Highly stereoselective and stereospecific syntheses of a variety of quercitols from d-(-)-quinic acid

Article abstract of DOI:10.1016/j.tet.2004.11.084

The highly stereoselective synthesis of (-)-epi-, (-)-allo- and neo-quercitols as well as stereospecific synthesis of (-)-talo- and (+)-gala-quercitols have been achieved. The general strategy is employing dihydroxylation of the isolated double bond of various kinds of protected chiral (1,4,5)-cyclohex-2-ene-triols, which are derived from d-(-)-quinic acid. The choosing of protecting groups from either BBA (butane 2,3-bisacetal) or acetyl groups will result in the various degrees of stereoselectivity of dihydroxylation. On the other hand, the cyclohexylidene acetal moiety is attributed to the stereospecificity during dihydroxylation to afford the request molecules.

Full text of DOI:10.1016/j.tet.2004.11.084

Tetrahedron 61 (2005) 1919–1924
Highly stereoselective and stereospecific syntheses of a variety
of quercitols from D-(K)-quinic acid
*
Tzenge-Lien Shih, Ya-Ling Lin and Wei-Shen Kuo
Department of Chemistry, Tamkang University, Tamsui 25137, Taipei County, Taiwan, ROC
Received 1 September 2004; revised 22 November 2004; accepted 29 November 2004
Available online 25 December 2004
Abstract—The highly stereoselective synthesis of (K)-epi-, (K)-allo- and neo-quercitols as well as stereospecific synthesis of (K)-talo-
and (C)-gala-quercitols have been achieved. The general strategy is employing dihydroxylation of the isolated double bond of various kinds
of protected chiral (1,4,5)-cyclohex-2-ene-triols, which are derived from D-(K)-quinic acid. The choosing of protecting groups from either
BBA (butane 2,3-bisacetal) or acetyl groups will result in the various degrees of stereoselectivity of dihydroxylation. On the other hand, the
cyclohexylidene acetal moiety is attributed to the stereospecificity during dihydroxylation to afford the request molecules.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Quercitol, which is a generic term for cyclohexanepentol or
deoxyinositol, has 16 stereoisomers in its family.1 Among
these isomers, there were only (C)-proto-, (K)-proto- and
(K)-vibo-quercitols to be found in nature.2 Due to their
biological activities against glycosidases, their syntheses
have been attracting a great deal of interest to the synthetic
community.3 At present, ten possible diasteroisomers,
proto-,4,5,6 allo-,7,8 talo-,1,2,8,9,10 epi-,1,11 vibo-,12,13,14
gala-,4c,15,16,17 scyllo-,12,18 neo-,1 cis-19 and muco-querci-
tols,20 have been synthesized from different approaches to
provide their either racemic or chiral forms. Recently, we
have reported a facile synthesis of (C)-proto-quercitol
through an important intermediate, (1R,4R,5R)-triacetoxy-
cyclohex-2-ene, which was derived from D-(K)-quinic
acid.21 During this course, one key step was employing
this intermediate to be dihydroxylated stereospecifically
with KMnO4/MgSO4 condition resulting in moderate yield.
This success prompted us that a variety of quercitols might
be efficiently synthesized from dihydroxylation of different
kinds of protecting chiral (1,4,5)-cyclohex-2-ene-triol
analogues. Throughout dihydroxylation, we have found
that the protecting groups could affect the outcomes in either
stereoselective or stereospecific manners by analysis the
resulting quercitols.
Our synthesis is depicted in Scheme 1 and the results are
summarized in Table 1. Compounds 1a,21 3a21 and 5a22
were acetylated to afford 2a, 4a and 6a, respectively. While
1a and 2a were individually dihydroxylated under KMnO4/
MgSO4 condition,2,4b,4d the oxidation step gave one product
in each case with moderate yield. The resulting stereo-
chemistry of 1b and 2b was not determined at this stage.
However, the same quercitol 1c was obtained from either 1b
or 2b until the removal of their protecting group(s). The
spectroscopic data of the resulting quercitol 1c, (K)-talo-
quercitol, are in accordance with that of (C)-talo-
quercitol10 except the sign of optical rotation. Based on
this result, it was obvious that the oxidation proceeded
stereospecifically at the same side with the hydroxyl and
acetoxy groups but anti relationship to the cyclohexylidene
acetal group in both cases. Consequently, the same
procedure was also employed on compounds 3a and 4a.
Not surprisingly, the (C)-gala-quercitol23 (3c) was
received as the sole product. The oxidation happened
preferably to the face that was opposite to the stereo-
chemistry of C1 as well as the cyclohexylidene acetal
protection of C4 and C5. The stereospecific reactions that
occurred in 1a–4a might be explained by the steric effect.
The different quercitols will be received if permanganate
ion is approaching to the same face with the pseudoaxial
oxygen at C4, but that causes the destabilization (Fig. 1).
Thus, this factor mainly controlled the stereochemical
outcome of dihydroxylation no matter the stereochemistry
of C1 with or without protection by acetyl group. Therefore,
dihydroxylation occurred at the anti relationship to the
Keywords: Quercitol; D-(K)-Quinic acid; Dihydroxylation; Glycosidase.
* Corresponding author. Tel./fax: C886 2 86315024;
e-mail: tlshih@mail.tku.edu.tw
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.11.084

