Stereospecific synthesis of β-D-allopyranosides by dihydroxylation of β-D-erythro-2,3-dideoxyhex-2-enopyranosides

Article abstract of DOI:10.1016/S0008-6215(01)00181-1

The synthesis of 4,6-O-benzylidene-β-D-erythro-2-3-dideoxyhex-2-enopyranosides and their osmium and ruthenium catalysed dihydroxylation reactions have been investigated. These reactions have been shown, for a range of monosaccharides and a disaccharide, to proceed stereospecifically to give β-D-allopyranosides in moderate to excellent yield.

Full text of DOI:10.1016/S0008-6215(01)00181-1

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Carbohydrate Research 334 (2001) 327–335
Note
Stereospecific synthesis of b-
D
-allopyranosides by
dihydroxylation of
b-
D
-erythro-2,3-dideoxyhex-2-enopyranosides
Paul V. Murphy,a,* Julie L. O’Brien,a Amos B. Smith IIIb,*
aDepartment of Chemistry, Conway Institute of Biomolecular and Biomedical Research, Uni6ersity College Dublin,
Belfield, Dublin 4, Ireland
bDepartment of Chemistry, Uni6ersity of Pennsyl6ania, Philadelphia, PA 19104, USA
Received 28 May 2001; accepted 29 June 2001
Abstract
The synthesis of 4,6-O-benzylidene-b-
D-erythro-2-3-dideoxyhex-2-enopyranosides and their osmium and ruthe-
nium catalysed dihydroxylation reactions have been investigated. These reactions have been shown, for a range of
monosaccharides and a disaccharide, to proceed stereospecifically to give b-D-allopyranosides in moderate to
excellent yield. © 2001 Published by Elsevier Science Ltd.
Keywords: Stereospecific synthesis; b-
sion of configuration
D
-Allopyranoside; Dihydroxylation; b-D-erythro-2,3-Dideoxyhex-2-enopyranosides; Inver-
The stereospecific synthesis of glycosides is
of interest due to the biological and medical
importance of oligosaccharides, glycoproteins
and glycolipids and also because of interest in
carbohydrates as peptidomimetics1 and as
scaffolds for the synthesis of pharmacophore
mapping libraries.2 Methodology that can be
used for inversion of configuration at a partic-
ular stereogenic centre of a pyranose or furan-
ose is also of interest. These methods facilitate
the synthesis of carbohydrates for evaluation
as substrates of enzymes, as well as for other
structure activity studies that could lead to the
discovery of more selective enzyme inhibitors.3
Studies on the biological activity of b- -
D
mannopyranoside derivatives have been of in-
terest to us as part of a project on the design
and synthesis of novel carbohydrate based
enzyme inhibitors. Difficulties in the stereose-
lective synthesis of b- -mannopyranosides are
D
well documented and progress in this area has
recently been reviewed.4 There have been re-
ports in the literature describing the dihydrox-
ylation reactions of some 2,3-dideoxyhex-
2-enopyranosides12–16 that give a-
D
-mannopy-
ranosides but none that we could find on the
corresponding reactions of the b- -erythro-
2,3-dideoxyhex-2-enopyranosides which could
-allose deriva-
D
yield the b-
D
-mannose or b-
D
tives as products. Herein we describe the re-
sults of dihydroxylation reactions of these
* Corresponding authors. Tel.: +353-1-7162504; fax: +
353-1-7162127.
E-mail address: paul.v.murphy@ucd.ie (P.V. Murphy).
compounds that stereospecifically gave b- -
D
allopyranosides.
0008-6215/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0008-6215(01)00181-1

328
P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
Methods that have been used previously for
The osmium catalysed dihydroxylation of
syntheses of the b-
D
-allopyranosides include
alkenes 4 proceeded in moderate to excellent
yield and for all reactions examined were
stereospecific (Scheme 1, Table 1) i.e., the
reduction of ketosucroses,5 epoxidation-ring
closure of open-chain hydroxyenol ethers,6
SN2 displacement of leaving groups at C-3 of
b- -mannopyranosides, possible products in
D
b-
chemical manipulation of 1,2:5,6-di-O-iso-
-ery-
D
-glucopyranose derivatives7–10 and by
these reactions, were not detected by 1H NMR
analysis of the crude reaction mixture in any
1
propylidene-a-
D
-allofuranose.11 The b-
D
case. The H NMR spectra of 5a–e showed
thro-2,3-dideoxyhex-2-enopyranosides 4 used
herein were synthesised as shown in Scheme 1.
The benzylidene protected derivatives 2 were
signals for their anomeric protons from l
4.50–5.50 as doublets with coupling constants
of 7.5–8.0 Hz. Hydroxylation reactions of the
n-octyl derivative 4d and the disaccharide 4e
were sluggish using osmium, possibly due to
decreased solubility of these alkenes under
these conditions. This led to lower isolated
yields in the case of the disaccharide. How-
ever, this problem could be overcome by car-
rying out the dihydroxylation reaction with
RuCl3–NaIO4 as reported previously by
Shing;18 the reaction proceeded in good yield
with no loss in stereoselectivity for the two
cases examined (Table 1).
conveniently obtained from reaction of b- -
D
glucose derivatives 1 in the presence of cam-
phorsulfonic acid and benzaldehyde dimethyl
acetal in acetonitrile. The syntheses of the
alkenes 4 from diols 2 were explored by a
number of different methods (Table 1). It was
found that, in general, the use of
triphenylphosphine, iodine and imidazole in
toluene was the most satisfactory method for
this transformation.17 The synthesis of 4a was
carried out via the dimesylate 3a.
Scheme 1.
Table 1
Compound no.
% yield of 2 from 1 a
% yield of 4 from 2
% yield of 5 from 4
a
b
80
88
47 b
92 e
89 f
95 e
62 c
53 d
67 c
46 c
85 c
c
d
e
100
81
71
95 e
79 e
32 e
70 f
Reagents and conditions:
a PhCH(OMe)2, camphorsulfonic acid, MeCN, rt.
b ClPPh2, I2, Im., toluene, then Zn, EtOH.
c PPh3, I2, Im., toluene.
d MsCl, Py then NaI, Zn dust, DMF, microwave oven, 3 min.
e K2OsO2(H2O)2, NMO, DABCO, t-BuOH, H2O, 60 °C.
f RuCl3, NaIO4, CH2Cl2, rt.

