial cell wall has been uncovered to find that arabinose and galactose in furanosyl form
along with other sugars.3 Arabinogalactan (AG) and Lipoarabinomannan (LAM) are the broad constituents
of the mycobacterial cell wall and the terminal arabinofuranosyl residues of AG are esterified with mycolic
acid.3 The presence of 1,2ꢀcis arabinofuranosyl residues at the terminal position of AG is yet another
characteristic that distinguishes AG and LAM.
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
Figure 1. Motif A of Mycobacterium tuberculosis cell wall
Chemical synthesis of oligosaccharides is important for understanding disease processes and the
development of various therapeutic agents.4a Chemical synthesis of 1,2ꢀcis furanosides is more challenging
compared to 1,2ꢀtrans furanosides.4b Several approaches have been developed for the synthesis of both 1,2ꢀ
trans and 1,2ꢀcis linkages of arabinofuranosides.5 Various glycosyl donors such as thio glycosides,5aꢀd alkyl
glycosides,5a,6a silyl glycosides,6b esters,5g haloꢀ,6c,d imidate,6e 1,2ꢀanhydro,6f,g orthoesters6hꢀj
were
investigated for the synthesis of mycobacterial arabinan fragments. One of the fragments of mycobacterial
cell wall is the motif A (1) which is a hexaarabinofuranoside containing two 1,2ꢀcis and four 1,2ꢀtrans
linkages (Figure 1).3
RESULTS AND DISCUSSION
ACS Paragon Plus Environment

Page 3 of 26
The Journal of Organic Chemistry
The synthesis of motif A has attracted the attention of many researchers and culminated into the
1
2
3
4
5
6
7
8
9
investigation of variety of glycosyl donors.7,6a,j,5a,g
Previous report5a on the synthesis of
pentaarabinofuranosyl motif A of Mycobacterium tuberculosis showed stereoselective formation of 1,2ꢀcis
disaccharide 4 from the thiopyridyl donor 2 and nꢀpentenyl furanoside 3. However, very little is mentioned
about the origin of the selectivity; further investigation on the stereochemical influence on the
stereoselectivity might pave way for a milder and general method for the synthesis of 1,2ꢀcis
arabinofuranosides. Hence, the initial aim of this research has therefore been to understand the factors that
influence stereoselectivity of the thiopyridylꢀbased arabinofuranosidation.
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
Scheme 1. Influence of anomeric configuration of the arabinofuranosyl acceptor on the furanoside formation
The furanosidation reaction between thiopyridyl donor 25a and βꢀpentenyl acceptor 3 afforded 1,2ꢀcis
disaccharide as observed earlier;5a surprisingly, the same reaction between αꢀpentenyl acceptor 5 and donor
2 resulted in the formation of disaccharides 6a and 6b in 1:1 ratio (Scheme 1).8 A possible explanation for
the difference in stereoselectivity may be the temperature and the steric environment around the C2ꢀOH of
acceptors 3 and 5. Earlier reports9aꢀb on the reciprocal donorꢀacceptor selectivity (RDAS) put forward by
FraserꢀReid have focused largely on the donor; however, the difference in outcome of the glycosidation due
to acceptors′ steric environment in this reaction is unique.9c
Formation of the 1,2ꢀtrans disaccharide 6a at 57 ⁰C can be ascribed to the lesser steric crowding around
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 26
the glycosyl acceptor 5 compared to the acceptor 3. In lieu of this, sterically less demanding methyl (7,8)
and more demanding decanyl (9,10) arabinofuranosides were thought out to study the effect of C1ꢀ
substituent of the glycosyl acceptor on the stereoselectivity (Table 1). The αꢀacceptors 7 and 9 afforded an
α,βꢀmixture of disaccharides 11 and 13 with thiopyridyl donor 2.8 Gratifyingly, the βꢀselectivity increased
from acceptor 7 to acceptor 9 which in turn was found to be equal to that of acceptor 5 which can be
attributed to the gradual increase in the steric crowding around the –OH of the acceptor. Less hindered βꢀ
acceptor 8 showed α,βꢀmixture (0.4:1.0) of disaccharides 12 whereas the sterically demanding decanyl
furanosyl acceptor 10 gave fully βꢀdiastereoselective product 14 (Table 1).8 Here again, the selectivity
towards βꢀdisaccharide formation was observed to be dependent on the overall steric crowding around the –
OH of the acceptor. The very high βꢀselectivity was observed for the acceptors 3 and 10 compared to that of
acceptor 8.8
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
Quantum chemical calculations were performed on the reactants and products to unravel the preferred
formation of products. Initially conformations were generated using the Macromodel module of
Schrodinger10 by employing MMFF94 force field with a convergence threshold of 0.005. Among the
conformations generated for the complexes, reactants (acceptors) and products, those conformations within
an energy cutꢀoff of <5.0 kcal/mol compared to the most stable conformation were selected. The selected
structures were optimized at M06ꢀ2X/STOꢀ3G level of theory as M06ꢀ2X method is found to be reliable for
modelling nonꢀcovalent interactions such as πꢀπ. It was shown previously that nonꢀcovalent interactions,
such as πꢀπ and hydrogen bonding interactions, play a major role in deciding the stability of molecules.11
Among these optimized structures the most stable structure in each case was considered and further
optimized at M06ꢀ2X/6ꢀ31G(d) level to understand the relative stability of α and β isomers. All the
optimizations were performed using Gaussian 09 programme package.12
The optimized structures of the most stable conformations show that β isomer is thermodynamically
preferred to α isomer.8 However, experimentally the α isomer is observed in minor quantities in the cases of
5,7ꢀ9 while 3 and 10 show no traces of α isomer. To account for this unexpected behaviour, atoms in
molecules (AIM13) analysis is carried out by considering the various arabinofuranosyl acceptors 3,5,7-10.
Fewer bond critical points and cage critical points are observed around the OH group in 5,7,8,9 (Table 2).
This also suggests a small number of nonꢀcovalent interactions around OH group. This in turn causes the
ACS Paragon Plus Environment

Page 5 of 26
The Journal of Organic Chemistry
donor molecule to experience less steric hindrance from the bulky substituents of acceptor and, therefore is
less accessible for the attack from both the sides resulting in the formation of α and β isomers, the later being
formed in major quantities. In case of 3 and 10 the ꢀOH group is surrounded by various nonꢀcovalent
interactions and also crowded by the bulky substituent which makes the ꢀOH group less accessible for the
attack from one of the faces. Also these systems show a greater number of cage critical points in turn
making the OH group less accessible for attack. Thus in these cases the donor group can attack only from
the side where the steric hindrance from the bulky substituent is less thereby forming βꢀisomer alone. These
results clearly suggest that the steric and electronic effects from the bulky substitutents and the nature of
substituents have a major influence on the product formation.
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
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 26
1
2
3
Table 1. Effect of steric crowding around the alcohol of the glycosyl acceptor
4
5
6
R1O
OH
O
7
8
9
OR2
OR1
BnO
BnO
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
5,7 9
,
conditions
LG
+
OR
Disaccharides (4,6,11-14)
OR2
R1O
HO
OBn
O
OR1
3,8,10
2
15 16
LG = -SPy ( ); -OC(=NH)CCl3 ( ); -STol ( )
R1 = -CH2Ph; R2 = -CH3 (7,8), -(CH2)3CH=CH (3,5), -(CH2)9CH3 (9,10)
Acceptor
BnO
OH
O
O
Donor
OBn
9
5
%
3
%
7
8
9
%
10
%
Product
No.
6
6
ND
α:β
Product
No.
4
4
ND
α:β
Product
No.
11
%
α:β
Product
No.
12
%
α:β
Product
No.
13
α:β
Product
No.
14
α:β
Yield Ratio
71
62
Yield Ratio
Yield Ratio
Yield Ratio
Yield Ratio
Yield Ratio
2a
1.0:1.0
0.1:1.0
ND
73
61
ND
0.0:1.0
0.0:1.0
ND
69
60
83
1.0:0.3
0.3:1.0
1.0:1.0
75
63
88
0.4:1.0
0.1:1.0
0.4:1.0
64
62
86
1.0:1.0
0.0:1.0
0.3:1.0
67
63
85
0.0:1.0
0.0:1.0
0.0:1.0
15b
16c
11
11
12
12
13
13
14
14
ND
aCH3I, CH2Cl2, 57 ⁰C, 4 Å MS powder, 15 h; bTMSOTf, CH2Cl2, ꢀ78 to ꢀ40 ⁰C; 4 Å MS powder, 1 h; c NIS, AgOTf, CH2Cl2, 0 ⁰C, 4 Å MS powder, 15 h; ND
denotes not determined
ACS Paragon Plus Environment

Page 7 of 26
The Journal of Organic Chemistry
1
2
3
Table 2. Optimized structures of the acceptors 5,3,7ꢀ10 along with bond critical points and electron density(ρ) values.
