Glucofuranosylation with penta-O-propanoyl-β-D-glucofuranose

Article abstract of DOI:10.1016/S0008-6215(02)00300-2

Readily available, crystalline penta-O-propanoyl-β-D-glucofuranose is shown to be a suitable glycosylating agent for the acid-catalysed, direct synthesis of O-, S- and N-glucofuranosyl compounds. β-Linked products are formed with good selectivity. Reactio

Full text of DOI:10.1016/S0008-6215(02)00300-2

Carbohydrate Research 337 (2002) 1999–2004
www.elsevier.com/locate/carres
Glucofuranosylation with penta-O-propanoyl-b-
D-glucofuranose
Richard H. Furneaux,a Be´ne´dicte Martin,b Phillip M. Rendle,a,* Carol M. Taylorb
aIndustrial Research Limited, PO Box 31-310, Lower Hutt, New Zealand
bInstitute of Fundamental Sciences, Massey Uni6ersity, Pri6ate Bag 11-222, Palmerston North, New Zealand
Received 1 May 2002; accepted 10 June 2002
Dedicated to Professor Derek Horton on the occasion of his 70th birthday
Abstract
Readily available, crystalline penta-O-propanoyl-b-
D
-glucofuranose is shown to be a suitable glycosylating agent for the
acid-catalysed, direct synthesis of O-, S- and N-glucofuranosyl compounds. b-Linked products are formed with good selectivity.
Reaction with cyanotrimethylsilane gave the 1,2-O-(1-cyanopropylidene)acetal rather than the C-glycosyl cyanide. By selective
acid-catalysed hydrolysis, the title compound was converted to the 1-hydroxy analogue from which the trichloroacetimidates were
made as further potential glycosylating agents. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Glycosylation;
D-Glucofuranosides; 1-Thio-D-glucofuranosides; N-Glucofuranosylamine
1. Introduction
somewhat structurally related to the sugar nucleotides,
for example uridine diphosphoglucose (UDPG). Other-
wise, -glucofuranose occurs in the fruit of the cuckoo-
pint plant linked to N-7 of a purine derivative in an
analogue of the natural nucleosides,4 and C-linked in a
C-glycosylchromone from the leaves of a species of
Aloe5 and in metabolites of tannins in the heartwood of
Japanese Chestnut.6 Synthetic studies of relevant aryl
C-glucofuranosides have been reported.7
In consequence of the above there seems to be little
incentive to synthesise glucofuranosyl compounds for
the purpose of producing bioactive natural products or
their analogues. However, there is reason to believe
that some, like galactofuranosyl derivatives,8 could be
antigenic in nature, and, presumably, some carbohy-
drate-processing enzymes could bind furanosyl deriva-
tives as substrate analogues and could perhaps be
selectively inhibited by them. Otherwise, attached to
appropriate bioactive compounds, furanoid units could
conceivably increase bioavailability without being vul-
nerable to such enzymes as glucosidases. Under acidic
conditions they would be particularly susceptible to
hydrolysis, and that property could conceivably also be
exploited.
A notable feature of the natural occurrence of the
common monosaccharides is that while several, notably
D
D
-fructose,
cantly -ribose and its 2-deoxy derivative, frequently
occur in the furanosyl form, the same does not apply to
the most common natural sugar, -glucose. Whether
D-galactose, D-arabinose and most signifi-
D
D
this is because the five-membered ring forms of this
sugar are energetically less favoured relative to the
six-membered pyranoid forms more than is the case for
all other sugars is a matter for speculation.
Only a few
D-glucofuranosyl compounds appear to
have been isolated from natural sources (mostly plant),
and some of the methods used for identifying their
sugar ring sizes, for example their relative stability in
acid media, may have been unreliable. Examples are
cardenolide1 and flavone2 glucosides and the unusual
Agrobacterium tumefaciens product Agrocin 84 that
inhibits crown gall disease, a plant cancer.3 In this last
compound
D-glucofuranose is linked via the anomeric
centre through phosphate to the 6-amino group of an
adenine nucleoside derivative. Agrocin 84 is therefore
Furanosyl glycosides can be made using classical
* Corresponding author. Fax: +64-4-569-0055
E-mail address: p.rendle@irl.cri.nz (P.M. Rendle).
methods9 such as the Koenigs–Knorr reaction, or by
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00300-2

2000
R.H. Furneaux et al. / Carbohydrate Research 337 (2002) 1999–2004
more modern procedures10 based, for example, on O-
substituted thio-, seleno- or n-pentenyl furanosides, or
glycosyl trichloroacetimidates. Useful precursors for all
these glycosylating agents are the corresponding glyco-
furanosyl peresters, crystalline and anomerically pure
examples of which are rare but particularly attractive.
sugar by the boric acid procedure. We now report the
-glucofuran-
ose in the preparation of representative O-, S- and
N-glycosylated compounds, 1,2-O-(1-cyanopropyli-
useof the crystalline penta-O-propanoyl-b-
D
dene)-3,5,6-tri-O-propanoyl-a-
D-glucofuranose, 2,3,5,6-
tetra-O-propanoyl- -glucose and the derived mixed
D
glucofuranosyl trichloroacetimidate tetraesters.