P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
329
13C. Coupling constants are reported in hertz.
IR spectra were recorded with a Mattson
Galaxy Series FTIR 3000 using either thin
film between NaCl plates or KBr discs, as
specified. Melting points were measured on a
Gallenkamp melting point apparatus. Elemen-
tal analysis was performed on an Exeter Ana-
lytical CE440 elemental analyser. Low and
high resolution mass spectra were measured
on either a micromass VG 70/70H or VG
ZAB-E or autospec spectrometers and were
measured in ES positive mode unless other-
wise indicated. TLC was performed on alu-
minium sheets precoated with Silica Gel 60
(HF254, E. Merck) and spots visualised by UV
and charring with 1:20 H2SO4–EtOH. Flash-
column chromatography was carried out with
Silica Gel 60 (0.040–0.630 mm, E. Merck) and
using a stepwise solvent polarity gradient cor-
related with TLC mobility. Chromatography
solvents used were EtOAc (Riedel–deHaen)
and petroleum ether (bp 40–60 °C, BDH lab-
oratory supplies). Acetonitrile, toluene, ben-
zene and CH2Cl2 reaction solvents were
freshly distilled from CaH2 and anhyd DMF
was used as purchased from Sigma–Aldrich.
Scheme 2. Reagents and conditions: (a) MeI2, DMF; (b)
BzCl, Py, 0 °C; (c) Bu2SnO, benzene then Bu4NI, BnBr; (d)
NIS, AgOTf, CH2Cl2; (e) NaOMe, MeOH.
The disaccharide 1e, used for the synthesis
of allose containing disaccharide 5e, was syn-
thesised by AgOTf–NIS promoted coupling
of the thioglycoside donor 7 with acceptor 819
and subsequent removal of the benzoyl groups
using NaOMe–MeOH (Scheme 2). The thio-
glycoside donor was first prepared by methy-
lation and subsequent benzoylation of
The b- -glucopyranosides 1a–d were pur-
D
chased from Sigma–Aldrich.
Phenyl 4,6-O-benzylidene-i-
commercially available sodium 1-thio-b- -
D
D
-glucopyran-
glucopyranose. The acceptor 8 was prepared
by regioselective benzylation of the 3-OH
group of 2a.
oside (2a).—A solution of 1a (10 g, 39 mmol),
camphorsulphonic acid (50 mg) and benzalde-
hyde dimethylacetal (11.8 mL, 78.8 mmol) in
MeCN (300 mL) was stirred for 12 h at rt.
Triethylamine (5 mL) was added and the solu-
tion was allowed to stir for a further 1 h. The
product was then filtered off as a white solid,
washed with petroleum ether and dried under
diminished pressure (11.8 g, 88%); mp 163–
165 °C, [h]D −51.5° (c 2.0, acetone) (lit.:20 mp
179–181 °C (EtOH); [h]D −66.5° (c 2.0, ace-
In summary, osmium or ruthenium
catalysed dihydroxylation of 4,6-di-O-benzyli-
dene-b-
osides can be used for the stereospecific
-allopyranosides and the se-
D
-erythro-2,3-dideoxyhex-2-enopyran-
synthesis of b-
D
quence described is convenient for preparing
these carbohydrates.
1
tone)); H NMR (270 MHz, CDCl3): l 7.52–
1. Experimental
7.04 (ms, 10 H, aromatic H), 5.54 (s, 1 H,
CHPh), 5.04 (d, 1 H, J1,2 7.5 Hz, H-1), 4.39
(dd, 1 H, J5,6a 5.0, J6a,6b 10.5 Hz, H-6), 3.90
(apt t, 1 H, J2,3 9.0, J3,4 9.0 Hz, H-3), 3.84–
3.77 (overlapping signals, 2 H, H-2, H-6), 3.63
(apt t, 1 H, J4,5 9.0 Hz, H-4), 3.57 (m, 1 H,
H-5), 2.81 (br s, 1 H, OH), 2.70 (br s, 1 H,
OH); 13C NMR (270 MHz, CDCl3): l 156.7,
137.2 (each s, each aromatic C) 129.7, 129.4,
128.4, 126.3, 123.3, 116.8 (each d, each aro-
Optical rotations were determined with a
Perkin–Elmer 241 model polarimeter at the
sodium D line at 23 °C. NMR spectra were
recorded with JEOL JNM-GX270 and Varian
Inova 300 spectrometers. Chemical shifts are
reported relative to internal Me4Si in CDCl3
(l 0.0), Me2SO-d6 (l 2.50) or acetone-d6 (l
2.20) for 1H and either CDCl3 (l 77.0),
Me2SO-d6 (l 43.5) or acetone-d6 (l 205.1) for

330
P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
7.52–7.32 (ms, 5 H, aromatic H), 5.53 (s, 1 H,
CHPh), 4.39 (d, 1 H, J1,2 8.0 Hz, H-1), 4.33
(dd, 1 H, J5,6a 5.0, J6a,6b 10.5 Hz, H-6a), 3.90
(m, 1 H, OC(H)HCH2), 3.82 (apt t, 1 H, J2,3
9.5, J3,4 9.5 Hz, H-3), 3.79 (apt t, 1 H, J5,6b
10.5 Hz, H-6b), 3.59–3.41 (overlapping sig-
nals, 4 H, H-2,4,5 and OC(H)HCH2), 2.16 (br
s, 1 H, OH), 2.04 (br s, 1 H, OH), 1.66 (m, 2
H, OCH2CH2), 1.37–1.23 (m, 10 H, octyl
matic CH), 102.0, 101.1, 80.3, 74.3, 73.2 (each
d), 68.6 (t, C-6), 66.6 (d); IR (KBr): 3584,
3371, 2925, 2885, 1634, 1592, 1497, 1386,
1228, 1082, 1031, 751, 698 cm−1. ESHRMS:
Found 345.1338, required 345.1338 [M+H]+.