4
5
Optimized structure
Bond critical pointsa
Optimized structure
Bond critical pointsa
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
5
3
7
8
9
10
a:The side of attack by the donor is indicated by green (indicating feasibility of attack) and red (indicating nonꢀfeasibility of attack) curves. The OH group, which is the site of
attack, in the acceptor is highlighted.
40
41
42
43
44
45
46
47
48
49
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 26
1
2
3
4
5
6
7
8
9
Temperature of the reaction is yet another major influencing factor for the
diastereoselectivity. Accordingly, the arabinofuranosyl imidate 156e,5h and thiotolyl 165d
donors were synthesized and reacted at ꢀ78 ⁰C → ꢀ40 ⁰C and 0 ⁰C with glycosyl acceptors 3,
5, 7ꢀ10 respectively.8 The furanosidation between imidate 15 and acceptors 5, 7 and 9
showed increased ratio of βꢀdisaccharide compared to the corresponding thiopyridyl donor 2.
βꢀDisaccharides are observed when the furanosidation was conducted between imidate donor
15 and acceptors 3, 8 and 10.
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
Activation of thiotolyl donor 16 could not be carried out on glycosyl acceptors 3 and 5
since conditions employed (NIS/AgOTf) for the activation of thiotolyl donor 16 can also
activate nꢀpentenyl glycosides at 0 ⁰C. Further α:β ratios were measured for the
furanosidation between the thiotolyl donor 16 and the acceptors 7ꢀ10.
Mixture of
disaccharides was observed with acceptors 7, 8, 9 whereas the sterically demanding acceptor
10 gave βꢀdisaccharide only in good yield (Table 1).8 Hence, the stereoselectivity of the
arabinofuranosidation was observed to be influenced by the temperature and the steric
crowding around the glycosyl acceptor also.
Further, Cꢀ5 position of terminal residues of motif A (1) is esterified with mycolic acid
which can also impart steric crowding on the CꢀOH of the glycosyl acceptor.
Aforementioned discussion encouraged to consider three model disaccharides 17ꢀ19 which
are very similar to the motif A (1) in order to find out the steric influence of the Cꢀ5
substituent on the stereochemical outcome. Firstly, the silyl protected furanosyl acceptor 17
was subjected to the furanosidation with donor 15 at ꢀ78 ⁰C → ꢀ40 ⁰C to afford an α:β
mixture (0.4:1.0) of trisaccharides 20 in 60% yield. Further, furanosidation was performed
between the benzyl protected disaccharide 18 and donor 15 to observe an α:β mixture
(0.1:1.0) of trisaccharides 21 in 64% yield with increased ratio of βꢀtrisaccharides (Scheme
2). Subsequent furanosidation between the linoleate 19 as the glycosyl acceptor and the
ACS Paragon Plus Environment

Page 9 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
imidate donor 15 resulted in the formation of βꢀtrisaccharide 22 only suggesting that the
overall stereoelectronic conditions around the furanosyl acceptor influence the
stereochemical outcome (Scheme 2).8
9
Scheme 2. Effect of protecting groups at Cꢀ5 on the furanoside formation
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
Donor
Acceptor Product
% Yield
α:β Ratio
60
64
63
0.4:1.0
0.1:1.0
0.0:1.0
15
15
15
17
18
19
20
21
22
In continuation, tetrasaccharides 23-25 reacted with imidate donor 15 to afford an α:β
mixture of hexaarabinofuranosides 26-28 (Scheme 3). The individual ratios could not be
determined; however, the ratio shifted towards more βꢀhexaarabinofuranoside from
26→27→28 which further shows that the diastereoselectivity of the arabinofuranosidation
depends on the stereochemical factors around the hydroxyl group of the glycosyl acceptor.8,15
CONCLUSIONS
In conclusion, βꢀarabinofuranosidation was found to be influenced by the stereochemical
environment around the hydroxyl group of the acceptor and the temperature of the reaction.
1,2ꢀcis Arabinofuranosides can be synthesized conveniently by conducting the reaction at
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 26
1
2
3
4
Scheme 3. Synthesis of hexaarabinofuranosyl motif A
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
lower temperature on sterically demanding and less reactive substrates. Trends noticed in
monoꢀ, diꢀ saccharides were noticed to follow even for tetraꢀ saccharide acceptor. These
observations further support the hypothesis of reciprocal donor acceptor selectivity
matching.9c
EXPERIMENTAL SECTION
General Methods. Unless otherwise noted, materials were obtained from commercial
suppliers and were used without further purification. Unless otherwise reported all reactions
were performed under argon atmosphere. Removal of solvent in vacuo refers to distillation
using a rotary evaporator attached to an efficient vacuum pump. Products obtained as solids
or syrups were dried under high vacuum. Analytical thinꢀlayer chromatography was
performed on preꢀcoated silica plates (F254, 0.25 mm thickness); compounds were visualized
by UV light or by staining with anisaldehyde spray. Optical rotations were measured on a
digital polarimeter. IR spectra were recorded on a FTꢀIR spectrometer. NMR spectra were
ACS Paragon Plus Environment

Page 11 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
recorded either on a 400 or a 500 MHz with CDCl3 as the solvent and TMS as the internal
standard. High resolution mass spectroscopy (HRMS) was performed using a ESIꢀTOF mass
analyzer. Low resolution mass spectroscopy (LRMS) was performed on UPLCꢀMS with
TLC interface.
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
a) Synthesis of glycosyl acceptors (3,5,7-10): 3,5ꢀdiꢀOꢀbenzyl arabinofuranosyl acetonide5a,14
(4.00 g, 10.8 mmol), PTSA (0.23 g, 1.35 mmol) and alcohol (ROH, 13.5 mmol) were
⁰
dissolved in anhydrous CH2Cl2 and was stirred at 60 C for 2 h. The reaction mixture was
cooled to room temperature, neutralized with Et3N and purified by silica gel flash column
chromatography (nꢀhexane/EtOAc) to afford glycosyl acceptors 3, 5, 7ꢀ10 in 72ꢀ81% yield.
b) General procedure5a for the glycosylation using thiopyridyl donor 2: To a solution of
furanosyl acceptor (3,5,7ꢀ10) (250 µmol) and donor 2 (326 µmol) in anhydrous CH2Cl2 (10
mL) was added freshly activated 4Å molecular sieves powdered (0.40 g) and 5% CH3I in
CH2Cl2 at 25 ⁰C. The reaction mixture was heated to 57 ⁰C for 15 h, the reaction mixture
was filtered through a pad of Celite®. The filtrate was concentrated in vacuo to afford an
yellow coloured oil which was purified by silica gel flash column chromatography (nꢀ
hexane/EtOAc, 9:1, v/v) to obtain furanosides in 64ꢀ75% yield.
b) General procedure5g,6e for the glycosylation using imidate donor 15: To the solution of
acceptor (3,5,7ꢀ10) (250 µmol) and donor 15 (326 µmol) in anhydrous CH2Cl2 (10 mL) was
added freshly activated 4Å MS powder (0.400 g) at 25 ⁰C. After cooling to ꢀ78 °C, TMSOTf
(37.6 µmol) was added to the reaction mixture and gradually increased the temperature to ꢀ40
°C over 5 min. After 1.0 h, the reaction was neutralized by Et3N and filtered through a bed of
Celite®. The filtrate was concentrated in vacuo to obtain brown coloured oil that was purified
by silica gel flash column chromatography (nꢀhexane/EtOAc, 9:1, v/v) to afford furanosides
in 61ꢀ63% yield.
c) General procedure5d for the glycosylation using p-thiotolyl donor 16: To a solution of
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 26
1
2
3
4
5
6
7
8
9
acceptor (7ꢀ10) (250 µmol) and donor 16 (326 µmol) in anhydrous CH2Cl2 (10 mL) was
added freshly activated 4Å MS powder (0.400 g) at 25 ⁰C. After cooling to 0 °C, NIS (502
µmol) and AgOTf (50 µmol) were added to the reaction mixture and stirred for 1.5h at 0 °C,
the reaction was neutralized by Et3N and filtered through a bed of Celite®. The filtrate was
concentrated in vacuo to obtain reddish coloured oil that was purified by silica gel flash
column chromatography (nꢀhexane/EtOAc, 9:1, v/v) to afford furanosides in 83ꢀ88% yield.
General procedure2,3 for the preparation of trisaccharides (20,21,22) and hexasaccharides
(26,27,28) using imidate donor (15): To the solution of acceptor (17ꢀ19 or 23ꢀ25) (106 µmol)
and donor 15 (320 µmol) in anhydrous CH2Cl2 (10 mL) was added freshly activated 4Å MS
powder (0.400 g) at 25 ⁰C and stirred at 25 ⁰C for 10 minutes. After cooling to ꢀ78 °C,
TMSOTf (37.6 µmol) was added to the reaction mixture and gradually increased the
temperature to ꢀ40 °C over 5 min. After 1.0h, the reaction was neutralized by Et3N and
filtered through a bed of Celite®. The filtrate was concentrated in vacuo to obtain brown
coloured oil that was purified by silica gel flash column chromatography (nꢀhexane/EtOAc)
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
to afford furanosides in 46ꢀ50% yield.
