Synthesis of α,α-, α,β-, and β,β-(dimaltoside)s of ethane-1,2-diol, propane-1,3-diol, and butane-1,4-diol: A proposal for an initial adhesion mode

Article abstract of DOI:10.1016/S0008-6215(98)00191-8

Nine dimaltoside derivatives of ethane-1,2-diol, propane-1,3-diol, and butane-1,4-diol having the α,α, α,β, and β,β anomeric configurations at the linkage sites have been synthesized. Suitably protected maltosyl halides or a 1-(phenylthio) derivative were condensed with the foregoing diols and the resulting monomaltosyl derivatives were further condensed with the maltosyl donors to give, after deprotection, the title compounds. Their structures were fully characterized by NMR spectroscopy. Interactions between the three α,α-(dimaltoside)s and cinnamyl alcohol are briefly discussed. Copyright (C) 1997 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(98)00191-8

Carbohydrate Research 311 (1998) 11±24
Synthesis of ꢀ,ꢀ-, ꢀ,ꢁ-, and
ꢁ,ꢁ-(dimaltoside)s of ethane-1,2-diol,
propane-1,3-diol, and butane-1,4-diol:
A proposal for an initial adhesion mode
Mina Tsuzuki, Tsutomu Tsuchiya *
Institute of Bioorganic Chemistry, 3-34-17 Ida, Nakahara-ku Kawasaki 211, Japan
Received 10 February 1998; accepted in revised form 30 June 1998
Abstract
Nine dimaltoside derivatives of ethane-1,2-diol, propane-1,3-diol, and butane-1,4-diol having
the ꢀ,ꢀ, ꢀ,ꢁ, and ꢁ,ꢁ anomeric con®gurations at the linkage sites have been synthesized. Suitably
protected maltosyl halides or a 1-(phenylthio) derivative were condensed with the foregoing diols
and the resulting monomaltosyl derivatives were further condensed with the maltosyl donors to
give, after deprotection, the title compounds. Their structures were fully characterized by NMR
spectroscopy. Interactions between the three ꢀ,ꢀ-(dimaltoside)s and cinnamyl alcohol are brie¯y
discussed. # 1998 Elsevier Science Ltd. All rights reserved
Keywords: Maltoside; Dimaltoside; Ethane-1,2-diol; Propane-1,3-diol; Butane-1,4-diol; Adhesion
1. Introduction
between the two parts of the complex are fully
manifested. Even in a simple disaccharide, or a
combination of a carbohydrate and an amino acid
in water, the ®nal conformation of the carbohy-
drates may be determined by diverse forces work-
ing between any set of functional groups, including
those of water. These forces may originate from
hydrogen bonding [4], from dipolar and CH/ꢂ
interactions [5], from hydrophobic-group aggrega-
tion (for example, in water), and others.
To commence a basic study on the problem of
molecular recognition processes involving sugars,
which could be useful for a general understanding
of the adhesion phenomenon, we initiated exam-
ination of the di€erence in chemical shift in the
1H NMR spectra of various newly-prepared
Non-covalent interactions between two carbo-
hydrates, between a carbohydrate and a protein,
and similar molecular combinations, as exempli®ed
by enzyme±substrate interactions and many other
kinds of molecular recognition processes, such as
adhesions [1], antigen±antibody interactions [2],
and receptor binding [3], are signi®cant research
targets in biological chemistry. However, even if
the structures of these complexes are clari®ed by X-
ray crystallography, NMR spectroscopy, or other
modern techniques, it does not necessarily mean
that the attractive (or repulsive) forces operating
* Corresponding author.
0008-6215/98/$Ðsee front matter # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00191-8

12
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
(dimaltoside)s described here in D2O, both in the
presence and absence of a second compound. It
was hoped that the added compound might inter-
act variably with the (dimaltoside)s depending on
their structures. To make the conformations of the
(dimaltoside)s ¯exible under minimal external
force, two maltoses were linked, head to head, via
a small alkylene chain ꢀCH2†n; n ˆ 2 4 . These
(dimaltoside)s might chelate a foreign (or a guest)
compound between the two averaged planes of a
dimaltoside molecule, by bending the bond angles
of the chain, when the foreign compound matches
the dimaltoside well. In this paper we describe
mainly the synthesis of these (dimaltoside)s, and
touch brie¯y on the interaction between some of
them with cinnamyl alcohol.
Knorr conditions in CH2Cl2 in order to obtain the
dimaltoside derivative 21 in one step. However, the
yield of the desired compound was poor, and a
two-step synthesis was attempted. Treatment of 1
with a 5-molar excess of ethane-1,2-diol gave the
monomaltoside derivative 10 in 73% yield, toge-
ther with 21 (6.4%). No formation of ꢀ-anomeric
products was observed. Successive reaction of 10
with 1 gave 21 in good yield. Zemplen deacetyla-
tion gave the ®nal product 31. In a similar way,
1,3- and 1,4-di(O-ꢁ-maltosyl)alkanediols 34 and 37
were prepared by condensation of 1 with propane-
1,3-diol or butane-1,4-diol, with successive cou-
pling of the resulting monomaltosides (11 and 12)
with 1 to give the peracetyl (dimaltoside)s (25 and
28). These were deacetylated to give the ®nal pro-
ducts 34 and 37. Structures of 10±12, 21, 25, 28, 31,
Â
Ã
1
34, and 37 were con®rmed by their H and 13C
2. Results and discussion
NMR spectra (Tables 1±3).
(Dimaltoside)s having the ꢀ-anomeric con®g-
urations were next prepared. For this purpose
per-O-benzylmaltosyl bromide (7) was considered
suitable as the glycosylating agent. To obtain this,
4-methoxyphenylmethyl maltoside (3) was examined
as a starting material, because the methoxybenzyl
group was expected to be readily cleaved [7] from
the per(O-benzyl)ated products. Initially, maltose
was heated with an excess of neat 4-methoxy-
phenylmethanol in the presence of p-toluene-
sulfonic acid (modi®ed Fischer condensation),
Synthesis.Ð1,2-Di(O-maltosyl)ethanediol (31)
with two ꢁ-anomeric con®gurations was ®rst pre-
pared. Initially, per-O-acetylmaltosyl bromide (1)
[6] was treated with a 0.5-molar proportion of
ethane-1,2-diol under rigorously anhydrous Konigs±
whereupon,
however,
only
bis(4-methoxy-
phenylmethyl) ether was produced. Accordingly,
per-O-acetylmaltosyl bromide [6] (1) was treated
with 4-methoxyphenylmethanol in benzene in the
Chart 2.
Chart 1.

M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
13
4-methoxybenzyl group was successfully carried
out by merely heating 4 in an acidic medium,
without use of DDQ [9], Ce(NH4)2(NO3)6 (CAN)
[7,10], or NIS, to yield the free sugar 5. When
either DDQ or CAN was used, the yield of 5
turned out to be poor. To obtain the correspond-
ing bromide 7, compound 5, after acetylation (to
give the 1-acetate 8), was treated with TiBr4; how-
ever, the resulting 1-bromide was unstable and
decomposed rapidly during the next condensation
reaction without contributing as the glycosyl
donor. Therefore, 5 was treated with SOCl2 in
CH2Cl2 in the presence of catalytic amount of
DMF [11], whereupon the stable 1-chloride 6 [12]
was obtained in high yield.
Chart 3.
Condensation of 6 with ethane-1,2-diol (a 10-
molar excess for 6 was used) was performed under
Konigs±Knorr conditions in CH2Cl2; however, this
gave a mixture of ꢀ- (13) and ꢁ-monomaltoside
(14) in a ratio of 1:6.3 (88% overall yield). Chan-
ging the catalyst from Hg(CN)2 to HgI2±I2 or
CF3SO3Ag±s-collidine [13] slightly improved the
presence of Ag2CO3±I2 (modi®ed Konigs±Knorr
conditions [8]) and the resulting 4-methoxybenzyl
glycoside 2 (90%) was deacetylated to give 3,
which was then benzylated (PhCH2Br±NaH) to
give the per-O-benzylglycoside 4. Removal of the
Table 1
1H NMR chemical shiftsa (ꢃ, ppm, in CDCl3) of O-acetylated ꢁ-linked maltosides (10, 11, and 12) and ꢁ,ꢁ-linked (dimaltoside)s (21,
25, and 28)
10
11
12
21
25
28
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
4.58
4.54
4.82
5.25
3.99
3.68
4.22
4.53
4.53
4.57
4.48
4.50
4.85
5.27
3.98
3.74
4.19
4.54
4.81
5.25
3.99
3.68
4.22
4.51
4.80
5.25
3.99
3.68
4.22
4.52
4.80
5.25
3.98
3.67
4.22
4.48
4.80
5.25
3.99
3.67
4.22
4.48
H-10
H-20
H-30
H-40
H-50
H-60a
H-60b
5.40
4.86
5.35
5.04
3.97
4.05
4.25
5.41
4.86
5.36
5.05
3.97
4.06
4.25
5.41
4.86
5.36
5.05
3.97
4.05
4.25
5.41
4.86
5.36
5.05
3.97
4.05
4.25
5.40
4.86
5.36
5.05
3.97
4.05
4.25
5.41
4.86
5.36
5.05
3.97
4.05
4.25
H-100a
H-100b
H-200a
H-200b
H-300a
H-300b
H-400a
H-400b
3.83
3.83
3.71
3.71
3.67
3.98
1.80
1.80
3.71
3.71
3.55
3.89
1.68
1.68
1.61
1.61
3.63
3.63
3.74
3.88
3.74
3.88
3.57
3.83
1.83
1.83
3.57
3.83
3.47
3.84
1.56
1.62
1.56
1.62
3.47
3.84
OH
CH3CO
2.40
2.00
2.01
2.02 (6H)
2.04
2.10
1.91
2.00
2.01
2.02
2.03
2.04
2.10
2.15
1.71
2.00 (9H)
2.02
2.04
2.10
2.14
2.00 (6H)
2.02 (6H)
2.04
2.10
2.15
2.00 (6H)
2.02
2.03
2.04
2.10
2.00 (9H)
2.02
2.04
2.10
2.14
2.15
2.14
a
1
Con®rmed by H±1H COSY and, if necessary, by further HMQC.