Methyl 4,6-O-benzylidene-i- -glucopyran-
D
oside (2b).—Treatment of 1b (10.0 g, 49
mmol) as described for 1a gave 2b (11.0 g,
80%); mp 169–172 °C; [h]D −61.5° (c 0.2,
CHCl3) (lit.:21 mp 198–200 °C; [h]D −65.2° (c
13
CH2), 0.89 (t, 3 H, J 6.5 Hz, CH3); C NMR
1
1.0, CHCl3)); H NMR (300 MHz, CDCl3): l
(300 MHz, CDCl3) l 137.3 (s, aromatic C),
129.1, 128.2, 126.4 (each d, each aromatic
CH), 103.4, 101.8, 80.7, 74.8, 73.4 (each d),
70.4 (t, OCH2CH2), 68.8 (t, C-6), 66.4 (d),
31.8, 29.7, 29.3, 29.2, 25.9, 22.6 (each t, octyl-
CH2), 14.1 (q, CH3); IR (KBr) 3501, 3206,
2924, 2853, 1450, 1376, 1084, 1001, 747, 698
cm.−1 Anal. Calcd for C21H32O6: C, 66.29; H,
8.48. Found: C, 66.33; H, 8.43. ESHRMS:
Found 381.2293, required 381.2277 [M+H]+.
7.51–7.26 (ms, 5 H, aromatic H), 5.55 (s, 1 H,
CHPh), 4.36 (dd, 1 H, J5,6a 5.0, J6a,6b10.5 Hz,
H-6a), 4.33 (d, 1 H, J1,2 8.0 Hz, H-1), 3.82 (apt
t, 1 H, J2,3 9.0, J3,4 9.0 Hz, H-3), 3.80 (apt t, 1
H, J5,6b 10.5 Hz, H-6b), 3.59 (s, 3 H, OCH3),
3.48 (overlapping signals, 3 H, H-2,4,5); 13C
NMR (300 MHz, 1:10 Me2SO-d6-CDCl3): l
137.5 (s, aromatic C), 129.2, 128.2, 126.6 (each
d, each aromatic CH), 104.6, 101.9, 80.6, 74.9,
73.6 (each d), 68.9 (t, C-6), 66.5 (d), 57.4 (q,
OCH3); IR (KBr): 3385, 3241, 2981, 2942,
2882, 1452, 1388, 1227, 1087, 1038, 997, 694
Methyl (4,6-O-benzylidene-i-
osyl)-(1“2)-3-O-benzyl-4,6-O-benzylidene-
i- -glucopyranoside (2e).—Treatment of 1e
D
-glucopyran-
D
cm−1
4-Nitrophenyl
.
(0.41 g, 0.77 mmol) as described for 1a gave
2e (0.34 g, 71%); mp \250 °C; [h]D −72.5°
4,6-O-benzylidene-i- -
D
1
glucopyranoside (2c).—Treatment of 1c (2.0 g,
6.6 mmol) as described for 1a gave 2c (2.1 g,
81%); mp 180–182 °C; [h]D −116.7° (c 0.04,
CHCl3) (lit.:22 mp 184–85 °C; [h]D −44.9° (c
(c 0.12, 1:1 MeOH–CHCl3); H NMR (300
MHz, Me2SO-d6): l 7.39–7.22 (ms, 15 H,
aromatic H), 5.64 (s, 1 H, CHPh), 5.53 (s, 1
H, CHPh), 5.28 (2 H, overlapping signals),
4.83 and 4.70 (AB d, 2 H, J 11.0 Hz,
OCH2Ph), 4.75 (d, 1 H, J1,2 8.0 Hz, H-1), 4.46
(d, 1 H, J1%,2% 7.5 Hz, H-1%), 4.22 (dd, 1 H, J5%,6a%
5.0, J6a%,6b% 10.5 Hz, H-6a%), 4.21 (dd, 1 H, J5,6a
4.5, J6a,6b 10.0 Hz, H-6a), 3.81-3.64 (4 H,
overlapping signals), 3.60 (apt t, 1 H, J2%,3% 7.5
Hz, H-2%), 3.45 (m, 1 H, H-5), 3.36 (s, 3 H,
OCH3), 3.20 (overlapping signals, 2 H, H-5
1
2.0, acetone); H NMR (300 MHz, Me2SO-
d6:CDCl3, 1:10): l 8.20 (d, 2 H, J 9.5 Hz,
aromatic H), 7.54–7.33 (ms, 5 H, aromatic
H), 7.17 (d, 2 H, J 9.5 Hz, aromatic H), 5.56
(s, 1 H, CHPh), 5.18 (d, 1 H, J1,2 7.5 Hz, H-1),
4.36 (dd, 1 H, J5,6a 4.0, J6a,6b 10.0 Hz, H-6a),
3.86–3.58 (overlapping signals, 5 H, H-
2,3,4,5,6b); 13C NMR (300 MHz, CDCl3): l
161.4, 142.0 (each s, each aromatic C), 136.6,
128.5, 127.5, 125.9, 125.0, 116.1 (each d, each
aromatic CH), 102.2, 101.1, 79.7, 73.7, 72.8
(each d), 67.9 (t, C-6), 66.0 (d); IR (KBr):
13
and H-5%); C NMR (300 MHz, Me2SO-d6): l
139.3, 138.4, 138.3 (each s, each aromatic C),
129.5, 129.4, 128.8, 128.7, 128.7, 128.1, 127.0,
126.6, 103.6, 103.0, 101.29, 100.8, 81.5, 81.1,
81.0, 79.7, 75.3 (each d), 74.2 (t), 73.8 (d), 68.6
(t), 66.7, 65.6 (each d), 56.7 (q, OCH3); IR
(KBr): 3481, 2921, 1752, 1378, 1238, 1101,
1069 cm−1. ESHRMS: Found 645.2310, re-
quired 645.2312 [M+Na]+.
3500, 1595, 1515, 1350, 1250, 1087 cm−1
.
Anal. Calcd for C19H19NO8: C, 58.61; H, 4.92;
N, 3.60. Found: C, 57.86; H, 4.96; N, 3.51.
ESHRMS:
424.0799 [M+Cl]−.
Octyl 4,6-O-benzylidene-i-
Found
424.0797,
required
D
-glucopyran-
Phenyl 4,6-O-benzylidene-i-
dideoxyhex-2-enopyranoside (4a).—To
D
-erythro-2,3-
oside (2d).—Treatment of 1d (1.0 g, 3.4
mmol) as described for 1a gave 2d (1.2 g,
100%); mp 149–152 °C; [h]D −55° (c 0.02,
CHCl3); 1H NMR (300 MHz, CDCl3): l
a
stirred solution of 2a (0.1 g, 0.3 mmol), imida-
zole (80 mg, 1 mmol) and triphenylphosphine
(0.27 g, 1 mmol) in toluene (10 mL) at 80 °C

P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
331
78.9, 77.1, 76.7 (each d), 68.2 (t, C-6), 66.0 (d),
was added iodine (0.25 g, 1 mmol), portion
wise over 20 min. The reaction mixture was
heated at reflux and was complete after 1 h.