25
4ꢀPentenyl 3,5ꢀdiꢀOꢀbenzylꢀβꢀ
D
ꢀarabinofuranoside (3): Yield: (3.49g, 81%); [α]D = ꢀ39.0 (c
= 1.0, CHCl3); 1H NMR (399.78 MHz, CDCl3): δ 1.64 (td, J = 15.4, 14.7, 7.6 Hz, 2H), 1.96 –
2.17 (m, 2H), 2.59 (d, J = 9.6 Hz, 1H), 3.44 (dt, J = 9.6, 6.6 Hz, 1H), 3.52 (d, J = 5.9 Hz,
2H), 3.77 (dt, J = 9.6, 6.5 Hz, 1H), 3.83 (t, J = 5.7 Hz, 1H), 4.14 (q, J = 5.6 Hz, 1H), 4.19 –
4.30 (m, 1H), 4.56 (s, 2H), 4.62 (d, J = 11.9 Hz, 1H), 4.76 (d, J = 11.9 Hz, 1H), 4.93 – 5.04
(m, 3H), 5.78 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 7.27 – 7.35 (m, 10H); 13C NMR (100.53
MHz, CDCl3): δ 28.3, 29.9, 67.5, 71.5, 71.8, 72.9, 77.6, 80.4, 84.5, 101.3, 114.6, 127.3(2C),
127.4(4C), 128.0(4C), 137.6(2C), 137.7; IR (CHCl3); 3619, 3030, 2921, 1546, 1455, 1212,
1104, 699 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C24H30NaO5 421.1991, found
421.1989.
ACS Paragon Plus Environment

Page 13 of 26
The Journal of Organic Chemistry
1
2
3
4
5
4ꢀPentenyl
2ꢀOꢀ[2,3,5ꢀtriꢀOꢀbenzyl
βꢀDꢀarabinofuranosyl]ꢀ3,5ꢀdiꢀOꢀbenzyl
βꢀDꢀ
25
1
arabinofuranoside (4): Yield: (0.122g, 61%); [α]D = ꢀ43.8 (c = 1.0, CHCl3); H NMR
(399.78 MHz, CDCl3): δ 1.59 (q, J = 7.1 Hz, 2H), 2.01 (q, J = 7.3 Hz, 2H), 3.38 (dt, J = 9.6,
6.6 Hz, 1H), 3.46 – 3.56 (m, 3H), 3.57 – 3.62 (m, 1H), 3.71 (dt, J = 9.6, 6.9 Hz, 1H), 4.13 (td,
J = 9.9, 8.7, 5.7 Hz, 5H), 4.29 (d, J = 12.0 Hz, 1H), 4.37 – 4.45 (m, 2H), 4.49 (d, J = 11.3 Hz,
1H), 4.52 (s, 2H), 4.57 (s, 2H), 4.60 (d, J = 11.8 Hz, 1H), 4.68 (d, J = 11.8 Hz, 1H), 4.80 (d, J
= 11.3 Hz, 1H), 4.90 (t, J = 1.2 Hz, 1H), 4.92 – 4.96 (m, 1H), 5.09 (d, J = 4.2 Hz, 1H), 5.16
(d, J = 2.5 Hz, 1H), 5.70 (ddt, J = 17.1, 10.4, 6.6 Hz, 1H), 7.18 – 7.41 (m, 25H); 13C NMR
(100.53 MHz, CDCl3): δ 28.8, 30.2, 67.1, 71.6, 72.2(2C), 72.4, 72.5, 73.0, 73.2, 79.0, 80.2,
80.7, 82.6, 82.9, 83.9, 98.4, 100.0, 114.9, 127.5, 127.5, 127.6(2C), 127.6(2C), 127.7(2C),
127.7(2C), 127.8, 128.0(2C), 128.3(3C), 128.3(3C), 128.3(3C), 128.3(3C), 137.7(2C), 137.8,
137.9, 138.0, 138.0; IR (CHCl3): 3035, 2920, 1550, 1455, 1212, 1104, 699 cmꢀ1; HRMS
(TOF) m/z [M + Na]+ calcd. for C50H56NaO9 823.3822, found 823.3832.
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
4ꢀPentenyl 3,5ꢀdiꢀOꢀbenzylꢀαꢀD
ꢀarabinofuranoside (5): Yield: (3.49g, 81%); [α]D25 = +97.8 (c
= 1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 1.70 (dt, J = 14.2, 6.9 Hz, 2H), 2.05 – 2.19
(m, 2H), 3.31 (d, J = 10.2 Hz, 1H), 3.40 – 3.54 (m, 2H), 3.57 – 3.78 (m, 2H), 3.87 (s, 1H),
4.14 (d, J = 9.6 Hz, 1H), 4.26 (s, 1H), 4.50 (t, J = 10.8 Hz, 2H), 4.65 (dd, J = 22.6, 11.9 Hz,
2H), 4.98 (dt, J = 20.9, 10.4 Hz, 3H), 5.82 (td, J = 16.7, 16.2, 6.6 Hz, 1H), 7.24 – 7.35 (m,
10H); 13C NMR (100.53 MHz, CDCl3): δ 28.7, 30.2, 66.9, 69.8, 71.9, 73.7, 77.8, 83.3, 85.2,
109.1, 114.7, 127.7(3C), 127.8(2C), 128.0, 128.4(2C), 128.5(2C), 137.0, 137.9, 138.3; IR
(CHCl3): 3615, 3040, 2925, 1546, 1455, 1212, 1104, 712 cmꢀ1; HRMS (TOF) m/z [M + Na]+
calcd for C24H30NaO5 421.1991,found 421.1989.
4ꢀPentenyl
3,5ꢀdiꢀOꢀbenzylꢀ2ꢀOꢀ(2,3,5ꢀtriꢀOꢀbenzyl
αꢀarabinofuranosyl)
αꢀDꢀ
1
arabinofuranoside (6a) [as obtained from the 1:1 mixture of disaccharides 6a,6b]: H NMR
(399.78 MHz, CDCl3): δ 1.68 (q, J = 7.0 Hz, 2H), 2.10 (p, J = 6.9 Hz, 2H), 3.36 – 3.42 (m,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 26
1
2
3
4
5
6
7
8
9
2H), 3.44 (d, J = 3.0 Hz, 2H), 3.54 (m, 3H), 3.61 (d, J = 3.8 Hz, 2H), 3.73 (dt, J = 9.6, 6.6
Hz, 1H), 3.99 (dd, J = 6.4, 2.9 Hz, 1H), 4.11 (d, J = 2.0 Hz, 1H), 4.20 – 4.23 (m, 2H), 4.28 –
4.49 (m, 10H), 5.09 (s, 1H), 5.13 (s, 1H), 5.72 – 5.81 (m, 1H), 7.24 – 7.33 (m, 25H). 13C
NMR (100.53 MHz, CDCl3): δ 28.7, 28.7, 66.9, 69.8, 71.9, 72.0, 72.5, 73.0, 73.3, 77.2, 80.5,
80.8, 83.5, 84.0(2C), 86.3, 88.4, 105.6, 106.9, 114.8, 127.5(2C), 127.6(3C), 127.9(4C), 128.0,
128.1(4C), 128.2(4C), 128.4(4C), 137.4, 137.6, 137.8, 138.2, 138.3.
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
4ꢀPentenyl
3,5ꢀdiꢀOꢀbenzylꢀ2ꢀOꢀ(2,3,5ꢀtriꢀOꢀbenzyl
αꢀD
ꢀarabinofuranosyl)
βꢀDꢀ
1
arabinofuranoside (6b) [as obtained from the 1:1 mixture of disaccharides 6a,6b]: H NMR
(399.78 MHz, CDCl3): δ 1.68 (q, J = 7.0 Hz, 2H), 2.10 (p, J = 6.9 Hz, 2H), 3.36 – 3.42 (m,
2H), 3.44 (d, J = 3.0 Hz, 2H), 3.54 (dd, J = 8.6, 4.7 Hz, 3H), 3.61 (d, J = 3.8 Hz, 2H), 3.73
(dt, J = 9.6, 6.6 Hz, 1H), 3.99 (dd, J = 6.4, 2.9 Hz, 1H), 4.11 (d, J = 2.0 Hz, 1H), 4.20 – 4.23
(m, 2H), 4.28 – 4.49 (m, 10H), 4.98 (s, 1H), 5.07 (d, J = 4.2 Hz, 1H), 5.75 – 5.84 (m, 1H),
7.24 – 7.33 (m, 25H). 13C NMR (100.53 MHz, CDCl3): δ 28.7, 30.2, 66.8, 70.0, 72.1, 72.3,
72.4, 73.0, 73.2, 77.2, 79.9, 80.9, 82.8, 83.9(2C), 86.0, 92.2, 100.2, 105.8, 114.6, 127.5(2C),
127.6(3C), 127.9(4C), 128.0, 128.1(4C), 128.2(4C), 128.4(4C), 136.9, 137.1, 137.5, 138.0,
138.1.
