Selective epimerization of L-chiro-inositol to L-muco- and D-chiro-inositol derivatives

Article abstract of DOI:10.1016/S0008-6215(01)00281-6

In a one step procedure, L-1-O-benzyl-2-O-methyl-chiro-inositol (1) was acetalized to the L-muco-inositol derivatives 2, 3 and D-2-O-benzyl-3-O-cyclohexylcarbamoyl-4-deoxy-4-(N,N'-dicyclohexylureido)-1- O-methyl-5,6-O-trichloroethylidene-chiro-inositol (4). Complete conversion of L-1-O-benzyl-6-O-cyclohexylcarbamoyl-3-O-formyl-2-O-methyl-4,5-O- trichloroethylidene-muco-inositol (3) into L-1-O-benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-4,5-O-trichloroethylidene- muco-inositol (2) is feasible by deformylation in boiling methanolic triethylamine. Furthermore, stepwise deprotection of 2 and 4 is described. Thus, compounds 5, 10, and 7 were obtained by decarbamoylation of 2, 4, and 6, respectively, with boiling methanolic sodium methoxide. The trichloroethylidene group of L-1-O-benzyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (5) was removed in a two step procedure (hydrodechlorination-deacetalization) via the ethylidene acetal 7 to give L-1-O-benzyl-2-O-methyl-muco-inositol (9). On refluxing D-chiro-inositol derivative 4 with 99% acetic acid, the ureido moiety was cleaved generating D-2-O-benzyl-4-cyclohexylamino-3-O-cyclohexylcarbamoyl-4-deoxy-1-O-methyl-5, 6-O-trichloroethylidene-chiro-inositol (11). By contrast, cleavage of the ureido moiety of 10 was relatively difficult. The corresponding D-2-O-benzyl-4-cyclohexylamino-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene- chiro-inositol (12) was only formed in small amounts. The structures of 1, 3 and 10 were confirmed by X-ray analysis.

Full text of DOI:10.1016/S0008-6215(01)00281-6

Carbohydrate Research 337 (2002) 1–9
www.elsevier.com/locate/carres
Selective epimerization of
L
-chiro-inositol to
L-muco- and
D
-chiro-inositol derivativesꢀ
Ralf Miethchen,a,* Christian Sowa,a Michael Frank,a Manfred Michalik,b
Helmut Reinkea
aDepartment of Chemistry, Uni6ersity of Rostock, Albert-Einstein-Strasse 3A, D-18051 Rostock, Germany
bInstitute for Organic Catalysis Research at the Uni6ersity of Rostock, Buchbinderstrasse 5–6, D-18055 Rostock, Germany
Received 2 August 2001; accepted 22 October 2001
Dedicated to Professor Joachim Thiem on the occasion of his 60th birthday
Abstract
In a one step procedure,
-2-O-benzyl-3-O-cyclohexylcarbamoyl-4-deoxy-4-(N,N%-dicyclohexylureido)-1-O-methyl-5,6-O-trichloroethylidene-chiro-inositol
(4). Complete conversion of -1-O-benzyl-6-O-cyclohexylcarbamoyl-3-O-formyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inos-
itol (3) into -1-O-benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (2) is feasible by de-
L-1-O-benzyl-2-O-methyl-chiro-inositol (1) was acetalized to the L-muco-inositol derivatives 2, 3 and
D
L
L
formylation in boiling methanolic triethylamine. Furthermore, stepwise deprotection of 2 and 4 is described. Thus, compounds 5,
10, and 7 were obtained by decarbamoylation of 2, 4, and 6, respectively, with boiling methanolic sodium methoxide. The
trichloroethylidene group of
procedure (hydrodechlorination–deacetalization) via the ethylidene acetal 7 to give
On refluxing -chiro-inositol derivative 4 with 99% acetic acid, the ureido moiety was cleaved generating
hexylamino-3-O-cyclohexylcarbamoyl-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene-chiro-inositol (11). By contrast, cleavage of
the ureido moiety of 10 was relatively difficult. The corresponding -2-O-benzyl-4-cyclohexylamino-4-deoxy-1-O-methyl-5,6-O-
L
-1-O-benzyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (5) was removed in a two step
-1-O-benzyl-2-O-methyl-muco-inositol (9).
-2-O-benzyl-4-cyclo-
L
D
D
D
trichloroethylidene-chiro-inositol (12) was only formed in small amounts. The structures of 1, 3 and 10 were confirmed by X-ray
analysis. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Inositols; Epimerization; Acetals; Deprotection; X-ray analysis
1. Introduction and scope
tatives, so that various compounds of this type were
prepared by chemical methods.2–4,9 We focused our
efforts on opening a new short way to these stereoiso-
mers by epimerization from well accessible precursors.†
In former papers we reported about a one-pot proce-
dure for selective epimerizations of various pyranosides
using a chloral–DCC reagent combination.1,11 For this
reaction a cis–trans-sequence of three contiguous hy-
droxyl groups in the starting molecule is required. First
The biological relevance of inositols is well known.2–4
Partly phosphorylated derivatives take part in funda-
mental biological processes, e.g., as second messen-
gers.5,6 Inositols and related polyhydroxycyclohexanes
are also used as chiral auxiliaries in stereoselective
synthesis.7,8 However, the separation of inositol deriva-
tives from natural sources is limited to a few represen-
attempts to apply the method to inositols like
L-que-
brachitol and myo-inositol with five or six unpro-
tected OH-groups failed. Only (1S,2S,3S,4R,5R)-1-O-
methylcyclohexane-1,2,3,4,5-pentol was successfully
epimerized.12
ꢀ Epimerization of carbohydrates and cyclitols, Part 18.
For Part 17, see Ref. 1.
* Corresponding author. Tel.: +49-381-4986420; fax:
+49-381-4986412.
E-mail address: ralf.miethchen@chemie.uni-rostock.de (R.
Miethchen).
† The nomenclature used in this paper is in agreement with
the IUPAC-IUB rules for cyclitols.10
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00281-6

2
R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
The formyl group at C-3 of 3 results from a haloform
reaction of the chloral (see also Ref. 11). Compound 3
crystallized from diethyl ether–light petroleum ether
giving orthorhombic crystals which were suitable for an
X-ray analysis (Fig. 2). Boiling methanolic triethyl-
amine allows a selective removal of formyl groups. By
this procedure, compound 3 was quantitatively con-
verted into 2 within 15 min. Application of this de-
formylation procedure to the crude mixture of 2, 3, and
4 simplifies the chromatographic separation of the
D-
chiro derivative 4, because formyl derivative 3 eluted
closely to 4.