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T.-L. Shih et al. / Tetrahedron 61 (2005) 1919–1924
Scheme 1. Reagents and conditions: (a) 1.2 equiv Ac2O, pyridine; (b) 1.5 equiv KMnO4, 1.5 equiv MgSO4, EtOH, H2O, rt; (c) (i) 80% TFA (for 1b, 3b, 5b, 5c,
6b and 6c), (ii) 80% TFA then 7 N NH3/MeOH (for 2b and 4b); (d) excess Ac2O, pyridine; (e) 7 N NH3/MeOH.
Table 1. Dihydroxylation of 1a, 2a, 3a, 4a, 5a and 6a
Compound
Yielda
Quercitol
[a]D, mp 8C (literature)
Quercitol
pentaacetate
[a]D, mp 8C (literature)
1a/2a
3a/4a
5a/6a
51/63
48/88
57/55
1c
3c
5f
K64.4, 238–248 (C61, 248)b
C50, 220–230 (K48, 258)c
K3.3, 180–182 (K5, 194)d
191–192 (182)e
1d
3d
5d
5e
K25.4, 184–187 (C28, 183)b
C22, an oil (K24, 117)c
K14.5, an oil (not avilable)
237–242 (239)e
5g
a Yield of dihydroxylation: KMnO4, MgSO4, EtOH, H2O, rt.
b Ref. 1 for (C)-talo-quercitol and its pentaacetate.
c Ref. 1 for (K)-gala-quercitol and its pentaacetate.
d Ref. 1 for (K)-epi-quercitol and its pentaacetate.
e Ref. 1 for neo-quercitol and its pentaacetate.

T.-L. Shih et al. / Tetrahedron 61 (2005) 1919–1924
1921
sterically hindered face to give the neo-quercitol (5g) as
the main product.
In order to understand where the different kinds of
protecting groups affected the outcomes during dihydroxyl-
ation, we decided to prepare the triacetates of 7a, 8a and 9a
(Scheme 2). It was noteworthy that racemate 8a has been
used in the synthesis of (G)-gala-quercitol,4c but no study
has been shown whereas 7a and 9a were conducted under
dihydroxylation. We have experienced that moderate yields
were obtained from dihydroxylation in KMnO4/MgSO4
condition in Scheme 1. In order to compare their results, the
alternative oxidation using RuCl3$3H2O/NaIO4/H2SO4
condition24 allowed us to receive the better yields as
summarized in Table 2. However, we have found that either
stereoselectivity or stereospecificity of 7a and 9a decreased
dramatically in dihydroxylation except 8a which gave the
(C)-gala-quercitol (3c) only. The distinction between
Scheme 1 and 2 were attributed to both the cyclohexylidene
acetal and BBA protecting groups that restricted the more
rigid conformations than those of acetyl group upon
different chiral (1,4,5)-cyclohex-2-ene-triols. Thus, it is
not surprising that the more flexible conformations of 7a
and 9a gave all less stereoselectivity in dihydroxylation.
When compound 7a was dihydroxylated, an inseparable
mixture 7b and 7c was obtained. Their separation could be
easier after they were acetylated to afford 1d and 7d in 39
and 35% yields, respectively. Compound 7d was sub-
sequently deacetylated to give the (K)-allo-quercitol (7e).25
Therefore, the (K)-talo- (1d) and (K)-allo-quercitol penta-
acetates (7d) were received in almost 1:1 ratio with a 74%
combined yield. This observation was distinct from the
results of 1a and 2a in which the (K)-talo-quercitol (1c)
was the only isolated product (Scheme 1). These opposite
results were due to the pseudoequatorial acetyl groups at C1
and C4 of 7a to contribute equally in stereoselectivity upon
dihydroxylation. The (C)-gala-quercitol 3c obtained from
8a was the same result that appeared in 3a, 4a and in Balci’s
report.4c While compound 9a was dihydroxylated and
followed by acetylation, the resulting (K)-epi- (5d) and
neo-quercitol pentaacetates (5e) were with a 1:1.4 ratio
Figure 1. Rationalization of stereospecific dihydroxylation of compounds
1a and 2a.
cyclohexylidene acetal moiety and gave the stereospecific
oxidation in 1a, 2a, 3a and 4a. However, we could not
eliminate the possibility with respect to the hydroxyl group
orienting the dihydroxylation with the assistance of
hydrogen bonding in 3a, but the steric effect deriving
from the cyclohexylidene group was somewhat a more
determining factor. The above examples were the same as
those of Bacli’s reports in the syntheses of (G)-talo-2 and
(G)-gala-quercitols4c even though a different protecting
group was chosen in our case.
Consequently, compound 5a22 was dihydroxylated to give
an inseparable mixture of 5b and 5c. Thereafter, they were
subjected to acetylation and gave the separable compounds
5d and 5e with a ratio of 7.2:1 in 87% total yield.
Conversely, compound 5e was isolated as the dominant
product when 6a was dihydroxylated to afford 76% total
yield of 5d and 5e with a ratio of 1:6.5. Our explanation to
these opposite results is indicated in Figure 2. In compounds
5a and 6a, the stereo arrangements of BBA group were
located at pseudoequatorial positions to accommodate a
stable chair form. Therefore, it allowed a less sterically
crowded environment than those of previous cases thus
contributing equal stereoselectivity to both faces during
dihydroxylation. Based on AM1 calculation, the effective
distance of ideal intermolecular hydrogen bonding between
C1 hydroxyl group with one of closest permanganate’s
˚
oxygen is 2.17213 A (Fig. 2a) which is shorter than
˚
2.54892 A in case of permanganate ion approaching from
the opposite site (Fig. 2b). From this point of view, the
influence of hydroxyl directing the dihydroxylation through
intermolecular hydrogen bonding became the more impor-
tant factor in 5a. Consequently, the (K)-epi-quercitol (5f)
was isolated as a major product. On the other hand, the
hydroxyl directing effect diminished in 6a and the
permanganate ion was allowed to approach the less
1
based on H NMR integration. Although the neo-quercitol
5g was slightly dominant in this reaction, however, its
stereoselectivity was still far less to that of case of 6a. The
low stereoselectivity was defined the same reason as
mentioned in 7a.
Figure 2. The AM1 calculation of the ideal distance of intermolecular hydrogen bonding in stereoselective dihydroxylation of compound 5a.