14
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
Table 2
1H NMR chemical shiftsa (ꢃ, ppm, in D2O) of ꢁ,ꢁ-(31, 34, and 37), ꢀ,ꢀ-(32, 35, and 38), and ꢀ; ꢁ-linked dimaltosides (33, 36, and 39)
31
34
37
32
35
38
33
36
39
ꢀb
ꢁb
ꢀb
ꢁb
ꢀb
ꢁb
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
4.56
3.36
3.79
3.66
3.62
3.81
3.97
4.49
3.31
3.78
3.63
3.60
3.78
3.94
4.52
3.34
3.82
3.67
3.63
3.81
3.98
4.99
3.62
4.00
3.65
3.87
3.82
3.89
4.95
3.61
4.00
3.66
3.80
3.86
3.90
4.93
3.60
3.98
3.65
3.80
3.82
3.89
4.98
3.60
4.01
3.64
3.88
3.77c
3.88
4.55
3.34
3.79
3.65
3.61
3.79c
3.95
4.94
3.60
3.98
3.63
3.81
3.77d
3.88
4.48
3.31
3.78
4.93
3.60
3.98
3.64
3.80
3.78e
3.88
4.48
3.31
3.79
3.65
3.66
3.81e
3.94
3.62
3.81d
3.94
H-10
H-20
H-30
H-40
H-50
H-60a
H-60b
5.42
3.60
3.71
3.44
3.74
3.78
3.88
5.40
3.59
3.69
3.42
3.72
3.77
3.86
5.44
3.63
3.73
3.46
3.76
3.81
3.90
5.40
3.59
3.72
3.43
3.73
3.78
3.87
5.42
3.60
3.71
3.42
3.74
3.79
3.88
5.41
3.59
3.70
3.43
3.73
3.78
3.87
5.41
3.58
5.39
5.40
5.40
3.69
5.41
3.70
3.59
3.60
3.69
3.70
3.68
3.42
3.69
3.43
3.42
3.74
3.77
3.87
3.43
3.74
3.77
3.87
3.73
3.78
3.87
H-100a
H-100b
H-200a
H-200b
H-300a
H-300b
H-400a
H-400b
3.92
4.13
3.92
4.13
3.80
4.02
1.97
1.97
3.80
4.02
3.76
4.00
1.76
1.76
1.76
1.76
3.76
4.00
3.77
3.95
3.77
3.95
3.68
3.85
2.01
2.01
3.68
3.85
3.57
3.77
1.70
1.79
1.70
1.79
3.57
3.77
3.76
3.94
3.92
4.11
3.65
3.85
1.98
1.98
3.87
4.05
3.58
3.77
1.72
1.75
1.72
1.75
3.72
4.97
a
1
Con®rmed by H±1H COSY and, if necessary, by further HMQC.
b
ꢀ and ꢁ mean ꢀ- and ꢁ-linked maltoside portions, respectively.
c,d,e
Interconvertible, respectively.
ratios for the ꢀ anomer (1:3.3, 73% and 1:0.8,
78%, respectively). To enhance the yield of the ꢀ
anomer, synthesis of the 1-phenylthio derivative (9)
of 5 was attempted. Treatment of the 1-acetate 8
with PhSSiMe3 by a conventional method [14] gave
the 1-thio-ꢀ-glycoside 9, whose structure was con-
®rmed by its proton±carbon correlated spectrum
(HMQC) (see Experimental section). Condensation
of 9 with ethane-1,2-diol gave the ꢀ anomer 13
predominantly [ꢀ (13): ꢁ (14) = 1:0.36, 91%]. A
trial to obtain a better yield of the ꢀ anomer by
treating 9 and half-protected 2-(t-butyldimethyl-
silyl)ethanol was unsuccessful [ꢀ (15): ꢁ (16) =
1:0.5, overall yield 78%]. Condensation using the
imidate method [15] by utilizing the 1-trichloro-
acetimidate of 5 failed to give products in good
yields.
Preparations of benzylated monomaltosides of
propane-1,3-diol and butane-1,4-diol were next
tried using both 1-chloride 6 (with CF3SO3Ag±s-
collidine) and 9. The results were for propane-1,3-
diol, ꢀ (17): ꢁ (18) = 1:0.58 (81%) and 1:0.36
(75%), respectively; and for butane-1,4-diol, ꢀ (19):
ꢁ (20) = 1:0.78 (90%) and 1:0.53 (78%), respec-
tively, indicating that 9 gave better yields for the ꢀ
anomers, although the overall yields were some-
what diminished.
Table 3
13C NMR chemical shiftsa (ꢃ, ppm, in D2O) of ꢁ,ꢁ-linked
(dimaltoside)s (31, 34, and 37)
31
34
37
C-1
C-2
C-3
C-4
C-5
C-6
103.06
73.86
77.00
77.65
75.44
61.59
103.02
73.87
77.05
77.75
75.42
61.64
102.87
73.89
77.11
77.73
75.42
61.64
C-10
C-20
C-30
C-40
C-50
C-60
100.45
72.52
73.70
70.21
73.56
61.36
100.46
72.60
73.75
70.21
73.57
61.37
100.44
72.52
73.71
70.21
73.56
61.37
C-100
C-200
C-300
C-400
69.87
69.87
67.93
29.97
67.93
70.94
26.18
26.18
70.94
Next, maltosylation of the benzylated mono-
maltosides 13, 17, and 19 was performed similarly
by using the foregoing two reagents (6 and 9). The
a
1
Con®rmed by H±1H COSY and, if necessary, by further
HMQC.