The formation of
D
-chiro-inositol derivative 4 came
Fig. 1. Stereo drawing of
inositol (1) with 50% probability of the thermal ellipsoids.
L-1-O-benzyl-2-O-methyl-chiro-
as a surprise. Related to 1, the configuration at C-4 and
C-5 was inverted. It seems possible that the compound
results from a reaction sequence via the key intermedi-
ate B (Scheme 2). The latter may be formed via inter-
mediate A (addition of 4-OH to DCC after hemiacetal
displacement to 3-OH). Intermediate B allows a
tandem-sequence as marked by arrows (Scheme 2).
That would explain the regioselective introduction of a
carbamoyl group into the 6-position of compound 4, as
well as the formation of the CꢀN-bond at C-atom 5.
The CꢀN-bond formation corresponds to results pub-
lished by Vowinkel and Gleichenhagen.18
2. Synthesis and characterization
For the following reaction, we used
L
-1-O-benzyl-2-
-quebra-
O-methyl-chiro-inositol (1) synthesized from
L
chitol (Fig. 1).13‡ The molecular structure of the
compound is shown in Fig. 1.
On refluxing of
dichloroethane for 8 h, three products were formed, the
-muco-inositol derivatives 2, 3 and the -chiro-inositol
1 and chloral–DCC in 1,2-
L
D
derivative 4 (Scheme 1). Due to the pro-chirality of
chloral, diastereomeric mixtures of the endo-H and
exo-H forms of the cyclic acetals were expected. How-
ever, only the corresponding endo-H isomers were
found after column chromatographic separation by
yields of 25% (2), 16% (3) and 15% (4).
The configuration of 4 is identified as one of D-chiro-
inositol derivatives. Therefore, the numbering of 4 was
changed, i.e., adapted following the rules.10 The lower
constitutional formula of 4 in Scheme 1 shows the
upper one from the rear.
The stepwise deprotection of 2 is described in Scheme
3. Procedures to deprotect carbamoyl and trichloro-
ethylidene functions were already reported in former
papers.1,11,12 Thus, decarbamoylation of 2 was carried
out by refluxing in methanolic sodium methoxide giving
5 in 82% yield. Hydrodechlorination of 2 using tributyl-
stannane–AIBN19 was achieved in boiling toluene. Af-
ter 12 h two ethylidene derivatives, 6 (54%) and 7
Formation of the -muco-inositol derivatives 2 and 3
L
is in conformity with the mechanism of epimerizations
described for chloral–DCC acetalizations of pyran-
oses.11,16,17 As expected, the middle carbon atom of the
triol unit of 1 with cis–trans-sequence (C-4/C-5/C-6)
was inverted (Schemes 1 and 2).
‡ Compound 1 was synthesized from
-3,4:5,6-di-O-cyclohexylidene-2-O-methyl-chiro-inositol.14,15
L-quebrachitol via
L
Scheme 1. Epimerization of
L
-1-O-benzyl-2-O-methyl-chiro-inositol (1).

R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
3
Scheme 2. Proposed mechanisms for the epimerization of L-1-O-benzyl-2-O-methyl-chiro-inositol (1).
Structure assignment based on NMR and X-ray
data.—The assignment of signals in the 1H and 13C
NMR spectra was performed by recording DEPT and
(28%), were formed, because the reagent caused not
only hydrodechlorination, but also decarbamoylation.
The latter reaction gains importance with increasing
reaction time. Compound 6 was contaminated with
1
two-dimensional H,1H and 13C,1H correlation spectra
(comparative 13C NMR data see Ref. 20). Thus, the
signals for C-1 and C-2 could be confirmed by the
correlation over three bonds to the proton signals OBn
and OMe, respectively. On this basis, the assignment of
signals for the other ring atoms became possible. All
spectra show the characteristic signals of a carbamoyl
group and a trichloroethylidene group. The latter is
characterized by the singlet of the acetal proton (2–5,
10–12: l:5.36–5.46) and by the C signals of the
L
-1-O-benzyl-4,5-O-chloroethylidene-6-O-cyclohexyl-
carbamoyl-2-O-methyl-muco-inositol (about 2.5%). Be-
cause the separation of the monochloroethylidene
byproduct was difficult at this stage, the mixture of 6/7
containing this monochloro derivative was treated with
methanolic sodium methoxide (decarbamoylation) fol-
lowed by treatment with 80% aqueous trifluoroacetic
acid (deacetalization) at room temperature. The latter
reagent cleaves only the ethylidene group in
benzyl-4,5-O-ethylidene-2-O-methyl-muco-inositol (7)
forming -1-O-benzyl-2-O-methyl-muco-inositol (9)
which can be easily separated from the byproduct -1-
L-1-O-
acetal moiety (lCCl :98.9–99.8; lCH:105.9–107.2).
3
For compounds 4 and 10–12, the signal for C-4 is
significantly shifted to a higher field due to the N-sub-
stituent compared to the other ring-C-atom signals. In
L
L
O-benzyl-4,5-O-chloroethylidene-2-O-methyl-muco-
inositol (8) by column chromatography (Scheme 3).
Hydrodechlorination of 5 with tributylstannane–AIBN
yielded a mixture of 7 and 8 (ratio about 18–20:1).
1
the H spectrum of 4, recorded at room temperature,
some signals were displayed as broad signals which
were sharpened at a higher temperature indicating a
dynamic process due to the flexibility of the molecule.
Reactions of the
D
-chiro-inositol derivative 4 are
shown in Scheme 4. On heating 4 with methanolic
sodium methoxide for 24 h decarbamoylation to com-
pound 10 was achieved. The structure of this
D-chiro
derivative was confirmed by X-ray measurements (Fig.
3).
Treatment of 4 with boiling 99% acetic acid resulted
likewise in a lost of a carbamoyl moiety. However, in
this case the ureido moiety was cleaved generating
D
-2-O-benzyl-4-cyclohexylamino-3-O-cyclohexylcar-
bamoyl-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene-
chiro-inositol (11), i.e., the carbamoyl group at C-3 still
exists. Cleavage of the latter by refluxing with 2%
methanolic sodium methoxide was even more difficult.
On heating for 16 h, only 13% of the starting material
Fig. 2. Stereo drawing of
L-1-O-benzyl-6-O-cyclohexylcar-
11 was converted into
D-2-O-benzyl-4-cyclohexyl-
bamoyl-3-O-formyl-2-O-methyl-4,5-O-trichloroethylidene-
muco-inositol (3) with 50% probability of the thermal
ellipsoids.
amino-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene-
chiro-inositol (12) (Scheme 4).

