Synthesis of 6,6'-ether linked disaccharides from D-allose, D-galactose, D-glucose and D-mannose; evidence on the structure of coyolosa.

Article abstract of DOI:10.1039/b407468h

6,6'-Linked ethers derived from D-allose, D-galactose, D-glucose, and D-mannose have been prepared in order to allow comparisons with the reported 6,6'-linked hexopyranose coyolosa, an hypoglycemic compound which has been isolated by extraction of the roo

Full text of DOI:10.1039/b407468h

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A R T I C L E
Synthesis of 6,6′-ether linked disaccharides from D-allose,
D-galactose, D-glucose and D-mannose; evidence on the structure
of coyolosa
Alan H. Haines
Centre for Carbohydrate Chemistry, School of Chemical Sciences and Pharmacy,
University of East Anglia, Norwich, UK NR4 7TJ
Received 18th May 2004, Accepted 17th June 2004
First published as an Advance Article on the web 27th July 2004
6,6′-Linked ethers derived from D-allose, D-galactose, D-glucose, and D-mannose have been prepared in order to allow
comparisons with the reported 6,6′-linked hexopyranose coyolosa, an hypoglycemic compound which has been isolated
by extraction of the root of the palm Acrocomia mexicana. Comparison of NMR data from the ethers and their derived
peracetates with corresponding reported data from coyolosa and its peracetate indicate that coyolosa is not a 6,6′-linked
disaccharide. The synthesised compounds are representatives of a novel class of disaccharide derivatives which are linked
tail to tail in contrast to the more usual head to tail (e.g. maltose) or head to head (e.g. trehalose) disaccharides.
Introduction
In 1992, Pérez and co-workers reported1 that the methanol extract of
the charred root of the thorny palm Acrocomia mexicana exhibited
hypoglycemic activity on normal and alloxan-diabetic rats. The
charred root of this palm was reported to have been used in Mexico
intraditionalmedicineformanyyears.In1997,bycolumnchromato-
graphy of the methanol extract, the research group isolated2 from
the most pharmacologically active fractions a crystalline solid, mp
170–172 °C, which they named coyolosa. On the basis of elemental
analysis and that of its peracetate and also on NMR spectroscopic
and mass spectrometric data, the authors proposed a structure for
coyolosa as a 6,6′-ether linked disaccharide, an unusual tail-tail
type structure in view of the paucity of examples in Nature of
carbohydrates joined by ether links rather than by the more usual
head-head (e.g. trehalose) or head-tail (e.g. maltose) linkages. In an
attempt to provide evidence to identify coyolosa unequivocally, we
synthesised3 the 6,6′-linked D-allose derivative, since the formula
presented by Pérez and co-workers2 indicated allo-stereochemistry
albeit, perhaps unintentionally, with the two moieties being D- and
L-forms, but the physical properties of the synthetic material and its
peracetate did not agree with those reported for coyolosa. Further,
Ikegami and co-workers very recently reported a novel synthetic
route to several 6,6′-ether linked disaccharides4 and on the basis
Scheme 1 Reagents and conditions: (a) t-BuSiPh2Cl/C5H5N, 94%.
of structure–activity relationships they proposed that coyolosa may
be the 6,6′-ether linked D-mannose derivative. We now give full
synthetic details in support of our earlier preliminary publication
regarding the D-allose derived pseudo disaccharide and describe
the subsequent preparation and properties of the 6,6′-ether linked
derivatives of D-galactose, D-glucose, and D-mannose.
(b) NaH/PhCH2Br/DME, 68%. (c) Bu4NF/THF, 91%. (d) Tf2O/Et3N/
CH2Cl2, 80%.
of reaction in the D-glucopyranose series using the reaction of the
6-alkoxide with a 6-iodide or a 6-tosylate gave only low to moderate
yields and led them to develop an alternative synthetic strategy.
Catalytic hydrogenolysis of 8 to give 9 followed by de-O-
acetalation afforded 6-O-(6-deoxy-D-allos-6-yl)-D-allose 10 as a
hygroscopic solid. NMR spectroscopy in D2O indicated that in
this solution the ,-pyranose form (H 4.88, J1,2 8.2, 1-H) was
predominant to an extent of ~81%, with a minor amount (~13% of
the total anomeric signal) for an -anomeric form (H 5.13, J1,2 3.4,
1-H). Clearly, in this and other cases, the -anomeric moiety could
be associated with a -pyranose moiety, since it is most likely that
the two linked pyranose rings give rise to signals in the NMR spec-
trum independently of each other. Two small signals (6% of total)
were observed at H 5.23 and 5.36, and presumably represented
furanose forms. The proportions of the anomers agree well with
those reported6 for D-allose aqueous solution of 77.5% -pyranose,
14% -pyranose, and 8.5% furanose forms. In its 13C NMR spec-
trum in D2O, compound 10 showed signals for anomeric carbons at
C 94.19 (major) and 93.57 (minor) which are in close agreement
with those for - and -D-allose at 94.3 and 93.7, respectively7 and
Results and discussion
Selective protection of the primary hydroxy group in 3-O-
benzyl-1,2-O-isopropylidene--D-allofuranose5 3 (Scheme 1) by
reaction with tert-butyldiphenylsilyl chloride afforded 4 which on
benzylation gave the fully protected allofuranose derivative 5. De-
O-silylation was achieved in good yield on treatment with fluoride
ion to give the key intermediate 6, from which the corresponding
triflate 7 was prepared. In view of the relative instability of triflates
in general, the sulfonate was purified by rapid passage through a
column of silica, giving material homogeneous by TLC, and this
was then used immediately. Reaction of the pre-formed sodium
alkoxide derived from alcohol 6 with a slight excess of triflate 7
(Scheme 2) led to almost complete conversion to a new product in
high yield, the 6,6′-linked compound 8. The superiority of triflates
in this type of SN2 reaction is noteworthy; Ikegami and co-workers
reported4 that their attempts to forge a 6,6′-link in a similar type
2 3 5 2
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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Scheme 2 Reagents and conditions: (a) NaH/THF then 7, 89%. (b) H2/Pd–C/EtOH–EtOAc, 85%. (c) CF3CO2H/H2O (9:1), 96%. (d) Ac2O/C5H5N, 62%.
there was a characteristic shift in C of 6-C compared to that in the
monosaccharide of 9.2 ppm to lower field. Acetylation of 10 with
acetic anhydride in pyridine gave a crystalline octaacetate 11 with
the ,-configuration at the anomeric centres (H 5.97, J1,2 8.7, 1-H
and C 90.06, 1-C) but its mp (198–199 °C) is considerably higher
than that (132–134 °C) reported for the peracetate of coyolosa
prepared by the same method. This discrepancy together with other
NMR spectroscopic data (see later) indicates that coyolosa is not
the allo-isomer in this type of compound.
two signals for -anomeric forms at H 5.60 and 5.63, each being
a doublet with J1,2 8.2, these values comparing well with those of
authentic sample of penta-O-acetyl-,-D-galactose. The 13C NMR
spectrum with signals at C 89.50 and 92.02 confirmed the presence
of an ,-mixture of anomers.
