Synthesis of new heterocyclic derivatives of α,α-trehalose

Article abstract of DOI:10.1016/j.carres.2007.11.019

Several novel N-1, N-2, and S-5 tetrazole and 1,3,4-oxadiazole derivatives of α,α-trehalose disubstituted at C-6,6′, with potential synthetic and pharmacological interest were prepared from commercial tetrazoles and 1,3,4-oxadiazoles in reaction with hexa

Full text of DOI:10.1016/j.carres.2007.11.019

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 536–540
Note
Synthesis of new heterocyclic derivatives of a,a-trehalose
a,
a
a
b
*
´
Inacio Luduvico, Mara R. C. Couri, Leandro J. dos Santos, Maria A. F. Prado,
Rossimiriam P. Freitas Gila and Rosemeire B. Alvesa
a
ˆ
Departamento de Quı´mica—Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais,
ˆ
Avenida Antonio Carlos 6627, Belo Horizonte—MG. CEP.: 31270-901, Brazil
ˆ
ˆ
Avenida Antonio Carlos 6627, Belo Horizonte—MG. CEP.: 31270-901, Brazil
b
Departamento de Produtos Farmaceuticos—Faculdade de Farmacia, Universidade Federal de Minas Gerais,
´
Received 25 June 2007; received in revised form 11 November 2007; accepted 15 November 2007
Available online 23 November 2007
Abstract—Several novel N-1, N-2, and S-5 tetrazole and 1,3,4-oxadiazole derivatives of a,a-trehalose disubstituted at C-6,60, with
potential synthetic and pharmacological interest were prepared from commercial tetrazoles and 1,3,4-oxadiazoles in reaction with
hexa-O-benzyl-6,60-di-O-triflyl-a,a-trehalose.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: a,a-Trehalose; Alkylation; Tetrazole; 1,3,4-Oxadiazole
Most pharmaceuticals and biologically active agrochem-
icals are heterocyclic derivatives, as are numerous addi-
tives used in industries such as in cosmetics,
reprography, information storage, and plastics.1–5
Knowing the broad spectrum of biological activities
and the significant applications of heterocyclic ring sys-
tems, we have focused our interest on improving the
synthesis of tetrazole and oxadiazole compounds linked
to monosaccharides6–10 and disaccharides.11 In continu-
ation of this study, we now focus on the synthesis of tet-
razole and 1,3,4-oxadiazole derivatives of a,a-trehalose.
Among the methods of synthesis of substituted tetra-
zoles developed in the last few years, a simple and effec-
tive one involves the alkylation of tetrazole and
oxadiazoles.7,8,10,11,13 A convenient electrophilic deriva-
tive of a,a-trehalose for this purpose is the 6,60-di-O-tri-
flyl derivative 1 which was easily prepared from
2,20,3,30,4,40-hexabenzyl-a,a-trehalose.12 Reaction of
commercial tetrazoles (2, 3, or 4) or 1,3,4-oxadiazoles
(5 or 6) with 1 in acetone and K2CO3 gave the respective
derivatives 2a–b, 3a–b, 4a, 5a, or 6a (Scheme 1).
The reaction of heterocyclic thiols 4, 5, 6 with 1 gave
products 4a, 5a, and 6a in relatively good and similar
yields (either 76% or 77%). These results suggest that
nucleophilic substitution at C-6,60 of 1 is not affected
by either the heterocyclic ring or the substitution in
the ring. On the other hand, the reaction of either tetra-
zole 2 or 3 with 1 yielded the regioisomers N-2, N-2 and
N-1, N-2 in different yields and ratios. While the alkyl-
ation of 5-phenyltetrazole (3) furnished the mixture of
N-2, N-2 and N-1, N-2 isomers, 3a and 3b, in 2.5:1 ratio
(overall yield 81%), the reaction of unsubstituted tetra-
zole 2 led to a mixture of N-2, N-2 and N-1, N-2 prod-
ucts, 2a and 2b, in 1:1.7 ratio (overall yield 68%).
