Synthesis of phenyl-substituted conduritol B and its mechanism of formation

Article abstract of DOI:10.1002/hlca.200790231

The phenyl-substituted conduritol B 8 was prepared in racemic form in a five-step sequence starting from 2-phenyl-1,4-benzoquinone (10) (Scheme 1). The reaction mechanism of the key step 12b → 13 is discussed (Scheme 2).

Full text of DOI:10.1002/hlca.200790231

Helvetica Chimica Acta – Vol. 90 (2007)
2227
Synthesis of Phenyl-Substituted Conduritol B and Its Mechanism of
Formation
by Seda Cantekina), Ras¸it Þalıs¸kana)b), Ertan S¸ahinc)1), and Metin Balci*a)
a) Department of Chemistry, Middle East Technical University, TR-06531 Ankara
(e-mail: mbalci@metu.edu.tr)
b) Department of Chemistry, Süleyman Demirel University, TR-32260 Isparta
c) Department of Chemistry, Atatürk University, TR-25240, Erzurum(e-mail: mbalci@metu.edu.tr)
The phenyl-substituted conduritol B 8 was prepared in racemic form in a five-step sequence starting
from 2-phenyl-1,4-benzoquinone (10) (Scheme 1). The reaction mechanism of the key step 12b ! 13 is
discussed (Scheme 2).
Introduction. – Conduritols are tetrahydroxylated cyclohexene derivatives (for
reviews on conduritols, see [1]). The presence of four stereogenic C-atoms in the
framework of conduritols allows them to exist as 10 different stereoisomers. Two of
them are meso-compounds, i.e., conduritol A (1) and D (4), while the others constitute
four pairs of enantiomers, i.e., conduritol B (2), C (3), E (5) and F (6). Of these
compounds, only conduritol A (1) and conduritol F (6) are abundant in nature.
Conduritols and their derivatives have been found to possess antibiotic, antileukemic,
and tumor-inhibitory properties and glycosidase inhibitory activity [1a].
Conduritol B (2) [2] is the least accessible of the chiral conduritols, because it is the
only one that does not possess a cis-vicinal-diol pair which can be introduced by cis-
dihydroxylation reactions. Conduritol B epoxide is a potent, irreversible inhibitor of
various plant b-glucosidases [3] and mammalian glucocerebrosidase [4]. It also raises
intracellular levels of glucosylceramide by inhibiting glucosylceramidase [5]. There-
fore, the synthesis of conduritol B (2) and its derivatives is an active area of research.
Haines, Taylor, and co-workers [6] have developed a simple route leading to the
synthesis of (Æ)-conduritol B tetraacetate in three steps starting from p-benzoquinone
(¼cyclohexa-2,5-diene-1,4-dione). These promising results stimulated the study of
1
)
Corresponding author for X-ray crystallography.
ꢀ 2007 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 90 (2007)
benzoconduritol derivatives of the general formula 7 where the C¼C bond of the
conduritols is formally replaced by an aromatic ring [7], or other ring systems [8][9],
which may confer valuable properties to the molecule with such properly located
substituents.
The potential properties of such compounds led us to investigate phenyl-substituted
conduritol derivatives. We herein report a novel and efficient synthesis of 5-
phenylconduritol B (8) starting from a commercially available product, [1,1’-
biphenyl]-2-ol (9).
Results and Discussion. – 1. Synthesis. The key compound 10 in the synthesis of 8
was synthesized by the oxidation of 9 with PbO2 in AcOH as described in [10]
(Scheme 1). The resulting quinone 10 was brominated at low temperature to give only
the trans-dibromo compound 11 in high yield. The regiospecific addition of Br2 to the
unsubstituted C¼C bond can be attributed to the steric effect caused by the Ph
substituent and reduced electron density. Reduction of the carbonyl groups in 11 with
NaBH4, followed by the acetylation of the OH groups of 12a with Ac2O and pyridine
Scheme 1

Helvetica Chimica Acta – Vol. 90 (2007)
2229
gave the diacetate 12b. The 1H- and 13C-NMR spectra, in particular the 1H,1H-coupling
constants (Table 1), reveal the formation of only one isomer of the diacetate 12b. An X-
ray crystal-structure analysis of 12b (Fig. 1) provided further evidence for the proposed
structure.