A second report of a 6,6′-ether linked disaccharide prior to
present research3,4 dates from 1961 when Whistler and Frowein11
reported heating together equimolar amounts of 1,2-O-isopropyl-
idene--D-glucofuranose and 5,6-anhydro-1,2-O-isopropylidene-
-D-glucofuranose at 150 °C, which yielded, after hydrolysis of
the product and extensive purification by column chromatography,
a compound they named as 6,6′-di-D-glucose anhydride. A similar
method was used more recently by Villa and co-workers12 in
constructing amphiphiles based on 6,6′-ether linked D-glucose
residues. Although this general approach initially seemed attractive
for preparation of this type of compound, it was not followed in the
present work since an attempt (not reported) to prepare the 6,6′-ether
linked allo-derivative by fusing together 3,5-di-O-benzyl-1,2-O-
isopropylidene--D-allofuranose and 5,6-anhydro-3-O-benzyl-1,2-
O-isopropylidene-D-allofuranose13 was unsuccessful, the reactants
showing remarkable stability even at elevated temperatures. Instead,
a displacement reaction on the gluco 6-triflate 18, readily prepared
from the known14 17, with the sodium alkoxide of 17 was made to
give 19 as a crystalline solid in high yield (Scheme 4). Compound
19 showed the characteristic shift for 6-C to low field in its 13C
NMR spectrum compared to 17. Catalytic hydrogenolysis of 19
gave 20, which on acetylation gave the hexaacetate 21. Acetolysis
of the latter gave the crystalline octaacetate 22 as the ,-isomer
One of the few reports of a 6,6′-ether linked disaccharide prior
to the present studies3,4 is a patent8 (on which the author has been
unable to obtain any further details) on the preparation of such a
derivative from 1,2:3,4-di-O-isopropylidene-D-galactopyranose9
12. In our study, triflate 13, prepared in the usual manner by reaction
of 12 with triflic anhydride using pyridine as the base, was reacted in
THF solution with the sodium alkoxide of 12 to afford the 6,6′-ether
14 in good yield (Scheme 3). In investigating an alternative route,
a solution of the alcohol 12 and triflate 13 in 1,2-dichloroethane
was stirred under reflux in the presence of anhydrous potassium
carbonate for 10 days, which led to the gradual formation of the
same product 14, although starting alcohol 12 and, surprisingly, the
triflate 13 were still present in the reaction mixture even after this
extended reaction time. Acidic hydrolysis of the ether 14 gave 6-O-
(6-deoxy-,-D-galactopyranos-6-yl)-,-D-galactopyranose 15.
The NMR spectra of 15 in D2O clearly indicated the presence of -
and -pyranose rings in an / ratio of 0.59 with signals for 1-H at
H 5.25 (J1,2 3.7) and H 4.57 (J1,2 7.8), data which compare well with
those reported10 for - and -D-galactose at H 5.16 (J1,2 3.8) and H
4.48 (J1,2 8), respectively, and an / ratio6 of 0.47. The presence of
the two anomeric forms was confirmed by the 13C spectrum which
had signals at C 97.14 (major) and 93.05 (minor), in good agree-
ment with those reported7 for the monosaccharide. Three closely
spaced peaks for 6-C were apparent at C 71.14, 71.29 (major) and
71.41, which may be attributed to 6-C nuclei in the ,- (or ,-),
,-, and ,- (or ,-) isomers, respectively. The region of absorp-
tion for the 6-C nuclei in 15 showed the characteristic shift to low
field with respect to that of the anomers of D-galactose.7
1
containing a trace (<5% from the H NMR spectrum) of the -
pyranose ester, which on de-O-acetylation afforded the 6,6-gluco-
ether 23 as a hygroscopic solid. Doublets in its 1H NMR spectrum
in D2O at 5.21 (J1,2 3.7) and 4.63 (J1,2 8.6), indicated the presence
of - and -pyranose rings and signal integration indicated an /
ratio of 0.56, values which are very similar to those for D-glucose
[H 5.09 (J1,2 3.6) and H 4.51 (J1,2 7.8)]10 and 0.61.6 In the 13C NMR
spectrum of 23 in D2O, 12 signals of varying intensity could be
distinguished, representing the maximum number from a single
molecule containing - and -moieties; in theory 24 signals are
possible if distinguishable resonances were to arise from ,-, ,-,
and ,-isomers. The anomeric carbons in the - and -pyranose
Acetylation of 15 gave octaacetate 16 as a mixture of anomers
as evidenced by the complexity of the 1H spectrum which showed,
apart from the broad singlet for 1-H in the -anomer at H 6.27,
Scheme 3 Reagents and conditions: (a) Tf2O/C5H5N/CH2Cl2, 82%. (b) 12, NaH/THF then 13, 82%. (c) CF3CO2H–H2O (9:1), 97%. (d) Ac2O/C5H5N, 50%.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8
2 3 5 3

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Scheme 4 Reagents and conditions: (a) Tf2O/Et3N/CH2Cl2. (b) 17, NaH/THF then 18, 98%. (c) H2/Pd–C/EtOH–EtOAc, 86%. (d) Ac2O/C5H5N, 52%.
(e) Ac2O–AcOH–H2SO4, 73%. (f) EtONa/EtOH, 89%.
Scheme 5 Reagents and conditions: (a) Tf2O/Et3N/CH2Cl2, 82%. (b) 24, NaH/THF then 25, 79%. (c) H2/Pd–C/EtOH–EtOAc, 91%. (d) Ac2O/C5H5N, 97%.
(e) Ac2O–AcOH–H2SO4, 89%. (f) EtONa/EtOH, 95%.
A clear comparison of the NMR spectroscopic data presented
by Pérez and co-workers2 for coyolosa with data for compounds
obtained in the present research is hindered by an apparent
discrepancy in the stated solvent used in the original publication2
which reports measurement in CDCl3, a solvent in which the poly-
hydroxy compound is unlikely to be soluble. Significantly, however,
the stated 13C chemical shift for 6-C at C 61.1 lies within the range
of values observed7 (in D2O) for hexopyranosides of C 59.4–62.5.
None of the four 6,6′-ethers prepared in this work possess a 13C
resonance below the value of C 67.28, and it is clear from an
examination of data on the compounds prepared here in cases where
unequivocal comparisons are possible that the conversion of a
6-CH2OH group into the corresponding symmetrical ether brings
about a chemical shift to low field in the 13C resonance of between
7.4 and 9.6 ppm. Further, all four of the 6,6′-ethers 10, 15, 23, and
30 exhibit 13C spectra having more than the 6 signals reported2 for
coyolosa, as a result of the non-uniform anomeric composition of
these compounds. The generally hygroscopic nature of the 6,6′-
ethers compared to the reported crystalline nature of coyolosa is
also a significant difference.
rings resonate at C 92.83 and 96.68, respectively, in close agree-
ment with the values for D-glucose,7 and importantly there is no
signal below C 70, confirming the 6,6′-ether link, since 6-C of -
and -D-glucose resonate at C 61.6 and 61.7, respectively.7
The mp (204.5–212 °C) and []D (+125.4 in CHCl3) of the ,-
octaacetate 22 differ markedly from those reported by Whistler and
Frowein11 (mp 171 °C and []D +61 in CHCl3) for the compound
they term 6,6′-di-D-glucose anhydride octaacetate. This apparent
anomaly is readily explained by the fact that their peracetate was
prepared by treatment of their 6,6′-di-D-glucose anhydride with
acetic anhydride–sodium acetate at high temperature, reaction
conditions known15 to favour formation of -anomers. To gain
evidence on this point, compound 23 was subjected to the same
acetylation conditions with acetic anhydride–sodium acetate.
The 1H NMR spectrum of the product was fully consistent with a
peracetate, and showed an , anomeric ratio of 0.26, indicating
a preponderance of the -anomeric acetates. The lower optical
rotation reported earlier11 compared to that of the ,-isomer is also
in accord with the presence of the -anomer, considering the []D
values reported15 for the - and -D-glucopyranose pentaacetates
in CDCl3 (+102 and +4, respectively).