The alkylation of 5-substituted tetrazole derivatives, as
3, is known to lead to mixtures of N-1 and N-2 substi-
tuted products, the regioselectivity being dependent on
the reaction conditions and the nature of the C- and N-
substituents.3 To the best of our knowledge, the alkyl-
ation of 5-substituted tetrazoles in the presence of base
gives the N-2 isomers predominantly.3,7,8,10,11,14,15 Alkyl-
ated bis-tetrazole derivatives were obtained as N-2, N-2
and N-1, N-2 isomers with the predominance of the sym-
metrical product.11,13,15 Thus, the ratio of products
formed by the alkylation of 3 with the carbohydrate
derivative 1 is in agreement with the literature data.
*
Corresponding author. Tel.: +55 3134995721; fax: +55
3134995700; e-mail: i.luduvico@bol.com.br
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.11.019

I. Luduvico et al. / Carbohydrate Research 343 (2008) 536–540
537
R'
OTf
R''
TfO
O
O
BnO
BnO
BnO
BnO
OBn
OBn
OBn
OBn
BnO
BnO
reactants
K2CO3, acetone
1
O
O
O
O
BnO
BnO
Substitute
Reactants
SH
N
H
N
N
N
N
Ph
4=
N
N
Ph
N
N
N
N
N
R''=
2b R'=
2a R'=R''=
N
N
3=
N
2=
N
NH
N
N
N
N
N
N
N
25%
43%
Ph
Ph
Ph
N
SH
N
N
SH
N
N
3a R'=R''=
N
R''=
3b R'=
N
N
O
O
6=
N
N
N
N
58%
5=
N
N
23%
N
N
Ph
4-Py
S
S
S
Ph
N
N
O
O
4a R'=R''=
N
6a R'=R''=
5a R'=R''=
Ph
N
N
N
N
N
4-Py
76%
77%
76%
Scheme 1.
The synthesis of di-N-alkylated bis-tetrazoles deriva-
tives unsubstituted at position 5 has not been found in
the literature. This kind of compound has been obtained
by our research group and the unsymmetrical N-1, N-2
substituted tetrazoles have been obtained as main prod-
ucts.11 Similarly, the alkylation of 5-unsubstituted tetra-
zole 2 with the carbohydrate derivative 1 led to a
mixture of the symmetrical compound N-2, N-2 substi-
tuted 2a and the unsymmetrical N-1, N-2 isomer with
the predominance of 2b.
(5-substituted and 5-unsubstituted, respectively), while
both signals were apparent in N-1, N-2 substituted com-
pounds. For example, 2a has a single peak at 153.0 ppm,
while 2b has two peaks at 153.0 and 143.0 ppm. The main
difference between the 1H NMR spectra of the isomers is
the signal doubling in the case of N-1, N-2 derivatives 2b
and 3b. The position of the sugar unit at N-1 in the
compounds was confirmed by the cross-peak between
the C-6 methylene protons and C-5 of the tetrazole ring
in HMBC spectra. Such cross-peak resulted from J cou-
pling of these atoms through three bonds. No cross-peak
between C-6 of the carbohydrate moiety and C-5 of the
N-2 substituted tetrazole rings was observed in HMBC
spectra.