In the
tetra-O-benzoyl-b-
from ethyl tetra-O-benzoyl-1-thio-a-
D
-glucose series crystalline 1-O-acetyl-2,3,5,6-
-glucose can be made efficiently
-glucofura-
D
D
noside,11 the preparation of which requires three steps
from glucose. We have recently reported the prepara-
tion of the crystalline b-penta-O-propanoate in 58%
yield in a two-step, one-pot procedure involving the use
of boric acid to lock the sugar in the furanose ring
form.12
2. Results and discussion
Penta-O-propanoyl-b-D-glucofuranose was treated
separately with ethanol, phenol, 4-nitrophenol, thiophe-
nol, (methylthio)trimethylsilane and trimethylsilylated
uracil (1.5–3 mol equiv) in dichloromethane or acetoni-
trile (for the uracil derivative) in the presence of boron
trifluoride etherate (0.5–1.2 mol equiv) or trimethylsilyl
triflate (0.3–2 mol equiv for the silylated nucleophiles).
The conversions were efficient and showed b-selectivi-
ties ranging from \25:1 for the uracil derivatives to
1.5:1 in the case of the ethyl glycosides (Table 1). In this
latter example, however, when proportionately more
ethanol (5 instead of 2 mol equiv) and more catalyst (6
instead of 1 mol equiv) were used, the b,a-ratio im-
proved to 2.8:1. These results show that, with the ethyl
glycosides, at least, the unexpected a-product is present
in considerable proportions at early stages in the reac-
tion. This could be accounted for as indicated in
Scheme 1. Initial ionisation of the starting perester (1)
at the anomeric centre with neighbouring group partic-
ipation would give the acyloxonium ion 3, the precur-
sor of the b-glycoside 4b. However, rearrangement of
ion 3 to ion 5 could lead to kinetically favoured prod-
ucts 4a. No direct evidence for the participation of ion
5, for example the isolation of 1,3-orthoesters, was
found.
In the report of the preparation of the pen-
tapropanoate,12 it was shown that phenyl b-
D-gluco-
furanoside could be made by application of the
Helferich reaction to the syrupy, anomerically mixed
penta-O-acetyl-D-glucofuranoses derived from the free
Table 1
Glycosylations with 1,2,3,5,6-penta-O-propanoyl-b-D-gluco-
furanose
Deacylations of the glycosidic tetraesters (except in
the case of the methyl b-1-thioglycoside tetraester
which was not deacylated) were effected efficiently by
standard, base-catalysed reactions. Anomerically pure
b-glycosides were isolated in the majority of cases.
In an analogous reaction of b-D-glucofuranose pen-
tapropanoate with trimethylsilyl cyanide13 as nucle-
ophile, in the presence of boron trifluoride etherate, no
cyano C-glucoside was obtained; instead the 1,2-O-(1-
cyanopropylidene)acetal (2) was isolated in low yield
(24%) in consequence of attack by the nucleophile at
the ionic centre of the acyloxonium species 3. That the
product was a 1,2- and not a 1,3-cyanopropylidene
derivative was shown by the chemical shifts of H-2 and
H-3 (l 4.71 and 5.41, respectively) which revealed that
the deshielding ester group was at C-3 and that the new
ring involved C-2.
Selective hydrolysis of the pentapropanoate, which
could have been attempted using a wide range of
catalysts,14 occurred in acid conditions in the presence
Scheme 1.

R.H. Furneaux et al. / Carbohydrate Research 337 (2002) 1999–2004
2001
of water, and the resulting a,b-2,3,5,6-tetraesters (4a,b;
R=OH, a:b 1:1.5) were converted into the correspond-
ing trichloroacetimidates (4a,b; R=OC(ꢀNH)CCl3, a:b
1:1.5)15 by treatment with trichloroacetonitrile and
DBU in acetonitrile. Although these products are
rather reactive, they can serve potentially as other
glucofuranosylating agents.