The acetate of coyolosa is presumably a single anomeric form
in view of its reported2 crystalline nature (mp 132–134 °C) and the
ring carbons resonances measured in CDCl3 which were allocated2
as 91.77 (1-C), 72.82 (2-C), 89.13 (3-C)†, 69.90 (4-C), 67.88 (5-C),
and 61.54 (6-C). The lowest 13C resonance in acetates 11, 16, 22,
and 29 were at C 65.90, 66.48, 68.27 and 66.17, respectively,
a clear indication of non-identity of any of these compounds
The synthesis of the 6,6′-ether linked manno-isomer 30 followed
a similar route to that of the gluco-compound. Methyl 2,3,4-tri-O-
benzyl--D-mannopyranoside16 24 was converted into the triflate
25 (Scheme 5) which was then reacted with the alkoxide of 24
in THF solution to give the 6,6′-ether 26. Removal of the benzyl
groups by hydrogenolysis gave 27 which on acetylation afforded
the hexaacetate 28. Acetolysis of the latter compound gave a
single stereoisomer, the ,-octaacetate 29, as evidenced by the
signal for 1-H in its 1H NMR spectrum at H 6.03 (J1,2 1.6) and a
13C NMR spectrum showing only 6 signals for ring carbons with
1-C at C 90.42. Zemplén de-O-acetylation of 29 gave the 6,6′-
1
with coyolosa peracetate. Considering the H and 13C NMR data
together, it is clear that coyolosa is not, as reported, a 6,6′-ether
linked disaccharide and it seems likely that the spectroscopic data
are more in agreement with a 1,1′-linked symmetrical disaccharide,
an interesting possibility in view of the hypoglycemic activity of
the compound.
1
manno ether 30, as a hygroscopic foam. The H NMR spectrum
in D2O of 30 contained resonances for 1-H in - and -pyranose
moieties as broad singlets at H 5.16 and 4.89, respectively, in
an , ratio of 1.82, in agreement with the H values for 1-H in
D-mannose10 in D2O and the , ratio of 1.9 in aqueous solution.6
Conclusion
The non-identity of coyolosa with the 6,6′-ethers of the hexo-
pyranoses prepared in this work has been demonstrated, pointing
to the need for further structural studies on this natural product.
Attention has been drawn, however, to this relatively unexplored
type of disaccharide, which may possess interesting biological
The predominance of the -anomeric form is confirmed in the 13
C
NMR spectrum, in which the peak for the -anomeric carbon at
C 94.82 is more intense than that for the -anomeric carbon at
C 94.44, the values of these shifts agreeing well with those of
D-mannose7 in the same solvent. The shift for 6-C at C 70.86 has
the characteristic shift to low field compared to that at C 62.1 in
D-mannose.7
† This allocation is clearly erroneous since this value for C lies within the
region in which the anomeric carbon resonances are normally found.
2 3 5 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8

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properties, especially in view of the report17 that an ether-linked
pseudo-disaccharide containing a 5→4 D-ribose to D-glucose ether
link was a constituent of the exotoxin from Bacillus thuringiensis,
which has inhibitory action on the de novo synthesis of RNA
and the DNA dependent RNA polymerase. Since the synthesis18
of the sugar fragment of this endotoxin, in 1971, relatively little
work on such compounds has been performed. The potential for
synthesis of novel oligosaccharides by extension of the pseudo-
disaccharide chain through normal glycosidation methodology,
and of eventual ring closure to form novel modified cyclodextrins
is being explored.
3,5-Di-O-benzyl-6-O-(tert-butyldiphenysilyl)-1,2-O-
isopropylidene--D-allofuranose 5
Silyl ether 4 (2.31 g, 4.21 mmol) was dissolved in 1,2-dimethoxy-
ethane (15 ml) and sodium hydride (0.304 g, 12.7 mmol) was
added to the stirred solution followed by benzyl bromide (1.26 ml,
10.6 mmol). After 12 h, Et3N (1 ml) was added to the mixture and
after 3 h, it was partitioned between CH2Cl2 and water. Column
chromatography of the residue obtained on concentration of the
dried organic layer, with EtOAc–hexane as eluent, gave as a syrup
the benzyl ether 5 (1.83 g, 68%); []D +37 (c 0.67); H 1.03 (9 H, s,
CMe3), 1.34 and 1.57 (each 3 H and s, CMe2), 3.80 (2 H, d, J5,6a and
J5,6b 6.2, 6a- and 6b-H), 3.97 (1 H, ddd, J4,5 1.6, 5-H), 4.01 (1 H, dd,
J2,3 4.2 and J3,4 8.8, 3-H), 4.28 (1 H, dd, 4-H), 4.44 and 4.61 (each
1 H and d, JAB 11.6, OCH2Ph), 4.49 (1 H, dd, J1,2 3.7, 2-H), 4.67
and 4.73 (each 1 H and d, JAB 11.6, OCH2Ph), 5.68 (1 H, d, 1-H),
7.18–7.42 and 7.61–7.68 (20 H, 2 × m, Ar-H); C 19.03 (SiCMe3),
26.61 (CMe3, CMeMe), 26.81 (CMeMe), 63.79 (6-C), 71.95
and 73.90 (2 × CH2Ph), 77.13 (3-C), 77.79 (2-C), 79.13 (4-C),
79.42 (5-C), 104.11 (1-C), 112.98 (CMe2), 127.35–137.68 (12 C,
Ar-C); m/z (CI): 656.4 [M + NH4]+. (Found: [M + NH4]+ 656.3395.
C39H50NO6Si requires m/z 656.3402).
Experimental
1H NMR spectra were recorded at 300 MHz on a Varian Gemini FT
spectrometer, or at 400 MHz on a Varian Unity Plus spectrometer
in CDCl3 unless stated otherwise, with Me4Si as internal standard.
13C NMR spectra were similarly recorded at 75 MHz on a Varian
Gemini FT spectrometer. For NMR spectra in D2O, H values
are referenced to Me2CO at 2.22 ppm and C values to Me2CO at
30.89 ppm. Coupling constants (J values) are given in Hz. Where
appropriate, signal assignments were deduced by DEPT, COSY
and HSQC NMR experiments. NMR data are recorded for one
ring moiety only for compounds in which the two carbohydrate
rings are related by symmetry. Optical rotations were measured at
ambient temperature with a Perkin-Elmer model 141 polarimeter
for solutions in CHCl3 unless stated otherwise and []D values are
given in 10−1 deg cm2 g−1. Low and high resolution mass spectra
were recorded by the EPSRC Mass Spectrometry Service Centre at
the University College of Swansea. TLC was performed on silica
gel (Machery-Nagel) SIL G-25UV254 and compounds on developed
plates were detected either by viewing with a UV lamp (254 nm),
or by dipping into 5% solution of sulfuric acid in ethanol followed
by heating to 150 °C. Column chromatography was performed
Kieselgel 60 (70–230 mm mesh, Merck). Where mixed solvents
were used, the ratios given are v/v. Tetrahydrofuran (THF) was
obtained anhydrous by distillation from sodium metal and benzo-
phenone once the blue colouration due to the ketyl radical had
been achieved; methanol was dried by distilling from the alkoxide
(formed by reaction with activated magnesium). Sodium hydride,
purchased as a 60% dispersion in mineral oil, was washed with
hexane before use and the weights reported refer to the oil-free
material. Organic solutions were dried over anhydrous Na2SO4.
Reactions were maintained at −78 °C by means of a dry ice-acetone
bath, and at 0 °C by means of an ice bath. Compounds 3,5 12,9 17,14
and 2416 were prepared by literature procedures. Triflates 7, 13, 18,
and 25 were used immediately without characterisation, but were
homogeneous by TLC.