25
Methyl 3,5ꢀdiꢀOꢀbenzylꢀαꢀ
D
ꢀarabinofuranoside (7): Yield: (2.90g, 78%); [α]D = +122.8 (c
= 1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 3.39 (s, 3H), 3.43 (m, 2H), 3.63 (dd, J =
10.4, 2.5 Hz, 1H), 3.82 (d, J = 3.3 Hz, 1H), 4.12 (d, J = 6.9 Hz, 1H), 4.21 – 4.29 (m, 1H),
4.48 (dd, J = 19.6, 12.1 Hz, 2H), 4.58 (d, J = 11.9 Hz, 1H), 4.67 (d, J = 12.3 Hz, 1H), 4.89 (s,
1H), 7.22 – 7.35 (m, 10H); 13C NMR (101 MHz, CDCl3): δ 55.1, 69.6, 71.9, 73.5, 78.0, 83.2,
84.8, 110.2, 127.7(3C), 127.8(2C), 127.9, 128.3(2C), 128.4(2C), 136.9, 137.6; IR (CHCl3):
3618, 3042, 2925, 1550, 1455, 1215, 1100, 688 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for
C20H24NaO5 367.1521, found 367.1521.
25
Methyl 3,5ꢀdiꢀOꢀbenzylꢀβꢀ
D
ꢀarabinofuranoside (8): Yield: (2.90g, 78%); [α]D = ꢀ39.8 (c =
ACS Paragon Plus Environment

Page 15 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1.0, CHCl3); 1H NMR (399.78 MHz, CDCl3): δ 2.67 (bs, 1 H), 3.38 (s, 3H), 3.52 (d, J = 5.7
Hz, 2H), 3.84 (t, J = 5.8 Hz, 1H), 4.14 (q, J = 5.6 Hz, 1H), 4.24 (t, J = 5.3 Hz, 1H), 4.55 (d, J
= 2.2 Hz, 2H), 4.61 (d, J = 11.9 Hz, 1H), 4.74 (d, J = 11.9 Hz, 1H), 4.83 (d, J = 4.7 Hz, 1H),
7.23 – 7.38 (m, 10H); 13C NMR (100.53 MHz, CDCl3): δ 55.3, 71.8, 72.0, 73.2, 77.9, 80.7,
84.5, 102.6, 127.6(4C), 127.7(2C), 128.3(4C), 137.9, 137.9; IR (CHCl3): 3612, 3032, 2922,
1555, 1455, 1218, 1104, 685 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C20H24NaO5
367.1521, found 367.1519 .
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
Decanyl 3,5ꢀdiꢀOꢀbenzylꢀαꢀD
ꢀarabinofuranoside (9): Yield: (3.81g, 75%); [α]D25 = +91.6 (c =
1
1.0, CHCl3); H NMR (399.78MHz, CDCl3): δ 0.81 – 0.93 (m, 3H), 1.16 – 1.38 (m, 14H),
1.59 (q, J = 6.7 Hz, 2H), 3.34 – 3.53 (m, 3H), 3.61 – 3.75 (m, 2H), 3.86 (d, J = 3.1 Hz, 1H),
4.14 (s, 1H), 4.21 – 4.27 (m, 1H), 4.45 – 4.53 (m, 2H), 4.64 (dd, J = 27.6, 12.1 Hz, 2H), 5.00
(s, 1H), 7.21 – 7.39 (m, 10H); 13C NMR (10.53 MHz, CDCl3): δ 14.1, 22.6, 26.0, 29.3, 29.4,
29.5, 29.5, 29.6, 31.8, 67.6, 69.7, 71.8, 73.6, 78.0, 83.0, 85.2, 108.9, 127.6, 127.7(2C),
127.8(2C), 127.9, 128.3(2C), 128.5(2C), 137.0, 137.9; IR (CHCl3): 3622, 3030, 2925, 1552,
1455, 1219, 1104, 683 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C29H42NaO5 493.2930,
found 493.2929.
25
Decanyl 3,5ꢀdiꢀOꢀbenzylꢀβꢀ
D
ꢀarabinofuranoside (10): Yield: (3.66g, 72%); [α]D = +39.6 (c
= 1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H), 1.26 (s, 14H), 1.43
– 1.62 (m, 2H), 2.64 (d, J = 9.0 Hz, 1H), 3.41 (dt, J = 9.5, 6.7 Hz, 1H), 3.53 (d, J = 5.9 Hz,
2H), 3.74 (dt, J = 9.5, 6.8 Hz, 1H), 3.83 (t, J = 5.7 Hz, 1H), 4.14 (q, J = 5.7 Hz, 1H), 4.24 (dt,
J = 9.9, 5.5 Hz, 1H), 4.55 (s, 2H), 4.62 (d, J = 11.9 Hz, 1H), 4.76 (d, J = 11.9 Hz, 1H), 4.95
(dd, J = 4.7, 2.8 Hz, 1H), 7.24 – 7.35 (m, 10H); 13C NMR (100.53 MHz, CDCl3): δ 14.1,
22.6, 26.0, 29.3, 29.4, 29.4, 29.5(2C), 31.8, 68.4, 71.7, 72.1, 73.2, 77.9, 80.6, 84.9, 101.5,
127.6(2C), 127.6(4C), 128.3(4C), 138.0(2C); IR (CHCl3): 3625, 3025, 2921, 1548, 1458,
1212, 1113, 698 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C29H42NaO5 493.2930, found
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 26
1
2
3
4
5
6
493.2929.
Methyl
2ꢀOꢀ[2,3,5ꢀtriꢀOꢀbenzyl
βꢀ
Dꢀarabinofuranosyl]ꢀ3,5ꢀdiꢀOꢀbenzyl
αꢀDꢀ
7
8
arabinofuranoside (11): An analytical sample for characterization purposes was obtained by
9
purification of the residue resulting from the aforementioned general reaction procedure
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
25
using the imidate donor (15) as the glycosyl donor. Yield: (0.13g, 60%); [α]D = ꢀ49.0 (c =
1
1.0, CHCl3); H NMR (399.78 MHz, CDCl3): δ 3.37 (s, 3H), 3.48 – 3.63 (m, 3H), 3.94 – 4.
01 (m, 1H), 4.09 (dd, J = 5.8, 2.5 Hz, 2H), 4.18 – 4.23 (m, 1H), 4.26 (s, 1H), 4.36 (td, J =
12.3, 1.7 Hz, 2H), 4.43 – 4.69 (m, 10H), 4.89 (s, 1H), 5.06 (d, J = 3.9 Hz, 1H), 7.16 – 7.38
(m, 25H); 13C NMR (100.53 MHz, CDCl3): δ 54.9, 70.1, 72.0, 72.2, 72.3, 72.5, 73.0, 73.3,
80.0, 81.3, 82.9, 83.9, 84.0, 85.9, 100.2, 106.9, 127.5(3C), 127.5(3C), 127.6, 127.7(5C),
127.9, 128.0(2C), 128.2(2C), 128.3(5C), 128.4(3C), 137.6, 138.0(2C), 138.1(2C); IR
(CHCl3): 3033, 2923, 1552, 1459, 1213, 1101, 695 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd
for C46H50NaO9 769.3353, found 769.3358.
Methyl
2ꢀOꢀ[2,3,5ꢀtriꢀOꢀbenzyl
βꢀ
D
ꢀarabinofuranosyl]ꢀ3,5ꢀdiꢀOꢀbenzyl
βꢀDꢀ
arabinofuranoside (12): An analytical sample for characterization purposes was obtained by
purification of the residue resulting from the aforementioned general reaction procedure
25
using the imidate donor (15) as the glycosyl donor. Yield: (0.14g, 63%); [α]D = ꢀ7.6 (c =
1
1.0, CHCl3); H NMR (399.78 MHz, CDCl3): δ 3.23 (s, 3H), 3.50 (qd, J = 9.8, 6.2 Hz, 2H),
3.56 – 3.66 (m, 2H), 4.05 – 4.17 (m, 6H), 4.49 – 4.55 (m, 6H), 4.57 (s, 1H), 4.58 – 4.71 (m,
3H), 4.76 (d, J = 4.1 Hz, 1H), 5.17 (d, J = 4.3 Hz, 1H), 7.08 – 7.37 (m, 25H); 13C NMR
(100.53 MHz, CDCl3): δ 54.2, 71.9, 72.2, 72.3, 72.5, 72.6, 73.1, 73.3, 79.7, 80.1, 82.9, 83.1,
83.5, 84.2, 102.0(2C), 127.5(2C), 127.6(3C), 127.7(4C), 127.7(5C), 128.3(5C), 128.3(4C),
128.4(2C), 137.4, 137.9(2C), 137.9, 138.1; IR (CHCl3): 3030, 2921, 1546, 1455, 1212, 1104,
699 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C46H50NaO9 769.3353, found 769.3358.