phy, was dissolved in MeOH satd with NH3 (8 mL) and
left at rt overnight. After the volatiles had been re-
moved in vacuo, the residue was purified by flash silica
chromatography, elution with MeOH (5%) in CHCl3,
to give ethyl a,b-
D
-glucofuranoside (374 mg, 94%,
a:b=1:2.8). The first fractions gave ethyl a-
D-gluco-
furanoside as colourless needles, mp 82.5–84 °C (lit.16
82–83 °C), [h]D21 +95.8° (c 0.8, H2O) [lit.16 [h]D23 +98°
(H2O)]; NMR (D2O): lH 5.18 (d, 1 H, J1,2 4.2 Hz, H-1),
4.27 (dd, 1 H, J2,3 3.6, J3,4 4.2 Hz, H-3), 4.12 (dd, 1 H,
H-2), 4.08 (dd, 1 H, J4,5 7.9 Hz, H-4), 3.85 (ddd, 1 H,
J5,6a 6.3, J5,6b 2.8 Hz, H-5), 3.79 (1 H, qd, J 7.2, 9.3 Hz,
CHCH3), 3.77 (dd, 1 H, J6a,6b 12.0 Hz, H-6b), 3.62 (dd,
1 H, H-6a), 3.60 (qd, 1 H, CHCH3), 1.18 (t, 3 H, J 7.2
Hz, CH3); lC (D2O) 102.4 (C-1), 78.2 (C-4), 75.0 (C-2),
76.1 (C-3), 70.1 (C-5), 65.6 (CH2), 63.6 (C-6), 14.7
3. Experimental
General methods.—1,2,3,5,6-Penta-O-propanoyl-b-D-
glucofuranose12 is available from Aldrich Chemical Co.
(cat. no. 53,227-4) and in bulk from New Zealand
Pharmaceuticals Ltd (www.nzp.co.nz). Analytical TLC
was carried out on pre-coated 0.25 mm thick E. Merck
Silica Gel 60 F254 plates and visualisation was by
thermal development after dipping in ammonium
molybdate and cerium(IV) sulfate in dil H2SO4 or
anisaldehyde in EtOH containing H2SO4. Flash column
chromatography was conducted using Silica Gel 60
(40–60 mm). Melting points were measured on a Re-
ichert hot-stage microscope and are uncorrected. Opti-
cal rotations were measured using a Perkin–Elmer 241
polarimeter, and [h]D values are reported in 10−1 deg
cm2 g−1. Microanalyses were carried out at the Camp-
bell Microanalytical Laboratory, University of Otago.
1H and 13C NMR spectra were recorded at 300 or 400
MHz and 75 or 100 MHz, respectively. The assign-
ments of peaks were carried out with the assistance of
DEPT and COSY (1H,1H and 1H,13C) experiments.
Mass spectra were recorded by Mr. J. M. Allen, Horti-
cultural and Food Research Institute of New Zealand,
in EI or FAB positive-ion modes at 15 keV with
ionisation effected by use of a caesium ion gun in a
p-nitrobenzyl alcohol–CH2Cl2 or glycerol–MeOH ma-
trix. Petroleum spirits refers to the fraction with bp
60–80 °C.
(CH3). The last fractions gave ethyl b-D-glucofura-
noside as a colourless oil, (lit.16 mp 59–60 °C), [h]2D4
27
−77.2° (c 1.0, H2O) [lit.16 [h]D −86° (H2O)]; NMR
(D2O): lH 4.94 (s, H-1), 4.19 (d, 1 H, J3,4 4.4 Hz, H-3),
4.11 (dd, 1 H, J4,5 8.9 Hz, H-4), 4.08 (s, 1 H, H-2), 3.93
(ddd, 1 H, J5,6a 6.0, J5,6b 2.6 Hz, H-5), 3.80 (dd, 1 H,
J6a,6b 12.0 Hz, H-6b), 3.71 (qdd, 1 H, CHCH3), 3.64
(dd, 1 H, H-6a), 3.53 (qdd, 1 H, J 7.1, 10.0 and 0.6 Hz,
CHCH3), 1.15 (td, 3 H, J 7.1, 0.6 Hz, CH3); lC (D2O)
108.3 (C-1), 81.4 (C-4), 80.2 (C-2), 75.3 (C-3), 70.1
(C-5), 64.8 (CH2), 63.9 (C-6), 14.6 (CH3).