The toluene was decanted off and the residue
was dissolved in aq NaOH (1 M, 20 mL) and
the product extracted into EtOAc, which was
combined with the toluene layer, washed with
aq NaHCO3 (2×20 mL), water (1×20 mL),
dried over MgSO4 and concentrated. The re-
sulting residue was purified by chromatogra-
phy (petroleum ether–EtOAc) to give 4a (55
39.8, 39.2 (each q, each SO2CH3); IR (KBr)
1593, 1489, 1372, 1228, 1094, 972, 826 cm−1
.
Anal. Calcd for C21H24O10S2: C, 50.39; H,
4.83; S, 12.81. Found: C, 50.32; H, 4.76; S,
13.15. ESLRMS: Found 523.1, required 523.1
[M+Na]+.
Sodium iodide (0.68 g, 4.6 mmol), zinc dust
(0.30 g) and 3a (0.5 g, 1 mmol) in DMF (10
mL) were heated and stirred at reflux for 16 h.
The mixture was diluted with CH2Cl2 (20 mL)
and filtered through celite. It was then washed
with aq NaHCO3 (2×20 mL), dried over
MgSO4 and concentrated. The product 4a (34
mg, 11%) was isolated by chromatography
(petroleum ether–EtOAc). Alkene 4a was ob-
tained in higher yield from 3a using a mi-
crowave method. Thus to an open 100 mL
Erlenmeyer flask was added sodium iodide
(0.68 g, 4.6 mmol), zinc dust (0.3 g) and 3a
(0.5 g, 1 mmol) in DMF (30 mL). The mixture
was stirred and then heated in a standard
microwave oven for 3 min at 350 W power.
The product 4a (0.16 g, 53%) was obtained as
described above.
mg, 62%); mp 136–138 °C (EtOAc); [h]D
−
1
28° (c 0.25, CHCl3); H NMR (270 MHz,
CDCl3): l 7.51–7.00 (ms, 10 H, aromatic H),
6.24 (br d, 1 H, J2,3 10.5 Hz, H-2), 5.93 (apt
dt, 1 H, J1,2 1.5, J1,3 1.5, J1,4 3.0 Hz, H-1), 5.82
(1 H, ddd, J3,4 2.5 Hz, H-3), 5.60 (s, 1 H,
CHPh), 4.44 (m, 1 H, H-4), 4.34 (m, 1 H,
H-6), 3.91 (overlapping signals, 2 H, H-5,
H-6); 13C NMR (270 MHz, CDCl3): l 156.7,
137.2 (each s, each aromatic C), 132.0, 129.5,
129.2, 128.3, 127.2, 126.2, 122.6, 116.7 (each
d), 102.1 (d, CHPh), 96.5 (d, C-1), 74.7, 70.9
(each d), 69.0 (t, C-6); IR (KBr): 1598, 1493,
1380, 1229, 1082 cm−1. Anal. Calcd for
C19H18O4: C, 73.53; H, 5.85. Found: C, 73.43;
H, 5.91.
Methyl 4,6-O-benzylidene-i-
dideoxyhex-2-enopyranoside (4b).—To
D
-erythro-2,3-
a
Compound 4a was also prepared by two
methods from 3a. Thus to a solution of 2a
(0.50 g, 1.52 mmol) in pyridine (1.5 mL) at
0 °C was added a solution of methanesulfonyl
chloride (0.52 g, 4.6 mmol) also in pyridine
(2.8 mL), dropwise over 0.5 h. After stirring
for 1 h the solution was allowed to warm to rt
and was stirred for a further 1 h. The pyridine
was then removed under diminished pressure
and the resulting white foam recrystallised
from toluene–EtOH to provide the white
solid 3a (0.62 g, 85%); [h]D −56° (c 0.25,
CHCl3); mp 202–203 °C; 1H NMR (300 MHz,
CDCl3): l 7.48–7.08 (ms, 10 H, aromatic H),
5.59 (s, 1 H, CHPh), 5.15 (d, 1 H, J1,2 8.5 Hz,
H-1), 4.97 (apt t, J2,3 8.5, J3,4 8.5 Hz, H-3),
4.94 (apt t, H-2), 4.45 (dd, 1 H, J5,6a 5.0, J6a,6b
10.5 Hz, H-6a), 3.86 (apt t, J4,5 8.5 Hz, H-4),
3.86 (apt t, J5,6b 10.5 Hz, H-6b), 3.67–3.65 (m,
1 H, H-5), 3.24 (s, 3 H, SO2CH3), 3.09 (s, 3 H,
SO2CH3); 13C NMR (270 MHz, CDCl3): l
156.4, 136.2 (each s, each aromatic C), 129.8
(2d), 129.5, 128.5, 126.0, 124.0, 117.4 (each d,
aromatic CH), 101.7 (d, CHPh), 99.6 (d, C-1),
stirred solution of 2b (1.0 g, 3.55 mmol),
imidazole (1.1 g, 15.5 mmol) and
chlorodiphenylphosphine (1.9 g, 1.5 mL, 8.5
mmol) in toluene (90 mL) at 80 °C was added
iodine (2.2 g, 8.5 mmol), portion wise over 0.5
h. The solution was heated and stirred at
reflux until 1b had been converted into an
iododiphenylphosphonate intermediate (16
h).23 The toluene layer was washed with aq
sodium thiosulfate (3×100 mL), aq NaOH
(2×100 mL) and water (1×100 mL). It was
dried over MgSO4, concentrated and the inter-
mediate (1.3 g) was isolated by chromatogra-
phy (petroleum ether–EtOAc). It was then
dissolved in EtOH (120 mL) and zinc dust (1.2
g) was added and the mixture stirred and
heated at reflux for 5 h. It was then filtered
through celite, concentrated and passed
through a bed of silica to provide 4b (0.38 g,
47% over two steps); mp 86–87 °C (EtOAc)
[h]D +31° (c 0.1, CHCl3) (lit.:24 mp 94–95 °C;
1
[h]D +43° (c 1.0, CHCl3); H NMR25 (300
MHz, CDCl3): l 7.51–7.24 (ms, 5 H, aromatic
H), 6.15 (br d, 1 H, J2,3 10.5 Hz, H-2), 5.66 (1

332
P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
3 H, J 6.5 Hz, CH3); 13C NMR (300 MHz,
CDCl3): l 137.6 (s, aromatic CH), 131.4,
129.4, 128.9, 128.6, 126.5, (each d), 102.4 (d,
CHPh), 99.0 (d, C-1), 75.4, 70.7 (each d), 69.4,
68.7 (each t), 32.1, 30.0, 29.6, 29.5, 26.3, 22.9
(each t, each octyl-CH2), 14.3 (q, CH3); IR
(KBr) 2956, 2919, 2854, 1378, 1298, 1100,
1001 cm−1. ESHRMS: Found 347.2222, re-
quired 347.2221 [M+H]+.