Table 1. 1H,1H Coupling Constants [Hz] for Compounds 12b, 13, and 152)
J(1,6)
J(5,6)
J(4,5)
J(3,4)
J(1,3)
J(1,4)
12b
15
13
6.9
5.3
6.6
10.8
2.6
10.2
7.2
6.3
7.1
2.6
3.7
2.0
1.9
2.6
2.0
2.0
Fig. 1. a) The molecular structure of 12b, showing the atom-numbering scheme (arbitrary; thermal
ellipsoids at the 50% probability level). b) Packing diagram and H-bonding geometry.
1
The H,1H-coupling constant J(5,6) ¼ 10.8 Hz of 12b (Table 1), which is consistent with the typical
axial/axial coupling constant in a cyclohexene ring, indicates the trans-configuration as well as the
equatorial/equatorial position of the Br-atoms. Additionally, the coupling constants J(1,6) and J(4,5)
confirm the trans-(axial/axial) arrangement of the AcO groups and Br-atoms. Also, large long-range
coupling constants J(1,3) and J(1,4) of 1.9 and 2.6 Hz, respectively, are observed. Such allylic and
homoallylic couplings strongly depend on the conformation of the molecule and generally have values
2
)
For convenience, the atom numbering of 12b, 13, and 15 is the same; for systematic names, see
Exper. Part.

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Helvetica Chimica Acta – Vol. 90 (2007)
between 0.0 – 3.0 Hz. Since the homoallylic coupling operates through s – p interaction, the dihedral
angle also plays an important role. In homoallylic systems, there are two different dihedral angles. When
both of these angles are in the range of 908, the coupling reaches a maximum value [11]. The coupling
constant J(1,4) of 2.6 Hz indicates an axial/axial alignment of HÀC(1) and HÀC(4), i.e., a trans,-
trans,trans-relationship of the substituents in 12b.
Compound 12b was then treated with AcOK and Ac2O in AcOH in order to
substitute the Br-atoms by AcO groups. The obtained product consisted mainly of
tetraacetate 13 which was separated by column chromatography (silica gel). The
structure of tetraacetate 13 was elucidated on the basis of the 1H- and 13C-NMR spectra
in conjunction with 2D-NMR (DEPT-90, HMQC, HMBC, and COSY) experiments.
1
The measured H,1H-coupling constants J(1,6) ¼ 6.6, J(4,5) ¼ 7.1, and J(5,6) ¼ 10.2 of
13 (Table 1) indicate that the corresponding H-atoms are axially disposed1). Thus the
relative configuration of 13 was defined as trans,trans,trans. An X-ray crystal-structure
analysis of 13 confirmed the proposed structure (Fig. 2). Removal of the AcO groups
by ammonia in MeOH resulted in the formation of conduritol B derivative 8.
Fig. 2. a) The molecular structure of 13, showing the atom-numbering scheme (arbitrary; thermal
ellipsoids at the 50% probability level). b) Packing diagram and H-bonding geometry.
During the transformation of compound 12b into 13, a monobromo derivative 15
was formed, in amounts depending on the reaction time (Scheme 2). Prolonged
reaction times reduced the amount of 15 to 5% or less. Pure 15 was characterized by
spectroscopic methods. The formation of this intermediate was important not only in
view of the synthetic aspect, but also in view of the mechanism [12] of the
transformation of 12b into 13 where the overall configurations of the substituents
were retained. First of all, it was important to figure out the exact position of the Br-
atom and the constellation of the AcO groups in 15. The position of the Br-atom was
determined by means of a COSY experiment. The magnitude of the coupling constant
J(5,6) ¼ 2.6 Hz clearly indicates the cis-relation of the Br-atom and AcO group at
C(6)2). The observed J(1,6) ¼ 5.3 and J(4,5) ¼ 6.3 Hz establish the trans-arrangement
of the substituents attached to C(1) and C(4).