4
R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
Scheme 3. Deprotection of
L
-1-O-benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (2).
The ethylidene acetal group in compounds 6 and 7 is
represented by a quadruplet of the acetal proton (l:
5.28–5.30) and a doublet (l:1.32–1.34, J:5.0 Hz) of
the methyl group. The location of these groups is
detectable by the upfield shifts of the nearest ring
protons compared to the spectra of the corresponding
trichloroethylidene derivatives 2 and 5.
The X-ray analyses of compounds 1 and 3 show that
1 adopts a distorted 1C4 chair conformation in the
crystal lattice whereas the muco-derivative 3 adopts a
4
distorted C1 conformation. However, ring flip seems to
occur when compound 3 was dissolved in chloroform.
This behavior is indicated by the fact that long range
coupling of H-1 and H-5 (4J:1.0 Hz) was found in the
corresponding 1H NMR spectrum. Such a coupling
requires a W-arrangement of these two protons which is
Scheme 4. Reactions of
bamoyl-4-deoxy-4-(N,N%-dicyclohexylureido)-1-O-methyl-5,6-
O-trichloroethylidene-chiro-inositol (4).
D-2-O-benzyl-3-O-cyclohexylcar-
1
1
only present in the case of a C4 conformation. A C4
chair conformation was also observed for -1-O-benzyl-
L
2-O-methyl-chiro-inositol (1) in methanolic solution.
This is indicated by 1,3-diaxial interactions of H-2 and
H-4 (NOE). Because H-2 and H-4 interactions were also
found for the epimeric L-1-O-benzyl-2-O-methyl-muco-
1
inositol (9) in methanolic solution, a similar C4 chair
conformation can also be assumed for this compound.
The puckering parameters21 for the six-membered
,
rings of 1, 3 and 10 are as follows: Q=0.573(3) A
(puckering amplitude), [=4.3(3)°, ƒ=274(4)° for 1,
,
Q=0.543(2) A (puckering amplitude), [=154.7(2)°,
,
ƒ=181.1(5)° for 3, Q=0.765(5) A (puckering ampli-
tude), [=85.0(4)°, ƒ=32.2(4)° for 10.
Single crystals of 1 and 10 were tested by rotational
photographs on a Bruker P4 four circle diffractometer
equipped with a Mo Ka sealed tube and a graphite
monochromator. Suitable reduced cells were found by
the automatic cell-determination routine of the Bruker
SHELXTL software. The data collections were performed
in routine ꢀ-scans. For 3, the data collection was done
on a Bruker SMART area detector system.
Fig. 3. Stereo drawing of D-2-O-benzyl-4-deoxy-4-(N,N%-dicy-
clohexylureido)-1-O-methyl-5,6-O-trichloroethylidene-chiro-
inositol (10) with 30% probability of the thermal ellipsoids.

R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
5
The structures were solved by direct methods (Bruker
4. Experimental
SHELXTL) and refined by the full-matrix least-squares
methods of SHELXL-97.§ All non-hydrogen atoms were
refined anisotropically while the hydrogens were put
into theoretical positions and refined according to the
‘riding model’.¶ However, the OH-groups were allowed
to rotate and this special refinement procedure resulted
in an improvement of the hydrogen bond directionality.
Although hydrogen bonding occurs in all three investi-
gated solids, the most interesting network of hydrogen
bonds can be observed in the crystals of 1. In this
compound, the dominating motif is formed by four
molecules. In the direction of the b-axis, two molecules
are linked together by a hydrogen bridge between O-2
in the first and O-6 in the second molecule, the distance
General.—Melting points were obtained on a polar-
izing microscope Leitz (Laborlux 12 Pol) equipped with
1
a hot stage (Mettler FP 90). H and 13C NMR spectra
were recorded on a Bruker ARX-300 spectrometer
(300.13 and 75.5 MHz, respectively). Calibration of
spectra was carried out by means of solvent peaks.
1
1
(CDCl3: l H 7.25; l 13C 77.0; CD3OD: l H 3.30; l
13C 49.0). Optical rotations were measured on a Polar
LmP (IBZ Meßtechnik). Infrared spectra were recorded
on a Protege´ Nicolet 460 IR-spectrometer (Nujol).
Column chromatography: E. Merck Silica Gel 60 (40–
63 mm); thin-layer chromatography (TLC): E. Merck
Silica Gel 60 F254 foils.
,
between the oxygens being 2.699 A. This pair of
molecules is in turn connected with another pair of two
L
-1-O-Benzyl-2-O-methyl-chiro-inositol (1).—To a
stirred solution of 80% aq trifluoroacetic acid (60 mL),
L-1-O-benzyl-3,4:5,6-di-O-cyclohexylidene-2-O-methyl-
molecules in the a-axis direction. There are links be-
chiro-inositol13 (7.20 g, 16.1 mmol) was added at rt and
stirring continued overnight. After concentration of the
solution under reduced pressure, the crude product was
purified by column chromatography (Rf 0.24, 5:1
CHCl3–MeOH); colorless crystals 4.46 g, 97%: mp
153–154 °C (acetone–EtOH); [h]2D4 −54.2° (c 1.0,
MeOH).
,
tween the OH-groups of O-3ꢀO-4 (2.711 A), O-3ꢀO-6
,
,
(2.806 A) and O-4ꢀO-5 (2.811 A). Hence the three
groups O-3ꢀH, O-4ꢀH and O-6ꢀH show both donating
and accepting features.
In the crystal of 3, there are hydrogen bridges only in
the direction of the a-axis, between the NH as donating
and the ring O-4 as accepting group, the distance being
3.183 A.
In the solid of 10, infinite chains of molecules can be
1H NMR (300.13 MHz, CD3OD): l 7.38–7.22 (m, 5
H, Ph), 4.70, 4.61 (AB, 2 H, JAB:12.0 Hz, CH2ꢀPh),
4.02 (dd, 1 H, J1,6:4.0, J5,6:3.0 Hz, H-6), 3.92 (dd, 1
H, J1,2:3.0 Hz, H-1), 3.66 (dd, 1 H, J4,5:9.5 Hz,
H-5), 3.66 (dd, 1 H, J3,4:9.1 Hz, H-3), 3.53 (dd, 1 H,
H-4), 3.39 (dd, 1 H, J2,3:10.0 Hz, H-2), 3.39 (s, 3 H,
OMe); 13C NMR (75.5 MHz, CD3OD): l 139.9 (i-Ph),
129.3 (m-Ph), 128.9 (o-Ph), 128.7 (p-Ph), 82.5 (C-2),
76.6 (C-1), 74.9 (C-4), 74.1 (CH2ꢀPh), 74.0, 72.6 (C-3,
5), 71.0 (C-6), 58.3 (OMe). Anal. Calcd for C14H20O6
(284.3): C, 59.14; H, 7.09. Found: C, 58.87; H, 6.91.