Phenyl
i-D-glucofuranoside.—1,2,3,5,6-Penta-O-
propanoyl-b-
D-glucofuranose (1.0 g, 2.2 mmol) and
phenol (0.41 g, 4.3 mmol) were dissolved in CH2Cl2 (10
mL), and BF3·OEt2 (134 mL, 1.1 mmol) was added
dropwise. The solution was left at 20 °C overnight by
which time the reaction was complete (TLC). The reac-
tion mixture was washed with NaHCO3 (satd aq, 30
mL) and water, was dried (MgSO4) and concentrated in
vacuo. Flash silica chromatography of the residue, elu-
tion with 15:85 EtOAc–light petroleum, gave phenyl
2,3,5,6-tetra-O-propanoyl-a,b- -glucofuranoside (4a,b;
D
R=OPh) as a colourless syrup (0.8 g, 77%, a:b B1:7);
[h]2D3 −81.0° (c 0.5, CHCl3); NMR (CDCl3): lH (b
anomer) 7.29 (dd, 2 H, J 7.4, 8.4 Hz, H-3%, 5%), 7.02 (t,
1 H, J 7.4 Hz, H-4%), 7.01 (d, 2 H, J 8.4 Hz, H-2%,6%),
5.63 (s, 1 H, H-1), 5.46 (d, 1 H, J3,4 5.0 Hz, H-3), 5.31
(ddd, 1 H, J4,5 9.4, J5,6a 4.6, J5,6b, 2.4 Hz, H-5), 5.27 (s,
1 H, H-2), 4.62 (dd, 1 H, H-4), 4.54 (1 H, dd, J6a,6b 12.3
Hz, H-6b), 4.09 (dd, 1 H, H-6a), 2.42 (q, 2 H, J 7.5 Hz,
CH2), 2.39 (q, 2 H, J 7.5, CH2), 2.33 (q, 2 H, J 7.5,
CH2), 2.25 (q, 2 H, J 7.5, CH2), 1.17 (3 H, t, J 7.5,
CH3), 1.15 (t, 3 H, J 7.5, CH3), 1.13 (t, 3 H, J 7.5,
CH3), 1.08 (t, 3 H, J 7.5, CH3); lC (CDCl3) 174.3,
173.3, 173.3, 173.0 (4×CꢀO), 156.6 (C-1%), 130.0 (C-
3%,5%), 122.9 (C-4%), 116.9 (C-2%,6%), 104.6 (C-1), 80.7
(C-2), 79.7 (C-4), 73.6 (C-3), 68.9 (C-5), 63.2 (C-6),
27.8, 27.8, 27.8, 27.7 (4×CH2), 9.4, 9.2, 9.2, 9.1 (4×
CH3).
Ethyl h- and i-
D-glucofuranoside.—1,2,3,5,6-Penta-
O-propanoyl-b-
D
-glucofuranose (1)12 (220 mg, 0.47
mmol) was dissolved in CH2Cl2 (2.5 mL), and anhyd
EtOH (50 mL, 0.89 mmol) was added, followed by
BF3·OEt2 (60 mL, 0.47 mmol) dropwise. After 24 h at
20 °C, the solution was diluted with CH2Cl2 (100 mL),
washed with NaHCO3 (satd aq, 30 mL) and water and
was dried (MgSO4) and concentrated in vacuo. Flash
silica chromatography of a portion of the residue (150
mg), elution with 1:9 EtOAc–petroleum ether, gave
ethyl 2,3,5,6-tetra-O-propanoyl-a,b-D-glucofuranoside
(4a,b; R=OEt) as a colourless syrup (0.92 mg, 65%).
1
The H and 13C NMR spectra indicated that the un-
purified product consisted of \95% of these glycosides
(a,b 1:1.5). A mixture of these compounds (830 mg, 1.9
mmol), made less efficiently (56%) under more forcing
conditions (EtOH, 5.0 mol equiv; BF3·OEt2 6.0 mol
equiv, 20 °C, 1 h), and purified by flash chromatogra-
This anomeric mixture was dissolved in MeOH (10
mL), and NaOMe (1 M in MeOH) was added to pH

2002
R.H. Furneaux et al. / Carbohydrate Research 337 (2002) 1999–2004
(C-3), 69.3 (C-5), 63.4 (C-6); FABMS: m/z 302.0875
12. The solution was left for 2 h and then neutralised
with Amberlite IRC-50 (H+) resin, filtered and the
filtrate was concentrated in vacuo. The residue was
purified by flash silica chromatography, elution with 1:9
MeOH–CHCl3, to give a colourless oil (390 mg) which
crystallised from 2-butanone–light petroleum to afford
(MH)+; C12H16NO8 requires 302.0876.
Methyl 2,3,5,6-tetra-O-propanoyl-1-thio-i-
D
-gluco-
R=SMe).—1,2,3,5,6-Penta-O-
D-glucofuranose (614 mg, 1.3 mmol) was
furanoside
(4i,
propanoyl-b-
dissolved in CH2Cl2 (5 mL) and cooled to 0 °C.