Helvetica Chimica Acta – Vol. 90 (2007)
2231
Having ascertained the configuration of 15, we suggest the following mechanism for
the formation of 13 from 12b (Scheme 2). The stereospecific synthesis of 13 can be
explained by neighboring-group participation [12]. From the structure of the
monobromo derivative 153), it is clear that at first, the carbonyl O-atom of AcOÀC(1)
attacks C(6) of 12b. This can be attributed to the possible steric effects between the
benzene ring and the AcO group. The formed cyclic oxonium ion 14 undergoes ring
opening through attack by acetate ions, most likely at the allylic C-atom to produce the
monobromo derivative 15. The displacement takes place with inversion of the
configuration. The observed cis-relation of the Br-atom and AcOÀC(5)2) in 15 can be
explained by this mechanism. A second attack by AcOÀC(4) at C(5) and formation of
a second cyclic oxonium ion 16, followed by ring opening as described above, produces
the tetraacetate 13, where the configuration of all C-atoms are inverted, compared with
those of the dibromo derivative 12b.
Scheme 2
2. X-Ray Diffraction Studies. Compound 12b crystallized in the monoclinic form
with four molecules per unit cell (Fig. 1,b). The cyclohexene ring is in a ꢁtwist-chairꢂ
conformation, and the puckering parameters of this ring are Q ¼ 0.514(7) Š, q ¼
129.7(8)8, and f ¼ 38.5(1)8, as calculated according to Cremer and Pople [14]. The
two Br-atoms are trans-related to each other. The C(10)ÀBr(1) and C(11)ÀBr(2) bond
lengths are 1.951(3) and 1.448(3) Š, respectively. Furthermore, the AcO moieties are
trans to each other. Regarding the crystal lattice of 12b (Fig. 1,b), there are no
significant intermolecular interactions. The C(14) atom, however is involved in a weak
3
)
Altenbach and co-workers have also isolated a similar intermediate during the reaction of 5,6-
dibromocyclohex-2-en-1,4-diol diacetate with AcONa/AcOH, however with a different configura-
tion, see [13].

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Helvetica Chimica Acta – Vol. 90 (2007)
H-bond with Br(2) of a vicinal host molecule (C(14) ··· Br(2)a ¼ 3.774(5) Š, C(14)ÀH
··· Br(2)a ¼ 1658, a ¼À 1 þ x,y,z). These H-bonded chains propagate along the a-axis.
Molecules are stacked along the a-axis and distances between adjacent successive
molecules are 5.318(3) Š.
Compound 13 crystallized in the triclinic form, with two molecules per unit cell
(Fig. 2,b). The cyclohexene ring is in a ꢁtwist chairꢂ configuration like 12b with the
puckering parameters Q ¼ 0.447(2) Š, q ¼ 132.6(3)8, and f ¼ 49.0(4)8. The four AcO
moieties are trans-positioned to each other along the carbocyclic cyclohexene ring. The
crystal structure is stabilized through intermolecular H-bonding, involving the vicinal
host acetate O- and C-atoms. Two acetate moieties are joined by two C(20) ··· O(8)
(C(20)ÀH ··· O(8)a ¼ 3.538(3) Š, C(20)ÀH ··· O(8)a ¼ 1748, a ¼ 1 À x,2 À y,1 À z) H-
bonds, which lead to the formation of a centrosymmetric dimer of the molecule in the
crystal unit cell (Fig. 2,b). The C(9) atom of the cyclohexene is also involved in
intermolecular H-bonding with another neighboring acetate O-atom along the a-axis
(C(9)ÀH ··· O(7)b ¼ 3.241(3) Š, C(9)ÀH ··· O(7) ¼ 1318, b ¼ À1 þ x,y,z)).
Conclusions. – In summary, with relatively little synthetic effort, we achieved the
synthesis of the phenyl-substituted conduritol B 8 in five steps, starting from
commercially available [1,1’-biphenyl]-2-ol. In addition, we determined a step-by-step
mechanism of the transformation 12b ! 13 with the help of intermediate 15. We
assume that 8 may have important biological activity and may be used as a precursor for
the synthesis of other cyclitol derivatives.