,
observed which are made up of hydrogen links between
the O-3ꢀH and the carbonyl oxygen of O-7, the O···O
distance being 2.775 A.
,
The weighting scheme was calculated as follows, for
1 w−1=|2(F2o)+(0.0608P)2+0.0119P, for 3 w−1
|2(F2o)+(0.0510P)2+0.0000P and for 10 w−1
=
=
|2(Fo2)+(0.0679P)2+0.1457P with P=(Fo2 +2F2c)/3 in
all cases.
L
-1-O-Benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-
4,5-O-trichloroethylidene-muco-inositol (2), -1-O-ben-
zyl-6-O-cyclohexylcarbamoyl-3-O-formyl-2-O-methyl-4,
5-O-trichloroethylidene-muco-inositol (3) and -2-O-
3. Conclusions
L
An inositol derivative containing four contiguous
hydroxyl groups with cis–trans–trans sequence turn
out to be precursors for two competing epimerization
reactions achieved in a facile one-pot procedure with
chloral–DCC. The results are not only of outstanding
interest with regard to the compounds obtained, but
also for the assumed tandem mechanism. Various op-
portunities for subsequent synthetic steps at each of the
new inositol’s chiral centers are offered by the diversity
of the protecting group pattern.
D
benzyl - 3 - O - cyclohexylcarbamoyl - 4 - deoxy - 4 - (N,N%-
dicyclohexylureido)-1-O-methyl-5,6-O-trichloroethyli-
dene-chiro-inositol (4).—Compound 1 (2.80 g, 9.85
mmol), DCC (5.0 g, 24.2 mmol) and chloral (5.0 g, 33.9
mmol) in 1,2-dichloroethane (100 mL) were refluxed for
8 h. After cooling to rt and addition of CH2Cl2 (150
mL) and 10% aq AcOH (200 mL), the reaction mixture
was shaken for about 30 min to destroy excess DCC.
The precipitated N,N%-dicyclohexyl urea was removed
by filtration, the organic phase was separated, and the
aqueous phase was washed with CHCl3 (3×70 mL).
The combined extracts were washed with satd aq
NaHCO3 (100 mL) and water (2×70 mL), dried
(Na2SO4) and concentrated under reduced pressure.
The crude product was treated with acetone (50 mL) to
dissolve the products 2, 3 and 4; further crystalline
§ G.M. Sheldrick, Universita¨t Go¨ttingen, 1997.
¶ See web pages: http://util.ucsf.edu/local/programs/shelxl/
ch 04.htmlc4.5 for further information on this terminology.
–

6
R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
1
N,N%-dicyclohexyl urea remains undissolved. The
filtrate was concentrated. The TLC (2:1 heptane–
EtOAc) of the residue showed four spots. Compounds
2 (Rf 0.11), 3 (Rf 0.40) and 4 (Rf 0.28) were isolated
from the mixture by column chromatography. The
syrupy product 2 (1.32 g, 25%) crystallized from hep-
tane colorless needles: mp 124–124.5 °C, [h]2D9 −12.9°
(c 1.34, CHCl3). The formyl derivative 3 (0.90 g, 16%)
crystallized from 2:1 light petroleum ether–Et2O: mp
142–143 °C (143–144 °C; DSC measurement); [h]D29
−7.7° (c 1.37, CHCl3); 1.1 g (15%) of compound 4 was
isolated [h]2D2 +7.4° (c 1.07, CHCl3). The latter is easily
soluble in light petroleum ether and numerous other
organic solvents like acetone, EtOAc, and CHCl3.
However, 4 did not crystallize. Only a porous-amor-
phous solid (melting range 85–90 °C) was obtained by
concentration of its light petroleum solution under
reduced pressure.
4: H NMR (300.13 MHz, CDCl3, 55 °C): l 7.39–
7.22 (m, 5 H, Ph), 5.30 (dd, 1 H, J3,4:8.2 Hz, H-3),
5.45 (s, 1 H, CHꢀCCl3), 5.14 (dd, 1 H, J5,6:6.7,
J4,5:9.8 Hz, H-5), 4.80 (d, 1 H, JAB:12.0 Hz,
CH2ꢀPh), 4.79 (dd, 1 H, J1,6:5.5 Hz, H-6), 4.71 (d, 1
H, JAB:12.0 Hz, CH2ꢀPh), 4.89 (br, 1 H, H-4), 4.54
(d, 1 H, J:7.5 Hz, NH), 4.41 (d, 1 H, J:7.5 Hz,
NH), 3.79 (dd, 1 H, J2,3:3.5 Hz, H-2), 3.70 (dd, 1 H,
J1,2:2.0 Hz, H-1), 3.67 (m, 1 H, cyclohexyl-CH), 3.48
(m, 1 H, cyclohexyl-CH), 3.44 (s, 3 H, OMe), 3.24 (br,
1 H, cyclohexyl-CH), 2.04–0.99 (m, 30 H, cyclohexyl-
CH2); 13C NMR (75.5 MHz, CDCl3):
l 156.7
(NHC(O)N), 154.4 (NHC(O)O), 137.9 (i-Ph), 128.3
(m-Ph), 127.7 (o-Ph), 127.6 (p-Ph), 107.2 (CHꢀCCl3),
99.7 (CCl3), 80.3 (C-6), 78.8 (C-1), 77.6 (C-2), 76.9
(C-5), 72.1 (CH2ꢀPh), 70.7 (C-3), 58.0 (OMe), 56.3
(C-4), 55.9 (cyclohexyl-CH), 49.9, 49.4 (cyclohexyl-
CH), 33.8, 33.7, 33.3, 33.2, 32.7, 32.1, 26.6, 26.5, 25.6,
25.6, 25.4, 25.0, 25.0, 24.71, 24.66 (cyclohexyl-CH2); IR
(Nujol): 1631 cm−1 (CꢁO, urea moiety), 1722 cm−1
(CꢁO, carbamoyl moiety), 3330, 3381 cm−1 (NH).
Anal. Calcd for C36H52Cl3N3O7 (745.2): C, 58.03; H,
7.03; N, 5.64. Found: C, 57.69; H, 7.03; N, 5.51.