(Methylthio)trimethylsilane (567 mL, 4.0 mmol) was
added dropwise, followed by trimethylsilyl trifl-
uoromethanesulfonate (72 mL, 0.4 mmol). After 20 min
at rt, the mixture was heated at 50 °C for 3 h, cooled,
diluted with CHCl3, washed with NaHCO3 (50% aq, 30
mL) and brine, dried (MgSO4) and concentrated in
vacuo. Flash silica chromatography of the residue, elu-
tion with 1:9 EtOAc–petroleum ether, gave methyl
phenyl b-
(mp and [h]D) to a sample made from penta-O-acetyl-
a,b-
-glucofuranose.12
4-Nitrophenyl h-
1,2,3,5,6-Penta-O-propanoyl-b-
D-glucofuranoside (220 mg, 52%) identical
D
and
i-D-glucofuranoside.—
D-glucofuranose (1.0 g,
2.2 mmol) and 4-nitrophenol (604 mg, 4.3 mmol) were
dissolved in CH2Cl2 (10 mL), and BF3·OEt2 (134 mL,
1.1 mmol) was added dropwise. The solution was left
overnight and was then washed with NaHCO3 (satd aq,
30 mL), water, and dried (MgSO4) and concentrated in
vacuo. Flash silica chromatography of the residue, elu-
tion with 1:4 EtOAc–light petroleum, gave a colourless
syrup containing the 4-nitrophenyl 2,3,5,6-tetra-O-
2,3,5,6-tetra-O-propanoyl-1-thio-b-D-glucofuranoside
(4b, R=SMe) as a colourless solid (470 mg, 81%, a:b
B1:7). A sample was recrystallised from EtOH to give
colourless needles, mp 62–63 °C, [h]2D2 −50.5° (c 1.0,
CHCl3); NMR (CDCl3): lH 5.37 (d, 1 H, J3,4 4.2 Hz,
H-3), 5.33 (ddd, 1 H, J4,5 9.3, J5,6b 5.1, J5,6a 2.5 Hz,
H-5), 5.07 (d, 1 H, J1,2 2.2 Hz, H-2), 5.00 (d, 1 H, H-1),
4.62 (dd, 1 H, J6a,6b 12.3 Hz, H-6a), 4.36 (dd, 1 H, H-4),
4.17 (dd, 1 H, H-6b), 2.39 (q, 2 H, J 7.6 Hz, CH2), 2.37
(q, 2 H, J 7.6 Hz, CH2), 2.35 (q, 2 H, J 7.6 Hz, CH2),
2.26 (q, 2 H, J 7.6 Hz, CH2), 2.23 (s, 3 H, SCH3), 1.16
(t, 3 H, J 7.6 Hz, CH3), 1.14 (t, 3 H, J 7.6 Hz, CH3),
1.13 (t, 3 H, J 7.6 Hz, CH3), 1.09 (t, 3 H, J 7.6 Hz,
CH3); lC 174.4, 173.3, 173.1, 173.1 (4×CꢀO), 89.6
(C-1), 81.6 (C-2), 79.1 (C-4), 74.7 (C-3), 68.4 (C-5), 63.4
(C-6), 27.7 (4×CH2), 14.4 (SCH3), 9.4, 9.2, 9.2, 9.1
(4×CH3); FABMS: m/z 435.1697 (MH)+; C19H31O9S
requires 435.1689. Anal. Calcd for C19H30O9S: C, 52.5;
H, 7.0; S 7.4. Found: C, 52.7; H, 7.2; S, 7.4.
propanoyl-a,b-
D-glucofuranosides
(4a,b;
R=
OC6H4NO2(p)) (0.99 g, 88%), which were dissolved in
MeOH (20 mL), and NaOH (1 M, aq) was added to
pH 10. The solution was left overnight and then neu-
tralised with Amberlite IRC-50 (H+) resin and filtered.
The filtrate was then concentrated in vacuo. The result-
ing residue was purified by flash silica chromatography,
elution with 1:9 MeOH–CHCl3, to give 4-nitrophenyl
a,b-
61% overall, a:b=2:9). Further chromatography al-
lowed separation of the anomers. 4-Nitrophenyl a-
glucofuranoside was recrystallised from 2-butanone to
give colourless needles, mp 117.5–119.5 °C, [h]D24
D-glucofuranoside as a pale-yellow oil (400 mg,
D-
+
Phenyl 1-thio-i-
D-glucofuranoside.—1,2,3,5,6-Penta-
211.5° (c 1.0, H2O); NMR (DMSO-d6): lH 8.22 (d, 2 H,
J 9.2 Hz, H-3%,5%), 7.17 (d, 2 H, J 9.2 Hz, H-2%,6%), 5.59
(d, 1 H, J1,2 4.2 Hz, H-1), 5.41 (s, 1 H, HO), 5.05 (s, 1
H, HO), 4.66 (s, 1 H, HO), 4.41 (s, 1 H, HO), 4.28 (dd,
1 H, J2,3 4.3 Hz, H-2), 4.14 (1 H, dd, 1 H, J3,4 2.7 Hz,
H-3), 3.98 (1 H, dd, J4,5 8.4 Hz, H-4), 3.79 (ddd, 1 H,
J5,6a 5.9, J5,6b 2.8 Hz, H-5), 3.55 (dd, 1 H, J6a,6b 11.2 Hz,
H-6b), 3.34 (dd, 1 H, H-6a); lC (DMSO-d6): 162.7
(C-1%), 141.9 (C-4%), 126.2 (C-3%,5%), 116.9 (C-2%,6%), 106.7
(C-1), 81.6 (C-4), 77.7 (C-2), 71.0 (C-3), 69.3 (C-5), 63.4
(C-6); FABMS: m/z 302.0874 (MH)+; C12H16NO8 re-
quires 302.0876. Anal. Calcd for C12H15NO8: C, 47.8;
H, 5.0; N 4.7. Found: C, 47.3; H, 5.1; N, 4.7. 4-Nitro-
O-propanoyl-b- -glucofuranose (2.0 g, 4.3 mmol) in
D
CH2Cl2 (10 mL) was cooled in an ice–salt bath, and
thiophenol (670 mL, 6.5 mmol) was added, followed by
the dropwise addition of BF3·OEt2 (640 mL, 5.2 mmol).