3,5-Di-O-benzyl-1,2-O-isopropylidene--D-allofuranose 6
Benzyl ether 5 (1.8 g, 2.8 mmol) was dissolved in tetrahydrofuran
(2 ml) and a 1 M solution of tetrabutylammonium fluoride in
tetrahydrofuran (5.64 ml) was added. After storage at ambient
temperature for 12 h, the solution was concentrated and the residue
subjected to column chromatography (elution with EtOAc–hexane
1:9 to remove tert-butyldiphenylsilyl fluoride, followed by
EtOAc–hexane 1:1) to give the syrupy alcohol 6 (1.03 g, 91%);
[]D +103.5 (c 0.32); H 1.36 and 1.58 (each 3 H and s, CMe2), 2.22
(1 H, br s, OH), 3.65 (1 H, dd, J5,6a 5.4, J6a,6b 12, 6a-H), 3.68 (1 H,
dd, J5,6b 5.4, 6b-H), 3.88 (1 H, ddd, J4,5 2, 5-H), 4.04 (1 H, dd, J2,3
4.4, J3,4 8.8, 3-H), 4.22 (1 H, dd, 4-H), 4.56 and 4.75 (each 1 H
and d, JAB 11.6, OCH2Ph), 4.57 (1 H, dd, J1,2 3.6, 2-H), 4.64 and
4.72 (each 1 H and d, JAB 11.6, OCH2Ph), 5.72 (1 H, d, 1-H); C
26.49 (CMeMe), 26.73 (CMeMe), 61.87 (6-C), 72.13 and 73.39
(2 × CH2Ph), 76.76 (3-C), 77.26 (2-C), 78.05 (5-C), 79.94 (4-C),
104.07 (1-C), 113.10 (CMe2), 127.70–138.61 (7 C, Ar-C); m/z (CI):
418.3 [M + NH4]+. (Found: [M + NH4]+ 418.2219. C39H50NO6Si
requires m/z 418.2224).
6-O-(3,5-Di-O-benzyl-6-deoxy-1,2-O-isopropylidene--D-
allofuranos-6-yl)-3,5-di-O-benzyl-1,2-O-isopropylidene--D-
allofuranose 8
A solution of alcohol 6 (0.388 g, 0.97 mmol) in dichloromethane
(4 ml) containing Et3N (0.18 ml, 1.26 mmol) was added dropwise
to a cooled (−10 °C) and stirred solution of triflic anhydride (0.2 ml,
1.19 mmol) in dichloromethane (3 ml). The solution was allowed
to warm to ambient temperature and then passed rapidly through a
column of silica (12 g), eluting with more dichloromethane. Evapo-
ration of the eluate at room temperature gave the triflate 7 (0.41 g,
0.77 mmol, homogeneousbyTLC)whichwasthendissolvedinTHF
(5 ml). This solution was added via a syringe to a cooled (0 °C) and
stirred solution of the sodium salt of 6, made by addition of sodium
hydride (0.3 g, 1.25 mmol) to a solution of 6 (0.24 g, 0.6 mmol) in
THF. The mixture was allowed to warm to ambient temperature,
and after 12 h was concentrated to dryness, and the residue was
purified by column chromatography with EtOAc–hexane 1:4 as
eluent to give ether 8 (0.426 g, 91%); []D +85.7 (c 0.43); H 1.33
and 1.56 (each 3 H and s, CMe2), 3.54 (2 H, d, J5,6a and J5,6b 6, 6a-
and 6b-H), 3.91 (1 H, m, 5-H), 4.00 (1 H, dd, J2,3 3.7, J3,4 8.5, 3-H),
4.19 (1 H, dd, J4,5 1.6, 4-H), 4.44 (1 H, dd, J1,2 3.3, 2-H), 4.51 and
4.68 (each 1 H and d, JAB 11.8, OCH2Ph), 4.63 (2 H, s, OCH2Ph),
5.65 (1 H, d, 1-H), 7.17–7.38 (10 H, m, Ar-H); C 26.54 and 26.84
(CMe2), 71.41 (6-C), 72.04 and 73.52 (2 × CH2Ph), 77.13 (3-C),
77.43 (5-C), 77.68 (2-C), 79.45 (4-C), 104.15 (1-C), 112.98 (CMe2),
127.35–139.04 (8 C, Ar-C); m/z (CI): 800.5 [M + NH4]+. (Found:
[M + NH4]+ 800.3995. C46H58NO11 requires m/z 800.4004).
3-O-Benzyl-6-O-(tert-butyldiphenysilyl)-1,2-O-isopropylidene-
-D-allofuranose 4
To a solution of 3-O-benzyl-1,2-O-isopropylidene--D-allofuranose
3 (1.42 g, 4.6 mmol) in pyridine (10 ml) was added tert-butyl-
diphenylsilyl chloride (1.43 ml, 5.5 mmol), and after 12 h at room
temperature methanol (1 ml) was added and the solution was
concentrated to an oil which was partitioned between CH2Cl2 and
water. Concentration of the organic layer afforded an oil which was
purified by column chromatography eluting with CH2Cl2–EtOAc
(49:1 increasing in polarity to 19:1) to yield as an oil the silyl
ether 4 (2.36 g, 94%); []D +39 (c 0.6); H 1.07 (9 H, CMe3), 1.35
and 1.57 (each 3 H and s, CMe2), 3.72–3.82 (2 H, complex, 6a- and
6b-H), 3.93 (1 H, dd, J2,3 4.2, J3,4 8.7, 3-H), 4.05 (1 H, m, 5-H), 4.10
(1 H, dd, J4,5 3.9, 4-H), 4.52 (1 H, dd, J1,2 3.6, 2-H), 4.50 and 4.67
(each 1 H and d, JAB 12, OCH2Ph), 5.72 (1 H, d, 1-H), 7.26–7.30,
7.33–7.48, 7.62–7.72 (15 H, 3 × m, Ar-H); C 19.11 (SiCMe3),
26.51 (CMeMe), 26.69 (CMe3, CMeMe), 64.47 (6-C), 71.88 (5-C),
72.05 (CH2Ph), 77.52 (3-C), 77.74 (2-C), 77.88 (4-C), 104.10
(1-C), 112.95 (CMe2), 127.81–137.55 (10 C, Ar-C); m/z (CI): 566.3
[M + NH4]+. (Found: [M + NH4]+ 566.2935. C32H44NO6Si requires
m/z 566.2932).
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8
2 3 5 5

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solidified on storage; mp 105–106 °C; []D −85.4 (c 1.48); H 1.31,
1.32, 1.43 and 1.52 (each 3 H and s, 2 × CMe2), 3.63 (1 H, dd, J5,6a
6.8, J6a,6b 10.2, 6a-H), 3.73 (1 H, dd, J5,6b 6.2, 6b-H), 3.98 (1 H, ddd,
J4,5 2, 5-H), 4.26 (1 H, dd, J3,4 8, 4-H), 4.29 (1 H, dd, J1,2 4.8, J2,3
2.4, 2-H), 4.58 (1 H, dd, 3-H), 5.51 (1 H, d, 1-H); C 24.32, 24.86,
25.88 and 25.98 (2 × C(Me)2), 66.48 (5-C), 69.81 (6-C), 70.60
(2-C), 70.63 (4-C), 71.01 (3-C), 96.34 (1-C), 108.56 and 109.19
(2 × CMe2); m/z (CI): 520.4 [M + NH4]+. (Found: [M + NH4]+.
520.2755. C24H42NO11 requires m/z 520.2758).
6-O-(6-Deoxy-1,2-O-isopropylidene--D-allofuranos-6-yl)-1,2-
O-isopropylidene--D-allofuranose 9
A solution of ether 8 (0.29 g, 0.37 mmol) in a mixture of EtOAc–
EtOH (1:1, 8 ml) was stirred under an atmosphere of hydrogen in
the presence of 10% palladium–charcoal catalyst (73 mg) for 12 h.