Moreover, N-acetyl-N,N%-dicyclohexyl-urea (Rf 0.20)
was isolated as crystalline byproduct, mp 126–127 °C
(heptane). It was characterized by X-ray, NMR and
MS analyses.
2: 1H NMR (300.13 MHz, CDCl3): l 7.40–7.22 (m, 5
H, Ph), 5.52 (dd, 1 H, J1,6:3.7, J5,6:2.0 Hz, H-6),
5.39 (s, 1 H, CHꢀCCl3), 4.79 (d, 1 H, JAB:12.0 Hz,
CH2ꢀPh), 4.67 (d, 1 H, JNH,CH:8.0 Hz, NH), 4.59 (d,
1 H, JAB:12.0 Hz, CH2ꢀPh), 4.58 (dd overlapped to
CH2, 1 H, H-5), 4.54 (dd, 1 H, J4,5:6.3 Hz, H-4), 4.16
(dd, 1 H, J3,4:6.3 Hz, H-3), 3.93 (ddd, 1 H, J1,2:2.6,
4J1,5:1.0 Hz, H-1), 3.47 (m, 1 H, cyclohexyl-CH), 3.30
(s, 3 H, OMe), 3.22 (dd, 1 H, J2,3:9.8 Hz, H-2), 2.88
(br, 1 H, OH), 2.00–1.05 (m, 10 H, cyclohexyl-CH2);
13C NMR (75.5 MHz, CDCl3): l 153.5 (C(O)NH),
137.7 (i-Ph), 128.3 (m-Ph), 127.9 (o-Ph), 127.6 (p-Ph),
105.9 (CHꢀCCl3), 99.2 (CCl3), 81.7 (C-4), 78.9 (C-2),
77.8 (C-5), 72.4 (C-1), 71.8 (CH2ꢀPh), 68.6 (C-3), 67.0
(C-6), 57.5 (OMe), 50.2 (cyclohexyl-CH), 33.2, 25.3,
24.7 (cyclohexyl-CH2). Anal. Calcd for C23H30Cl3NO7
(538.8): C, 51.27; H, 5.61; N, 2.60. Found: C, 51.32; H,
5.63; N, 2.74.
L
-1-O-Benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-
4,5-O-trichloroethylidene-muco-inositol (2).—A solu-
tion of muco-inositol 3 (300 mg, 0.5 mmol) in dry
MeOH (10 mL) and Et3N (0.5 mL) was refluxed for 15
min and concentrated under reduced pressure yielding
285 mg (100%) of 2; mp 124 °C (heptane).
L
-1-O-Benzyl-2-O-methyl-4,5-O-trichloroethylidene-
muco-inositol (5).—Compound 2 (446 mg, 1.0 mmol)
was dissolved in 2% methanolic NaOMe (20 mL) and
was refluxed for about 16 h (TLC control). Subse-
quently, the reaction mixture was cooled and neutral-
ized with an acidic ion-exchanger resin (Amberlite
IR-120). After evaporation of the solvent under re-
duced pressure and column chromatographic purifica-
tion (Rf 0.13, 1:2 toluene–EtOAc) 300 mg (85%) of
syrupy 5 was isolated. The product is easily soluble in
Et2O and less soluble in light petroleum, however, it did
not crystallize. Concentration of the ethereal solution of
5 under reduced pressure yielded an amorphous solid
(melting range 52–60 °C); [h]2D9 −25.8° (c 0.9, CHCl3).
1H NMR (250.13 MHz, CDCl3): l 7.41–7.26 (m, 5
H, Ph), 5.40 (s, 1 H, CHꢀCCl3), 4.67 (s, 2 H, CH2ꢀPh),
4.59 (m, 2 H, H-4, H-5), 4.32 (ddd, 1 H, J1,6:6.5,
1
3: H NMR (300.13 MHz, CDCl3): l 8.14 (d, 1 H,
J:1.0 Hz, CHꢁO), 7.40–7.24 (m, 5 H, Ph), 5.54–5.45
(m, 2 H, H-3, H-6), 5.46 (s, 1 H, CHꢀCCl3), 4.76 (d, 1
H, JAB:12.0 Hz, CH2ꢀPh), 4.64 (d, 1 H, JAB:12.0
Hz, CH2ꢀPh), 4.65–4.59 (m, 2 H, H-4, H-5), 4.61 (br, 1
4
H, NH), 3.91 (ddd, 1 H, J1,6:4.8, J1,2:2.5, J:1.0
Hz, H-1), 3.48 (m, 1 H, cyclohexyl-CH), 3.42 (dd, 1 H,
J2,3:9.1 Hz, H-2), 3.34 (s, 3 H, OMe), 2.00–1.05 (m,
10 H, cyclohexyl-CH2); 13C NMR (75.5 MHz, CDCl3):
l 160.2 (CHꢁO), 153.6 (C(O)NH), 137.6 (i-Ph), 128.3
(m-Ph), 127.9 (o-Ph), 127.8 (p-Ph), 106.0 (CHꢀCCl3),
98.9 (CCl3), 79.4, 78.4 (C-4, C-5), 76.9 (C-2), 73.7 (C-1),
72.3 (CH2ꢀPh), 70.2 (C-3), 67.3 (C-6), 58.2 (OMe), 50.3
(cyclohexyl-CH), 33.3, 25.4, 24.7 (cyclohexyl-CH2).
Anal. Calcd for C24H30Cl3NO8 (566.9): C, 50.85; H,
5.33; N, 2.47. Found: C, 50.68; H, 5.19; N, 2.47.
4
J5,6:3.2, J:1.0 Hz, H-6), 4.28 (ddd, 1 H, J3,4:3.3,
4J:1.3 Hz, H-3), 3.77 (dd, 1 H, J1,2:2.8 Hz, H-1),
3.48 (dd, 1 H, J2,3:7.0 Hz, H-2), 3.42 (s, 3 H, OMe),
2.53 (br, 2 H, 2OH); 13C NMR (62.9 MHz, CDCl3): l
137.9 (i-Ph), 128.5 (m-Ph), 127.9 (p-Ph), 127.8 (o-Ph),
106.3 (CHꢀCCl3), 99.6 (CCl3), 81.1, 80.9 (C-4, 5), 78.7
(C-2), 75.9 (C-1), 68.2 (C-3), 68.0 (C-6), 72.4 (CH2ꢀPh),
58.2 (OMe). Anal. Calcd for C16H19Cl3O6 (413.6): C,
46.46; H, 4.63. Found: C, 46.55; H, 4.60.