Decanyl
3,5ꢀdiꢀOꢀbenzylꢀ2ꢀOꢀ(2,3,5ꢀtriꢀOꢀbenzyl
αꢀ
D
ꢀarabinofuranosyl)
βꢀDꢀ
ACS Paragon Plus Environment

Page 17 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
arabinofuranoside (13): An analytical sample for characterization purposes was obtained by
purification of the residue resulting from the aforementioned general reaction procedure
using the imidate donor (15) as the glycosyl donor. Yield: (0.11g, 62%); [α]D25 = ꢀ31.4 (c =
1.0, CHCl3). 1H NMR (399.78 MHz, CDCl3): δ 0.87 (t, J = 6.8 Hz, 3H), 1.24 (s, 14H), 1.52 –
1.59 (m, 2H), 3.42 (d, J = 3.0 Hz, 1H), 3.45 (d, J = 2.9 Hz, 1H), 3.83 (dd, J = 6.4, 2.8 Hz,
1H), 4.06 (d, J = 4.2 Hz, 1H), 4.11 (dt, J = 7.5, 4.3 Hz, 3H), 4.14 – 4.27 (m, 5H), 4.45 – 4.61
(m, 10H), 5.02 (d, J = 4.3 Hz, 1H), 5.19 (s, 1H), 7.27 – 7.34 (m, 25H). 13C NMR (100.53
MHz, CDCl3): δ 14.1 , 22.7 , 26.1 , 29.3 , 29.4 , 29.6(2C) , 31.9 , 67.8 , 69.1 , 70.0 71.8 ,
72.2 , 73.8 , 73.6 , 80.8 , 80.6 , 81.1 , 81.4 , 82.9 , 83.2 , 83.9 , 87.4 , 100.4 , 106.2 , 127.6(3C)
, 127.7(4C) , 127.8(2C) , 128.0(2C) , 128.2 , 128.3(3C) , 128.4(4C) , 128.5(2C), 136.9(4C) ,
136.9 , 137.1 , 137.6 , 138.1(2C). IR (CHCl3): 3014, 2928, 1555, 1453, 1219, 1117, 696 cmꢀ
1. HRMS (TOF) m/z [M + Na]+ calcd for C55H68NaO9 895.4761, found 895.4752.
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
Decanyl
2ꢀOꢀ[2,3,5ꢀtriꢀOꢀbenzyl
βꢀDꢀarabinofuranosyl]ꢀ3,5ꢀdiꢀOꢀbenzyl
βꢀDꢀ
arabinofuranoside (14): An analytical sample for characterization purposes was obtained by
purification of the residue resulting from the aforementioned general reaction procedure
25
using the imidate donor (15) as the glycosyl donor. Yield: (0.12g, 63%); [α]D = +5.4 (c =
1
1.0, CHCl3); H NMR (399.78 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H), 1.25 (s, 14H), 1.52
(s, 2H), 3.21 – 3.32 (m, 1H), 3.56 (dddd, J = 39.9, 18.2, 9.6, 6.4 Hz, 5H), 4.06 – 4.16 (m,
6H), 4.47 – 4.63 (m, 8H), 4.67 (d, J = 11.9 Hz, 2H), 4.86 (d, J = 4.1 Hz, 1H), 5.18 (d, J = 3.9
Hz, 1H), 7.16 – 7.38 (m, 25H); 13C NMR (100.53 MHz, CDCl3): δ 14.1, 22.7, 26.3, 29.4,
29.6, 29.6, 29.7, 29.8, 31.9, 67.6, 71.9, 72.4, 72.5, 72.6, 72.9, 73.0, 73.3, 79.5, 80.0, 83.2(2C),
83.5, 84.5, 101.0, 102.2, 127.5, 127.5(5C), 127.6, 127.7(5C), 127.7, 128.3(5C), 128.3(5C),
128.4(2C), 137.7, 137.8, 138.0, 138.1, 138.1; IR (CHCl3): 3012, 2928, 1552, 1455, 1218,
1114, 697 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C55H68NaO9 895.4761, found
895.4752.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 26
1
2
3
4
5
6
1,2ꢀOꢀIsopropylidene 3ꢀOꢀ[3ꢀOꢀbenzylꢀ5ꢀOꢀtertꢀbutyldiphenylsilylꢀαꢀ
D
ꢀarabinofuranosyl]ꢀ5ꢀ
25
1
Oꢀtertꢀbutyldiphenylsilylꢀβꢀ
D
ꢀarabinofuranose (17): [α]D = +58.2 (c = 1.0, CHCl3); H
7
8
9
NMR (399.78MHz, CDCl3): δ 1.07 (s, 9H), 1.10 (s, 9H), 1.37 (s, 3H), 1.42 (s, 3H), 3.52 –
3.62 (m, 2H), 3.79 – 3.88 (m, 2H), 3.89 – 3.97 (m, 1H), 4.10 (s, 1H), 4.20 (s, 1H), 4.30 (dd, J
= 10.6, 2.7 Hz, 2H), 4.57 (dd, J = 12.1, 1.7 Hz, 1H), 4.67 (s, 1H), 4.69 – 4.75 (m, 2H), 5.28 –
5.39 (m, 1H), 5.96 (d, J = 3.6 Hz, 1H), 7.30 – 7.40 (m, 11H), 7.41 – 7.55 (m, 6H), 7.65 – 7.69
(m, 2H), 7.73 (td, J = 7.5, 3.9 Hz, 6H); 13C NMR (100.53 MHz, CDCl3): δ 19.0, 19.1, 26.0,
26.7(3C), 26.7(3C), 26.9, 63.2, 63.8, 71.8, 77.4, 78.8, 84.6, 84.6, 84.9, 85.9, 105.8, 107.2,
112.4, 127.6(5C), 127.7, 127.9(4C), 128.3(2C), 129.6, 129.6, 130.0, 130.0, 132.0, 132.2,
133.1, 133.2, 135.5(4C), 135.5(5C), 137.8; IR (CHCl3): 3618, 3031, 2921, 1547, 1456, 1212,
1104, 691 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C52H64NaO9Si2 911.3987, found
911.3979.
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
1,2ꢀOꢀIsopropylidene
3ꢀOꢀ[3,5ꢀdiꢀOꢀbenzylꢀαꢀDꢀarabinofuranosyl]ꢀ5ꢀOꢀbenzylꢀβꢀDꢀ
arabinofuranose (18): [α]D25 = +42.2 (c = 1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 1.32
(s, 3H), 1.52 (s, 3H), 2.34 (s, 1H), 3.60 (td, J = 11.8, 11.3, 3.9 Hz, 2H), 3.70 – 3.80 (m, 2H),
3.92 – 3.96 (m, 1H), 3.99 – 4.02 (m, 1H), 4.15 (dd, J = 8.7, 3.5 Hz, 2H), 4.17 – 4.20 (m, 1H),
13
4.41 – 4.60 (m, 7H), 5.16 (s, 1H), 5.85 (d, J = 3.9 Hz, 1H), 7.23 – 7.38 (m, 15H); C NMR
(100.53 MHz, CDCl3): δ 26.3, 27.1, 62.5, 69.4, 72.1, 72.2, 73.3, 80.4, 80.7, 83.4, 85.5, 86.2,
88.3, 105.2, 105.8, 112.9, 127.6, 127.7(4C), 127.9(4C), 128.3(4C), 128.4(2C), 137.3, 137.6,
137.8; IR (CHCl3): 3617, 3036, 2918, 1549, 1445, 1222, 1114, 689 cmꢀ1; HRMS (TOF) m/z
[M + Na]+ calcd for C34H40NaO9 615.2570, found 615.2561.