After filtration through kieselguhr, the filtrate was concentrated to
give compound 9 as an oil (0.133 g, 85%); []D +56.7 (c 1.33); H
1.29 and 1.51 (each 3 H and s, CMe2), 3.60 (1 H, dd, J5,6a 3.9, J6a,6b
10, 6a-H), 3.68 (1 H, dd, J5,6b 3.4, 6b-H), 3.85 (1 H, dd, J3,4 8.6, J4,5
3.5, 4-H), 4.01 (1 H, m, 5-H), 4.09 (1 H, dd, J2,3 4.3, 3-H), 4.58
(1 H, dd, J1,2 3.7, 2-H), 5.71 (1 H, d, 1-H); C 26.31–26.64 (CMe2),
68.88 (5-C), 69.94 (3-C), 71.30 (6-C), 79.75 (2-C), 81.08 (4-C),
103.42 (1-C), 112.78 (CMe2); m/z (CI): 440.3 [M + NH4]+ (Found:
[M + NH4]+ 440.2129. C18H34NO11 requires m/z 440.2126).
6-O-(6-Deoxy-,-D-galactopyranos-6-yl)-,-D-
galactopyranose 15
Ether 14 (0.12 g) was dissolved in trifluoroacetic acid–water (9:1,
2 ml) and solvent was removed after 2 h at <40 °C. The residue was
triturated with a mixture of MeOH–EtOAc (1:1, 5 ml) giving the
6,6′-ether 15 as colourless solid (0.08 g, 97%), which on heating
softened to a glass at ~97 °C; []D +55 (c 0.35, H2O, 24 h), 1-H-/1-
H- isomer ratio: 0.59, -isomer; H (D2O) 3.68–3.89 (4 H, complex,
2-, 3-, 6a-, and 6b-H), 3.97 (1 H, d, J3,4 3.2, J4,5 <1, 4-H), 4.22 (1 H,
dd, J5,6a and J5,6b 5.9, 5-H), 5.25 (1 H, J1,2 3.7, 1-H); -isomer, H
3.48 (1 H, dd, J1,2 7.8, J2,3 10, 2-H), 3.66 (1 H, dd, J3.4 3.4, 3-H),
3.68–3.89 (3 H, complex, 5-, 6a-, 6b-H), 3.91 (1 H, d, J4,5 <1, 4-H),
4.57 (1 H, d, 1-H); -isomer, C (D2O) 68.98 (2-C), 69.36 (5-C),
69.74 (3-C), 70.19 (4-C), 71.14 and 71.41 (6-C, , and ,), 93.05
(1-C); -isomer C 69.66 (4-C), 71.29 (6-C), 72.49 (2-C), 73.38 (3-
C), 74.06 (5-C), 97.14 (1-C); m/z (ES): 360.1 [M + NH4]+. (Found:
[M + NH4]+ 360.1504. C12H26NO11 requires m/z 360.1500).
6-O-(6-Deoxy-D-allos-6-yl)-D-allose 10
Compound 9 (0.122 g, 0.29 mmol) was dissolved in trifluoroacetic
acid–water (9:1, 1 ml) and after 10 min at room temperature the
solution was evaporated to dryness at <30 °C. Ether was then
added to, and evaporated from the residue several times and
finally a solution of the residue in water was freeze-dried to give,
as a feathery, light, hygroscopic solid, ether 10 (0.095 g, 96%);
[]D +19.1 (c 0.83, H2O), 1-H-/1-H- pyranose ratio: 0.16; H
(D2O) (major isomer) 3.41 (1 H, dd, J1,2 8.2, J2,3 3, 2-H), 3.61–3.76
(2 H, complex, 4- and 6a-H), 3.81 (1 H, br d, J6a,6b 11, 6b-H), 3.86–
3.94 (1 H, complex, 5-H), 4.16 (1 H, dd, J3,4 3, 3-H), 4.88 (1 H, d,
1-H); (minor isomer) 5.13 (d, J1,2 3.4, 1-H); C (D2O) 67.55 (4-C),
71.30 (6-C), 71.81 (2-C or 3-C), 71.86 (3-C or 2-C), 73.10 (5-C),
93.57 (minor anomer 1-C-), 94.19 (major anomer 1-C-); m/z
(ES): 365.2 [M + Na]+. (Found: [M + Na]+ 365.1059. C12H22O11Na
requires m/z 365.1054).
6-O-(1,2,3,4-Tetra-O-acetyl-6-deoxy-,-D-galactopyranos-6-
yl)-1,2,3,4-tetra-O-acetyl-,-D-galactopyranose 16
Acetylation of 15 (0.21 g, 0.6 mmol) with acetic anhydride–
pyridine yielded a product which was purified by chromatography
(EtOAc–hexane, 1:1) to yield as a foam and a mixture of isomers
octaacetate 16 (0.20 g, 50%); []D +46.6 (c 0.41), 1-H-/1-H-
isomer ratio: 0.83; H 1.92, 1.93, 1.94, 1.95, 1.97, 2.04(7), 2.05(2),
2.06(8), 2.07, 2.08, 2.09, 2.10, 2.11 (CH3CO), -isomer‡, 3.30–3.60
(2 H, complex, 6a- and 6b-H), 4.15 and 4.27 (1 H, both dd, J5,6a and
J5,6b 6.1, 5-H), 5.18–5.28 (2 H, complex, 2- and 3-H), 5.38 and 5.40
(1 H, each br s, 4-H), 6.27 (1 H, br s, 1-H); -isomer, H 3.30–3.60
(2 H, complex, 6a- and 6b-H), 3.87 and 3.90 (1 H, each dd, J5,6a and
J5,6b 6, 5-H), 5.00 and 5.01 (1 H, each dd, J2,3 10, J3,4 3.3, 3-H), 5.18–
5.28 (1 H, complex, 2-H), 5.31 and 5.33 (1 H, each d, 4-H), 5.60 and
5.63 (1 H, each d, J1,2 8.2, 1-H); C 20.39, 20.45, 20.50, 20.64, 20.78
(CH3CO), 66.48, 67.10, 67.27, 67.31, 67.74, 67.82, 67.88, 69.13,
69.39, 69.48, 69.66, 69.78, 70.03, 70.68, 70.74, 72.79, 72.98, 89.50
(1-C-), 92.02 (1-C-), 168.91, 169.04, 169.32, 169.72, 169.81,
169.89 (-CO-); m/z (CI): 696.4 [M + NH4]+. (Found: [M + NH4]+
696.2353. C28H42NO19 requires m/z 696.2346).
6-O-(1,2,3,4-Tetra-O-acetyl-6-deoxy--D-allos-6-yl)-1,2,3,4-
tetra-O-acetyl-6-deoxy--D-allose 11
Acetylation of 10 (0.051 g, 0.15 mmol) with acetic anhydride–
pyridine gave, after chromatography with EtOAc–hexane (1:1)
the octaacetate 11 (0.063 g, 62%) which afforded the crystalline
product from EtOAc–hexane; mp 198–199 °C; []D −4 (c 0.45);
H 2.00, 2.01, 2.11, 2.15, (each 3 H and s, CH3CO), 3.56 (1 H, dd,
J5,6a 4.8, J6a,6b 11.8, 6a-H), 3.67 (1 H, dd, J5,6b 3, 6b-H), 4.10 (1 H,
ddd, J4,5 8.4, 5-H), 4.97 (1 H, dd, J1,2 8.7, J2,3 3, 2-H), 4.98 (1 H, dd,
J3,4 3, 4-H), 5.70 (1 H, dd, 3-H), 5.97 (1 H, d, 1-H); C 20.38 (× 2),
20.52, 20.76 (CH3CO), 65.90 (2- or 4-C), 68.03 (4- or 2-C), 68.28
(3-C), 70.22 12 (6-C), 72.90 (5-C), 90.06 (1-C), 169.09, 169.13,
169.95, 169.34 (4 × -CO-); m/z (CI): 696.3 [M + NH4]+. (Found:
[M + NH4]+ 696.2348. C28H42NO19 requires m/z 696.2346).