The structures of the compounds 2a, 2b, 3a, 3b, 4a, 5a,
and 6a were determined by the assignment of 1H and 13
C
NMR spectra involving COSY, HMQC, and HMBC
experiments. Product purity was confirmed by elemental
analysis. The structure of the isomeric N-2, N-2 and N-1,
N-2 derivatives (2a/2b and 3a/3b) is readily distinguish-
able by their 1H and 13C NMR. It is well established that
the 13C carbon atom of the tetrazole ring in N-1 substi-
tuted derivatives is more shielded by ca. 10 ppm relative
1. Experimental
1.1. General methods
to their corresponding N-2 substituted isomer.16 The 13
C
NMR chemical shift of the tetrazole carbon atom
appears at ca. 154.0 and 164.0 in 1,5- and 2,5-disubsti-
tuted tetrazoles, respectively.8,11,13,16 The 13C chemical
shift of 5-unsubstituted N-1and N-2 substituted tetra-
zoles appears at ca. 143 and 153, respectively.10,11 The
symmetrical N-2, N-2 substituted compounds thus gave
rise to a single resonance at either ca. 164 or 154 ppm
Melting points were determined in a Mettler FP80HT
apparatus and are uncorrected. Optical rotation was
determined in a Perkin–Elmer 341 Polarimeter at
20 ꢁC. NMR spectra were recorded in either Bruker
Avance DRX-200 or DRX-400 spectrometers. Chemical
shifts are reported in d units downfield from TMS and J
values are given in Hz. Elemental analyses were carried

538
I. Luduvico et al. / Carbohydrate Research 343 (2008) 536–540
out in a Perkin–Elmer 2400 CHN apparatus. IR spectra
were obtained in a Perkin–Elmer Spectrum One sP-IR
Spectrometer. Column chromatography was performed
with Silica Gel 60, 70–230 mesh (E. Merck). The term
‘standard work-up’ means that the organic layer was
dried over anhyd Na2SO4, filtered, and the solvent was
removed under diminished pressure.
1.3.1. 2,3,4-Tri-O-benzyl-6-deoxy-6-N-(tetrazol-2-yl)-a-
D-glucopyranosyl 2,3,4-tri-O-benzyl-6-deoxy-6-N-(tetra-
zol-2-yl)-a-D-glucopyranoside (2a). 42 mg (25%); oil;
20
½aꢁD +110 (c 0.9, CHCl3); Rf 0.60 (1:1 EtOAc–hexane);
IR: m 3031, 2920, 1728, 1453, 1361, 1281, 1066, 988,
734, 695 cmꢀ1 1H NMR (400 MHz, CDCl3): d ppm
;
8.44 (s, 1H, H-50), 7.35–7.22 (m, 30H, C6H5), 5.04 (d,
2H, J1–2 3.9, H-1), 5,02 (d, 2H, Jgem 11.8, ØCH2), 4.98
(d, 2H, Jgem 10.8, ØCH2), 4.88 (d, 2H, Jgem 10.9,
ØCH2), 4.82 (d, 2H, Jgem 10.8, ØCH2), 4.65 (s, 4H,
ØCH2), 4.59 (dd, 2H, J5–6 4.9, J6–6 14,4, H-6), 4.47–
4.40 (m, 4H, H-5, H-6), 4.08 (t, 2H, J2–3 9.2, H-3),
3.41 (dd, 2H, J1–2 3.9, J2–3 9.2, H-2), 3.36 (t, 2H, J3–4
9.4, H-4); 13C NMR (50 MHz, CDCl3): d ppm 152.9
(C-50), 138.5, 138.3, 138.0 (6C-ipso), 128.7, 128.3,
128.2, 128.1, 127.9, 127,5 (30C6H5), 93.9 (2C-1), 81.8
(2C-3), 79.4 (2C-2), 78.1 (2C-4), 75.8, 75.2, 73.3
(6ØCH2), 68.9 (2C-5), 52.7 (2C-6); Anal. Calcd for
C56H58N8O9: C, 68.14; H, 5.92; N,11.35. Found: C,
67.92; H, 5.59; N, 11.14.