H, ddd, J1,3 1.5, J3,4 2.5 Hz, H-3), 5.59 (s, 1 H,
CHPh), 5.27 (apt dt, 1 H, J1,2 1.5, J1,4 3.0 Hz,
H-1), 4.29–4.35 (overlapping signals, 2 H, H-4
and H-6a), 3.89 (apt t, 1 H, J5,6b 10.0, J6a,6b
10.0 Hz, H-6b), 3.89 (s, 3 H, OCH3), 3.75
(ddd, 1 H, J4,5 8.0, J5,6a 4.5 Hz, H-5); 13C
NMR (270 MHz, CDCl3): l 137.3 (s, aromatic
C), 131.5, 129.1, 128.3, 128.1, 126.2 (each d),
102.0 (d, CHPh), 99.2 (d, C-1), 75.0, 70.4
(each d), 69.0 (t, C-6), 55.0 (q, OCH3); IR
(KBr): 2934, 1744, 1453, 1378, 1378, 1206,
1096, 1001, 750, 693, 654 cm−1. Anal. Calcd
for C14H16O4: C, 67.73; H, 6.50. Found: C,
67.46; H, 6.46.
Methyl (4,6-O-benzylidene-i-
dideoxyhex - 2 - enopyranosyl) - (1“2) - 3 - O-
benzyl-4,6-O-benzylidene-i- -glucopyranoside
D
-erythro-2,3-
D
(4e).—Treatment of 2e (0.3 g, 0.48 mmol)
with imidazole, triphenylphosphine and iodine
as described for 2b gave 4e (0.24 g, 85%); mp
171–173 °C (EtOAc); [h]D −8.3° (c 0.05,
CHCl3); 1H NMR (300 MHz, CDCl3): l
7.49–7.26 (ms, 15 H, aromatic H), 6.09 (br d,
1 H, J2,3 10.5 Hz, H-2), 5.68 (1 H, dt, J3,4 2.5,
J1,3 2.5 Hz, H-3), 5.58 (3 H, overlapping sig-
nals, 2×CHPh, H-1), 4.93 and 4.75 (AB d, 2
H, J 11.5 Hz, OCH2Ph), 4.43 (d, 1 H, J1%,2% 7.5
Hz, H-1%), 4.40-4.34 (overlapping signals, 2 H,
H-4,4%), 4.27 (dd, 1 H, J5%,6a% 4.5, J6a%,6b% 10.0
Hz, H-6a%), 3.85 (apt t, 1 H, J5a%,6b% 10.0 Hz,
H-6b%), 3.82–3.65 (overlapping signals, 5 H,
H-2,6a,5%,2%,3%), 3.56 (s, 3 H, OCH3), 3.44 (m,
1 H, H-5); 13C NMR (300 MHz, CDCl3): l
138.5, 137.6, 137.5 (each s, each aromatic C),
131.2, 129.4, 129.2, 128.7, 128.6, 128.5, 128.3,
128.1, 126.5, 126.2, 103.9, 102.3, 101.4, 100.0,
81.8, 81.2, 80.4 (each d), 75.4 (t, CH2), 75.1,
71.1 (each d), 69.4, 69.1 (each t), 66.1 (d), 57.4
(q, OCH3); IR (KBr): 2922, 1452, 1370, 1093,
1003, 697 cm.−1 ESHRMS: Found 589.2434,
required 589.2438 [M+H]+.
4-Nitrophenyl 4,6-O-benzylidene-i- -ery-
D
thro-2,3-dideoxyhex-2-enopyranoside (4c).—
Treatment of 2c (0.55 g, 1.41 mmol) with
imidazole, triphenylphosphine and iodine as
described for 2b gave 4c (0.23 g, 46%); mp
163–164 °C (EtOAc); [h]D −102.5° (c 0.04,
1
CHCl3); H NMR (300 MHz, CDCl3): l 8.20
(d, 2 H, J 9.0 Hz, aromatic H), 7.52–7.35 (ms,
5 H, aromatic H), 7.17 (d, 2 H, aromatic H),
6.35 (br d, 1 H, J2,3 10.5 Hz, H-2), 6.05 (apt
dt, 1 H, J1,2 1.5, J1,3 1.5, J1,4 3.0 Hz, H-1), 5.85
(1 H, dt, J3,4 1.5 Hz, H-3), 5.63 (s, 1 H,
CHPh), 4.40 (dd, 1 H, J5,6a 4.0, J6a,6b 10.0 Hz,
H-6a) 4.43 (d, 1 H, J4,5 8.5 Hz, H-4), 3.97–
3.86 (overlapping signals, 2 H, H-5, H-6b); 13C
NMR (300 MHz, CDCl3): l 161.6, 137.0
(each s, each aromatic C), 133.2, 129.3, 128.4,
126.2, 125.9, 125.8, 116.6 (each d), 102.3 (d,
CHPh), 96.1 (d, C-1), 74.5, 71.3 (each d), 68.9
(t, C-6); IR (KBr): 1594, 1519, 1340, 1244,
1111 cm−1. ESHRMS: Found 356.1134, re-
quired 356.1134 [M+H].+
Octyl 4,6-O-benzylidene-i-
D
-erythro-2,3-
Phenyl
4,6-O-benzylidene-i- -allopyran-
D
dideoxyhex-2-enopyranoside (4d).—Treatment
of 2d (1.2 g, 3.4 mmol) with imidazole,
triphenylphosphine and iodine as described
for 2b gave 4d (0.73 g, 67%); [h]D +40.9° (c
oside (5b).—To a solution of 4b (0.22 g, 0.74
mmol) in tert-butanol and water (1:1, 16 mL)
at 60 °C was added 4-methylmorpholine-N-
oxide (0.8 g, 0.7 mL, 0.54 mmol), K2CO3 (0.9
g, 6.55 mmol), potassium osmate dihydrate (2