Experimental Part
General. TLC: 0.2 mm silica gel 60 F254 aluminium plates (Merck). Column chromatography (CC):
silica gel (60 mesh; Merck). IR Spectra: Mattson 1000 FT-IR apparatus; soln. in 0.1 mm cells or KBr
pellets; in cmÀ1. 1H- and 13C-NMR Spectra: Bruker Avance-400; at 400 (1H) and 100 MHz (13C); apparent
multiplicities are given in all cases; d in ppm, J in Hz. MS: Agilent 5975C apparatus; in m/z (rel. %).
2-Phenylbenzo-1,4-quinone (¼2-Phenylcyclohexa-2,5-diene-1,4-dione; 10) [10]. A soln. of [1,1’-
biphenyl]-2-ol (9; 10 g, 59 mmol) in AcOH (40 ml) was added dropwise within 10 min to a magnetically
stirred, heterogeneous mixture of PbO2 (35g, 147 mmol), 70% HClO 4 soln. (20 ml), and AcOH (60 ml).
The resulting mixture was stirred for 15min and filtered into a flask containing H 2O (150 ml). The filter
cake was washed with CH2Cl2 into the same flask. The black powder collected on the filter paper
consisted of unreacted PbO2. The contents of the flask were extracted with CH2Cl2. The org. extract was
washed with H2O, dried (MgSO4), and concentrated, and the residue was crystallized from MeOH: 10
(9.0 g, 84%). Deep yellow crystals. M.p. 108 – 1118. 1H-NMR (400 MHz, CDCl3/CCl4): 7.49 – 7.43 (m,
5H); 6.88 ( d, A of AB, J ¼ 10.1, 1 H); 6.87 (d, J ¼ 2.2, 1 H); 6.83 (dd, B of AB, J ¼ 10.1, 2.2, 1 H).
13C-NMR (100 MHz, CDCl3/CCl4): 187.0; 186.1; 145.8; 136.9; 136.1; 132.7; 132.6; 130.0; 129.2; 128.4.
rel-(5R,6R)-5,6-Dibromo-2-phenylcyclohex-2-ene-1,4-dione (11). To a soln. of 10 (9.0 g, 49 mmol) in
CH2Cl2 was added dropwise a soln. of Br2 (7.8 g, 49 mmol) in CH2Cl2 at À 108 during 1 h. The mixture
was stirred at À 108 for 1 h and then allowed to warm to r.t. The solvent was evaporated: 11 (15.8 g,
94%). Yellow solid. M.p. 103 – 1058 (from CHCl3). IR (CHCl3): 2934, 1673, 1592, 1348, 1254, 1227, 1162,
1016, 768, 709, 687, 638. 1H-NMR (400 MHz, CDCl3/CCl4): 7.54 – 7.45 (m, 5H); 6.78 ( d, J ¼ 1.9, 1 H); 4.93
(d, A of AB, J ¼ 2.8, 1 H); 4.87 (dd, B of AB, J ¼ 2.8, 1.9, 1 H). 13C-NMR (100 MHz, CDCl3/CCl4): 187.5;
187.1; 146.7; 132.4; 131.3; 131.0; 129.1; 128.8; 47.1; 45.1. EI-MS: 342, 344, 346 (8, 14, 7, Mþ); 262, 263, 264,
265(25, 29, 28, 27, [ M À BrÀ H]þ); 185(40); 184 (90, [ M À 2 Br]þ); 183 (100, [M À 2 BrÀ H]þ); 157 (30);
156 (75); 135 (45); 127 (35); 102 (65); 82 (55); 63 (25). Anal. calc. for C 12H8Br2O2: C 41.90, H 2.34;
found: C 41.92, H 2.42.

Helvetica Chimica Acta – Vol. 90 (2007)
2233
rel-(1R,4R,5S,6S)-5,6-Dibromo-2-phenylcyclohex-2-ene-1,4-diol (12a). To a soln. of 11 (15g,
44 mmol) in Et2O (45ml) cooled to 0 8 in an ice bath, an aq. NaBH4 soln. (4.1 g, 109 mmol) was added
dropwise at 08. After completion of the reaction (TLC monitoring), the aq. phase was extracted with
Et2O (3 Â 50 ml), the combined org. extract dried (Na2SO4), and the solvent evaporated: oily 12a (12.0 g,
80%) which was readily converted to 12b.