1.2. 2,3,4-Tri-O-benzyl-6-O-trifluoromethylsulfonyl-a-D-
glucopyranosyl 2,3,4-tri-O-benzyl-6-O-trifluoromethyl-
sulfonyl-a-D-glucopyranoside (1)12
To an ice-cold soln of dry CH2Cl2 (12 mL) and pyridine
(0.40 mL, 4.9 mmol) was added triflic anhydride drop by
drop (1.03 mL, 6.12 mmol). After 10 min, the ice bath
was removed and a soln of 2,3,4-tri-O-benzyl-a-D-gluco-
pyranosyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside (1.08 g,
1.22 mmol12) in anhyd CH2Cl2 (13 mL) was added. The
reaction mixture was stirred for 2 h at room tempera-
ture, and then water was added. The reaction mixture
was extracted with CH2Cl2 (3 · 20 mL), and the com-
bined organic extracts were submitted to standard
work-up to give 1.25 g of product 1 (1.09 mmol, 90%)
as an oil; Rf 0.80 (1:4 EtOAc–hexane); IR: m 3066,
3030, 2919, 2860, 1454, 1411, 1357, 1244, 1206, 1142,
1.3.2. 2,3,4-Tri-O-benzyl-6-deoxy-6-N-(tetrazol-1-yl)-a-
D-glucopyranosyl 2,3,4-tri-O-benzyl-6-deoxy-6-N-(tetra-
zol-2-yl)-a-D-glucopyranoside (2b). 73 mg (43%); oil;
20
½aꢁD +73 (c 0.7, CHCl3); Rf 0.10 (1:1 EtOAc–hexane);
1093, 1070, 986, 928, 734, 697 cmꢀ1
;
1H NMR
IR: m 3031, 2923, 1729, 1453, 1362, 1281, 1066, 988,
(400 MHz, CDCl3): d ppm 7.37–7.23 (m, 30H, C6H5),
5.15 (d, 2H, J1ꢀ2 3.6, H-1), 5,04 (d, 2H, Jgem 11.0,
ØCH2), 4.91 (d, 2H, Jgem 10.8, ØCH2), 4.89 (d, 2H, Jgem
11.0, ØCH2), 4.76 (d, 2H, Jgem 11.8, ØCH2), 4.61 (d, 2H,
Jgem 11.8, ØCH2), 4.54 (d, 2H, Jgem 10.9, ØCH2), 4.20–
4.14 (m, 4H, H-5, H-6), 4.07 (d, 2H, J6ꢀ6 9.2, H-6), 4.02
(t, 2H, J3ꢀ4 9.2, H-3), 3.57 (dd, 2H, J2ꢀ3 9.6, H-2), 3.49
(t, 2H, J4ꢀ5 9.4, H-4); 13C NMR (50 MHz, CDCl3): d
ppm 138.4, 137.8, 137.6 (6C-ipso), 129.4, 128.7, 128.6,
128.5, 128.3, 128.2, 127.9, 127.8, 127.3 (30C6H5), 118.6
(q, JC–F 317.6, 2 CF3), 94.6 (2 C-1), 81.6 (2 C-3), 79.4
(2 C-2), 77.1 (2C-4), 75.7, 75.3 (4 ØH2), 74.4 (2 C-6),
73.4 (2ØCH2), 68.7 (2 C-5); Anal. Calcd for C56H56-
F6O15S2: C, 58.63; H, 4.92. Found: C, 58.86; H, 5.20.
734, 695 cmꢀ1 1H NMR (400 MHz, CDCl3): d ppm
;
8.46 (s, 1H, H-50), 8.38 (s, 1H, H-500), 7.36–7.23 (m,
30H, C6H5), 5.06 (d, 1H, J1–2 = 3.4, H-1), 5.02–4.95
(m, 3H, H-1, ØCH2), 4.92–4.84 (m, 4H, ØCH2), 4.74–
4.60 (m, 6H, H-6, ØCH2), 4.50–4.40 (m, 4H, H-5, H-6,
ØCH2), 4.24 (2t, 1H, J4–5 10.0, H-5), 4.09–4.01 (2t, 2H,
J2–3 9.3, H-3), 3.98–3.93 (dd, 1H, J5–6 2.9, J6–6 14.5,
H-6), 3.41–3.34 (m, 3H, H-2, H-4), 2.98 (t, 1H, J3–4
9.8, H-4); 13C NMR (100 MHz, CDCl3): d ppm 153.0
(C-50), 143.0 (C-500), 138.4, 138.3, 138.1, 138.0, 137.9
(6C-ipso), 128.8, 128.7, 128.6, 128.5, 128.4, 128.3,
128.2, 128.1, 128.0, 127.9, 127.5, 127.4 (30C6H5), 94.4,
94.2 (2C-1), 81.9, 81.5 (2C-3), 79.5 (2C-2), 78.1, 77.4
(2C-4), 75.8, 75.8, 75.4, 75.3, 73.6, 73.5 (6ØCH2), 69.1,
68.9 (2C-5), 52.6, 47.9 (2C-6); Anal. Calcd for
C56H58N8O9: C, 68.14; H, 5.92; N,11.35. Found: C,
67.97; H, 5.63; N, 11.21.