6-O-(6-Deoxy-1,2:3,4-di-O-isopropylidene--D-galactopyranos-
6-yl)-1,2:3,4-di-O-isopropylidene--D-galactopyranose 14
Methyl 2,3,4-tri-O-benzyl-6-O-(methyl 2,3,4-tri-O-benzyl-6-
deoxy--D-glucopyranos-6-yl)--D-glucopyranoside 19
A solution of 1,2:3,4-di-O-isopropylidene--D-galactopyranose 12
(1.3 g, 5 mmol) in CH2Cl2 containing pyridine (0.40 ml, 5 mmol)
was added dropwise to a stirred and cooled (0 °C) solution of
triflic anhydride (1 ml, 6.1 mmol) in CH2Cl2, the resulting solution
allowed to reach room temperature, and then extracted rapidly
with ice–water. The organic layer was dried, concentrated and the
crude triflate 13 (1.61 g, 4.1 mmol) was dissolved in THF (6 ml).
This solution was added to a cooled (0 °C) solution of the sodium
alkoxide of 12 prepared by reacting, under nitrogen, a solution of
12 (1.09 g, 4.2 mmol) in THF (10 ml) with NaH (0.21 g, 8.6 mmol).
The stirred mixture was allowed to reach ambient temperature and,
after 48 h, EtOH (0.5 ml) was added and solvent was then removed
under reduced pressure. The residue was distributed between
CH2Cl2 and water and the organic layer dried and concentrated to
yield material which TLC (EtOAc–hexane 1:4, 3 developments)
showed to contain some starting alcohol 12 and a predominant
amount of a faster moving component. Column chromatography
(EtOAc–hexane 1:2) gave the ether 14 (1.0 g, 82% based on reacted
12) and then recovered alcohol 12 (0.47 g). The initially syrupy 14
Compound 17 (0.68 g, 1.46 mmol) was dissolved in CH2Cl2 (5 ml)
containing Et3N (0.33 ml, 2.38 mmol) and the solution was added
dropwise to a stirred, cooled (−10 °C) solution of triflic anhydride
(0.39 ml, 2.38 mmol) in CH2Cl2 (4 ml). The reaction mixture was
allowed to warm to room temperature, partially concentrated, and
the solution added to a chromatographic column (25 g of silica)
which was then eluted CH2Cl2. Concentration of the eluate gave
the crude triflate 18, which was dissolved in THF (5 ml) and added
to a cooled (0 °C) and stirred solution of the alkoxide of 17 (under
nitrogen) prepared by adding NaH (0.058 g, 2.43 mmol) to alcohol
17 (0.54 g, 1.16 mmol) dissolved in THF (4 ml). The coolant was
removed, and after stirring for a further 12 h, the solution was
concentrated and the residue distributed between CH2Cl2 and water.
The dried organic layer showed by TLC (EtOAc–hexane, 1:1)
‡ In some cases, two signals can arise from a hydrogen at one position in
an - or -anomeric form of one pyranose ring, depending on the anomeric
configuration in the attached pyranose ring.
2 3 5 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8

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no alcohol at Rf 0.33 and a new component with Rf 0.55. Column
chromatography of the crude product gave the syrupy 6,6′-ether 19
(1.03 g, 98% based on 17), which crystallised on standing to a solid;
mp 84–86 °C; []D +34.7 (c 1.67); H 3.36 (3 H, s, OMe), 3.51 (1 H,
dd, J1,2 3.4, J2,3 9.3, 2-H), 3.59 (1 H, dd, J3,4 9.3, J4,5 9.3, 4-H), 3.66
(1 H, br d, J5,6a <1, J6a,6b 10.8, 6a-H), 3.74 (1 H, dd, J5,6b 4.2, 5-H),
3.80 (1 H, dd, 6b-H), 4.00 (1 H, dd, 3-H), 4.58 (1 H, d, 1-H), 4.64
and 4.78 (each 1 H, d, JAB 12.3, OCH2Ph), 4.67 and 4.89 (each
1 H, d, JAB 10.8, OCH2Ph), 4.84 and 4.99 (each 1 H, d, JAB 10.8,
OCH2Ph); C 54.96 (OMe), 70.35 (5-C an 6-C), 73.30 (OCH2Ph),
74.89 (OCH2Ph), 75.72 (OCH2Ph), 77.71 (4-C), 80.02 (2-C), 82.01
(3-C), 97.93 (1-C), 127.61–138.85 (18 C, Ar-C); m/z (ES): 928.5.
[M + NH4]+. (Found: [M + NH4]+ 928.4638. C56H66NO11 requires
m/z 928.4630).
6-O-(6-Deoxy-,-D-glucopyranos-6-yl)-,-D-glucopyranose 23
To a solution of the octaacetate 22 (0.139, 0.22 mmol) in dry
ethanol (3 ml) was added small amount (~2 mg) of sodium to
produce a catalytic amount of sodium ethoxide to bring about
deacylation. A precipitate formed which was collected after 12 h
and dried over P2O5 to afford a light brown product (0.068 g, 89%).
A portion (0.052 g) was eluted from a small column of silica with
EtOAc–MeOH (1:1) to give the sample for optical rotation and
NMR spectroscopy of the 6,6′-ether 23 (0.029 g) as a hygroscopic
solid; []D +46.2 (c 0.29, H2O), 1-H-/1-H- isomer ratio: 0.56,
-isomer; H (D2O) 3.38–3.88 (6 H, complex, 2-, 3-, 4-, 6a-, and
6b-H), 3.94 (1 H, ddd, J4,5 9.9, J5,6a and J5,6b 3.6, 5-H), 5.21 (1 H, d,
J1,2 3.7, 1-H); -isomer, H 3.24 (1 H, dd, J1,2 and J2,3 8.6, 2-H), 3.47
(1 H, dd, J3,4 9, 3-H), 3.38–3.88 (4 H, complex, 4-, 5-, 6a-, and 6b-
H), 4.63 (1 H, d, 1-H); C (D2O) 70.32, 70.41, 70.71, 70.83, 70.96,
72.12, 73.42, 74.76 (2-C-), 75.40, 76.40, 92.83 (1-C-), 96.68 (-
1-C); m/z (ES): 360.1 [M + NH4]+. (Found: [M + NH4]+ 360.1496.
C12H26NO11 requires m/z 360.1500).
Methyl 6-O-(methyl-6-deoxy--D-glucopyranos-6-yl)--D-
glucopyranoside 20
Asolution of the 6,6′-ether 19 (0.62 g, 0.68 mmol) in EtOAc–EtOH
(1:9, 20 ml) was stirred under hydrogen in the presence of 10%
palladium–charcoal catalyst (0.1 g). After 24 h, TLC (EtOAc–
MeOH) indicated formation of a component, Rf 0.5 with loss of
19. After filtration through Celite® the solution was concentrated
to give material (0.23 g) which was subjected to chromatography
using EtOAc–MeOH (1:1) as eluent on silica pre-washed with
the same solvent, to give, initially as an oil, compound 20 (0.22 g,
86%), which crystallised on standing to a solid; mp 81.5–87.5 °C;
[]D +130.6 (c 0.12, H2O); H (D2O) 3.26 (3H, s, OMe), 3.28 (1 H,
dd, J3,4 9, J4,5 9, 4-H), 3.41 (1 H, dd, J1,2 3.6, J2,3 9.9, 2-H), 3.51
(1 H, dd, J, 3-H), 3.58–3.70 (3 H, complex, 5-, 6a-, 6b-H), 4.64
(1 H, d, 1-H); C (D2O) 55.92 (OMe), 70.92 (4-C), 71.15 (6-C),
71.80 (5-C), 72.58 (2-C), 74.38 (3-C), 100.61 (1-C); m/z (ES):
388.2 [M + NH4]+. (Found: [M + NH4]+ 388.1812. C14H30NO11
requires m/z 388.1813).