M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
15
results were for 13, ꢀ (22): ꢁ (23) = 1:0.33 (56%)
and 1:0.47 (64%); for 17, ꢀ (26): ꢁ (27) = 1:0.5
(69%) and 1:1 (74%); and for 19, ꢀ (29): ꢁ (30) =
1:0.72 (79%) and 1:0.9 (65%). This result indicates
that, in these second condensations, 6 was superior
to 9 in production of the ꢀ anomer. As the pair of
ꢀ and ꢁ anomers had close mobilities, respectively,
they were separated by successive chromatographic
runs.
Finally, debenzylation of these synthetic pro-
ducts (22±24, 26, 27, 29, and 30) was performed
conventionally using Na in liquid NH3 [16], which
proved to be superior to hydrogenolysis with Pd-
black catalyst [17] for removing the benzyl groups
rapidly and completely. The products thus
obtained were, however, considerably con-
taminated with inorganic salts, and therefore they
were removed by successive acetylation, washing
the products with water, and by deacetylation to
give the ®nal products 32, 35, and 38 (each, ꢀ,ꢀ
structure) and 33, 36, and 39 (each, ꢀ,ꢁ structure).
The structures were con®rmed based on the 1H and
13C NMR spectroscopy (Tables 2, 4±6).
the interaction of the (dimaltoside)s prepared here
with several candidate compounds, we wanted
initially to inspect the 1H NMR spectra of the ꢀ,ꢀ-
(dimaltoside)s (32, 35, and 38) in the presence of
cinnamyl alcohol. The reason for choice of this
alcohol was based on its having a similar molecular
length with that of the maltosides, together with
the aromatic and ¯at structure. Our interest con-
cerning the interaction was in the following points:
that the slightly positively charged hydrogens in
the dimaltoside molecules (such as H-1 or 10) might
attract the aromatic ꢂ-electrons of cinnamyl alco-
hol, and whether this phenomenon, if it occurred,
1
could be detected in the H NMR spectra. As it
was found dicult to dissolve both dimaltoside
and (an excess of) cinnamyl alcohol in D2O, the
maltoside was dissolved in CD3OD and all of the
ꢁ
1H-shifts were measured at 40 C in the presence
and absence of cinnamyl alcohol (sharp signals
were obtained at that temperature). The results are
shown in Tables 7 and 8.
Noteworthy is the fact that all of the skeletal
protons shifted down®eld roughly linearly with the
concentration of cinnamyl alcohol added, and the
protons in the spacer alkylenes were shifted up®eld,
although only to a slight extent. No indication of
the sought-after chelation of a cinnamyl alcohol
molecule between the two wings of the di(malto-
side) molecule was observed. To clarify the spatial
relationship, maltose (as an anomeric mixture) and
methyl ꢀ-d-glucopyranoside were similarly mea-
sured with addition of cinnamyl alcohol, whereupon
all of the proton signals of both compounds shifted
down®eld, as likewise observed for the skeletal
protons in the (dimaltoside)s. Ethane-1,2-diol
dimethyl ether and propane-1,3-diol were mea-
sured in the same manner and all protons were
found to show up®eld shifts (Table 8), a result
similar to that for the spacer alkylenes.
These results suggest that the mode of interac-
tion is di€erent from that of cyclodextrins forming
inclusion complexes with aromatic compounds
(cyclodextrins usually show up®eld shifts in the
skeletal protons [18]). To assist in understanding
the NMR spectroscopic feature, the electron-
charge distributions for methyl ꢀ-d-glucopyr-
anoside (I), ethane-1,2-diol dimethyl ether (II),
propane-1,3-diol (III), methanol, and cinnamyl
alcohol were calculated by MOPAC94/PM3 (see
Experimental section). The results indicated that
OH-hydrogens are strongly positive (ꢂ0.24) as
compared to the CH-hydrogens (0.03ꢂ0.1 for
Interaction between cinnamyl alcohol and 32, 35,
or 38.ÐBefore carrying out a broader study on
Table 4
1H NMR chemical shiftsa (ꢃ, ppm, in CDCl3) of O-benzylated
ꢀ-linked maltosides (13, 17, and 19) and ꢀ,ꢀ-linked (dimalto-
side)s (22, 26, and 29)
13
17
19
22
26
29
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
4.76
3.60
4.07
3.97
3.98
3.64
3.76
4.70
3.58
4.04
3.99
3.87
3.65
3.79
4.73
3.58
4.07
4.01
3.87
3.65
3.81
4.83
3.58
4.09
4.06
3.86
3.63
3.84
4.78
3.58
4.09
4.05
3.88
3.64
3.84
4.76
3.60
4.09
4.04
3.88
3.64
3.83
H-10
H-20
H-30
H-40
H-50
H-60a
H-60b
5.65
3.48
3.88
3.64
3.71
3.42
3.52
5.65
3.48
3.89
3.62
3.71
3.41
3.50
5.67
3.48
3.90
3.63
3.72
3.41
3.50
5.70
3.48
3.89
3.65
3.72
3.38
3.49
5.70
3.48
3.92
3.64
3.74
3.39
3.49
5.70
3.48
3.91
3.64
3.73
3.39
3.49
H-100a
H-100b
H-200a
H-200b
H-300a
H-300b
H-400a
H-400b
OH
3.69
3.69
3.74
3.74
3.48
3.90
1.83
1.90
3.80
3.80
3.42
3.70
1.71
1.71
1.67
1.67
3.67
3.67
1.94
3.71
3.79
3.71
3.79
3.57
3.73
1.99
1.99
3.57
3.73
3.41
3.67
1.74
1.74
1.74
1.74
3.41
3.67
2.80
2.58
a
1
Con®rmed by H±1H COSY and, if necessary, by further
HMQC.

16
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
Table 5
1H NMR chemical shiftsa (ꢃ, ppm, in CDCl3) of O-benzylated ꢁ-linked maltosides (14, 18, and 20) and ꢀ,ꢁ-linked (dimaltoside)s (23,
27, and 30)
14
18
20
23
27
30
ꢀ
ꢁ
ꢀ
ꢁ
ꢀ
ꢁ
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
4.40
3.51
3.78
3.96
3.62
3.68
3.75
4.43
3.49
3.77
3.98
3.58
3.73
3.75
4.42
3.49
3.77
4.02
3.55
3.77
3.79
4.87
3.59
4.06
4.03
3.90
3.62
3.85
4.43
3.50
3.78
4.04
3.55
3.70
3.86
4.76
3.58
4.08
4.07
3.86
3.60
3.78
4.42
3.48
3.76
4.03
3.56
3.74
3.81
4.76
3.59
4.08
4.03
3.87
3.62
3.79
4.42
3.50
3.78
4.01
3.54
3.75
3.83
H-10
H-20
H-30
H-40
H-50
H-60a
H-60b
5.60
3.47
3.85
3.60
3.69
3.42
3.55
5.62
3.47
3.87
3.61
3.71
3.43
3.55
5.64
3.47
3.88
3.62
3.75
3.44
3.57
5.65
5.70
3.48
3.88
5.65
3.47
3.90
5.71
3.89
5.65
3.90
3.45
3.48
3.48
3.63
3.86
3.63
3.73
3.64
3.71
3.37
3.48
3.75
3.42
3.55
3.72
3.39
3.50
3.75
3.43
3.56
3.38
3.48
3.42
3.56
H-100a
H-100b
H-200a
H-200b
H-300a
H-300b
H-400a
H-400b
OH
3.83
3.95
3.68
3.80
3.79
4.02
1.85
1.85
3.73
3.82
3.61
3.96
1.74
1.74
1.68
1.68
3.64
3.64
1.49
3.72
4.77
3.77
4.13
3.54
3.76
2.00
2.00
3.65
4.03
3.40
3.66
1.75
1.75
1.75
1.75
3.56
3.97
3.03
2.23
a
1
Con®rmed by H±1H COSY and, if necessary, by further HMQC.
b
ꢀ and ꢁ mean ꢀ- and ꢁ-linked maltoside portions, respectively.
Table 6
13C NMR chemical shiftsa (ꢃ, ppm, in D2O) of ꢀ,ꢀ-(32, 35, 38) and ꢀ,ꢁ-linked (dimaltoside)s (33, 36, and 39)
32
35
38
33
36
39
ꢀb
ꢁb
ꢀb
ꢁb
ꢀb
ꢁb
C-1
C-2
C-3
C-4
C-5
C-6
98.97
72.02
74.41
78.08
71.15
61.43
98.92
72.03
74.41
77.81
77.14
61.43
98.78
72.03
74.46
77.82
77.17
61.46
98.98
72.06
74.37
77.82
71.13
61.36
103.00
73.85
77.06
77.68
75.47
61.62
98.86
72.03
74.40
77.95
71.13
61.42
103.02
73.88
77.08
77.79
75.43
61.65
98.78
72.02
74.44
77.90
71.17
61.45
102.92
73.90
77.12
77.70
75.42
61.64
C-10
C-20
C-30
C-40
C-50
C-60
100.66
72.65
73.77
70.21
73.56
61.37
100.50
72.60
73.75
70.21
73.57
61.37
100.50
72.61
73.74
70.22
73.55
61.37
100.52
72.64
73.78
100.46
72.53
73.71
100.58
72.62
73.76
100.47
72.53
73.71
100.53
72.61
73.75
100.44
72.52
73.71
70.21
61.36
70.21
73.57
61.37
70.21
73.56
61.37
73.55
73.57
C-100
C-200
C-300
C-400
67.57
67.57
66.25
29.62
66.25
68.83
26.34
26.34
68.83
67.79
69.87
65.75
29.77
68.20
68.83
26.07
26.54
71.05
a
1
Con®rmed by H±1H COSY and, if necessary, by further HMQC.
b
ꢀ and ꢁ mean ꢀ- and ꢁ-linked maltoside portions, respectively.
alkyl-H and ꢂ0.13 for arom.-H) or carbons [0.00±
0.11 for alkyl carbons except for the anomeric car-
bon (0.18 in I) and C-2 carbons ( 0.19 in III), and
0.07 to 0.2 for arom.-C], and all of the oxygens
are strongly negative ( 0.3 to ꢂ 0.4). One expla-
nation satisfying the foregoing numerical data
would be that some of the CD3OD molecules sur-
rounding a maltoside molecule through hydrogen