1.3. General tetrazole and 1,3,4-oxadiazole alkylation
procedure7,8,10,11,13,14
To a stirred soln of either tetrazole (2, 3, or 4) or oxadi-
azole (5 or 6) (0.52 mmol) and anhyd K2CO3
(5.23 mmol) in dry acetone (7 mL) was added triflate 1
(0.17 mmol). The soln was stirred overnight. After com-
plete conversion to the corresponding product, as indi-
cated by TLC, the solvent was removed under
diminished pressure. The residue was diluted with
CH2Cl2 (30 mL) and washed with water (3 · 20 mL).
The organic phase was submitted to standard work-up
and the product was purified by column chromato-
graphy (hexane!EtOAc–hexane) to give the respective
alkylated tetrazoles and 1,3,4-oxadiazoles.
1.3.3. 2,3,4-Tri-O-benzyl-6-deoxy-6-N-(5-phenyltetrazol-
2-yl)-a-D-glucopyranosyl 2,3,4-tri-O-benzyl-6-deoxy-6-N-
(5-phenyltetrazol-2-yl)-a-D-glucopyranoside (3a). 115 mg
20
(58%); oil; ½aꢁD +107 (c 1.05, CHCl3); Rf 0.40 (1:4
EtOAc–hexane); IR: m 3031, 2922, 1729, 1450, 1361,
1207, 1067, 989, 731, 692 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d ppm 8.09–7.20 (m, 40H, C6H5), 5.09 (d, 2H,
J1–2 3.6, H-1), 5.01 (d, 4H, Jgem 10.7, ØCH2), 4.92 (d,
2H, Jgem 12.8, ØCH2), 4.89 (d, 2H, Jgem 10.8, ØCH2),
4.69–4.43 (m, 10H, H-5, H-6, ØCH2), 4.10 (t, 2H, J2–3
9.2, H-3), 3.47–3.41 (m, 4H, H-2, H-4); 13C NMR
(50 MHz, CDCl3): d ppm 165.2 (C-50),138.5, 138.4,

I. Luduvico et al. / Carbohydrate Research 343 (2008) 536–540
539
137.9 (6C-ipso), 130.4, 129.0, 128.7, 128.6, 128.3, 128.2,
128.1, 127.9, 127.5 (38C6H5), 127.4 (2C-ipso), 127.0
(2C6H5), 93.8 (2C-1), 81.8 (2C-3), 79.5 (2C-4), 78.2 (2C-
2), 75.8, 75.3, 73.3 (6ØCH2), 68.9 (2C-5), 52.9 (2C-6);
Anal. Calcd for C68H66N8O9: C, 71.69; H, 5.84; N,
9.84. Found: C,71.02; H,5.84; N, 9.84.
d ppm 7.95–7.92 (m, 4H, C6H5), 7.51–7.17 (m, 36H,
C6H5), 5.18 (d, 2H, J1–2 = 3.4, H-1), 4.99 (d, 2H, Jgem
10.9, ØCH2), 4.92 (d, 2H, Jgem 10.9, ØCH2), 4.87 (d,
2H, Jgem 10.9, ØCH2), 4.75 (s, 4H, ØCH2), 4.65 (d,
2H, Jgem 10.9, ØCH2), 4.37 (ddd, 2H, J4–5 9.7, J5–6
6.3, J5–6 3.2, H-5), 4.10 (t, 2H, J2–3 9.3, H-3), 3.60 (dd,
2H, J1–2 3.4, H-2), 3.55–3.37 (m, 6H, H-4, H-6); 13C
NMR (50 MHz, CDCl3): d ppm 165.8, 164.3 (C-20,
C-50),138.6, 137.9 (6 C-ipso), 131.7, 129.1, 128.6, 128.5,
128.4, 128.0, 127.7, 127.4, 126.7 (40C6H5), 123.7 (2C-
ipso), 93.3 (2C-1), 81.5 (2C-3), 80.0 (2C-4), 79.4 (2C-
2), 75.7, 75.3, 73.3 (6ØCH2), 69.7 (2C-5), 34.8 (2C-6);