1,2ꢀOꢀIsopropylidene
3ꢀOꢀ[3ꢀOꢀbenzylꢀ5ꢀOꢀ(((9Z,12Z)ꢀoctadecaꢀ9,12ꢀdienoyl))ꢀαꢀDꢀ
25
arabinofuranosyl]ꢀ5ꢀOꢀ[(((9Z,12Z)ꢀoctadecaꢀ9,12ꢀdienoyl))]ꢀβꢀ
D
ꢀarabinofuranose (19): [α]D
= +49.6 (c = 1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 0.87 – 0.89 (m, 6H), 1.20 – 1.37
(m, 35H), 1.53 (s, 3H), 1.59 (d, J = 7.2 Hz, 2H), 2.04 (dt, J = 14.9, 7.2 Hz, 8H), 2.30 (dt, J =
ACS Paragon Plus Environment

Page 19 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
11.4, 7.4 Hz, 4H), 2.77 (t, J = 6.4 Hz, 2H), 3.76 (d, J = 5.8 Hz, 3H), 4.10 – 4.19 (m, 3H), 4.20
– 4.26 (m, 3H), 4.52 (d, J = 12.0 Hz, 1H), 4.64 – 4.72 (m, 2H), 5.10 (d, J = 1.7 Hz, 1H), 5.13
(s, 1H), 5.35 (tq, J = 7.3, 4.7, 3.6 Hz, 8H), 5.90 (d, J = 4.1 Hz, 1H), 7.28 – 7.37 (m, 5H);13C
NMR (100.53 MHz, CDCl3): δ 14.1, 14.1, 22.5, 22.6, 24.8, 24.8, 25.6, 26.4, 27.2(4C),
29.1(4C), 29.2, 29.3(3C), 29.5, 29.6, 29.7, 29.7, 31.5, 31.9, 34.0, 34.0, 63.3, 63.5, 72.3, 80.1,
80.2, 80.6, 82.6, 85.0, 85.1, 105.4, 107.5, 113.3, 127.7(2C), 127.8, 128.0, 128.0, 128.5(2C),
129.7, 129.7, 130.0, 130.0, 130.0, 130.2, 137.4, 173.2, 173.4; IR (CHCl3): 3627, 3031, 2921,
1753, 1551, 1448, 1218, 1104, 698 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C56H88NaO11
959.6224, found 959.6216.
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
1,2ꢀOꢀIsopropylidene 3ꢀOꢀ[(3ꢀOꢀbenzylꢀ5ꢀOꢀtertꢀbutyldiphenylsilylꢀαꢀDꢀarabinofuranosyl)ꢀ
2ꢀOꢀ(2,3,5ꢀtriꢀOꢀbenzyl βꢀ ꢀarabnofuranosyl)]ꢀ5ꢀOꢀtertꢀbutyldiphenylsilylꢀβꢀDꢀ
D
arabinofuranose (20) [resonances for the major βꢀisomer as obtained from the 0.4:1.0 α,β
mixture of trisaccharides]: 1H NMR (399.78 MHz, CDCl3): δ 0.89 (s, 9H), 0.95 (s, 9H), 1.20
(s, 3H), 1.25 (s, 3H), 3.48 (d, J = 5.2 Hz, 2H), 3.67 – 3.73 (m, 4H), 3.98 – 4.02 (m, 1H), 4.02
– 4.06 (m, 2H), 4.12 (dd, J = 6.0, 3.2 Hz, 3H), 4.27 (d, J = 3.5 Hz, 2H), 4.31 – 4.36 (m, 1H),
4.37 – 4.61 (m, 8H), 4.95 (d, J = 4.1 Hz, 1H), 5.05 (s, 1H), 5.74 (d, J = 4.0 Hz, 1H), 7.16 –
7.28 (m, 32H), 7.53 – 7.59 (m, 8H). 13C NMR (100.53 MHz, CDCl3): δ 19.1 , 19.3 , 26.7(3C)
, 26.9(3C) , 63.3 , 72.2 , 72.2 , 72.3 , 72.5 , 73.1 , 79.4 , 80.0 , 80.8 , 82.8 , 83.1 , 83.8 , 84.0 ,
84.8 , 85.7 , 88.5 , 99.9 , 104.2 , 105.6 , 112.5 , 127.4(2C) , 127.5(5C) , 127.6(13C) ,
127.9(3C) , 128.2(2C) , 128.3(2C) , 128.3(2C) , 128.4(2C) , 129.5 , 129.69 , 133.1 , 133.2 ,
133.3 , 133.4 , 135.6(9C) , 137.7 , 137.9 , 138.1(2C) .
1,2ꢀOꢀIsopropylidene 3ꢀOꢀ[(3,5ꢀdiꢀOꢀbenzylꢀαꢀDꢀarabinofuranosyl)ꢀ2ꢀOꢀ(2,3,5ꢀtriꢀOꢀbenzyl
βꢀDꢀarabnofuranosyl)]ꢀ5ꢀOꢀbenzylꢀβꢀDꢀarabinofuranose (21) [resonances for the major βꢀ
1
isomer as obtained from the 0.1:1.0 α,β mixture of trisaccharides]: H NMR (399.78 MHz,
CDCl3): δ 1.32 (s, 3H), 1.51 (s, 3H), 3.49 – 3.63 (m, 4H), 3.65 – 3.83 (m, 2H), 3.93 – 4.23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 26
1
2
3
4
5
6
7
8
9
(m, 9H), 4.50 (ddd, J = 15.4, 10.0, 2.7 Hz, 12H), 5.12 (d, J =3.8Hz,1H), 5.18 (s, 1H), 5.86 (d,
J = 4.1 Hz, 1H), 7.24 – 7.34 (m, 30H). 13C NMR (100.53 MHz, CDCl3): δ 26.4 , 27.1 , 66.5 ,
69.3 , 71.8 , 72.1(3C) , 72.7 , 73.1 , 73.3 , 80.1 , 80.2 , 81.0 , 83.4 , 84.1 , 84.4 , 85.2 , 88.3 ,
88.5 , 100.9 , 105.3 , 105.5 , 112.9 , 127.6(6C) , 127.8(4C) , 127.8(4C) , 128.2(5C) ,
128.2(5C) , 128.4(6C) , 137.4 , 137.7 , 137.9(2C) , 138.1(2C) .
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
1,2ꢀOꢀIsopropylidene 3ꢀOꢀ[3ꢀOꢀbenzylꢀ5ꢀOꢀ(((9Z,12Z)ꢀoctadecaꢀ9,12ꢀdienoyl))ꢀ2ꢀOꢀ(2,3,5ꢀ
triꢀOꢀbenzylꢀβꢀ
D
ꢀarabinofuranosyl)ꢀαꢀ
D
ꢀarabinofuranosyl]ꢀ5ꢀOꢀ[(((9Z,12Z)ꢀoctadecaꢀ9,12ꢀ
25
dienoyl))]ꢀβꢀ
D
ꢀarabinofuranose (22): Yield: (90 mg, 63%); [α]D = +20.4 (c = 1.0, CHCl3);
1H NMR (399.78 MHz, CDCl3): δ 0.64ꢀ1.04(m, 6H), 1.23 – 1.34 (m, 35H), 1.51 (s, 3H), 1.56
(d, J = 7.2 Hz, 2H), 1.97 – 2.08 (m, 8H), 2.19 – 2.26 (m, 2H), 2.30 (t, J = 7.5 Hz, 2H), 2.77 (t,
J = 6.1 Hz, 2H), 3.52 – 3.58 (m, 2H), 3.65 – 3.73 (m, 1H), 3.77 (dd, J = 11.2, 4.3 Hz, 2H),
4.07 (dd, J = 4.5, 2.3 Hz, 2H), 4.09 – 4.14 (m, 2H), 4.19 (d, J = 3.6 Hz, 2H), 4.23 (dd, J =
7.0, 3.6 Hz, 2H), 4.47 – 4.55 (m, 4H), 4.55 – 4.60 (m, 2H), 4.65 (dd, J = 13.6, 3.9 Hz, 2H),
4.68 – 4.75 (m, 2H), 5.09 (d, J = 3.2 Hz, 1H), 5.18 (d, J = 3.4 Hz, 1H), 5.28 – 5.42 (m, 8H),
5.90 (d, J = 4.1 Hz, 1H), 7.29 (m, 20H); 13C NMR (100.53 MHz, CDCl3): δ 14.1, 14.1, 24.8,
25.6, 26.4, 27.0, 27.2(2C), 29.1(3C), 29.2, 29.2, 29.3(3C), 29.5, 29.6, 29.7(2C), 29.7(2C),
31.5(2C), 31.9, 33.9, 34.0, 66.6, 71.9, 72.1(2C), 72.2, 72.6, 73.2(2C), 80.2, 80.4, 80.7, 81.3,
83.1, 83.2, 84.0, 84.2, 85.0, 100.8, 105.4, 105.6, 112.9, 127.5(2C), 127.7(3C), 127.7(3C),
127.8(3C), 127.8, 127.9, 128.1(3C), 128.3(3C), 128.3(3C), 128.4(2C), 129.9, 130.0, 130.0,
130.2, 137.2, 137.8, 138.2(2C), 172.7, 173.3; IR (CHCl3): 3032, 2917, 1749, 1546, 1455,
1212, 1117, 693 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C82H114NaO15 1361.8055 found
1361.8049.