M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
17
Table 7
ꢁ
Chemical shiftsa (ꢃ, ppm) of 33, 35, and 38 and four reference compoundsb (9.0Â10 3 mmol/mL) in CD3OD at 40 C
33
35
38
Maltose
I
ꢀ
ꢁ
H-1
H-2
H-3
H-4
4.853
3.466
3.900
3.490
3.770
3.804
3.871
5.135
3.457
3.676
3.280
3.727
3.669
3.834
3.656
3.936
4.797
3.443
3.894
3.508
3.670
3.807
3.843
5.168
3.441
3.642
3.268
3.710
3.662
3.837
3.603
3.848
1.951
4.787
3.449
3.890
3.505
3.652
3.808
3.837
5.156
3.444
3.636
3.271
3.708
3.663
3.832
3.507
3.760
1.745
5.101
3.408
3.910
4.489
3.169
3.603
4.666
3.385
3.612
3.283
3.528
3.672
3.808
3.519
H-5
3.845
5.157
3.378
5.150
H-6a
H-6b
H-10
3.787
3.874
H-20
3.439
H-30
3.654
3.267
3.614
3.272
H-40
H-50
3.708
3.663
3.822
H-600a
H-600b
H-1 a
H-100b
H-200a,b
OCH3
3.406
HOCH2CH2CH2OH:
H3COCH2CH2OCH3:
for OCH2C
for CH2
3.666,
3.524,
for CCH2C
for OCH3
1.748
3.351
a
Estimated error is ‹0.0007 ppm.
Maltose, methyl ꢀ-d-glucopyranoside (I), propane-1,3-diol, and ethane-1,2-diol dimethyl ether.
b
bonding are substituted by some cinnamyl alcohol
molecules through OD-hydrogen bonding (we used
the usual term ``hydrogen bonding'' although deu-
terium plays the role) brought from the attractive
forces working between the positively charged HO-
hydrogen of cinnamyl alcohol and the negatively
charged HO-oxygens of the maltoside. However, as
the skeletal protons of the (dimaltoside)s show
down®eld shifts, suggesting operation of the mag-
netic anisotropy e€ect [19] via the cinnamyl plane,
the foregoing explanation has little validity in view
of the disposition of the cinnamyl plane; overall,
cinnamyl alcohol is expected to be located closer to
the di(maltoside) in order to satisfy the observed
deshieldings. If the cinnamyl plane is arranged face
to face to the maltoside plane, or takes a similar
disposition, the dimaltoside skeleton protons
should shift up®eld, as seen in cyclodextrins when
including an aromatic molecule [18]. Therefore, the
cinnamyl plane must approach the maltoside plane
from the perpendicular direction or more precisely,
approach the skeleton hydrogens from the exten-
ded plane of cinnamyl alcohol, and not from the
up (or down) face of the plane. However, such a
disposition seemed dicult to realize by operation
only of the hydrogen-bonding force of the DO-
group of cinnamyl alcohol, as already described.
Table 8
1
Increasea of the chemical shifts in the H NMR spectra of 32,
35, 38, and four reference compoundsb measured in CD3OD
(9.0 mM solution, 40 C) after addition of cinnamyl alcoholc
ꢁ
32
35
38
Maltose
ꢁ
I
ꢀ
H-1
H-2
H-3
H-4
1
8
7
5
3
7
5
4
7
11
7
8
7
9
6
3
4
5
5
3
4
3
2
3
6
4
4
5
4
4
1
2
13
12
9
9
9
10
11
9
7
9
8
3
3
1
3
2
2
6
7
4
5
4
4
5
6
5
5
5
5
H-5
H-6a
H-6b
H-10
9
9
15
8
H-20
12
15
13
14
13
10
1
12
15
10
13
10
12
4
H-30
H-40
H-50
H-600a
H-600b
H-100a
H-1 b
H-200a,b
OCH3
8
1
1
4
6
3
1
HOCH2CH2CH2OH:
H3COCH2CH2OCH3:
for OCH2C 7, for CCH2C 2
for CH2 6, for OCH3
5
a
Áꢃ (ppm)Â103 (estimated error is ‹0.7).
b
c
See Table 7.
24 Molar excess for 33, 35, and 38, and 12 molar excess
for the other compounds were added, respectively.

18
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
We considered, however, that such a situation
would be possible if approach of the cinnamyl
plane having a comparatively electron-de®cient
outside zone [originating from its seven acidic
hydrogens interacting with the negatively charged
oxygens of the maltoside moiety (O-2,3,6,20,30,40,60,
at least)] is facilitated by the formation of multiple
From the foregoing discussion, it may be
deduced that the inclusion of an aromatic com-
pound in a cyclodextrin cavity is initiated by the
attachment of the guest compound by the extended
hydroxyl groups of the cyclodextrin. However,
compounds 32, 35, or 38 have no cavity for
receiving a foreign molecule, and they, therefore,
only draw the molecule near the outside oxygen
atoms. We suppose this kind of initial attraction by
the extended placement of oxygen atoms of carbo-
hydrates may occur during the initial stage of some
biological adhesions.
...
arom.-H O bonds (more correctly, if such an
approach would be slightly favored over a random
one). This presumption was basically supported by
MOPAC calculation to ®nd energy-minimal geo-
1
metries, which showed 3±6 kcal mol of stabiliza-
tion by such an approach (see A and C in Fig. 1). It
seems this mode of attraction is not fully explained.
As regards the alkylene protons of the (dimalto-
side)s, and also compounds II and III, they were
shifted up®eld, respectively, and thus there might
be a slight preference for the alkylene chain to face
up (or down) to the cinnamyl plane over the ran-
dom approach; this may satisfy the anisotropic
shielding. This explanation is valid if we consider
that the weakly acidic alkylene hydrogens
approach, perpendicularly, the electron-rich (by
the ꢂ cloud) cinnamyl plane (see B in Fig. 1) by
CH/ꢂ interaction [5], and if the situation is aided
by the hydrophobic group assembly arising from
the exclusion of both the spacer chain and the cin-
namyl group from the hydrogen-bond network
formed by CD3OD molecules.
3. Experimental
General methods.ÐOptical rotations were deter-
1
mined with a Perkin±Elmer 241 polarimeter. H-
and 13C-NMR spectra were recorded at 500 and
125.8 MHz with a Bruker AMX-500 spectrometer,
using Me4Si as the internal reference, respectively.
The signals were mostly con®rmed by 1H±1H
1
COSY and HMQC. The H NMR spectra of 32,
35, 38, and of a mixture of the each compound
and cinnamyl alcohol in CD3OD were measured
ꢁ
(5.9 data points/Hz) at 40‹0.05 C in the absence
of reference (the shifts were measured from the
frequency of single Me4Si in CD3OD). TLC was
performed on Silica Gel 60 F254 (Merck 5715 and
Fig. 1. Stereoview of a model of the interaction between 35 and cinnamyl alcohol, as generated by CAChe. The starting geometry
of 35 (before minimization) having the shape of spread bird-wings (slightly curved inside) was chosen, and after energy-minimiza-
tion, a molecule of cinnamyl alcohol was positioned close to the structure of 35, in order, as much as possible, to re¯ect the situa-
tion as described in the text (three such relationships were chosen, that is, A: a cinnamyl alcohol was positioned along the edge of a
maltoside including O-2, 3, 20 with the cinnamyl OH close to O-2; B: along the spacer chain; C: near the O-6, 60 atoms), then each
combination was minimized (during the process, both 35 and cinnamyl alcohol minimized changed the conformations only slightly,
mainly by altering the intermolecular atom±atom distances). The three ®nal arrangements thus obtained are shown together.
1
Characteristic points are that the pairs were stabilized by ÁH (heat of formation) 3.1 (A), 4.6 (B), and 6.1 kcal mol (C), respec-
tively, relative to the additive H values of the starting mixture (35 and cinnamyl alcohol, both minimized). The distances (shown by
0
...
solid lines) are as follows: (ma0l0tosyl and cinnamyl portions are denoted as M and Ci, respectively) A: O-3 (M) H-2 (Ci) 2.99, O-2
0
0
00
0
0
0
...
...
...
...
...
(M) H-2 (Ci) 1.88 A; B: H-1 a (M) C-2 (Ci) 2.71, H-3 a (M) C-6 (Ci) 2.77 A; and C: O-6 (M) H-3 (Ci) 3.34, O-6 (M) H-2
(Ci) 1.88 A.