Anal. Calcd for C70H66N4O11S2: C, 69.86; H, 5.53; N,
4.66. Found: C, 69.30; H, 5.41; N, 4.65.
1.3.4. 2,3,4-Tri-O-benzyl-6-deoxy-6-N-(5-phenyltetrazol-
1-yl)-a-D-glucopyranosyl 2,3,4-tri-O-benzyl-6-deoxy-6-N-
(5-phenyltetrazol-2-yl)-a-D-glucopyranoside (3b). 46 mg
(23%); oil; ½aꢁ2D0 +114 (c 0.8, CHCl3); Rf 0.13 (1:4 EtOAc–
hexane); IR: m 3031, 2923, 1730, 1451, 1361, 1208, 1067,
989, 731, 693 cmꢀ1; 1H NMR (400 MHz, CDCl3): d ppm
8.04–7.09 (m, 40H, C6H5), 5.03–4.99 (m, 4H, H-1,
ØCH2), 4.95–4.87 (m, 6H, ØCH2), 4.69–4.37 (m, 10H,
H-5, H-6, ØCH2), 4.20 (dd, 1H, J5–6 4.8, J6–6 14.6,
H-6), 4.11 (t, 2H, J2–3 9.2, H-3), 3.99 (dd, 1H, J5–6 3.4,
J6–6 14.6, H-6), 3.61 (t, 1H, J3–4 9.8, H-4), 3.46–3.40
(m, 3H, H-2, H-4); 13C NMR (100 MHz, CDCl3): d
ppm 165.0 (C-50), 155.8 (C-500), 138.4, 138.3, 138.2,
138.1, 137.8, 137.7 (6C-ipso), 131.0, 130.4, 129.3, 128.9,
128.9, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1,
128.0, 127.9, 127.8, 127.6, 127.3, 127.1, 126.9 (40C6H5),
124.2, 124.1 (2C-ipso), 93.7, 93.6 (2C-1), 81.7, 81.6 (2C-
3), 79.1, 77.9 (2C-2, 2C-4), 75.7, 75.5, 75.1, 73.3, 72.9
(6ØCH2), 68.9 (2C-5), 52.6, 46.8 (2C-6); Anal. Calcd
for C68H66N8O9: C, 71.69; H, 5.84; N, 9.84. Found: C,
72.19; H, 5.24; N, 9.71.
1.3.7.