Methyl 2,3ꢀdiꢀOꢀbenzylꢀ5ꢀOꢀ[2ꢀOꢀbenzylꢀ3,5ꢀdiꢀOꢀ(3ꢀOꢀbenzylꢀ5ꢀOꢀtertꢀbutyldiphenylsilylꢀ
αꢀDꢀarabinofuranosyl)ꢀαꢀDꢀarabinofuranosyl]ꢀαꢀD
ꢀarabinofuranoside (23): [α]D25 = +81.8 (c =
1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 1.05 (d, J = 2.9 Hz, 18H), 3.37 (d, J = 9.3 Hz,
ACS Paragon Plus Environment

Page 21 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1H), 3.42 (s, 3H), 3.44 (d, J = 8.7 Hz, 1H), 3.55 (ddd, J = 10.9, 7.5, 2.2 Hz, 2H), 3.72 (t, J =
3.2 Hz, 1H), 3.74 (d, J = 3.8 Hz, 2H), 3.79 (dd, J = 13.2, 2.2 Hz, 1H), 3.93 (dd, J = 11.4, 4.3
Hz, 1H), 4.00 – 4.07 (m, 4H), 4.09 (dd, J = 6.7, 3.2 Hz, 1H), 4.16 (dd, J = 3.1, 1.1 Hz, 1H),
4.17 – 4.27 (m, 6H), 4.42 – 4.48 (m, 2H), 4.48 – 4.54 (m, 2H), 4.56 – 4.63 (m, 5H), 4.65 (dd,
J = 12. 1, 3.8 Hz, 2H), 4.97 (s, 1H), 5.18 (s, 1H), 5.22 (s, 1H), 5.22 (s, 1H), 7.27 – 7.41 (m,
35H), 7.42 – 7.48 (m, 2H), 7.62 (ddd, J = 5.4, 4.0, 1.9 Hz, 4H), 7.66 – 7.70 (m, 4H); 13C
NMR (100.53 MHz, CDCl3): δ 19.0, 19.0, 26.6(3C), 26.6(3C), 54.9, 63.7, 63.7(2C), 65.7,
71.7(3C), 71.9, 72.2, 77.8, 78.1, 79.0, 80.3, 81.0, 83.0, 83.3, 83.7, 84.1, 84.3, 87.6, 88.3,
106.1, 107.1, 107.4, 108.9, 127.5, 127.6(2C), 127.7(5C), 127.7(3C), 127.7(3C),
127.8(5C),127.8, 127.9(2C), 127.9(3C), 128.3(4C), 128.3(3C), 128.3(3C), 128.4(2C), 129.7,
129.8 (2C), 129.8, 132.4, 132.4, 132.4, 132.5 , 135.5(3C), 135.5, 137.3, 137.4, 137.8(2C),
137.9; IR (CHCl3): 3619, 3035, 2920, 1546, 1455, 1210, 1100, 693 cmꢀ1; HRMS (TOF) m/z
[M + Na]+ calcd for C88H102NaO17Si2 1509.6553, found 1509.6548.
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
Methyl 2,3ꢀdiꢀOꢀbenzylꢀ5ꢀOꢀ[2ꢀOꢀbenzylꢀ3,5ꢀdiꢀOꢀ(3,5ꢀdiꢀOꢀbenzylꢀαꢀDꢀarabinofuranosyl)ꢀ
25
αꢀD
ꢀarabinofuranosyl]ꢀαꢀ
D
ꢀarabinofuranoside (24): [α]D = ꢀ31.8 (c = 1.0, CHCl3); 1H NMR
(399.78MHz, CDCl3): δ 3.39 (s, 3H), 3.49 (qd, J = 7.1, 6.5, 4.2 Hz, 4H), 3.61 (dd, J = 10.5,
2.5 Hz, 1H), 3.65 (d, J = 2.4 Hz, 1H), 3.69 (dd, J = 11.7, 4.2 Hz, 1H), 3.75 (dd, J = 10.8, 5.7
Hz, 1H), 3.85 (dd, J = 4.4, 1.8 Hz, 1H), 3.87 – 3.98 (m, 3H), 4.00 – 4.06 (m, 2H), 4.16 (dq, J
= 10.2, 3.5 Hz, 3H), 4.22 (t, J = 5.6 Hz, 2H), 4.26 (d, J = 4.0 Hz, 1H), 4.32 (dd, J = 6.9, 4.8
Hz, 2H), 4.42 – 4.52 (m, 4H), 4.52 – 4.61 (m, 6H), 4.62 – 4.72 (m, 4H), 4.94 (s, 1H), 5.11 (s,
1H), 5.15 (s, 1H), 5.18 (s, 1H), 7.31 (ddt, J = 15.3, 7.3, 4.4 Hz, 35H); 13C NMR (100.53
MHz, CDCl3): δ 54.9, 66.3, 68.0, 69.6, 69.6, 71.7, 71.8, 71.8, 71.9, 72.2, 73.4, 73.5, 78.3,
78.7, 80.1, 80.4, 82.6, 82.7, 82.8, 83.2, 84.6, 84.8, 88.1, 88.5, 106.4, 107.0, 108.7, 109.1,
127.4, 127.5, 127.6(3C), 127.7(3C), 127.7(6C), 127.8, 127.8(3C), 127.9(3C), 128.1(2C),
128.2(2C), 128.3(6C), 128.4(2C), 128.4(2C), 137.1, 137.2, 137.4, 137.6, 137.8(2C), 137.9;
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 26
1
2
3
4
5
IR (CHCl3): 3621, 3028, 2921, 1556, 1455, 1218, 1111, 699 cmꢀ1; HRMS (TOF) m/z [M +
Na]+ calcd for C70H78NaO17 1213.5137, found 1213.5134.
6
7
8
9
Methyl
2,3ꢀdiꢀOꢀbenzylꢀ5ꢀOꢀ[2ꢀOꢀbenzylꢀ3,5ꢀdiꢀOꢀ(3ꢀOꢀbenzylꢀ5ꢀOꢀ(((9Z,12Z)ꢀoctadecaꢀ
ꢀarabinofuranosyl)ꢀαꢀ ꢀarabinofuranosyl]ꢀαꢀ ꢀarabinofuranoside (25):
9,12ꢀdienoyl))ꢀαꢀ
D
D
D
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
[α]D25 = +80.0 (c = 1.0, CHCl3); 1H NMR (399.78MHz, CDCl3): δ 0.88 (t, J = 3.5 Hz, 6H),
1.30 (m, 32H), 1.56 (d, J = 6.7 Hz, 2H), 1.91 – 2.11 (m, 8H), 2.27 (td, J = 7.8, 4.2 Hz, 4H),
2.77 (t, J = 6.4 Hz, 2H), 3.35 (s, 3H), 3.63 (dd, J = 11.3, 3.1 Hz, 1H), 3.71 (dt, J = 9.1, 2.8
Hz, 3H), 3.85 (dd, J = 11.3, 3.8 Hz, 1H), 3.92 (dd, J = 12.1, 3.5 Hz, 1H), 4.00 (dd, J = 3.2,
1.0 Hz, 1H), 4.02 – 4.08 (m, 3H), 4.14 (ddq, J = 14.0, 7.0, 2.3 Hz, 6H), 4.18 – 4.19 (m, 1H),
4.21 (dd, J = 6.1, 2.4 Hz, 2H), 4.23 – 4.25 (m, 1H), 4.28 (dd, J = 5.5, 1.9 Hz, 1H), 4.40 – 4.66
(m, 11H), 4.89 (s, 1H), 4.94 (d, J = 1.7 Hz, 1H), 5.01 (d, J = 2.5 Hz, 1H), 5.13 (s, 1H), 5.27 –
5.44 (m, 8H), 7.23 – 7.34 (m, 25H); 13C NMR (100.53 MHz, CDCl3): δ 14.1, 14.1, 22.5, 22.7,
24.8, 25.6, 27.2(3C), 29.1(2C), 29.1(2C), 29.2, 29.3(2C), 29.3(2C), 29.5, 29.6(2C), 29.7,
29.7, 31.5, 31.9, 34.0, 54.9, 63.4, 63.5, 64.8, 66.6, 71.9, 72.0, 72.2, 72.2, 72.3, 79.0, 79.4,
79.6, 80.0, 80.6, 80.7, 82.3, 82.9, 83.2, 84.3, 86.5, 88.4, 105.7, 106.8, 107.1, 109.1,
127.7(2C), 127.8(2C), 127.8(3C), 127.9(2C), 128.0(2C), 128.1, 128.1, 128.2(3C), 128.2(3C),
128.4(2C), 128.4(2C), 128.42(2C), 128.5(4C), 129.7, 130.0, 130.0, 130.2, 136.9, 137.1,
137.5, 137.7, 137.7, 173.4(2C); IR (CHCl3): 3622, 3031, 2917, 1761, 1546, 1455, 1217,
1104, 699 cmꢀ1; HRMS (TOF) m/z [M + Na]+ calcd for C92H126NaO19 1557.8791, found
1557.8787.
Hexasaccharides 26: Individual resonances could not be determined due to overlapping
signals in the anomeric region. However, the ratio of isomers was obtained by taking both the
1
13C and H NMR signals. The integration ratio of ꢀOCH3 (δ 3.18ꢀ3.22 ppm) present at the
reducing end showed that the ratio is 0.4:1.0. The anomeric proton resonances were noticed
from δ 4.73ꢀ5.38 ppm with overlapping signals. The 13C NMR spectrum showed that the
ACS Paragon Plus Environment

Page 23 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
resonances diagnostic for βꢀisomer are noticed from δ 99.4ꢀ100.1ppm and those of αꢀisomer
were noticed from δ 104.7ꢀ107.2 ppm.