mg, 8 mmol), and DABCO (80 mg, 0.74
mmol). The mixture was stirred and heated at
80 °C for 16 h until complete. 4,5-Dihydroxy-
1,3-benzenedisulfonic acid disodium salt (5
mg, 15 mmol) was added and the reaction was
stirred for further 1 h. It was then diluted with
EtOAc (30 mL), washed with water (50 mL),
dried over MgSO4 and concentrated to
provide 5b as a white solid (0.24 g, quantita-
1
1.3, acetone); H NMR (300 MHz, CDCl3): l
7.51–7.25 (ms, 5 H, aromatic H), 6.13 (br d, 1
H, J2,3 10.5 Hz, H-2), 5.70 (1 H, ddd, J1,3 1.5,
J3,4 2.5 Hz, H-3), 5.60 (s, 1 H, CHPh), 5.33
(apt dt, 1 H, J1,2 1.5, J1,4 3.0 Hz, H-1), 4.35–
4.27 (overlapping signals, 2 H, H-4, H-6a),
3.71–3.91 (overlapping signals, 3 H, H-6b,
OCH2), 3.51 (apt dt, 1 H, J5,6a 7.0, J5,6b 9.5,
J4,5 9.5 Hz, H-5); 1.50–1.66 (m, 2 H, octyl
CH2), 1.37–1.23 (m, 10 H, octyl CH2), 0.88 (t,

P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
333
10.0 Hz, H-5), 4.39 (dd, 1 H, J6a,6b 10.0 Hz,
H-6a), 3.77 (br s, 1 H, H-2), 3.75 (apt t, 1 H,
H-6b), 3.66 (dd, 1 H, H-4); 13C NMR (300
MHz, CDCl3) l 162.3, 142.4 (each s, each
aromatic C) 138.5, 128.9, 128.2, 126.7, 125.8,
116.8 (each d, each aromatic CH), 101.7, 99.6,
78.9, 71.1 (each d), 69.6 (t, C-6), 68.8, 63.6
(each d); IR (KBr): 3491, 1593, 1511, 1346,
1247, 1081, 971 cm−1. Anal. Calcd for
C19H19O8N: C, 58.61; H, 4.92; N, 3.60. Found:
C, 58.45; H, 4.78; N, 3.83.
tive); mp 155–157 °C (water); [h]D −40° (c
1
0.4, CHCl3); H NMR (300 MHz, CDCl3): l
7.52–7.04 (ms, 10 H, aromatic H), 5.60 (s, 1
H, CHPh), 5.35 (d, 1 H, J1,2 8.0 Hz, H-1), 4.49
(apt t, 1 H, J2,3 2.5, J3,4 2.5 Hz, H-3), 4.43 (dd,
1 H, J5,6a 5.5, J6a,6b 10.0 Hz, H-6), 4.15 (dt, 1
H, J4,5 10.0, J5,6b 10.0 Hz, H-5), 3.80 (overlap-
ping signals, 2 H, H-2, H-6b) 3.70 (dd, 1 H,
H-4), 2.72 (br s, 1 H, OH), 2.54 (br s, 1 H,
OH); 13C NMR (270 MHz, CDCl3): l 157.0,
136.9 (each s, each aromatic C), 129.6, 129.4,
128.4, 126.3, 122.9, 116.7 (each d, each aro-
matic CH), 102.0 (d, CHPh), 99.3 (d, C-1),
78.5, 70.9 (each d), 69.0 (t, C-6), 69.0, 63.2
(each d); IR (KBr): 3415, 2919, 1597, 1491,
1391, 1228, 1076, 1011, 761 cm−1. Anal.
Calcd for C19H20O6: C, 66.27; H, 5.85. Found:
C, 65.97; H, 5.55.
Octyl 4,6-O-benzylidene-i- -allopyranoside
D
(5d).—Treatment of 4d (0.46 g, 1.56 mmol) as
described for 4b gave 5d (0.54 g, quantitative);
mp 112–114 °C (water); [h]D −42° (c 0.2,
CHCl3); 1H NMR (300 MHz, CDCl3): l
7.52–7.32 (ms, 5 H, aromatic H), 5.56 (s, 1 H,
CHPh), 4.69 (d, 1 H, J1,2 8.0 Hz, H-1), 4.39
(br s, 1 H, H-3), 4.38 (dd, 1 H, J5,6a 5.5, J6a,6b
10.0 Hz, H-6a) 3.96 (apt dt, 1 H, J5,6b 10.0, J4,5
10.0 Hz, H-5), 3.89 (m, 1 H, OCH(H)CH2),
3.75 (apt t, 1 H, H-6b), 3.58 (dd, 1 H, J3,4 2.5
Hz, H-4), 3.51 (m, 2 H, H-2, OCH(H)CH2),
2.57 (2 H, br s, OH), 1.65 (m, 2 H, octyl-CH2),
1.28 (10 H, m, octyl-CH2), 0.88 (3 H, t, J 6.5
Hz, CH3); 13C NMR (300 MHz, CDCl3): l
137.3 (s, aromatic C), 129.5, 128.6, 126.5 (each
d, each aromatic H), 102.2, 101.5, 79.1, 71.6
(each d), 70.8, 69.4 (each t), 69.2, 63.5 (each
d), 32.0, 29.9, 29.6, 29.5, 26.2, 22.9 (each t,
octyl-CH2), 14.3 (q, CH3); IR (KBr): 3501,
3206, 2924, 2853, 1450, 1376, 1085, 1001, 747,
698 cm.−1 Anal. Calcd for C21H32O6: C, 66.31;
H, 8.48. Found: C, 66.08; H, 8.31. ESHRMS:
Found 403.2079, required 403.2097 [M+
Na]+.