M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
19
5717), and detected by charring with aq 50%
H2SO4. Column chromatography was performed
on Wakogel C-200.
1.87 mmol) in DMF (25 mL) was stirred vigorously
with NaH (1.05 g, 60% in mineral oil; 26 mmol) for
30 min at room temperature. After cooling to 0 ꢁC,
benzyl bromide (2.4 mL, 19.6 mmol) was added,
and the mixture was stirred for 3 h at room tem-
perature. TLC (3:1 CHCl3±MeOH) of the solution
gave a single spot at Rf 0.3. After addition of
MeOH (10 mL), most of the solvent was removed
by coevaporation with toluene, and an EtOAc
solution of the residue was washed with water,
dried (Na2SO4), and concentrated. The residue was
chromatographed (5:1 hexane±EtOAc) to give 4 as
a syrup (1.99 g, 98%), [ꢀ]2d5+18.5 ꢁ (c 1.4, CHCl3);
1H NMR (CDCl3): ꢃ (selected signals) 3.80 (s, 3 H,
OMe), 4.43, 4.55, 4.57, 4.62, 4.72, 4.74, 4.82, and
4.83 (each ABq of 2 H, 8 PhCH2), 4.51 (d, 1 H, J
8.0 Hz, H-1), 5.65 (d, 1 H, J 3.8 Hz, H-10). Anal.
Calcd for C69H72O12: C, 75.80; H, 6.64. Found: C,
75.98; H, 6.56.
Computation.ÐAll calculations were performed
on a Macintosh 9500 with CAChe (Sony Tektronix
Corporation, Japan) using MOPAC94/PM3 based
on MOPAC6 by J.J.P. Stewart. Geometry optimi-
zation was performed by the eigenvector following
method (for Fig. 1). When optimization in MeOH
was required, the structures obtained by the above
MOPAC94/PM3 method were further optimized
with the COSMO method by setting the dielectric
constant as 32.63.
4-Methoxyphenylmethyl 2,3,6-tri-O-acetyl-4-O-
(2,3,4,6-tetra-O-acetyl-a-d-glucopyranosyl)-b-d-
glucopyranoside (2).ÐA mixture of 1 [6] (2.06 g,
2.95 mmol) and molecular sieves 3 A (4.12 g) in
benzene (30 mL) was stirred for 30 min, and 4-
methoxyphenylmethanol (1.87 mL, 15.0 mmol),
Ag2CO3 (2.44 g, 8.84 mmol), and I2 (1.50 g,
5.89 mmol) were added, and the mixture was stir-
red overnight at room temperature. After ®ltration
through a layer of Celite, the ®ltrate and the com-
bined washings (benzene) were washed successively
with aq 20% Na2S2O3, aq NaHCO3 (saturated),
and water, dried (Na2SO4), and concentrated. The
residue was chromatographed (1:2 acetone±hexane)
2,3,6-Tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-
d-glucopyranosyl)-d-glucopyranose (5).ÐA solution
of 4 (3.02 g, 2.76 mmol) in 1:1:0.2 CHCl3±
CF3CO2H±H2O (66 mL) was kept for 1 h at room
temperature. Removal of the solvent by coeva-
poration with toluene gave a residue, which was
chromatographed (3:2 hexane±EtOAc) to give 5
[12] as an amorphous powder (2.83 g, 94%),
ꢁ
1
to give 2 as a syrup (2.01 g, 90%), mp 108±109 C
[ꢀ]2d1+34 ꢁ (c 0.8, CHCl3); H NMR (CDCl3): ꢃ
(EtOH), [ꢀ]2d3+23 ꢁ (c 0.7, CHCl3); 1H NMR
(CDCl3): ꢃ (selected signals) 1.97, 1.98, 1.99, 2.00,
2.02, 2.10, and 2.17 (each s of 3 H, 7 Ac), 3.81 (s, 3
H, OMe), 4.56 (d, 1 H, J1,2 8.0 Hz, H-1), 5.40 (d, 1
(selected signals) 3.10 [d, ꢂ0.63 H, HO-1 (ꢀ-
anomer)], 5.22 [t, ꢂ0.63 H, J1,2=J1,OH 3.3 Hz, H-1
(ꢀ±anomer)], 5.62 (d, 1 H, J1 ,2 3.8 Hz, H-10).
2,3,6-Tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-
d-glucopyranosyl)-a-d-glucopyranosyl chloride (6).Ð
To a solution of 5 (534 mg, 0.55 mmol) in CH2Cl2
(5.9 mL), SOCl2 (237 ꢄL, 3.3 mmol) and DMF
(64 ꢄL. 0.83 mmol) were added, and the solution
was kept overnight at room temperature. TLC (2:1
hexane±EtOAc) of the solution showed a single
spot at Rf 0.65 (cf. 5: Rf 0.4).
0
0
H, J1 ,2 4.0 Hz, H-10). Anal. Calcd for C34H44O19:
C, 54.00; H, 5.86. Found: C, 53.84; H, 5.71.
0
0
4-Methoxyphenylmethyl 4-O-(a-d-glucopyrano-
syl)-b-d-glucopyranoside (3).ÐTo a solution of 2
(1.50 g, 1.98 mmol) in 1:1 CH2Cl2±MeOH (45 mL)
was added 1 M NaOMe in MeOH (5 mL), and the
solution was kept for 1.5 h at room temperature.
After neutralization with Dowex 50W (H+) resin,
the mixture was ®ltered, and the solution was
concentrated. The residue was puri®ed on a short
column of silica gel (4:1 CHCl3±MeOH) to give 3
as an amorphous powder (900 mg, 95%),
Concentration gave a residue, which was dis-
solved in 3:1 hexane±EtOAc and passed through a
layer of silica gel. Concentration of the ®ltered
solution gave 6 as an amorphous powder (500 mg,
92%), [ꢀ]2d2+86 ꢁ (c 1, CHCl3) [lit. [12],
[ꢀ]2d6+89.5 ꢁ (c 1.6, CHCl3); obtained via a di€er-
[ꢀ]2d3+24.6 ꢁ (c 0.7, MeOH); H NMR (D2O): ꢃ
1
1
(selected signals) 3.86 (s, 3 H, OMe), 4.51 (d, 1 H,
J1,2 8.0 Hz, H-1), 5.39 (d, 1 H, J1 ,2 4.0 Hz, H-10).
ent route]; H NMR (CDCl3): ꢃ (benzyl signals
were omitted) 3.41 (dd, 1 H, H-60a), 3.50 (dd, 1 H,
H-20), 3.53 (dd, 1 H, H±60b), 3.63 (dd, 1 H, H-6a),
3.65 (t, 1 H, H-40), 3.75 (m, 1 H, H-50), 3.75 (dd, 1
H, H±2), 3.91 (dd, 1 H, H-6b), 3.92 (t, 1 H, H-30),
4.08±4.18 (m, 3 H, H-3, 4, 5), 5.63 (d, 1 H, H-10),
6.06 (d, 1 H, H-1). J1,2 3.8, J2,3 9.0, J5,6a 2.2, J5,6b
0
0
.
Anal. Calcd for C20H30O12 H2O: C, 50.00; H, 6.71.
Found: C, 50.37; H, 6.93.
4-Methoxyphenylmethyl 2,3,6-tri-O-benzyl-4-O-
(2,3,4,6-tetra-O-benzyl-a-d-glucopyranosyl)-b-d-
glucopyranoside (4).ÐA solution of 3 (864 mg,

20
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
0
0
0
0
0
0
0
0
3.5, J6a,6b 11, J1 2 3.8, J2 ,3 &J3 ,4 &J4 ,5 9.0±9.5,
were added, and the solution was kept for 4 h at
room temperature. TLC (2:1 hexane±EtOAc) of
the solution showed a single spot at Rf 0.65 (cf. 8:
Rf 0.55). After neutralization with triethylamine,
the solution was washed with water, dried
(Na2SO4), and concentrated. The residue was chro-
matographed with 3.5:1 hexane±EtOAc to give 9 as
a syrup (978 mg, quant), [ꢀ]2d6+103 ꢁ (c 0.8, CHCl3);
1H NMR (CDCl3): ꢃ (selected signals) 3.50 (dd, 1
H, H-20), 3.64 (t, 1 H, H-40), 3.78 (ddd, 1 H, H-50),
3.92 (dd, 1 H, H-2), 3.94 (t, 1 H, H-30), 3.97 (t, 1 H,
H-3), 4.06 (dd, 1 H, H-4), 4.41 (ddd, 1 H, H-5),
5.62 (d, 1 H, H-10), 5.63 (d, 1 H, H-1); J1,2 6.0,
J5 ,6 a 2, and J5 ,6 b 3.0 Hz; 13C NMR (CDCl3):
ꢃ 93.27 (C-1), 80.10 (C-2), 81.26 (C-3), 71.86
(C-4), 73.16 (C-5), 68.29 (C-6,60), 97.05 (C-10),
79.50 (C-20), 81.96 (C-30), 77.71 (C-40), and
71.18 (C-50), 68.29 (C-60). The H and 13C signals
were con®rmed by mononuclear COSY and
HMQC experiments.
0
0
0
0
1
2,3,6-Tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-
d-glucopyranosyl)-d-glucopyranosyl bromide (7).Ð
A mixture of 8 (20 mg, 0.02 mmol) and TiBr4
(10.9 mg, 0.03 mmol) in 10:1 CH2Cl2±EtOAc
(0.45 mL) was stirred overnight at room tempera-
ture. TLC (2:1 hexane±EtOAc) of the solution
showed a spot at Rf 0.65 (cf 8: Rf 0.55). After
addition of CH3CN (0.8 mL), the solution was
poured on to powdered, anhydrous NaOAc
(34 mg), and the mixture was stirred for 20 min at
room temperature. After ®ltration with the aid of
toluene, the ®ltrate was concentrated to give 7 as a
syrup (20 mg), which was used without puri®cation.
1-O-Acetyl-2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-
O-benzyl-a-d-glucopyranosyl)-d-glucopyranose (8).Ð
A mixture of 5 (380 mg, 0.39 mmol) and Ac2O
(55 ꢄL, 0.6 mmol) in pyridine (5 mL) was kept for
1.5 h at room temperature. Methanol (2 mL) was
added and the solution was concentrated by coe-
vaporation with toluene to give a syrup, that was
puri®ed by chromatography (3.2:1 hexane±EtOAc)
to give 8 as a syrup (395 mg, quant), [ꢀ]2d1+53 ꢁ (c
1.1, CHCl3); 1H NMR (CDCl3): ꢃ (selected signals)
2.03 (1.3 H, Ac of ꢁ-anomer), 2.15 (1.7 H, Ac
of ꢀ-anomer), 3.49 (dd, 0.43 H, H-20 of ꢁ-anomer),
3.50 (dd, 0.57 H, H-20 of ꢀ-anomer), 3.62 (t, 0.43
H, H-2 of ꢁ-anomer), 3.67 (t, 1 H, H-40), 3.68 (ddd,
0.43 H, H-5 of ꢁ-anomer), 3.72 (dd, 0.57 H, H-2 of
ꢀ-anomer), 3.77 (ddd, 1 H, H±50), 3.82 (t, 0.43 H,
H-3 of ꢁ-anomer), 3.91 (dd, 1 H, H-30), 3.97 (ddd,
0.57 H, H-5 of ꢀ±anomer), 4.04 (d, 0.57 H, H-3 of
ꢀ-anomer), 4.13 (t, 0.43 H, H-4 of ꢁ-anomer), 4.15
(t, 0.57 H, H-4 of ꢀ-anomer), 5.58 (0.43 H, H-10 of
ꢁ-anomer), 5.65 (d, 0.43 H, H-1 of ꢁ±anomer), 5.69
(d, 0.57 H, H-10 of ꢀ-anomer), 6.36 (d, 0.57 H, H-1
of ꢀ-anomer); J1,2 3.8 (ꢀ) and 8.0 (ꢁ), J2,3=J3,4
0
0
0
0
0
0
0
0
J2,3&J3,4&J4,5 9±9.5, J1 ,2 3.8, J2 ,3 =J3 ,4 =J4 ,5
9±9.5 Hz. Anal. Calcd for C67H68O10S: C, 75.54; H,
6.43; S, 3.01. Found: C, 75.77; H, 6.49; S, 3.21.
General procedure for 2-hydroxyethyl (10), 3-
hydroxypropyl (11), and 4-hydroxybutyl 2,3,6-tri-
O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-d-glucopyr-
anosyl)-b-d-glucopyranoside (12).ÐA mixture of 1
(0.5 mmol), a corresponding diol (distilled or dried
over molecular sieves 4 A, 2.5±5 mmol), powdered
Drierite (CaSO4, 250 mg), and Hg(CN)2 (1.5 mmol)
in CH2Cl2 (3±4 mL) was stirred for 5.5 h under
re¯ux. The mixture was ®ltered through a layer of
Celite with the aid of CH2Cl2, and the solution was
washed with aq NaHCO3, and dried (Na2SO4).
Concentration followed by chromatography (1:2.5
acetone±toluene or 2:1 toluene±acetone for 11 and
12) gave the product 10 (73%) together with 21
(6.4%); and 11 (78%) and 12 (70%), respectively,
as a syrup.
Compound 10: [ꢀ]2d6+49.5 ꢁ (c 0.9, CHCl3).
Anal. Calcd for C28H40O19: C, 49.41; H, 5.92.
Found: C, 49.42; H, 5.71.
Compound 11: [ꢀ]2d4+44 ꢁ (c 1, CHCl3). Anal.
Calcd for C29H42O19: C, 50.14; H, 6.09. Found: C,
50.11; H, 6.01.
Compound 12: [ꢀ]d23+45 ꢁ (c 0.9, CHCl3). Anal.
Calcd for C30H44O19: C, 50.85; H, 6.26. Found: C,
50.56; H, 6.22.
General procedure for 2-hydroxyethyl (13), 3-
hydroxypropyl (17), and 4±hydroxybutyl 2,3,6-tri-
O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-d-glucopyr-
anosyl)-a- (19) and the corresponding b-d-
glucopyranosides (14, 18, and 20).Ð
0
0
=J4,5 9.0, J5,6a 2.0, J5,6b 3.5, J1 ,2 3.5 (ꢀ) and 3.8 (ꢁ),
0
0
0
0
0
0
J2 ,3 =J3 ,4 =J4 ,5 9.0 Hz. Anal. Calcd for C63H66
O12: C, 74.53; H, 6.55. Found: C, 74.65; H, 6.64.
Phenyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-a-d-glucopyranosyl)±1-thio-a-d-glucopyrano-
side (9).ÐTo a cold (0 C) solution of 8 (932 mg,
0.92 mmol) in CH2Cl2 (12 mL), PhSSiMe3 (0.57 mL,
3.0 mmol) and CF3SO2SiMe3 (0.36 mL, 1.85 mmol)
Method A [from 6 and Hg(CN)2]. A mixture of
6 (0.05 mmol), a corresponding diol (distilled or
dried over molecular sieves 4 A, 0.5 mmol), Drierite
(30 mg), and Hg(CN)2 (0.15 mmol) in CH2Cl2
(0.5 mL) was re¯uxed overnight. The solution was
®ltered through a Celite layer with the aid of
ꢁ