7
8
9
Hexasaccharides 27: Individual resonances could not be determined due to overlapping
signals in the anomeric region. However, the ratio of isomers was obtained by taking both the
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
1
13C and H NMR signals. The anomeric proton resonances were noticed from δ 4.83ꢀ5.45
ppm with overlapping signals. The 13C NMR spectrum showed that the resonances
diagnostic for βꢀisomer are noticed from δ 100.3ꢀ101.0 ppm and those of αꢀisomer were
noticed from δ 105.7ꢀ107.0 ppm.
Hexasaccharides 28: Individual resonances could not be determined due to overlapping
signals in the anomeric region. However, the ratio of isomers was obtained by taking both the
1
13C and H NMR signals. The integration ratio of ꢀOCH3 (δ 3.28ꢀ3.31 ppm) present at the
reducing end showed that the ratio is 0.2:1.0. The anomeric proton resonances were noticed
from δ 4.85ꢀ5.42 ppm with overlapping signals. The 13C NMR spectrum showed that the
resonances diagnostic for βꢀisomer are noticed from δ 99.7ꢀ100.2ppm and those of αꢀisomer
were noticed from δ 105.0ꢀ107.2 ppm.
ACKNOWLEDGEMENTS
MI thanks the CSIR New Delhi; GG and SH thank the DST New Delhi for the financial
assistance in the form of Fast Track Young Scientist (GG) SwarnaJayanthi Fellowship (SH).
Authors thank and acknowledge fruitful discussions with Dr. Harinath Chakrapani (IISER
Pune) and Dr. G Narahari Sastry (IICT Hyderabad).
SUPPORTING INFORMATION
Computational data and copies of H, 13C and DEPT NMR spectra for all compounds. This
1
material is available free of charge via the Internet at http://pubs.acs.org
REFERENCES
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 26
1
2
3
4
5
6
7
8
9
1. (a) Samandari, T.; Agizew, T. B.; Nyirenda, S.; Tedla, Z.; Sibanda, T.; Shang, N.;
Mosimaneotsile, B.; Motsamai, O. I.; Bozeman, L.; Davis, M. K.; Talbot, E. A.; Moeti,
T. L.; Moffat, H. J.; Kilmarx, P. H.; Castro, K. G.; Wells, C. D. Lancet 2011, 377,
1588ꢀ98. (b) Ginsberg, A. M.; Spigelman, M. Nat. Med. 2007, 13, 290ꢀ294.
2. (a) Lowary, T. L. Curr. Opin. Chem. Biol. 2003, 7, 749ꢀ756. (b) Miletti, L. C.; Marino,
C.; Marino, K.; de Lederkremer, R. M.; Colli, W.; Alves, M. J. M. Carbohydr. Res.
1999, 320, 176ꢀ180. (c) Richards, M. R.; Lowary, T. L. ChemBioChem. 2009, 10,
1920ꢀ1938.
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
3. (a) Daffe, M.; Brennan, P. J.; McNeil, M. R. J. Biol. Chem. 1990, 265, 6734ꢀ6743. (b)
McNeil, M. R.; Daffe, M.; Brennan, P. J. J. Biol. Chem. 1990, 265, 18200ꢀ18206; (c)
Wolucka, B. A.; McNeil, M. R.; de Hoffman, E.; Chojnacki, T.; Brennan, P. J. J. Biol.
Chem. 1994, 269, 23328ꢀ23335. (d) Besra, G. S.; Khoo, K. –H.; McNeil, M. R.; Dell,
A.; Morris, H. R.; Brennan, P. J. Biochem. 1995, 34, 4257ꢀ4266.
4. a) Seeberger, P. H.; Werz, D. B. Nature 2007, 446, 1046ꢀ1051. (b) Zhu, X.; Schmidt,
R. R. Angew. Chem. Int. Ed. 2009, 48, 1900ꢀ1934.
5. (a) Mereyala, H. B.; Hotha, S.; Gurjar, M. K. Chem. Commun. 1998, 685ꢀ686. (b)
D′Souza, F. W.; Lowary, T. L. Org. Lett. 2000, 2, 1493ꢀ1495. (c) Yin, H.; D’Souza, F.
W.; Lowary, T. L. J. Org. Chem. 2002, 67, 892ꢀ903. (d) Gadikota, R. R.; Callam, C.
S.; Wagner, T.; Del Fraino, B.; Lowary, T. L. J. Am. Chem. Soc. 2003, 125, 4155ꢀ
4165. (e) Callam, C. S.; Gadikota, R. R.; Krien, D. M.; Lowary, T. L. J. Am. Chem.
Soc. 2003, 125, 13112ꢀ13119. (f) Desire, J.; Prandi, J. Carbohydr. Res. 1999, 317,
110ꢀ118. (g) Lee, Y. J.; Lee, K.; Jung, E. H.; Jeon, H. B.; Kim, K. S. Org. Lett. 2005,
7, 3263ꢀ3266. (h) Ishiwata, A.; Akao, H.; Ito, Y.; Sunagawa, M.; Kusunose, N.;
Kashiwazaki, Y. Bioorg. Med. Chem. 2006, 14, 3049ꢀ3061. (i) Joe, M.; Bai, Y.;
Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885ꢀ9901. (j) Fraserꢀ
ACS Paragon Plus Environment

Page 25 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Reid, B.; Lu, J.; Jayaprakash, K. N.; Lopez, J. C. Tetrahedron: Asymm. 2006, 17,
2449ꢀ2463. (k) Lu, J.; FraserꢀReid, B. Chem. Commun. 2005, 862ꢀ864.
6. (a) Vidadala, S. R.; Gayatri, G.; Sastry, G. N.; Hotha, S. Chem. Commun. 2011, 47,
9906−9908. (b) Mukaiyama, T.; Yamada, M.; Suda, S.; Yokomizo, Y.; Kobayashi, S.;
Chem. Lett. 1992, 1401ꢀ1404. (c) Mukaiyama, T.; Hashimoto, Y.; Suda, S.; Chem.
Lett. 1983, 935ꢀ938. (d) Kawabata, Y.; Kaneko, S.; Kusakabe, I.; Gama Y.;
Carbohydr. Res. 1995, 267, 39ꢀ47. (e) Du, Y.; Pan, Q.; Kong, F. Synlett, 1999, 1648ꢀ
1650. (f) Ding, X.; Kong, F. Carbohydr. Res. 1996, 286, 161ꢀ166. (g) Gadikota, R. R.;
Callam, C. S.; Lowary, T. L. Org. Lett. 2001, 3, 607ꢀ610. (h) Banhaoud, T.; Sanchez,
S.; Prandi, J. Chem. Commun., 2000, 659ꢀ660. (i) Lu, J.; FraserꢀReid, B. Org. Lett.
2004, 6, 3051−3054. (j) Thadke, S. A.; Mishra, B.; Hotha, S. Org. Lett. 2013, 15,
2466ꢀ2469.
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
7. (a) Ishiwata, A.; Ito, Y. J. Am. Chem. Soc. 2011, 133, 2275–2291. (b) Imamura, A.;
Lowary, T. L. Org. Lett. 2010, 12, 3686ꢀ3689. (c) Ishiwata, A.; Akao, H.; Ito, Y. Org.
Lett. 2006, 8, 5525ꢀ5528. (d) Liu, Q.ꢀW.; Bin, H.ꢀC.; Yang, J.ꢀS. Org. Lett. 2013, 15,
3974−3977.
8. See supporting information
9. (a) FraserꢀReid, B.; López, J. C.; Radhakrishnan, K. V.; Nandakumar, N.; Gómez, A.
M.; Uriel, C. Chem. Commun. 2002, 2104ꢀ2105. (b) López, J. C.; Agocs, A.; Uriel, C.;
Gómez, A.; FraserꢀReid, B. Chem. Commun. 2005, 5088ꢀ5090. (c) FraserꢀReid, B.;
López, J. C.; Gómez, A. M.; Uriel, C. Eur. J. Org. Chem. 2004, 1387ꢀ1395.
10. Schrödinger Release 2012ꢀ2: Macromodel, version 9.9, Schrödinger, LLC, New York,
NY, 2012.
11. Mahadevi, A. S.; Sastry, G. N. Chem. Rev. 2013, 113, 2100ꢀ2138.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 26
1
2
3
4
5
6
7
8
9
12. Gaussian 09, Revision C.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G.
E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.;
Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers,
E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, M.
J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J.
B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009.
13. BieglerꢀKönig, F.; Schönbohm, J. AIM2000; Version 2.0, 2002.
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
14. Dahlman, O.; Garegg, P. J.; Meyer, H.; Schramek, S. Acta Chem. Scand., Ser. B, 1986,
40, 15ꢀ20.
15. Diastereoselectivity could not be measured due to overlaping NMR resonances.
ACS Paragon Plus Environment