Methyl
4,6-O-benzylidene-i- -allopyran-
D
oside (5a).—Treatment of 4a (0.25 g, 1 mmol)
as described for 4b gave 5b (0.26 g, 92% yield);
mp 157–158 °C (water); [h]D −63° (c 0.88,
CHCl3) (lit.:26 [h]D −45.1° (c 0.48, CHCl3));
1H NMR (300 MHz, 1:10 Me2SO-d6-CDCl3):
l 7.53–7.32 (ms, 5 H, aromatic H), 5.55 (s, 1
H, CHPh), 4.58 (d, 1 H, J1,2 7.5 Hz, H-1), 4.38
(dd, 1 H, J5,6a 5.0, J6a,6b 10.5 Hz, H-6), 4.31 (br
s, 1 H, H-3), 4.11 (br s, 1 H, OH), 4.00 (m, 1
H, H-5), 3.83 (br d, 1 H, J 6.0 Hz, OH), 3.74
(apt t, 1 H, J5,6b 10.5 Hz, H-6b), 3.56 (s, 3 H,
OCH3), 3.54 (dd, 1 H, J3,4 2.5, J4,5 9.5 Hz,
H-4), 3.46 (br s, 1 H, H-2); 13C NMR (270
MHz, CDCl3): l 137.4 (s, aromatic C), 129.1,
128.2, 126.4 (each d, each aromatic CH),
102.6, 101.8, 79.1, 71.1 (each d), 69.2 (t, C-6),
68.9, 62.9 (each d), 57.3 (OCH3); IR (KBr):
3490, 3403, 2923, 2862, 1451, 1385, 1209,
1109, 1014, 757, 701 cm−1; Anal. Calcd for
C14H18O6: C, 59.57; H, 6.43. Found: C, 59.32;
H, 6.46.
Methyl (4,6-O-benzylidene-i-
osyl)-(1“2)-3-O-benzyl-4,6-O-benzylidene-i-
-glucopyranoside (5e).—Treatment of 4e (90
D
-allopyran-
D
mg, 0.15 mmol) as described for 4b gave 5e
(30 mg, 32%); mp 194–196 °C (EtOAc); [h]D
4-Nitrophenyl
4,6-O-benzylidene-i- -
D
1
allopyranoside (5c).—Treatment of 4c (0.15 g,
0.42 mmol) as described for 4b gave 5c (0.13
g, 79%); mp 203–205 °C (water); [h]D −294°
(c 0.02, CHCl3); 1H NMR (300 MHz,
CDCl3:Me2SO-d6, 10:1): l 8.25–8.21 (d, 2 H,
J 9.0 Hz, aromatic H), 7.98–7.29 (ms, 5 H,
aromatic H), 7.18 (d, 2 H, J 9.0 Hz, aromatic
H), 5.67 (s, 1 H, CHPh), 5.52 (d, 1 H, J1,2 8.0
Hz, H-1), 4.42 (apt t, 1 H, J2,3 2.5, J3,4 2.5 Hz,
H-3), 4.21 (apt dt, 1 H, J4,5 10.0, J5,6a 5.0, J5,6b
−50.4° (c 0.25, CHCl3); H NMR (300 MHz,
CDCl3) l 7.50–7.25 (ms, 15 H, aromatic H),
5.57 and 5.54 (each s, each 1 H, each CHPh),
4.79 and 4.99 (AB d, 2 H, OCH2Ph, J 11.0
Hz), 4.93 (d, 1 H, J1,2 7.5 Hz, H-1), 4.41 (d, 1
H, J1%,2% 7.5 Hz, H-1%), 4.39–4.32 (overlapping
signals, 3 H, H-3,6,6%), 4.05 (apt d, 1 H, J5,6a
5.0, J6a,6b 9.5 Hz, H-5), 3.88–3.70 (overlapping
signals, 4 H, H-3%,4%,6%,6), 3.63 (apt t, 1 H, J2,3
7.5 Hz, H-2), 3.57 (dd, 1 H, J3%,4% 2.5, J4%5% 9.5

334
P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
Methyl 3-O-benzyl-4,6-O-benzylidene-i- -
D
Hz, H-4), 3.56 (s, 3 H, OCH3), 3.38–3.46
(overlapping signals, 2 H, H-2%,5%); 13C NMR
(270 MHz, CDCl3): l 137.3, 137.1 (each s,
aromatic C), 129.3, 129.1, 128.6, 128.5, 128.4,
128.2, 126.3, 126.0 (each d, each aromatic
CH), 104.1, 103.4, 102.1, 101.2, 82.0, 81.8,
79.7, 78.8, 75.0, 72.5 (each d), 69.1 (t), 68.9
(d), 68.7 (t), 65.7, 63.9 (each d), 57.8 (q,
OCH3); IR (KBr) 3450, 2881, 1462, 1368,
1275, 1084, 1002, 764 cm−1. ESHRMS:
Found 645.2317, required 645.2312 [M+
Na]+.
glucopyranoside (8).—Compound 2b (8.0 g,
28.4 mmol) and dibutyltin oxide (8.41 g, 34.6
mmol) were dissolved in benzene (400 mL)
and stirred for 16 h, with azeotropic removal
of water. The solution was concentrated to
200 mL and BnBr (7.81 mL, 30.4 mmol) and
tetrabutylammonium iodide (11.85 g, 32.1
mmol) were added and it was again allowed to
stir, heating at reflux, for a further 16 h. The
solution was then concentrated and the result-
ing yellow solid recrystallised from MeOH to
give 8 as a white solid (8.4 g, 85%); mp
Dihydroxylation using ruthenium trichlo-
ride.—To a stirred solution of 4b (30 mg, 0.12
mmol) in 1:1 EtOAc–MeCN (2 mL) at 0 °C
was added a solution of RuCl3 (2.0 mg) and
sodium periodate in distilled water (0.2 mL).
The two-phase reaction was stirred vigorously
for 2 min and was then diluted with EtOAc.
The organic layer was washed with satd aq
sodium thiosulfate (10 mL), then water (10
mL) and was dried over MgSO4 and concen-
trated to give 5b as a white solid (30 mg,
89%). Using this method 4e gave 5e (70%).
1
119–121 °C (MeOH). The H and 13C NMR
data is identical with that previously re-
ported.19 ESHRMS: Found 373.1654, required
373.1651 [M+Na]+.