M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
21
CH2Cl2, washed with aq NaHCO3 (saturated), and
dried (Na2SO4). Concentration of the solution
gave a residue, which was chromatographed (3:1
hexane±MeCOEt) to give, in the case of ethane-
1,2-diol, 13 (12%) and 14 (76%) each as a syrup.
Method B (from 6 and HgI2±I2). A mixture of 6
(0.05 mmol), HgI2 (0.15 mmol, dried in vacuo for
Compound 17: [ꢀ]d23+44 ꢁ (c 1.2, CHCl3). Anal.
Calcd for C64H70O12: C, 74.54; H, 6.84. Found: C,
74.66; H, 6.74. Compound 18: [ꢀ]2d3+34 ꢁ (c 1.1,
CHCl3). Anal. Calcd for C64H70O12: C, 74.54; H,
6.84. Found: C, 74.26; H, 6.69.
Compound 19: [ꢀ]d23+45 ꢁ (c 1.1, CHCl3). Anal.
Calcd for C65H72O12: C, 74.69; H, 6.94. Found: C,
74.32; H, 6.84. Compound 20: [ꢀ]2d3+32 ꢁ (c 0.9,
CHCl3). Anal. Calcd for C65H72O12: C, 74.69; H,
6.94. Found: C, 74.39; H, 6.90.
ꢁ
3 h at 80 C), I2 (0.1 mmol), and molecular sieves
3 A (100 mg) in CH2Cl2 (0.7 mL) was stirred for
1 h, a corresponding diol (0.5 mmol) was added,
and stirring was continued overnight at room tem-
perature. Filtration, washing of the ®ltrate with aq
20% Na2S2O3 and aq NaHCO3 (saturated), and
concentration gave a mixture of products, which
was separated as described for Method A to give, in
the case of ethane-1,2-diol, 13 (17%) and 14 (56%).
Method C (from 6 and AgOTf). A mixture of a
Reaction of 9 with 2-O-(t-butyldimethylsilyl)-
ethane-1,2-diol to give 15 and 16. A mixture of
9
(47 mg, 0.047 mmol), TBDMS-O(CH2)2OH
(84 mg, 0.47 mmol), and molecular sieves 4 A
(100 mg) in CH2Cl2 (0.3 mL) was stꢁirred for 30 min
at room temperature, cooled to 0 C, and treated
successively with N-iodosuccinimide (32 mg,
0.14 mmol) and CF3SO3H (2.2 ꢄL in 0.37 mL
CH2Cl2) as described for Method D. After the
usual work-up, chromatography (10:1 hexane±
acetone) of the crude products gave a mixture of
corresponding
diol
(0.5 mmol),
s-collidine
(0.1 mmol), and molecular sieves 4 A (100 mg) in
CH2Cl2 (0.6 mL) was stirred for 30 min at
room temperature, cooled to 40 ꢁC, AgOTf
(0.15 mmol) was added, 6 (0.05 mmol) in CH2Cl2
(0.6 mL) was added dropwise under stirring, and
stirring was continued overnight at room tempera-
ture. After ®ltration with the aid of CH2Cl2, the
solution was washed with aq 1 M HCl and aq
NaHCO3, and dried (Na2SO4). Chromatography
(12±15:1 toluene±acetone) of the products gave the
corresponding ꢀ and ꢁ anomers each as a syrup.
By using ethane-1,2-diol: 13 (43%) and 14 (35%);
by propane-1,3-diol: 17 (51%) and 18 (30%); by
butane-1,4-diol: 19 (47%) and 20 (43%).
1
15 and 16 (42 mg, 78%). H NMR (CDCl3): ꢃ
0.04±0.11 (6 H, SiMe2), 0.87±0.92 (9 H, CMe3),
4.47 (d, 0.35 H, J1,2 8.0 Hz, H-1 of 16), 4.87 (d,
0.65 H, J1,2 3.8 Hz, H-1 of 15), 4.26±5.05 (14 H,
CH2Ph), 5.65 (d, 0.35 H, J1 ,2 3.8 Hz, H-10 of 16),
0
0
5.69 (d, 0.65 H, J1 ,2 4.0 Hz, H-10 of 15), 7.05±7.35
(35 H, 7 Ph).
0
0
General procedure for 1,2-bis[O-[2,3,6-tri-O-
acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-d-glucopyrano-
syl)-b-d-glucopyranosyl]]ethane-1,2-diol (21), 1,3-
bis[O-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-ace-
tyl-a-d-glucopyranosyl)-b-d-glucopyranosyl]]prop-
ane-1,3-diol (25), and 1,4-bis[O-[2,3,6-tri-O-acetyl-
4-O±(2,3,4,6-tetra-O-acetyl-a-d-glucopyranosyl)-b-
d-glucopyranosyl]]butane-1,4-diol (28). A mixture
of 1 (0.75 mmol) and 10, 11, or 12 (0.5 mmol),
Drierite (1.3 g), and Hg(CN)2 (2.25 mmol) in
CH2Cl2 (2 mL) was stirred under re¯ux for 3 h.
Post treatment as described for 10 with chromato-
graphy (3ꢂ4:1 toluene±acetone!2:1 hexane±ace-
tone) gave 21 (70%), 25 (76%), and 28 (68%),
respectively, as an amorphous powder.
Compound 21: [ꢀ]d26+49 ꢁ (c 0.8, CHCl3). Anal.
Calcd for C54H74O36: C, 49.92; H, 5.74. Found: C,
49.70; H, 5.75.
Compound 25: [ꢀ]2d1+55 ꢁ (c 1, CHCl3). Anal.
Calcd for C55H76O36: C, 50.30; H, 5.83. Found: C,
50.59; H, 5.55.
Method D (from 9). A mixture of 9 (0.05 mmol),
a corresponding diol (0.5 mmol), and molecular
sieves 4 A (100 mg) in CH2Cl2 (0.4 mL) was stirred
for 30 min at room temperature. The mixture was
cooled to 0 ꢁC, N-iodosuccinimide (0.15 mmol) was
added, and stirring was continued for 30 min at the
ꢁ
temperature. After cooling to 40 C, CF3SO3H
(2.5 ꢄL) in CH2Cl2 (0.4 mL) was added dropwise,
ꢁ
and the mixture was stirred for 4 h at 0 C. Post
work-up as described for Method B gave the cor-
responding ꢀ and ꢁ anomers, each as a syrup.
From the reaction with ethane-1,2-diol: 13 (67%)
and 14 (24%); from propane-1,3-diol: 17 (48%)
and 18 (27%); from butane-1,4-diol: 19 (51%), 20
(27%).
Compound 13: [ꢀ]d23+33 ꢁ (c 1.1, CHCl3). Anal.
Calcd for C63H68O12: C, 74.39; H, 6.74. Found: C,
74.36; H, 6.48. Compound 14: [ꢀ]2d3+27 ꢁ (c 0.8,
CHCl3). Anal. Calcd for C63H68O12: C, 74.39; H,
6.74. Found: C, 74.12; H, 6.72.
Compound 28: [ꢀ]d21+47 ꢁ (c 1, CHCl3). Anal.
Calcd for C56H78O36: C, 50.68; H, 5.92. Found: C,
50.44; H, 5.93.