rel-(1R,4R,5S,6S)-5,6-Dibromo-2-phenylcyclohex-2-ene-1,4-diol Diacetate (12b). To a stirred soln. of
12a (12 g, 35.0 mmol) in pyridine (20 ml), Ac2O (11.0 g, 105mmol) was added dropwise at 0 8. The
mixture was stirred at r.t. for 8 h, then poured into conc. HCl soln. (50 ml) mixture with ice, and extracted
with Et2O (3 Â 50 ml). The combined org. extract was washed with NaHCO3 soln. and H2O and dried
(MgSO4), the solvent evaporated, and the residue subjected to CC (SiO2 (140 g), AcOEt/hexane 18 :1).
Crystallization from AcOEt/hexane 3 :1 gave 12b (11.0 g, 75%). Pure white crystals. M.p. 114 – 1168. IR
(CHCl3): 2924, 2853, 1772, 1758, 1371, 1194, 1154, 1081, 920, 850, 716. 1H-NMR (400 MHz, CDCl3/CCl4):
7.32 – 7.22 (m, 5H); 6.33 ( ddd, J ¼ 6.9, 1.9, 2.6, 1 H); 5.86 (dd, J ¼ 1.9, 2.6, 1 H); 5.80 (dt, J ¼ 7.2, 2.6, 1 H);
4.41 (dd, A of AB, J ¼ 10.8, 6.9, 1 H); 4.39 (dd, B of AB, J ¼ 10.8, 7.2, 1 H); 2.12 (s, 3 H); 1.86 (s, 3 H).
13C-NMR (100 MHz, CDCl3/CCl4): 169.3; 169.2; 140.3; 136.7; 128.5; 128.4; 126.6; 125.8; 73.7; 72.3; 52.7;
51.4; 20.7; 20.5. Anal. calc. for C16H16Br2O4: C 44.47, H 3.73; found: C 44.44, H 3.62.
rel-(1R,2S,3S,4R)-5-Phenylcyclohex-5-ene-1,2,3,4-tetrol Tetraacetate (13). A vigorously stirred
mixture of 12b (10 g, 23 mmol) in AcOH (150 ml), Ac2O (30 ml), and anh. AcOK (13.8 g, 140 mmol)
was refluxed for 3 days under N2. The solvent was evaporated, MeOH (20 ml) added to the residue, and
the mixture stirred for 10 min. The soln. was concentrated, and the residue was partitioned between Et2O
(50 ml) and H2O (75ml). The org. layer was washed with aq. NaHCO 3 soln., dried (MgSO4) and
concentrated, the solid residue subjected to CC (silica gel, AcOEt/hexane 1:9), and the product
crystallized from AcOEt/hexane 3 :1: 13 (6.0 g, 75%). Colorless crystals. M.p. 130 – 1328. IR (KBr): 2995,
1734, 1363, 1217, 1018, 964, 927, 766, 705. 1H-NMR (400 MHz, CDCl3/CCl4)1): 7.28 – 7.20 (m, 5H); 6.29
(dt, J ¼ 6.6, 2.0, 1 H); 5.83 (t, J ¼ 2.0, 1 H); 5.73 (dt, J ¼ 7.1, 2.0, 1 H); 5.47 (dd, A of AB, J ¼ 10.2, 7.1, 1 H);
5.40 (dd, B of AB, J ¼ 10.2, 6.6, 1 H); 2.09 (s, 3 H); 2.07 (s, 3 H); 2.05( s, 3 H); 1.80 (s, 3 H). 13C-NMR
(100 MHz, CDCl3/CCl4): 170.6; 170.5; 170.2; 170.1; 139.4; 136.6; 128.7; 128.6; 126.6; 125.5; 72.5; 71.9;
71.1; 71.0; 21.1; 20.9; 20.8; 20.7. EI-MS: 390 (Mþ), 270 (10), 229 (10), 228 (50), 187 (30), 186 (100), 158
(25), 157 (20). Anal. calc. for C20H22O8: C 61.53, H 5.68; found: C 61.06, H 5.68.
rel-(1R,2S,3R,4S)-3-Bromo-6-phenylcyclohex-5-ene-1,2,4-triol Triacetate (15). As described for 13,
with 12b (5g, 12 mmol), AcOH (75ml), Ac 2O (15ml), and anh. AcOK (6.9 g, 70 mmol) for 36 h.