Methyl (2,3,4,6-tetra-O-benzoyl-i-
pyranosyl)-(1“2)-3-O-benzyl-4,6-O-benzyli-
dene-i-
D
-gluco-
D
-glucopyranoside (9).—Thioglycoside
7 (1.0 g, 1.6 mmol) and 8 (0.61 g, 1.8 mmol,
1.1 equiv) were stirred in CH2Cl2 (40 mL)
,
containing 4 A molecular sieves under an inert
atmosphere. After 20 min N-iodosuccinimide
(0.38 g, 2.1 mmol) was added and AgOTf (10
mg) was added after a further 20 min. The
reaction was allowed to stir overnight and was
then quenched with triethylamine (0.1 mL).
The solution was filtered, concentrated and
purified by chromatography using a petroleum
ether and EtOAc gradient system as eluant to
provide 9 as a white solid (0.87 g, 38%); mp
86–88 °C (EtOAc); [h]D −6.3° (c 0.14,
CHCl3); 1H NMR (300 MHz, CDCl3): l
8.05–7.80 (ms, 10 H, aromatic H), 7.55–7.24
(ms, 20 H, aromatic H), 5.82 (dd, 1 H, J2,3 9.0,
J3,4 9.5 Hz, H-3), 5.74 (dd, 1 H, J4,5 9.0 Hz,
H-4), 5.67 (dd, 1 H, J1,2 7.5 Hz, H-2), 5.55 (s,
1 H, CHPh), 5.33 (d, 1 H, H-1), 4.65 (dd, 1 H,
J5,6a 3.5, J6a,6b 12.5 Hz, H-6a), 4.51 and 4.65
(AB d, 2 H, J 11.5 Hz, OCH2Ph), 4.51 (dd, 1
H, J5,6b 7.5 Hz, H-6b), 4.46 (d, 1 H, J1%,2% 7.5
Hz, H-1%), 4.31 (dd, 1 H, J5%,6a% 5.0, J6a%6b% 10.0
Hz, H-6a%), 4.10 (br s, 1 H, H-5), 3.78 (apt t,
1 H, J2%3% 7.5 Hz, H-2%), 3.71 (apt t, J5%,6b% 10.0
Hz, H-6b%), 3.67 (dd, 1 H, J3%,4% 10.0 Hz, H-3%),
3.60 (apt t, 1 H, J4%5% 10.0 Hz, H-4%), 3.53 (s, 3
H, OCH3), 3.47–3.31 (apt dt, 1 H, H-5%); 13C
NMR (300 MHz, CDCl3): l 166.4, 166.0
(each CꢀO), 165.5 (2s, each CꢀO), 138.5,
137.4, 133.6, 133.4, 133.3, 130.1, 130.0, 129.9,
Methyl 2,3,4,6-tetra-O-benzoyl-1-thio-i- -
D
glucopyranoside (7).—To a solution of sodium
thioglucose (20 g, 0.09 mol) in DMF at rt was
added MeI (17.1 g, 7.5 mL, 0.12 mol, 1.3
equiv) and the reaction mixture was allowed
to stir for 16 h after which BzCl (75 mL, 0.83
mol) and pyridine (100 mL) were added. The
solution was stirred for a further 16 h and
then washed with dilute HCl (3×200 mL).
The organic layer was then concentrated and
purified by chromatography to yield 7 as a
brown oil (25 g, 0.04 mmol, 44%); mp 64–
1
66 °C; H NMR (300 MHz, CDCl3): l 8.13–
7.24 (ms, 20 H, aromatic H), 5.94 (apt t, 1 H,
J3,4 9.5, J4,5 9.5 Hz, H-4), 5.68 (dd, 1 H, J1,2
9.5, J2,3, 10.0 Hz, H-2), 5.60 (apt t, 1 H, H-3),
4.76 (d, 1 H, H-1), 4.64 (dd, 1 H, J5,6a 3.0,
J6a,6b 12.5 Hz, H-6a), 4.50 (dd, 1 H, J5,6b 5.0
Hz, H-6b), 4.19 (m, 1 H, H-5), 2.25 (3 H,
SCH3); 13C NMR (270 MHz, CDCl3): l 166.1,
165.8, 165.2, 165.2 (each s, each CꢀO), 133.5,
133.4, 133.3, 133.1, 129.9, 129.8, 129.7, 129.0,
128.4, 128.3, 128.2 (each d, each aromatic
CH), 83.3 (d, C-1), 76.3, 74.0, 69.8, 69.5 (each
d), 63.2 (t, C-6), 21.5 (q, SCH3); ESHRMS
Found 649.1508, required 649.1529 [M+
Na]+.

P.V. Murphy et al. / Carbohydrate Research 334 (2001) 327–335
335
References
129.5, 129.2, 128.6, 128.4, 128.1, 127.8, 126.2
(aromatic C and CH), 103.4, 101.4, 100.9,
81.6, 81.0, 80.6 (each d), 74.9 (t), 73.5, 72.7,
72.4, 70.0 (each d), 69.0 (t), 65.8 (d), 63.5 (t),
57.3 (s, OCH3); IR (KBr) 1734, 1601, 1452,
1266, 1094, 1070, 706 cm−1. ESHRMS:
Found 973.3048, required 973.3047 [M+
Na]+.
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100%); mp 199–200 °C (MeOH); [h]D
−
1
116.7° (c 0.06, MeOH); H NMR (300 MHz,
acetone-d6): l 7.55–7.28 (ms, 10 H, aromatic
H), 5.71 (s, 1 H, CHPh), 4.92 (2 H, s, CH2Ph),
4.70 (d, 1 H, J1,2 8.0 Hz, H-1), 4.53 (d, 1 H,
J1%,2% 7.5 Hz, H-1%), 4.31 (dd, 1 H, J5%,6a% 5.0,
J6a%,6b% 10.5 Hz, H-6a%), 4.19 (2 H, br s, OH),
4.08 (br s, 1 H, OH), 3.91–3.70 (6 H, overlap-
ping signals), 3.51 (s, 3 H, OCH3), 3.57–3.11
(5 H, overlapping signals); 13C NMR (300
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76.9, 75.0, 74.4, 71.2, 68.7, 65.8, 62.4, 56.3; IR
(KBr): 3388, 2913, 1451, 1369, 1094, 1067,
1031, 896 cm−1. ESHRMS: Found 557.2005,
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Acknowledgements
The authors thank Enterprise Ireland for
funding
(International
Collaboration
26. Muddasan, P. R.; Bernet, B.; Vasella, A. Hel6. Chim. Acta
1994, 77, 334–350.
Programme).
.