The solution was allowed to warm to rt, and the
reaction was complete after 1 h. The reaction mixture
was washed with NaHCO3 (satd aq, 10 mL) and water,
dried (MgSO4) and concentrated in vacuo. Flash silica
chromatography of the residue, elution with 1:9
EtOAc–petroleum ether, gave phenyl 2,3,5,6-tetra-O-
propanoyl-1-thio-
D
-glucofuranoside (4a,b; R=SPh) as
a
colourless oil [2.17
g
(100%), a:b=1:8]. This
anomeric mixture was dissolved in MeOH (10 mL) and
K2CO3 (520 mg) was added. After being stirred for 1 h,
the mixture was neutralised with Amberlite IRC-50
(H+) resin, filtered and concentrated in vacuo. The
resulting residue (750 mg) was crystallised from EtOAc
phenyl b-D-glucofuranoside was isolated as a pale-yel-
low gum, [h]2D0 −114.6° (c 3.2, H2O); NMR
(DMSO-d6): lH 8.13 (d, 2 H, J 9.3 Hz, H-3%,5%), 7.09 (d,
2 H, J 9.3 Hz, H-2%,6%), 5.66 (s, 1 H, HO), 5.55 (1 H, s,
H-1), 5.06 (s, 1 H, HO), 4.59 (s, 1 H, HO), 4.38 (s, 1 H,
HO), 4.21 (s, 1 H, H-2), 4.13–4.09 (m, 2 H, H-3,4), 3.72
(ddd, 1 H, J4,5 8.1, J5,6b 6.0, J5,6a 2.8 Hz, H-5), 3.51 (dd,
1 H, J6a,6b 11.6 Hz, H-6a), 3.34 (dd, 1 H, H-6b); lC
(DMSO-d6) 161.7 (C-1%), 141.7 (C-4%), 126.0 (C-3%,5%),
116.6 (C-2%,6%), 105.9 (C-1), 83.0 (C-4), 80.5 (C-2), 74.6
to give phenyl 1-thio-b-D-glucofuranoside as colourless
needles (567 mg, 48% overall), mp 105–107 °C (lit.17
100 °C), [h]D23 −219.6° (c 1.0, EtOH), (lit.17 [h]2D1
−233° (c 3.0, EtOH); NMR (DMSO-d6): lH 7.41 (dd,
2 H, J 7.2, 1.3 Hz, H-2%,6%), 7.33 (dd, 2 H, J 7.7,
H-3%,5%), 7.22 (tt, 1 H, J 7.7, 1.3 Hz, H-4%), 5.63 (s, 1 H,

R.H. Furneaux et al. / Carbohydrate Research 337 (2002) 1999–2004
2003
HO), 5.13 (d, 1 H, J1,2 1.7 Hz, H-1), 5.09 (s, 1 H, HO),
4.59 (d, 1 H, J 4.8, HO), 4.40 (t, 1 H, J 5.6, HO), 4.05
(br s, 1 H, H-2), 3.99 (br s, 1 H, H-3), 3.91 (dd, 1 H,
J4,5 8.2, J3,4 3.5 Hz, H-4), 3.81 (m, 1 H, H-5), 3.60 (ddd,
1 H, J6a,6b 11.3, J5,6a 3.1 Hz, H-6a), 3.40 (ddd, 1 H, J5,6b
3.1 Hz, H-6b); lC (DMSO-d6) 137.4 (C-1%), 129.4, 129.3
(C-2%,3%,5%,6%), 126.5 (C-4%), 92.6 (C-1), 82.9 (C-2,4), 75.5
(C-3), 69.7 (C-5), 64.0 (C-6); FABMS: m/z 272.0709
(M)+, C12H16O5S requires 272.0718.