Workup with MeOH (10 ml), Et2O (50 ml), and H2O (75ml), CC, and crystallization as described for 13
gave 15 (3.3 g, 70%). Colorless crystals. M.p. 144 – 145.58. IR (CHCl3): 2357, 1745, 1549, 1219, 1020, 926,
1
749, 704. H-NMR (400 MHz, CDCl3/CCl4)1): 7.20 – 7.35( m, 5H); 6.07 ( m, 2 H); 5 .70 (dd, J ¼ 6.3, 3.7,
1 H); 5.40 (dd, J ¼ 5.3, 2.6, 1 H); 4.40 (dd, J ¼ 6.3, 2.6, 1 H); 2.20 (s, 3 H); 2.15( s, 3 H); 1.91 (s, 3 H).
13C-NMR (100 MHz, CDCl3/CCl4): 169.3; 169.0; 168.9; 138.9; 136.6; 128.6; 128.5; 126.2; 124.7; 71.4; 71.3;
68.3; 47.2; 20.8; 20.6; 20.5. Anal. calc. for C18H19BrO6: C 52.57, H 4.66; found: C 52.94, H 4.58.
rel-(1R,2S,3S,4R)-5-Phenylcyclohex-5-ene-1,2,3,4-tetrol (8). A soln. of 13 (5.0 g, 13 mmol) in abs.
MeOH (40 ml) was stirred for 2 h at r.t. while dry NH3 was passed through the soln. Evaporation of
MeOH and formed acetamide, and crystallization from EtOH/hexane 5:1 gave 8 (2.5g, 88%). White
solid. M.p. 132 – 1358. IR (KBr): 3352, 2990, 2214, 2071, 1121, 972, 822. 1H-NMR (400 MHz, D2O): 7.33
(br. s, 5 H); 5.71 (s, 1 H); 4.70 (br. s, 4 OH, 1 H); 4.27 (d-like, J ¼ 7.0, 1 H); 3.64 (dd, A of AB, J ¼ 10.5,
7.0, 1 H); 3.52 (dd, B of AB, J ¼ 10.5, 7.5, 1 H). 13C-NMR (100 MHz, D2O): 139.6; 138.3; 128.6; 128.1;
127.8; 127.1; 75.8; 75.0; 72.3; 72.1. Anal. calc. for C12H14O4: C 64.86, H 6.35; found: C 64.46, H 6.60.
X-Ray Structure Determination. The crystal-structure determination was performed with single
crystals of 12b and 13. For data collection, a four-circle Rigaku R-AXIS RAPID-S diffractometer
equipped with a two-dimensional area IP detector was used. The cylindrically shaped imaging plate
covered the 2q angular range between À 60 and 1408 with a crystal-film distance of 127.4 mm. The
graphite-monochromatized MoKa radiation (l ¼ 0.71073 Š) and oscillation-scans technique with Dw ¼
58 for one image were used for data collection. Images were taken successfully by varying w with three
sets of different c and f values. The 107 images for three different runs covering ca. 99.8% of the Ewald
spheres were performed. The lattice parameters were determined by the least-squares methods on the
basis of all reflections with F2 > 2s(F2). Integration of the intensities, correction for Lorentz and

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Helvetica Chimica Acta – Vol. 90 (2007)
polarization effects, and cell refinement were performed by using CrystalClear (Rigaku/MSC Inc., 2005)
software [15]. The structures were solved by the direct method with SHELXS [16]. The positional and
atomic displacement parameters were refined by the full-matrix least-squares method with SHELXL
[16]. The positional and isotropic atomic displacement parameters of H-atoms were refined together
with other structural parameters by the full-matrix least-squares procedure based on the squared value of
the structure factors. H-Atom positions were calculated from assumed geometries. H-Atoms were
included in structure-factor calculations, but they were not refined. The isotropic displacement
parameters of the H-atoms were approximated from the U(eq) value of the atom that they were bonded
to. The final difference Fourier maps showed no peaks of chemical significance. The details of the data
collection and final refinement parameters are listed in Table 2.