R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
7
L
-1-O-Benzyl-6-O-cyclohexylcarbamoyl-4,5-O-ethyli-
(m-Ph), 127.8 (o-Ph), 127.8 (p-Ph), 100.4 (CHꢀCH3),
78.8 (C-4), 78.8 (C-5), 78.7 (C-2), 76.0 (C-1), 67.9, 67.8
(C-3, 6), 72.1 (CH2ꢀPh), 58.2 (OMe), 20.4 (CHꢀCH3).
Anal. Calcd for C16H22O6 (310.4): C, 61.92; H, 7.15.
Found: C, 61.78; H, 7.11.
dene-2-O-methyl-muco-inositol (6) and -1-O-benzyl-
L
4,5-O-ethylidene-2-O-methyl-muco-inositol (7).—To a
stirred solution of 2 (540 mg, 1.0 mmol) in dry toluene
(20 mL), Bu3SnH (1.1 g, 3.75 mmol) and AIBN (20 mg,
0.12 mmol) were added (Ar atmosphere). After 16 h
heating under reflux (TLC control) the mixture was
shaken with satd aq KF (10 mL) for 2 h and filtered
through kieselguhr to remove Bu3SnF. Then the or-
ganic phase was separated, washed with water (2×5
mL), and dried (MgSO4). On cooling the solution
overnight (refrigerator) 160 mg of pure 6 crystallized.
The filtrate was concentrated under reduced pressure.
The residue was purified by column chromatography
(6: Rf 0.15, 7: Rf 0.10, 1:1 toluene–EtOAc) yielding
further 74 mg of 6 (over all yield 54%) and 88 mg (28%)
L
-1-O-Benzyl-2-O-methyl-muco-inositol (9).—A so-
lution of 7 (211 mg, 0.68 mmol) in 80% TFA (10 mL)
was stirred for about 22 h at rt (TLC control). Then
toluene (10 mL) was added and the mixture was con-
centrated at 40 °C under reduced pressure. After a
second co-distillation of the residue with toluene (10
mL), the brownish syrupy crude product was purified
by column chromatography (Rf 0.16, 6:1 CHCl3–
MeOH) yielding 180 mg (93%) of colorless syrupy 9;
[h]2D4 −5.5° (c 1.0, MeOH).
1H NMR (250.13 MHz, CD3OD): l 7.43–7.23 (m, 5
of
L
-1-O-benzyl-2-O-methyl-4,5-O-ethylidene-muco-
H, Ph), 4.70 (s, 2 H, CH2ꢀPh), 4.04 (t, 1 H, J1,6:J5,6:
inositol (7); for the physical data of compound 7 see the
following procedure. Compound 6 crystallized from
Et2O, mp 112–113 °C (colorless needles); [h]2D9 −25.8°
(c 0.88, CHCl3).
6.3 Hz, H-6), 3.99 (t, 1 H, J2,3:J3,4:7.0 Hz, H-3),
3.84 (dd, 1 H, J1,2:3.2 Hz, H-1), 3.78–3.69 (m, 2 H,
H-4, 5), 3.52 (dd, 1 H, J2,3:7.0 Hz, H-2), 3.42 (s, 3 H,
OMe); 13C NMR (75.5 MHz, CD3OD): l 139.6 (i-Ph),
129.4 (m-Ph), 129.2 (o-Ph), 128.8 (p-Ph), 82.9 (C-2),
79.8 (C-1), 74.3 (CH2ꢀPh), 74.6, 74.4 (C-4, 5), 70.3
(C-3), 70.3 (C-6), 59.1 (OMe). Anal. Calcd for
C14H20O6 (284.3): C, 59.14; H, 7.09. Found: C, 58.01;
H, 7.09.
6: 1H NMR (250.13 MHz, CDCl3): l 7.38–7.22 (m, 5
H, Ph), 5.45 (dd, J1,6:3.6, J5,6:2.2 Hz, 1 H, H-6),
5.30 (q, 1 H, CHꢀCH3), 4.77 (d, 1 H, JAB:12.0 Hz,
CH2ꢀPh), 4.58 (d, 1 H, JAB:12.0 Hz, CH2ꢀPh), 4.63
(d, 1 H, JNH,CH:8.0 Hz, NH), 4.24 (dd, 1 H, J3,4:6.8,
J4,5:6.0 Hz, H-4), 4.18–4.10 (m, 2 H, H-3, H-5), 3.90
L
-1-O-Benzyl-6-O-cyclohexylcarbamoyl-4,5-O-ethyli-
dene-2-O-methyl-muco-inositol (6), -1-O-benzyl-2-O-
methyl-muco-inositol (9) and -1-O-benzyl-4,5-O-
4
(ddd, 1 H, J1,2:2.6, J1,5:1.0 Hz, H-1), 3.46 (m, 1 H,
L
cyclohexyl-CH), 3.19 (dd, 1 H, J2,3:9.8 Hz, H-2), 3.28
(s, 3 H, OMe), 2.53 (br, 1 H, OH), 1.98–1.05 (m, 10 H,
L
chloroethylidene-2-O-methyl-muco-inositol (8).—To a
solution of 2 (0.57 g, 1.06 mmol) in dry toluene (25 mL)
Bu3SnH (1.1 g, 3.75 mmol) and AIBN (20 mg, 0.12
mmol) were added under stirring (Ar atmosphere).
After 8 h heating under reflux (TLC control) the mix-
ture was shaken with satd aq KF (10 mL) for 2 h and
filtered through kieselguhr to remove Bu3SnF. Then the
organic phase was separated, washed with water (2×5
mL) and dried (MgSO4). On cooling the solution
overnight (refrigerator), 300 mg (65%) of pure 6 crystal-
lized. The filtrate was concentrated under reduced pres-
sure. The residue was purified by column chromato-
graphy (1:1 toluene–EtOAc) and the fraction with
Rf:0.18 was concentrated, the residue (94 mg) was
dissolved in 2% methanolic sodium methoxide (5 mL),
and the mixture was refluxed for 16 h. After neutraliza-
tion using Amberlite IR120, filtration and concentra-
tion under reduced pressure, the residue was treated
with 80% TFA (5 mL) for 22 h at rt. Subsequently, the
solution was worked-up as described for compound 9.