2.7 Hz, H-4%), 4.12 (ddd, 1 H, J5%,6%a 5.4, J5%,6%b 2.7 Hz,
H-5%), 3.86 (dd, 1 H, J6%a,6%b 12.1 Hz, H-6%a), 3.37 (dd, 1
H, H-6%b); lC (D2O) 166.8 (C-4), 151.9 (C-2), 142.6
(C-6), 101.5 (C-5), 92.4 (C-1%), 82.8 (C-4%), 80.7, 74.7
(C-2%,3%), 68.9 (C-5%), 63.8 (C-6%); FABMS: m/z 275.0884
(MH)+; C10H15N2O7 requires 275.0880. Anal. Calcd for
C10H14N2O7 C, 43.8; H, 5.15; N, 10.2. Found: C, 44.0;
H, 5.0; N, 10.35.
1,2-O-[1-Cyanopropylidene]-3,5,6-tri-O-propanoyl-h-
1-(2,3,5,6-Tetra-O-propanoyl-i-
uracil (4i, R=uracyl-1-yl).—To a suspension of
1,2,3,5,6-penta-O-propanoyl-b- -glucofuranose (2.0 g,
D
-glucofuranosyl)-
D
-glucofuranose (2).—Cyanotrimethylsilane (120 mL,
0.30 mmol) and BF3·OEt2 (28 mL, 0.23 mmol) were
added to a solution of 1,2,3,5,6-penta-O-propanoyl-b-
D-glucofuranose (104.0 mg, 0.23 mmol) in CH3NO2 (1
D
4.3 mmol) and uracil (730 mg, 6.5 mmol) in CH3CN (30
mL), N,O-bis(trimethylsilyl)acetamide (6.4 mL, 26.1
mmol) was added dropwise. The mixture was heated at
60 °C for 1 h, by which time the suspended material
had dissolved. The mixture was cooled to 0 °C, and
trimethylsilyl trifluoromethanesulfonate (1.6 mL, 8.7
mmol) was added dropwise. After being heated under
reflux for 5 h, the solution was concentrated in vacuo to
half the volume and cooled in an ice-bath. NaHCO3
(satd aq, 60 mL) was added, and the mixture was
extracted with CH2Cl2 (3×30 mL). The combined
extracts were washed with brine, dried (MgSO4) and
concentrated in vacuo. Flash silica chromatography of
the residue, elution with 1:99 MeOH–CHCl3, gave the
title compound as a colourless syrup (2.1 g, 96%, a:b
B1:25), [h]2D2 +14.6° (c 1.0, CHCl3); NMR (CDCl3):
lH 9.34 (s, 1 H, NH), 7.47 (d, 1 H, J5,6 8.2 Hz, H-6),
6.06 (d, 1 H, J1%,2% 2.0 Hz, H-1%), 5.82 (d, 1 H, H-5), 5.45
(d, 1 H, J3%,4% 3.3 Hz, H-3%), 5.36 (ddd, 1 H, J4%,5% 9.6,
J5%,6%b 5.4, J5%,6%a 2.4 Hz, H-5%), 5.07 (d, 1 H, H-2%), 4.61
(dd, 1 H, J6%a,6%b 12.3 Hz, H-6%a), 4.38 (dd, 1 H, H-4%),
4.11 (dd, 1 H, H-6%b), 2.45 (qd, 2 H, J 7.5, 1.5 Hz,
CH2), 2.36 (q, 2 H, J 7.5 Hz, CH2), 2.35 (q, 2 H, J 7.5
Hz, CH2), 2.29 (q, 2 H, J 7.5 Hz, CH2), 1.18 (t, 3 H, J
7.5 Hz, CH3), 1.15 (t, 3 H, J 7.5 Hz, CH3), 1.12 (t, 3 H,
J 7.5 Hz, CH3), 1.10 (t, 3 H, J 7.5 Hz, CH3); lC 174.3,
173.4, 172.8, 172.3 (4×CꢀO), 163.2 (C-4), 150.4 (C-2),
139.4 (C-6), 103.5 (C-5), 89.7 (C-1%), 80.6 (C-2%), 79.3
(C-4%), 73.5 (C-3%), 67.1 (C-5%), 63.2 (C-6%), 27.7, 27.6,
27.6, 27.5 (4×CH2), 9.4, 9.1, 9.1, 9.0 (4×CH3); EIMS:
m/z 499.1914 (MH)+; C22H31N2O11 requires 499.1928).
Anal. Calcd for C22H30N2O11: C, 53.0; H, 6.1; N 5.6.