Table 2. Crystal Data and Structure Refinement of 12b and 13
12b
13
Chemical formula
Mr
C20H22O8
390.4
C16H16O4Br2
432.1
Temperature [K]
293(2)
293(2)
Wavelength [Š]
0.71073
0.71073
Crystal system, space group
Unit cell dimensions [Š or 8, resp.]
triclinic, P-1
a ¼ 5.5527(2)
b ¼ 10.8070(4)
c ¼ 17.6672(6)
a ¼ 71.42(4)
b ¼ 96.03(5)
g ¼ 84.64(4)
992.4(2)
2
1.31
0.102
412
0.20, 0.17, 0.150.23, 0.20, 0.17
2.5– 30.7
À 7 ꢀ h ꢀ 7
À 15 ꢀ k ꢀ 15
À 25 ꢀ l ꢀ 25
54775
monoclinic, P21/c
a ¼ 5.3179(2)
b ¼ 19.3018(6)
c ¼ 16.7417(5)
b ¼ 81.38(5)
Volume [Š3]
1709.1(2)
4
1.68
4.757
856
Z
Density (calc.) [Mg/m3]
Absorption coefficient [mmÀ1
F(000)
Crystal size [mm3]
q Range for collection [8]
Index ranges
]
2.4 – 23.3
À 5 ꢀ h ꢀ 5
À 21 ꢀ k ꢀ 21
À 18 ꢀ l ꢀ 18
22413
Refl. collected
Independent refl.
Observed refl.
Parameters
Goodness-of-fit on F2
Final R indices (I > 2s(I))a)
R Indices (all data)
6051 (Rint ¼ 0.047)
5788 (I > 2s(I))
278
2451(Rint ¼ 0.054)
2354 (I > 2s(I))
239
1.351.30
R1 ¼ 0.082, wR2 ¼ 0.184
R1 ¼ 0.086, wR2 ¼ 0.187
0.256 and 0.198
R1 ¼ 0.061, wR2 ¼ 0.111
R1 ¼ 0.064, wR2 ¼ 0.112
0.566 and 0.670
À3
Largest diff. peak and hole [Š
]
n
h
i h
P
=
w F02
io1=2
À
Á2
À
Á2
P
P
P
a) R1 ¼ jjF0j À jFcjj= jF0j, wR2 ¼
w F02 À Fc2
.
CCDC-653894 (12b) and CCDC-653895 (13) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 90 (2007)
2235
REFERENCES
[1] a) M. S. Gultekin, M. Celik, M. Balci, Curr. Org. Chem. 2004, 13, 1159; b) M. Balci, Pure Appl.
Chem. 1997, 69, 97; T. Hudlicky, D. A. Entwistle, K. K. Pitzer, A. J. Thorpe, Chem. Rev. 1996, 96,
1195; c) T. Hudlicky, J. W. Reed, ꢁAdvances in Asymmetric Synthesisꢂ, JAI Press, London, 1995,
Vol. 1, pp. 271 – 312; d) T. Hudlicky, M. Cebulak, ꢁCyclitols and Their Derivatives. A Handbook of
Physical, Spectral and Synthetic Dataꢂ, VCH Publishers: New York, 1993; e) H. A. J. Carless,
Tetrahedron: Asymmetry 1992, 3, 795; f) M. Balci, Y. Sütbeyaz, H. Secen, Tetrahedron 1990, 46,
3715; g) T. Posternak, ꢁThe Cyclitolsꢂ, Holden-Day, San Fransisco, 1965.
[2] E. J. Corey, R. A. E. Winter, J. Am. Chem. Soc. 1963, 85, 2677; H. Paulsen, W. Rçben, F. R. Heiker,
Chem. Ber. 1981, 114, 3242; C. L. Drian, J.-P. Vionnet, P. Vogel, Helv. Chim. Acta 1990, 73, 161; H.
SeÅen, Y. Sütbeyaz, M. Balci, Tetrahedron Lett. 1990, 31, 132; J.-L. Reymond, P. Vogel, Tetrahedron:
Asymmetry 1990, 1, 173; H. A. Carless, K. Busia, Tetrahedron Lett. 1990, 31, 3449; D. H. R. Barton, P.