22
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
General procedure for 1,2-bis[O-[2,3,6-tri-O-
CHCl3). Anal. Calcd for C124H130O22: C, 75.51; H,
6.64. Found: C, 75.23; H, 6.47.
benzyl-4-O-(2,3,4,6-tetra-O±benzyl-a-d-glucopyrano-
syl)-a-d-glucopyranosyl]]ethane-1,2-diol (22), 1-O-
[2,3,6±tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-
d-glucopyranosyl)-a-d-glucopyranosyl]-2-O-[2,3,6-
tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-d-gluco-
pyranosyl)-b-d-glucopyranosyl]ethane-1,2-diol (23);
1,3-bis[O-[2.3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-a-d-glucopyranosyl)-a-d-glucopyranosyl]]-
propane-1,3-diol (26), 1-O-[2,3,6-tri-O-benzyl-4-O-
(2,3,4,6-tetra-O-benzyl-a-d-glucopyranosyl)-a-d-
glucopyranosyl]-3-O-[2,3,6-tri-O-benzyl-4-O-(2,3,-
4,6-tetra-O-benzyl-a-d-glucopyranosyl)-b-d-gluco-
pyranosyl]propane-1,3±diol (27); 1,4-bis[O-[2,3,6-
tri-O-benzyl-4-O-(2,3,6-tetra-O-benzyl-a-d-gluco-
pyranosyl)-a-d-glucopyranosyl]]butane-1,4-diol (29)
and 1-O-[2,3,6-tri-O±benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-a-d-glucopyranosyl)-a-d-glucopyranosyl]-4-
O-[2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-
d-glucopyranosyl)-b-d-glucopyranosyl]butane-1,4-
diol (30). From 6. A mixture of 13, 17, or 19
(1.0 mmol), s-collidine (2.5 mmol) and molecular
sieves 4 A (2.0 g) in CH2Cl2 (25 mL) was stirred ꢁfor
30 min at room temperature, cooled to 40 C,
AgOTf (3.0 mmol) was added, then compound 6
(1.1 mmol) in CH2Cl2 (15 mL) was added dropwise
under stirring, and the mixture was stirred over-
night at room temperature. Puri®cation as descri-
bed for Method C gave a mixture of products,
which were separated by column chromatography
(double developments with 3.5:1 hexane±EtOAc
and 12±14:1 toluene±EtOAc) to give a pair of
products 22 (42%) and 23 (14%); 26 (46%) and
27 (23%); and 29 (46%) and 30 (33%), each as a
syrup, respectively, together with slight amounts
of starting materials recovered.
Compound 26: [ꢀ]2d3+71 ꢁ (c 1, CHCl3). Anal.
Calcd for C125H132O22: C, 75.58; H, 6.70. Found:
C, 75.19; H, 6.69. Compound 27: [ꢀ]2d3+42 ꢁ (c 1,
CHCl3). Anal. Calcd for C125H132O22: C, 75.58; H,
6.70. Found: C, 75.39; H, 6.63.
Compound 29: [ꢀ]2d1+60 ꢁ (c 1, CHCl3). Anal.
Calcd for C126H134O22: C, 75.65; H, 6.75. Found:
C, 75.61; H, 6.81. Compound 30: [ꢀ]2d1+47 ꢁ (c 1,
CHCl3). Anal. Calcd for C126H134O22: C, 75.65; H,
6.75. Found: C, 75.35; H, 6.70.
1-O-[2,3,6-Tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-a-d-glucopyranosyl)-a±d-glucopyranosyl]-2-
O-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-
d-glucopyranosyl)-b-d-glucopyranosyl]ethane-1,2-
diol (24).ÐCompound 1 (25 mg, 0.036 mmol) was
condensed with 13 (14 mg, 0.014 mmol) in CH2Cl2
(0.7 mL) in the presence of s-collidine (12 ꢄL,
0.09 mmol), AgOTf (28 mg, 0.11 mmol), and mole-
cular sieves 4 A (30 mg) as described for 22 to give,
after chromatography (6:1 toluene±acetone), 24 as a
syrup (14 mg, 62% based on 13), [ꢀ]2d2+54.0 ꢁ (c 1,
1
CHCl3); H NMR (CDCl3): ꢃ (selected signals; A
and B denote the benzylated and acetylated por-
tions of the maltosides, respectively) 1.96 (3 H), 2.00
(3 H), 2.02 (3 H), 2.07 (9 H), 2.08 (3 H) (each s, 7
Ac); 3.48 (dd, 1 H, H-20A), 3.59 (dd, 1 H, H-2A);
3.58 (m, 1 H), 3.66 (m, 1 H), and 3.74 (m, 2 H) (H±
100a,b and H-200a,b); 3.63 (m, 1 H, H-5B), 3.64 (t, 1
H, H-40A), 3.88 (m, 1 H, H-5A), 3.89 (t, 1 H, H-
30A), 3.91 (m, 1 H, H-50B), 4.02 (t, 1 H, H-4B), 4.04
(t, 1 H, H-4A), 4.07 (t, 1 H, H-3A), 4.08 (m, 1 H, H-
50A), 4.08 (dd, 1 H, H-60aB), 4.20 (dd, 1 H, H±6aB),
4.24 (dd, 1 H, H-60bB), 4.32 (dd, 1 H, H-6bB), 4.37
(dd 1 H, H-2B?), 4.39, 4.52, 4.52, 4.60, 4.61, 4.83,
and 4.91 (each ABq of 2 H, CH2Ph), 4.82 (d, 1 H, H-
1A), 4.88 (dd, 1 H, H-20B), 5.03 (t, 1 H, H-40B), 5.06
(t, 1 H, H-3B), 5.41 (dd, 1 H, H-30B), 5.48 (d, 1 H,
H-10B), 5.67 (d, 1 H, H-10A), 5.82 (d, 1 H, H-1B);
From 9. A mixture of 9 (1.1 mmol) and 13, 17 or
19 (1.0 mmol), and molecular sieves 4 A (4.0 g) in
CH2Cl2 (15 mL) was stirred for 1 h at room tem-
perature, cooled to 0 ꢁC, N-iodosuccinimide
(3.0 mmol) was added, stirring was ꢁcontinued for
20 min in the cold, cooled to 40 C, CF3SO3H
(60 ꢄL in 25 mL CH2Cl2) was added dropwise, and
the mixture was stirred for 4 h at 0 ꢁC. Puri®cation
as described for Method D followed by chromato-
graphy as described for the synthesis from 6 gave a
pair of products 22 (44%) and 23 (20%); 26 (37%)
and 27 (37%); and 29 (34%) and 30 (31%),
respectively.
00
00
00
00
0
0
0
0
J1 a,1 b=J2 a,2 b 12, J1A,2A =J1 A,2 A=J1 B,2 B 3.8,
J1B,2B 5.8, J2A,3A=J2 A,3 A 9, J2B,3B=J2 B,3 B 9.5. 13C
NMR (CDCl3): ꢃ (selected signals) 96.83 (C-1A),
80.01 (C-2A), 81.90 (C±3A), 68.27 (C-4A), 69.90 (C-
5A), 69.03 (C-6A), 96.73 (C-10A), 79.43 (C-20A),
82.01 (C-30A), 77.71 (C-40A), 71.08 (C-50A), 68.27
(C-60A), 96.86 (C-1B), 73.66 (C-2B), 68.93 (C-3B),
72.30 (C-4B), 73.18 (C-5B), 63.93 (C-6B), 95.02 (C-
10B), 70.25 (C-20B), 69.83 (C-30B), 68.33 (C-40B),
67.47 (C-50B), 61.84 (C-60B), 62.39 and 66.50 (two
bridge carbons). Anal. Calcd for C89H102O29: C,
65.35; H, 6.29. Found: C, 65.35; H, 6.29.
0
0
0
0
Compound 22: [ꢀ]d21+64 ꢁ (c 0.9, CHCl3). Anal.
Calcd for C124H130O22: C, 75.51; H, 6.64. Found:
C, 75.41; H, 6.59. Compound 23: [ꢀ]2d1+49 ꢁ (c 1.2,