Acetylation 23 with acetic anhydride–sodium acetate
Using the conditions reported by Whistler and Frowein,11 compound
23 (0.011 g) was treated with acetic anhydride (0.8 ml) and sodium
acetate (0.04 g) at an elevated temperature (oil bath, 150 °C).
Isolation of the product by pouring into ice–water followed by
extraction with CH2Cl2 gave a homogeneous, syrupy product (Rf 0.4
in EtOAc–hexane) (0.018 g, 83%); 1-H-/1-H- isomer ratio: 0.26,
-isomer; H 5.46 (dd, J2,3 and J3,4 9.9, 3-H), 6.31 (d, J1,2 3.8, 1-H);
-isomer, H 5.24 and 5.25 (each dd, J2,3 and J3,4 9.4, 3-H), 5.67 and
5.70 (each d, J1,2 8.2, 1-H) (only clearly resolved resonances are
reported in each case).
Methyl 2,3,4-tri-O-benzyl-6-O-(methyl 2,3,4-tri-O-benzyl-6-
deoxy--D-mannopyranos-6-yl)--D-mannopyranoside 26
Methyl 2,3,4-tri-O-acetyl-6-O-(methyl 2,3,4-tri-O-acetyl-6-
deoxy--D-glucopyranos-6-yl)--D-glucopyranoside 21
A solution of methyl 2,3,4-tri-O-benzyl--D-mannopyranoside
24 (1 g, 2.15 mmol) in CH2Cl2 (7 ml) containing Et3N (0.37 ml,
2.64 mmol) was added dropwise to a stirred, cooled (−10 °C)
solution of triflic anhydride (0.43 ml, 2.62 mmol) in CH2Cl2 (6 ml).
The temperature of the mixture was allowed to rise to ambient
temperature and TLC (CH2Cl2) showed complete conversion to a
new product (Rf 0.7). The solution was absorbed onto a column
of silica which was then eluted with CH2Cl2 and combination and
evaporation of the relevant fractions gave the triflate 25 (1.05 g,
1.76 mmol). The triflate was dissolved in THF (6 ml) and added
slowly under nitrogen to a cool (0 °C) solution of the alkoxide of 24,
prepared by adding NaH (0.083 g, 3.5 mmol) to alcohol 24(0.8 g,
1.72 mmol) dissolved in THF (6 ml). The coolant was removed, the
mixture stirred for 12 h, and the residue remaining after evaporation
of solvent from the mixture was distributed between CH2Cl2 and
water. The separated organic layer was dried and concentrated to a
syrup (1.33 g) which on TLC showed a new component (Rf 0.4) with
only a trace of starting alcohol (Rf 0.1). Column chromatography,
eluting initially with EtOAc–hexane (2:5) gave as a syrup the 6,6′-
ether 26 (0.95 g, 79% based on utilised alcohol, 0.19 g of 24 being
obtained by further elution); []D +31.1 (c 0.36); H 3.25 (3 H, s,
OMe), 3.72–3.84 (4 H, complex, 2-, 5-, 6a-, and 6b-H), 3.87 (1 H,
dd, J2,3 2.9, J3,4 9.3, 3-H), 3.93 (1 H, dd, J4,5 9.3, 4-H), 4.62 (2 H,
s, OCH2Ph), 4.66 and 4.71 (each 1 H, d, JA,B 12.8, OCH2Ph), 4.67
and 4.91 (each 1 H, d, JA,B 10.8, OCH2Ph), 4.69 (1 H, d, J1,2 1.8, 1-
H), 7.15–7.4 (15 H, complex, Ar-H); C 54.49 (OMe), 70.95 (6-C),
71.86 (5-C), 72.07 (OCH2Ph), 72.56 (OCH2Ph), 74.63 (2-C), 75.01
(OCH2Ph), 75.10 (4-C), 80.21 (3-C), 98.75 (1-C), 127.43–138.68
(11 C, Ar-C); m/z (CI): 928.6 [M + NH4]+. (Found: [M + NH4]+
928.4631. C56H66NO11 requires m/z 928.4630).
Acetylation of the alcohol 20 (0.099 g, 0.27 mmol) with acetic
anhydride (0.2 ml, 2.1 mmol) in pyridine (2 ml) afforded the
product containing (TLC in EtOAc–hexane, 2:1) a very minor
impurity, which was removed by chromatography in the same
solvent system to give the syrupy hexaacetate 21 (0.087 g, 52%);
[]D +152.1 (c 0.87); H 1.97, 1.99 and 2.03 (each H, and s, MeCO),
3.37 (3 H, s, OMe), 3.48–3.62 (2 H, complex, 6a- and 6b-H), 3.88
(1 H, ddd, J4,5 10.2, J5,6a 4, J5,6b 4, 5-H), 4.84 (1 H, dd, J1,2 3.3, J2,3
9.9, 2-H), 4.90 (1 H, d, 1-H), 4.99 (1 H, dd, J3,4 9.6, 4-H), 5.43 (1 H,
dd, 3-H); C 20.48 (× 2) and 20.84 (CH3CO), 55.14 (OMe), 68.66
(5-C), 69.00 (4-C), 70.09 (3-C), 70.49 (6-C), 70.82 (2-C), 96.48
(1-C), 169.71, 170.22 and 170.27 (3 × -CO-); m/z (ES): 640.2
[M + NH4]+. (Found: [M + NH4]+ 640.2446. C26H42NO17 requires
m/z 640.2447).
1,2,3,4-Tetra-O-acetyl-6-O-(1,2,3,4-tetra-O-acetyl-6-deoxy--D-
glucopyranos-6-yl)--D-glucopyranose 22
The hexaacetate 21 (0.123 g, 0.2 mmol) was dissolved in an
acetolysis mixture of acetic anhydride–acetic acid–sulfuric acid
(35:15:1 v/v/v, 1 ml) and after 12 h the mixture was diluted with
CH2Cl2 and the organic solution was washed with sat. aq. NaHCO3,
water and dried. Concentration gave the product 22, initially as a
syrup (0.098 g, 73%), which afforded crystals on trituration with
EtOH; mp 204.5–212 °C; []D +125.4 (c 0.36), H 1.99, 2.01. 2.03
and 2.15 (each 3H and s, MeCO), 3.53 (1 H, dd, J5,6a 3.4, J6a,6b 11.7,
6a-H), 3.58 (1 H, dd, J5,6b 3.4, 6b-H), 3.99 (1 H, ddd, J4,5 9.8, 5-H),
5.06 (1 H, dd, J1,2 3.6, J2,3 9.8, 2-H), 5.14 (1 H, dd, J3,4 9.8, 4-H), 5.44
(1 H, dd, 3-H), 5.65 (<5% of 1-H-, d, J1,2 8.1, 1-H-), 6.28 (1 H,
d, 1-H-); C 20.30, 20.45, 20.57, and 20.73 (CH3CO), 68.27 (4-C),
69.24 (2-C), 69.85 (3-C), 70.13 (6-C), 71.47 (5-C), 88.99 (1-C),
169.05, 169.51, 169.82 and 170.46 (4 × -CO-); m/z (CI): 696.3
[M + NH4]+. (Found: [M + NH4]+ 696.2344. C28H42NO19 requires
m/z 696.2346).