Found: C, 52.7; H, 6.1; N, 5.7.
mL). The mixture was stirred at rt under nitrogen for
70 min, then diluted with EtOAc (50 mL), washed with
water (50 mL), dried (MgSO4) and concentrated in
vacuo. Flash column chromatography, elution with a
gradient of 15“25% EtOAc–hexanes, gave the title
compound as an oil (22.2 mg, 24%); [h]2D3 +10.2° (c
0.47, CHCl3); NMR (CDCl3): lH 6.09 (d, 1 H, J1,2 4.0
Hz, H-1) 5.41 (d, 1 H, J3,4 3.0 Hz, H-3), 5.21 (ddd, 1 H,
J4,5 9.5, J5,6b 5.2, J5,6a 2.4 Hz, H-5), 4.71 (d, 1 H, H-2),
4.57 (dd, 1 H, J6a,6b 12.3 Hz, H-6a), 4.36 (dd, 1 H, H-4),
4.12 (dd, 1 H, H-6b), 2.21–2.36 (m, 6 H, 3×CH2O)
2.08 (q, 2 H, J 7.5 Hz, 2 H, CH2CCN), 1.08–1.18 (m,
12 H, 4×CH3); lC 174.3, 173.4, 173.2 (3×CꢀO), 116.5
(CN), 105.9 (C-1), 104.0 (CCN), 84.6 (C-2), 78.1 (C-4),
73.7 (C-3), 67.2 (C-5), 63.3 (C-6), 31.1 (CH2CCN),
27.8, 27.7, 27.6 (3×CH2), 9.4, 9.2, 9.1, 7.4 (4×CH3);
FABMS: m/z 414.1772 (MH)+; C19H28NO9 requires
414.1772. This was followed by 2,3,5,6-tetra-O-
propanoyl-a,b- -glucofuranose (4a,b; R=OH) (11.4
D
mg, 12%) (see below) and starting material that had
partly anomerised (53.4 mg, 51%).
2,3,5,6-Tetra-O-propanoyl-h,i-
chloroacetimidate (4h,i; R=OC(ꢀNH)CCl3).—1,2,3,
5,6-Penta-O-propanoyl-b- -glucofuranose (103 mg,
D-glucofuranosyl tri-
D
0.22 mmol) was dissolved in CH2Cl2 (1 mL). Water (20
mL, 1.11 mmol) and BF3·OEt2 (28 mL, 0.22 mmol) were
added, and the mixture was kept at 40 °C for 3 h. The
volatiles were evaporated, and the residue was dissolved
in CHCl3 (20 mL), washed with water (2×20 mL),
brine (20 mL), and dried (MgSO4), and the solvent was
removed. Flash chromatography of the residue, elution
with a gradient of 15“25% EtOAc–hexanes, gave
1-(i-
D
-Glucofuranosyl)uracil.—The above product
2,3,5,6-tetra-O-propanoyl-a,b- -glucofuranose (4a,b;
D
1
was dissolved in MeOH satd with NH3 (15 mL) and left
at rt overnight. After concentration in vacuo the result-
ing residue was purified by flash silica chromatography,
eluting with 84:15:1 CHCl3–CH3OH–NH3 aq, to give
the title compound as a colourless solid (680 mg, 75%).
A sample was recrystallised from EtOH to give the
product as colourless needles, mp 175–176.5 °C, [h]D21
+9.91° (c 1.1, H2O); NMR (D2O): lH 7.82 (d, 1 H, J5,6
8.1 Hz, H-6), 5.79 (d, 1 H, H-5), 5.75 (s, 1 H, H-1%),
4.27–4.25 (m, 2 H, H-2%,3%), 4.23 (dd, 1 H, J4%,5% 8.6, J3%,4%
R=OH) (46 mg, 51%) with H and 13C NMR spectra
consistent with expectations. A sample (88 mg, 0.22
mmol) was dissolved in CH3CN (1 mL) and DBU (24
mL, 0.16 mmol) and CCl3CN (132 mL, 1.32 mmol) were
added under nitrogen. After being stirred for 1.5 h at
20 °C, the solution was transferred to a flash chro-
matography column and eluted with 15:85 EtOAc–hex-
anes containing triethylamine (1%) to give the title
compounds as a syrup (88 mg, 73%; a:b 1:1.5); NMR
(CDCl3): lH 8.64 (s, 0.4 H, NHa), 8.61 (s, 0.6 H, NHb),

2004
R.H. Furneaux et al. / Carbohydrate Research 337 (2002) 1999–2004
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6.66 (d, 0.4 H, J1,2 4.8 Hz, H-1a), 6.30 (s, 0.6 H, H-1b),
5.63 (dd, 0.4 H, J3,4 4.8, J2,3 2.4 Hz, H-3a), 5.48 (d, 0.6
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2.30 (m, 8 H, 4×CH2), 1.15 (m, 12 H, 4×CH3); lC
173.7, 172.7, 172.6, 172.3 (4×CꢀO), 160.2, (CꢀNH),
102.1 (C-1b), 97.2 (C-1a), 80.1, 76.7, 74.0, 72.4, 68.2
(C-5b), 67.4 (C-5a), 62.8 (C-6b), 62.6 (C-6a), 27.4, 27.3,
27.2, 27.0, (4×CH2), 9.1, 8.9, 8.7, (4×CH3); FABMS:
m/z 548.0848 (MH)+; C20H29Cl3NO10 requires
548.0857.
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Acknowledgements
Professor Robin Ferrier assisted with the preparation
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