M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
23
General procedure for 1,2-Bis[O-[4-O-(a-d-gluco-
pyranosyl)-b-d-glucopyranosyl]]ethane-1,2-diol (31),
1,3-bis[O-[4-O-(a-d-glucopyranosyl)-b-d-glucopyr-
anosyl]]propane-1,3-diol (34), and 1,4-bis[O-[4-O-
(a-d-glucopyranosyl)-b-d-glucopyranosyl]]butane-
1,4-diol (37).ÐTo a solution of 21, 25 or 28
(0.5 mmol) in MeOH (20 mL) was added metha-
nolic 1 M NaOMe (2.0 mL), and the solution was
kept for 1 h at room temperature. Neutralization
with Dowex 50W-X2 (H+) resin, followed by con-
centration of the solution gave a solid, which was
thoroughly dried in vacuo (for 5 days in the pre-
sence of P2O5 in a desiccator) to give 31, 34, and 37
(each almost quant.) as an amorphous powder,
respectively.
Compound 31: TLC (4:1:1 1-propanol±AcOH±
H2O) Rf, maltose 0.3, [ꢀ]2d0+78 ꢁ (c, 1, H2O). Anal.
Calcd for C26H46O22: C, 43.94; H, 6.52. Found: C,
43.48; H, 6.78.
Compound 34: [ꢀ]2d0+84 ꢁ (c 1, H2O). Anal.
.
Calcd for C27H48O22 0.5H2O: C, 44.20; H, 6.73.
Found: C, 44.02; H, 6.67.
Compound 37: [ꢀ]2d1+63 ꢁ (c 1.1, H2O). Anal.
.
Calcd for C28H50O22 0.5H2O: C, 44.98; H, 6.88.
Found; C, 44.81; H, 6.79.
General procedure for 1,2-bis[O-[4-O-(a-d-
glucopyranosyl)-a-d-glucopyranosyl]]ethane-1,2-
diol (32), 1,3-bis[O-[4-O-(a-d-glucopyranosyl)-a-
d-glucopyranosyl]]propane-1,3-diol (35), and 1,4-
bis[O-[4-O-(a-d-glucopyranosyl)±a-d-glucopyrano-
Compound 35: [ꢀ]2d1+192 ꢁ (c 1, H2O). Anal.
.
Calcd for C27H48O22 0.5 H2O: C, 44.20; H, 6.73.
Found: C, 44.24; H, 6.70.
Compound 38: [ꢀ]2d2+184 ꢁ (c 1, H2O). Anal.
.
Calcd for C28H50O22 0.5H2O: C, 44.98; H, 6.88.
Found: C, 44.90; H, 6.61.
1-O-[4-O-(a-d-Glucopyranosyl)-a-d-glucopyrano-
syl]-2-O-[4-O-(a-d-glucopyranosyl)-b-d-glucopyr-
anosyl]ethane-1,2-diol (33).ÐFrom 23. Compound
23 (50 mg, 0.025 mmol) was treated as described for
32 to give 33 as an amorphous powder (0.5
hydrate, 13 mg, 71%), [ꢀ]2d1+125 ꢁ (c 1, H2O).
.
Anal. Calcd for C26H46O22 0.5H2O: C, 43.39; H,
6.58. Found: C, 43.89; H, 6.71.
From 24. Zemplen deacetylation of 24 (10 mg,
6.11 ꢄmol) followed by debenzylation of the pro-
duct [7.3 mg, [ꢀ]d22+53 ꢁ (c 0.5, CHCl3)] as descri-
bed for 32 gave 33 (2.5 mg, 58% based on 24),
identical with the specimen obtained from 23.
1-O-[4-O-(a-d-Glucopyranosyl)-a-d-glucopyrano-
syl]-3-O-[4-O-(a-d-glucopyranosyl)-b-d-glucopyr-
anosyl]propane-1,3-diol (36).ÐDebenzylation of 27
(88 mg, 0.044 mmol) as described for 32 gave 36 as
an amorphous powder (0.5 hydrate, 21 mg, 65%),
[ꢀ]2d1+111 ꢁ (c 1, H2O). Anal. Calcd for C27
.
H48O22 0.5H2O: C, 44.20; H, 6.73. Found: C,
44.08; H, 6.76.
1-O-[4-O-(a-d-glucopyranosyl)-a-d-glucopyrano-
syl]-4-O-[4-O-(a-d-glucopyranosyl)-b-d-glucopyr-
anosyl]butane-1,4-diol (39).ÐDebenzylation of 30
(105 mg, 0.053 mmol) as described for 32 gave 39 as
an amorphous powder (0.5 hydrate, 24 mg, 62%),
[ꢀ]2d2+117 ꢁ (c 1, H2O). Anal. Calcd for
syl]]butane-1,4-diol
(ꢂ10 mL) cooled to
(38).ÐTo
liquid
NH3
55 ꢁC, 22, 26 or 29
(0.05 mmol) in oxolane (1.0 mL) was added, then
Na (ꢂ100 mg) was added, and the deep-blue solu-
tion was kept for 30 min in the cold. After addition
of 2:1 oxolane±MeOH until the solution become
colorless, NH3 and the solvents were evaporated
under warming and ®nally under reduced pressure.
A strongly basic aq solution of the residue was
neutralized with Dowex 50W-X2 (H+) resin, ®l-
tered, and the ®ltrate was concentrated. The resi-
due dissolved in pyridine was acetylated with Ac2O
overnight at room temperature, following chroma-
tography (3:1 toluene±acetone) of the product and
deacetylated (Zemplen deacetylation) to give a
deprotected product, which was puri®ed as descri-
bed for 31 to give 32 (75%), 35 (69%), and 38
(56%) as an amorphous powder of 0.5 hydrate,
respectively.
.
C28H50O22 0.5H2O: C, 44.98, H, 6.88. Found: C,
44.78; H, 6.76.
Atomic charges in most stable conformations of
model compounds in a medium of dielectric constant
32.63 (MeOH) calculated by MOPAC 94/PM3.Ð
Methyl ꢀ-d-glucopyranoside: H-1 (0.108), H-2
(0.111), H-3 (0.106), H-4 (0.104), H±5 (0.092), H-
6a (0.077), H-6b (0.062), OCH3 (0.060, 0.045,
0.033), HO-2 (0.235), HO-3 (0.237), HO-4 (0.237),
HO-6 (0.240), C-1 (0.181), C-2 (0.001), C-3 (0.016),
C-4 (0.026), C-5 (0.001), C-6 (0.059) CH3 (0.053),
O-1 ( 0.329), O-2 ( 0.360), O-3 ( 0.362), O-4
( 0.358), O-5 ( 0.289), O-6 ( 0.387). H3COCH2-
CH2OCH3: H-1a and 2b (0.082), H-1b and 2a
(0.066), OCH3 (0.055, 0.042, 0.035), C-1 and 2
(0.010), CH3 (0.037), O-1 and
2 ( 0.327).
Compound 32: [ꢀ]2d1+185 ꢁ (c 1, H2O). Anal.
.
Calcd for C26H46O22 0.5H2O: C, 43.39; H, 6.58.
Found: C, 43.63; H, 6.51.
HOCH2CH2CH2OH: H-1a and 3b (0.046), H-1b
and 3a (0.061), H-2a and 2b (0.073), HO-1 and 3
(0.240), C-1 and 3 (0.075), C-2 ( 0.190), O-1 and 3

24
M. Tsuzuki, T. Tsuchiya/Carbohydrate Research 311 (1998) 11±24
( 0.401). H3COH: OCH3 (0.040, 0.026, 0.026), OH
(0.243), CH3 (0.075), OH ( 0.410). Cinnamyl
alcohol (trans): H-1a (0.070), H-1b (0.055), H-2
(0.132), H-3 (0.125), H±20 and 60 (0.133, 0.129), H-
30 and 50 (0.127, 0.126), H-40 (0.126), OH (0.242),
C-1 (0.105), C-2 ( 0.196), C-3 ( 0.113), C-10
( 0.072), C-20 and 60 ( 0.110, 0.121), C-30 and 50
( 0.118, 0.123), C-40 ( 0.119), OH ( 0.399).
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Acknowledgements
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The authors are grateful to Dr. Yoshihiko
Kobayashi for the computational work involving
the preparation of Fig. 1. We also thank Ms
Yoshiko Koyama and Ms Tomoko Yamaguchi of
our laboratory for measurements of NMR spectra
and assistance in preparing the manuscript,
respectively.
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