Column chromatographic separation gave 178 mg of 9
(59% related to 2) and 80 mg of the monochloro acetal
8 (syrup, 22% related to 2).
cyclohexyl-CH2), 1.34 (d, 3 H, JCH ,CH:5.0 Hz,
3
CHꢀCH3); 13C NMR (62.9 MHz, CDCl3): l 153.8
(C(O)NH), 137.8 (i-Ph), 128.2 (m-Ph), 127.8 (o-Ph),
127.6 (p-Ph), 100.5 (CHꢀCH3), 79.8 (C-4), 79.5 (C-2),
75.7 (C-5), 72.4 (C-1), 71.7 (CH2ꢀPh), 68.1 (C-3), 67.8
(C-6), 57.4 (OMe), 50.2 (cyclohexyl-CH), 33.3, 25.4,
24.7 (cyclohexyl-CH2), 20.4 (CHꢀCH3). Anal. Calcd for
C23H33NO7 (435.5): C, 63.43; H, 7.64; N, 3.22. Found:
C, 62.53; H, 7.77; N, 3.25.
L
-1-O-Benzyl-4,5-O-ethylidene-2-O-methyl-muco-
inositol (7).—To a solution of 6 (479 mg, 1.1 mmol) in
MeOH (20 mL), sodium (240 mg) was added forming
sodium methoxide. Subsequently, the mixture was
refluxed for 16 h, cooled to rt, neutralized using an
acidic ion-exchange resin (Amberlite IR120), filtered
and concentrated under reduced pressure. The residue
was purified by column chromatography (eluent: 1:2
toluene–EtOAc, Rf 0.13) yielding 301 mg (88%) of 7 as
colorless syrup.
7: 1H NMR (250.13 MHz, CDCl3): l 7.36–7.24 (m, 5
H, Ph), 5.28 (q, CHꢀCH3), 4.65 (s, 2 H, CH2ꢀPh),
4.26–4.15 (m, 4 H, H-3, 4, 5, 6), 3.72 (m, 1 H,
J1,2:3.0, J1,6:6.8 Hz, H-1), 3.47 (m, 1 H, J2,3:6.8
Hz, H-2), 3.39 (s, 3 H, OMe), 2.81, 2.81 (2d, 2 H,
J:6.0 Hz, 2 OH), 1.32 (d, 3 H, J:5.0 Hz, CHꢀCH3);
13C NMR (62.9 MHz, CDCl3): l 137.9 (i-Ph), 128.4
8: 1H NMR (250.13 MHz, CDCl3): l 7.36–7.25 (m, 5
H, Ph), 5.34 (t, 1 H, J:3.5 Hz, CHꢀCH2Cl), 4.67 (s, 2
H, CH2ꢀPh), 4.31–4.23 (m, 4 H, H-3, 4, 5, 6), 3.75 (m,
1 H, J1,2:2.8, J1,6:6.5 Hz, H-1), 3.54 (d, J:3.5 Hz,

8
R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
6.5 Hz, H-3), 4.76 (dd, 1 H, J1,6:5.6 Hz, H-6), 4.74 (d,
1 H, J:12.1 Hz, CH2ꢀPh), 4.68 (d, 1 H, J:12.1 Hz,
CH2ꢀPh), 4.66 (dd, 1 H, J5,6:6.3 Hz, H-5), 4.55 (d, 1
H, J:8.0 Hz, NH), 3.73 (dd, 1 H, J2,3:3.8 Hz, H-2),
3.62 (dd, 1 H, J1,2:2.3 Hz, H-1), 3.50 (br, 1 H,
cyclohexyl-CH), 3.40 (s, 3 H, OMe), 2.98 (dd, 1 H,
J4,5:8.5 Hz, H-4), 2.57 (m, 1 H, cyclohexyl-CH),
2.00–0.80 (m, 21 H, cyclohexyl-CH2, NH).; 13C NMR
(62.9 MHz, CDCl3): l 154.6 (CꢁO), 138.0 (i-Ph), 128.2
(m-Ph), 127.7 (o-Ph), 127.6 (p-Ph), 107.1 (CHꢀCCl3),
99.8 (CCl3), 81.5 (C-5), 79.7 (C-6), 78.4 (C-1), 77.4
(C-2), 74.7 (C-3), 72.2 (CH2ꢀPh), 58.1 (OMe), 55.8
(C-4), 54.8 (cyclohexyl-CH), 50.0, (cyclohexyl-CH),
34.3, 33.6, 33.5, 33.4, 26.1, 25.4, 25.1, 24.9, 24.8, 24.7
(cyclohexyl-CH2); IR (Nujol): 1719 cm−1 (CꢁO), 3270,
3330 cm−1 (NH), 3444 cm−1 (OH); MS (70 eV):
m/z=620 [M]. Anal. Calcd for C29H41Cl3N2O6 (620.0):
C, 56.18; H, 6.67; N, 4.52. Found: C, 56.15; H, 6.69; N,
4.27.
CHꢀCH2Cl), 3.49 (m, 1 H, J2,3:6.5 Hz, H-2), 3.41 (s,
3 H, OMe), 2.51 (br, 2 H, 2 OH); 13C NMR (62.9
MHz, CDCl3): l 138.0 (i-Ph), 128.4 (m-Ph), 127.9
(p-Ph), 127.8 (o-Ph), 101.2 (CHꢀCH2Cl), 79.5 (C-4),
79.5 (C-5), 78.9 (C-2), 76.1 (C-1), 72.3 (CH2ꢀPh), 67.9,
67.8 (C-3, 6), 58.3 (OMe), 44.9 (CHꢀCH2Cl). Anal.
Calcd for C16H21ClO6 (344.8): C, 55.74; H, 6.14.
Found: C, 55.49; H, 6.20.
D
-2-O-Benzyl-4-deoxy-4-(N,N%-dicyclohexylureido)-
1 - O - methyl - 5,6 - O - trichloroethylidene - chiro - inositol
(10).—Compound 4 (300 mg, 0.40 mmol) in anhyd
MeOH (10 mL)–sodium methoxide (0.13 g, 2.4 mmol)
was decarbamoylated by refluxing the solution for
about 14 h (TLC control). The reaction mixture was
worked-up as described for 5. After column chromato-
graphic purification (Rf 0.30, 2:1 heptane–EtOAc), 204
mg (82%) of syrupy 10 was obtained. The compound
crystallized from cyclohexane or 10:1 light petroleum
ether–Et2O in fine needles, mp 167–168 °C, [h]D25
+62.0° (c 1.0, CHCl3). Crystals suitable for an X-ray
measurement resulted from crystallization from 20:1
light petroleum ether–EtOAc, mp 165–166 °C.