2,3,4-Tri-O-benzyl-6-deoxy-6-S-[5-pyridin-4-yl-
1,3,4-oxadiazol-2-thiolyl]-a-D-glucopyranosyl 2,3,4-tri-
O-benzyl-6-deoxy-6-S-[5-pyridin-4-yl-1,3,4-oxadiazol-2-
thiolyl]-a-D-glucopyranoside (6a). 160 mg (76%); oil;
20
½aꢁD +80 (c 1.65, CHCl3); Rf 0.43 (1:1 EtOAc–hexane);
IR: m 3030, 2925, 1727, 1608, 1454, 1413, 1267, 1062,
1
988, 828, 734, 695 cmꢀ1; H NMR (400 MHz, CDCl3):
d ppm 8.77 (d, 4H, Jo–m 2.4, C5H4), 7.79 (d, 4H, Jo–m
2.4, C5H4) 7.34–7.16 (m, 30H, C6H5), 5.18 (d, 2H, J1–2
3.4, H-1), 4.98 (d, 2H, Jgem 10.8, ØCH2), 4.94 (d, 2H,
Jgem 11.0, ØCH2), 4.87 (d, 2H, Jgem 10.8, ØCH2), 4.74
(sl, 4H, ØCH2), 4.65 (d, 2H, Jgem 11.0, ØCH2), 4.38
(ddd, 2H, J4–5 9.7, J5–6 6.4, J5–6 3.2, H-5), 4.11 (t, 2H,
J3–4 9.1, H-3), 3.60 (dd, 2H, J2–3 9.1, H-2), 3.57 (dd,
2H, J6–6 13.1, H-6), 3.45 (t, 2H, J4–5 9.7, H-4), 3.38
(ddd, 2H, J5–6 6.4, J5–6 3.2, J6–6 13.1, H-6); 13C NMR
(50 MHz, CDCl3): d ppm 165.9, 163.8 (C-20, C-50),
150.7 (4C6H5), 138.4, 137.8 (6C-ipso), 130.8, 128.6,
128.5, 128.4, 128.3, 127.9, 127.8, 127.7, 127.2, 120.1
(36C6H5), 93.3 (2C-1), 81.4 (2C-3), 79.9 (2C-4), 79.3
(2C-2), 75.7, 75.3, 73.2 (6ØCH2), 69.7 (2C-5), 34.7
(2C-6); Anal. Calcd for C68H64N6O11S2: C, 67.76; H,
5.35; N, 6.97. Found: C, 67.16; H, 4.81; N, 6.41.
1.3.5. 2,3,4-Tri-O-benzyl-6-deoxy-6-S-(1-phenyltetrazol-
5-thiolyl)-a-D-glucopyranosyl 2,3,4-tri-O-benzyl-6-deoxy-
6-S-(1-phenyltetrazol-5-thiolyl)-a-D-glucopyranoside (4a).
20
159 mg (76%); oil; ½aꢁD +59 (c 0.6, CHCl3); Rf 0.14 (1:4
EtOAc–hexane); IR: m 3030, 2919, 1727, 1597, 1498,
1
1453, 1387, 1275, 1208, 1063, 987, 734, 694 cmꢀ1; H
NMR (400 MHz, CDCl3): d ppm 7.50–7.19 (m, 40H,
C6H5), 5.02 (d, 2H, J1–2 3.3, H-1), 4.97 (d, 2H, Jgem
10.8, ØCH2), 4.88 (d, 2H, Jgem 11.0, ØCH2), 4.85 (d,
2H, Jgem 11.1, ØCH2), 4.65–4.57 (m, 6H, ØCH2), 4.34
(dt, 2H, J4–5 9.3, J5–6 5.2, H-5), 4.05 (t, 2H, J2–3 9.2,
H-3), 3.68–3.57 (m, 4H, H-6), 3.48–3.41 (m, 4H, H-2,
13
H-4); C NMR (50 MHz, CDCl3): d ppm 154.2 (C-50),
138.5, 137.8, 133.7 (6 C-ipso), 130.2, 129.9, 128.6,
128.5, 128.4, 128.0, 127.9, 127.4, 123.9 (40C6H5), 121.3
(2C-ipso), 93.5 (2C-1), 81.4 (2C-3), 79.8, 79.2 (2C-2,
2C-4), 75.7, 75.3, 73.2 (6ØCH2), 69.5 (2C-5), 35.6 (2C-
6); Anal. Calcd for C68H66N8O9S2: C, 67.87; H, 5.53;
N, 9.31. Found: C, 67.85; H, 5.56; N, 9.40.
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2,3,4-Tri-O-benzyl-6-deoxy-6-S-(5-phenyl-1,3,4-
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20
glucopyranoside (5a). 162 mg (77%); oil; ½aꢁD +86 (c
1.25, CHCl3); Rf 0.21 (1:4 EtOAc–hexane); IR: m 3030,
2918, 1727, 1597, 1498, 1453, 1387, 1359, 1273, 1243,
1063, 988, 734, 694 cmꢀ1; 1H NMR (400 MHz, CDCl3):

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