Dalko, S. D. Gero, Tetrahedron Lett. 1991, 32, 2471; O. Arjona, A. Candilejo, A. de Dios, R. de la
Pradilla Fernandez, J. Plumet, J. Org. Chem. 1992, 57, 6097; T. Akiyama, H. Shima, M. Ohnari, T.
Okazaki, S. Ozaki, Bull. Chem. Soc. Jpn. 1993, 66, 3760; O. Arjona, A. de Dios, C. Montero, J.
Plumet, Tetrahedron 1995, 51, 9191; J. E. Innes, P. J. Edwards, S. V. Ley, J. Chem. Soc., Perkin Trans. 1
1997, 795; G. Legler, M.-T. Finken, S. Felsch, Carbohydr. Res. 1996, 292, 91; S.-K. Chung, Y.-U. Kwon,
Bioorg. Med. Chem. Lett. 1999, 9, 2135; B. M. Trost, D. E. Patterson, E. J. Hembre, J. Am. Chem.
Soc. 1999, 121, 10834; C. Sanfilippo, A. Patti, G. Nicolosi, Tetrahedron: Asymmetry 1999, 10, 3273; O.
Plettenburg, A. G. Vogel, H.-J. Altenbach, Tetrahedron: Asymmetry 2000, 11, 1057.
[3] G. Legler, H. Seylers, Z. Physiol. Chem. 1970, 351, 25 .
[4] A. Hara, N. S. Radin, Biochim. Biophys. Acta 1979, 582, 412; S. C. Datta N. S. Radin, Biochem.
Biophys. Res. Commun. 1988, 152, 155; D. S. Newburg, Biochim. Biophys. Acta 1986, 877, 121.
[5] E. Beiberisch, B. Freischütz, M. Suzuki, R. K. Yu, J. Neurochem. 1999, 72, 1040.
[6] Z.-X Guo, A. H. Haines, S. M. Pyke, S. G. Pyke, R. J. K. Taylor, Carbohydr. Res. 1994, 264, 147.
[7] F. Orsini, G. Sello, S. Bernasconi, G. Fallacara, Tetrahedron Lett. 2004, 45, 9253; M. Desjardins, M.-C.
Lallemand, S. Freeman, T. Hudlicky, K. A. Abboud, J. Chem. Soc., Perkin Trans. 1 1999, 621; M.-C.
Lallemand, M. Desjardins, S. Freeman, T. Hudlicky, Tetrahedron Lett. 1997, 38, 7693.
[8] D. Boyd, D. N. Sharma, C. R. Dowd, F. Hempenstall, Chem. Commun. 2000, 2151; G. Mehta, S.
Lakshminath, Tetrahedron Lett. 2000, 41, 3509.
[9] L. Kelebekli, Y. Kara, M. Balci, Carbohydr. Res. 2005, 340, 1940; Y. Kara, M. Balci, Tetrahedron
2003, 59, 2063; G. Mehta, S. S. Ramesh, Tetrahedron Lett. 2001, 42, 1987; G. Mehta, S. S. Ramesh,
Chem. Commun. 2000, 2429; Y. Kara, M. Balci, S. A. Bourne, W. H. Watson, Tetrahedron Lett. 1994,
35, 3349.
[10] K. Omura, Synthesis 1998, 1145.
[11] M. Balci, ꢁBasic 1H- and 13C-NMR Spectroscopyꢂ, Elsevier, Amsterdam, 2005.
[12] A. H. Haines, A. S. H. King, J. R. Knight, V.-A. Nguyen, Tetrahedron Lett. 1998, 39, 4393.
[13] M. Podeschwa, O. Plettenburg, J. vom Brocke, O. Block, S. Adelt, H.-J. Altenbach, Eur. J. Org.
Chem. 2003, 1958.
[14] D. Cremer, J. A. Pople, J. Am. Chem. Soc. 1975, 97, 1354.
[15] Rigaku/MSC, Inc., 9009 New Trails Drive, The Woodlands, TX 77381.
[16] G. H. Sheldrick, SHELXS-97 and SHELXL-97, University of Gçttingen, Gçttingen, 1997.
Received July 20, 2007