D
- 2 - O - Benzyl - 4 - cyclohexylamino - 4 - deoxy - 1 - O-
methyl-5,6-O-trichloroethylidene-chiro-inositol (12).—A
solution of 11 (290 mg, 0.46 mmol) was refluxed in 2%
methanolic MeONa (10 mL). Gradually, the spot of 12
was detectable by TLC (Rf 0.48; 4:2:1 toluene–EtOAc–
EtOH). After 16 h refluxing, the reaction was inter-
rupted and the mixture was worked-up as described for
5. Compound 12 (30 mg, 13%) and unreacted starting
material 11 were isolated after column chromato-
graphic separation. Yellowish syrup, [h]2D9 +22.4° (c
1
10: H NMR (250.13 MHz, CDCl3): l 7.36–7.26 (m,
5 H, Ph), 5.39 (s, 1 H, CHꢀCCl3), 5.00 (dd, 1 H,
J4,5:9.3 Hz, H-5), 4.74 (d, 1 H, J:11.8 Hz, CH2ꢀPh),
4.73 (dd, J1,6:4.3, J5,6:6.0 Hz, H-6), 4.68 (d, 1 H,
J:11.8 Hz, CH2ꢀPh), 4.50 (d, 1 H, J:7.5 Hz, NH),
4.19 (dd, 1 H, J3,4:9.0 Hz, H-3), 3.88 (dd, 1 H,
J1,2:2.4 Hz, H-1), 3.73–3.54 (m, 2 H, H-4, cyclohexyl-
CH), 3.63 (dd, 1 H, J2,3:6.5 Hz, H-2), 3.49 (s, 3 H,
OMe), 3.26 (br, 1 H, OH), 3.10 (m, 1 H, cyclohexyl-
CH), 2.07–0.99 (m, 20 H, cyclohexyl-CH2); 13C NMR
(62.9 MHz, CDCl3): l 138.1 (i-Ph), 128.5 (m-Ph), 127.6
(o-Ph), 127.8 (p-Ph), 158.3 (NꢁC(O)NH), 106.7
(CHꢀCCl3), 99.6 (CCl3), 80.7 (C-2), 78.8 (C-6), 77.8
(C-5), 77.2 (C-1), 72.8 (CH2ꢀPh), 68.7 (C-3), 60.5 (C-4),
59.3 (OMe), 56.5, 49.4 (cyclohexyl-CH), 33.8, 33.8,
33.1, 32.2, 26.7, 26.7, 25.7, 25.7, 25.0, 25.0 (cyclohexyl-
CH2); IR (Nujol): 1622 cm−1 (CꢁN), 3354 cm−1 (NH),
3463 cm−1 (OH); MS (CI-isobutane): m/z=621 [M+
1]. Anal. Calcd for C29H41Cl3N2O6 (620.0): C, 56.18; H,
6.67; N, 4.52. Found: C, 56.50; H, 6.61; N, 4.42.
1
0.9, CHCl3); H NMR (250.13 MHz, CDCl3): l 7.39–
7.26 (m, 5 H, Ph), 5.36 (s, 1 H, CHꢀCCl3), 4.72 (s, 2 H,
CH2ꢀPh), 4.62 (dd, 1 H, J1,6:3.8 Hz, H-6), 4.52 (dd, 1
H, J5,6:5.5 Hz, H-5), 3.89 (dd, 1 H, J1,2:2.8 Hz,
H-1), 3.71 (dd, 1 H, J3,4:9.2 Hz, H-3), 3.63 (dd, 1 H,
J2,3:8.2 Hz, H-2), 3.48 (s, 3 H, OMe), 2.85 (m, 1 H,
cyclohexyl-CH), 2.78 (dd, 1 H, J4,5:8.1 Hz, H-4), 2.26
(br, 2 H, NH, OH), 2.04–0.76 (m, 10 H, cyclohexyl-
CH2); 13C NMR (62.9 MHz, CDCl3): l 138.1 (i-Ph),
128.5 (m-Ph), 127.8 (p-Ph), 127.7 (o-Ph), 106.4
(CHꢀCCl3), 99.4 (CCl3), 83.0 (C-5), 79.6 (C-2), 77.8
(C-6), 76.3 (C-1), 72.8 (CH2ꢀPh), 70.0 (C-3), 59.6
(OMe), 57.9 (C-4), 54.1 (cyclohexyl-CH), 34.9, 33.4,
26.1, 25.1, 24.9 (cyclohexyl-CH2). Anal. Calcd for
C22H30Cl3NO5 (494.8): C, 53.40; H, 6.11; N, 2.83.
Found: C, 53.36; H, 6.59; N, 2.87.
D
-2-O-Benzyl-4-cyclohexylamino-3-O-cyclohexylcar-
bamoyl-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene-
chiro-inositol (11).—A solution of 4 (586 mg, 0.78
mmol) in 99% AcOH (20 mL) was refluxed for about 7
h (TLC control). Subsequently, the solution was con-
centrated under reduced pressure and purified by
column chromatography (Rf 0.23; 2:1 heptane–EtOAc)
yielding 390 mg (80%) of syrupy 11. The compound
crystallized from a 3:1 light petroleum ether–Et2O mix-
ture; colorless needles mp 109–110 °C; [h]2D5 +13.2° (c
1.1, CHCl3).
5. Supplementary material
Full crystallographic details (excluding structure fac-
tors) for the structures in this paper have been de-
posited at the Cambridge Crystallographic Data Centre
as supplementary publication nos. CCDC 167747 (1),
CCDC 167748 (3) and CCDC 167749 (10) Copies of
the data can be obtained, free of charge, on application
to The Director, CCDC, 12 Union Road, Cambridge
1H NMR (250.13 MHz, CDCl3): l 7.37–7.22 (m, 5
H, Ph), 5.39 (s, 1 H, CHꢀCCl3), 4.90 (dd, 1 H, J3,4
:

R. Miethchen et al. / Carbohydrate Research 337 (2002) 1–9
9
5. Billington, D. C. Chem. Soc. Re6. 1989, 18, 83–122.
CB2 1EZ, UK (Tel.: +44-1223-336408; fax: +44-
1223-336033; e-mail: deposit@ccdc.cam.ac.uk or www:
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The authors are very grateful to Professor Stephen J.
Angyal (Sydney) for interesting suggestions and discus-
sions and for a gift of quebrachitol. Furthermore, we
thank Angela Niemann and Claudia Vinke for techni-
cal assistance as well as Professor Ju¨rgen Kopf (Univer-
sity of Hamburg) for an X-ray analysis of compound 3.
The Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie promoted our research by finan-
cial support.
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