Methyl 6-O-(methyl 6-deoxy--D-mannopyranos-6-yl)--D-
mannopyranoside 27
A solution of the 6,6′-ether 26 (0.89 g, 0.98 mmol) in EtOAc–EtOH
(3:13, 20 ml) was stirred under hydrogen in the presence of 10%
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8
2 3 5 7

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palladium–charcoal catalyst (0.1 g). After 18 h TLC (EtOAc–
hexane, 1:1) showed reaction was not complete and acetic acid
(0.1 ml) was added. After a further 30 h some starting material
remained and a further amount of EtOH (3 ml) and acetic acid
(0.1 ml) was added and stirring continued for a further 24 h, after
which time starting material was no longer apparent by TLC. The
filtered solution was concentrated and the residue chromatographed
with EtOAc–MeOH (3:1) as eluent on a silica column pre-washed
in the same solvent to give a solid foam the title compound 27
(0.33 g, 91%); softens ~80 °C; []D +95.5 (c 0.18, MeOH); H
(D2O) 3.40 (3 H, s, OMe), 3.67 (1 H, dd, J3,4 9.5, J4,5 9.5, 4-H), 3.74
(1 H, ddd, J5,6b 1.6, 5-H), 3.75 (1 H, dd, J2,3 3.2, 3-H), 3.79 (1 H, dd,
J5,6a 5.9, J6a,6b 10.7, 6a-H), 3.87 (1 H, br d, 6b-H), 3.93 (1 H, dd, J1,2
1.4, 2-H), 4.74 (1H, d, 1-H); C (D2O) 55.49 (OMe), 67.50 (4-C),
70.54 (2-C), 70.93 (6-C), 71.20 (3-C), 72.05 (5-C), 101.67 (1-C);
m/z (ES): 371.2 [M + H]+. (Found: [M + H]+ 371.1547. C14H27O11
requires m/z 371.1548).
was repeatedly extracted with portions of a solvent mixture of
EtOAc–MeOH (1:1) and the extracts combined and concentrated to
yield as a hygroscopic foam the title compound 30 (0.158 g, 95%);
[]D +18.0 (c 0.66, H2O), 1-H-/1-H- isomer ratio: 1.82, -isomer;
H (D2O) 3.67 (1 H, dd, J3,4 and J4,5 10.6, 4-H), 3.73–3.98 (complex,
2-, 3-, 5-, 6a- and 6b-H), 5.16 (1 H, br s, 1-H); -isomer; H 3.50
(1 H, br ddd, 5-H), 3.59 (1 H, dd, J3,4 and J4,5 9.6, 4-H), 3.73–3.98
(complex, 2-, 3-, 6a- and 6b-H), 4.89 (1 H, br s, 1-H); -isomer, C
(D2O) 67.58 (4-C), 70.86 (3-C and 6-C), 71.34 (2-C), 71.75 (5-C),
94.82 (1-C); -isomer, C 67.28 (4-C), 70.86 (6-C), 71.88 (2-C),
73.67 (3-C), 75.52 (5-C), 94.44 (1-C); m/z (ES): 365.1 [M + Na]+.
(Found: [M + Na]+ 365.1066. C12H22O11Na requires m/z 365.1054).
Acknowledgements
I thank the Mass Spectrometry Service Centre at Swansea for
determination of the low and high resolution mass spectra, and
Dr Balaram Mukhopadhyay for his expert recording of the NMR
spectra, without which this work would not have been possible, and
for helpful discussion.
Methyl 2,3,4-tri-O-acetyl-6-O-(methyl 2,3,4-tri-O-acetyl-6-
deoxy--D-mannopyranos-6-yl)--D-mannopyranoside 28
Compound 27 (0.3 g, 0.81 mmol) was acetylated by treatment with
acetic anhydride (0.6 ml, 6.4 mmol) in pyridine (5 ml) to give as a
hard glass the hexaacetate 28 (0.49 g, 97%); []D +53.8 (c 0.92); H
(400 MHz) 1.92, 1.97 and 2.07 (each 3 H and s, MeCO), 3.33 (3H,
s, OMe), 3.50 (1 H, dd, J5,6a 6.3, J6a,6b 10.6, 6a-H), 3.54 (1 H, dd,
J5,6b 3, 6b-H), 3.88 (1 H, ddd, J4,5 10.1, 5-H), 4.62 (1 H, d, J1,2 1.6,
1-H), 5.09 (1 H, dd, J3,4 10.1, 4-H), 5.15 (1 H, dd, J2,3 3.3, 2-H), 5.26
(1 H, dd, 3-H); C 20.5, 20.6, and 20.7 (3 × CH3CO-), 54.92 (OMe),
66.72 (4-C), 68.96 (3-C), 69.45 (2-C), 69.72 (5-C), 71.03 (6-C),
98.23 (1-C), 169.98 (× 2), 170.12, (3 × -CO-); m/z (CI): 640.3
[M + NH4]+. (Found: [M + NH4]+ 640.2443. C26H42NO17 requires
m/z 640.2447).
References
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1,2,3,4-Tetra-O-acetyl-6-O-(1,2,3,4-tetra-O-acetyl-6-deoxy--D-
mannopyranos-6-yl)--D-mannopyranose 29
The hexaacetate 28 (0.4 g, 0.64 mmol) was dissolved in an
acetolysis mixture of acetic anhydride–acetic acid–sulfuric acid
(35:15:1 v/v/v, 3 ml) and after 12 h the mixture was diluted with
CH2Cl2 (100 ml) and the organic solution was washed with sat.
aq. NaHCO3, water and then dried. TLC (EtOAc–hexane, 1:1,
3 developments) indicated a pure compound Rf 0.6. Evaporation
of the solvent afforded the octaacetate 29 (0.39, 89%) as a foam;
[]D +58.2 (c 0.18); H 1.99 (3 H), 2.07 (3 H), and 2.15 (6 H) (each
s, MeCO), 3.48 (1 H, dd, J5,6a 6.2, J6a,6b 11.2, 6a-H), 3.63 (1 H, dd,
J5,6b 2.7, 6b-H), 3.98 (1 H, ddd, J4,5 10, 5-H), 5.21 (1 H, dd, J3,4 10,
4-H), 5.22 (1 H, dd, J1,2 1.6, J2,3 3.4, 2-H), 6.03 (1 H, dd, 3-H), 6.03
(1 H, d, 1-H); C 20.52, 20.57, 20.62, and 20.73 (4 × CH3CO), 66.17
(4-C), 68.30 (2-C), 68.68 (3-C), 70.97 (6-C), 72.11 (5-C), 90.42
(1-C), 168.35, 169.88, 169.94, and 170.12 (4 × -CO-); m/z (ES):
696.3 [M + NH4]+. (Found: [M + NH4]+ 696.2343. C28H42NO19
requires m/z 696.2346).
6-O-(6-Deoxy--D-mannopyranos-6-yl)--D-mannopyranose 30
17 J. Farkaš, K. Šebesta, K. Horská, Z. Samek, L. Dolejš and F. Šorm,
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18 M. Prystaš and F. Šorm, Collect. Czech. Chem. Commun., 1971, 36,
1448–1471.
Sodium (~1 mg) was added to a solution of octaacetate 29 (0.33 g,
0.49 mmol) in dry ethanol and after 12 h a chip of solid CO2 was
added and the solvent removed by evaporation. The solid residue
2 3 5 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 3 5 2 – 2 3 5 8