1922
T.-L. Shih et al. / Tetrahedron 61 (2005) 1919–1924
Scheme 2. Reagents and conditions: (a) Method A: 1.5 equiv KMnO4, 1.5 equiv MgSO4, EtOH, H2O, rt; (b) Method B: RuCl3$3H2O, NaIO4, H2SO4, EtOAc,
CH3CN, 0 8C; (c) 5 equiv Ac2O, pyridine; (d) 7 N NH3/MeOH.
3. Conclusion
cyclohexylidene acetal moiety was used as a protecting
group in 1a and 2a in which the (K)-talo-quercitol was the
only isolated product. To the contrary, (K)-talo- and (K)-
allo-quercitols were received with almost equal amounts in
7a while acetyl groups served as a protecting group. In
compounds 5a and 6a, the BBA group presented no
influence in stereospecificity but their stereoselectivity
was controlled by the directing effect of hydroxyl group.
Although their degrees of stereoselectivity were moderate,
We have successfully synthesized the (K)-talo-, (K)-epi-,
(C)-gala-, (K)-allo- and neo-quercitols from D-(K)-quinic
acid with an expedient method. We have learned that the
stereoselectivity and stereospecificity of dihydroxylation
can be manipulated by choosing the appropriate protecting
groups to the analogues of chiral (1,4,5)-cyclohex-2-ene-
triols. The stereospecific reaction occurred while
Table 2. Dihydroxylation of (1,4,5)-triacetoxy-cyclohex-2-enes 7a, 8a and 9a
Compound
Yielda/yieldb
Quercitol pentaacetate (yield)c [a]D, mp 8C (literature)
Quercitol
(yield)
[a]D, mp 8C (literature)
7a
67/73
1d (39%)
7d (35%)
3d (67%)
5d/5e (64%) (1:1.4)e
1c (90%)
7e (92%)
3c (87%)
5f/5gf (89%)
K15, 103–110 (C11.6, 114)d
K23, 237–258 (C23.3, O200)d
8a
9a
41/76
65/77
a Yield of dihydroxylation; Method A: KMnO4, MgSO4, EtOH, H2O, rt.
b Yield of dihydroxylation; Method B: RuCl3$3H2O, NaIO4, H2SO4, EtOAc/CH3CN (v/vZ1/1).
c From Method A.
d Ref. 8 for (C)-allo-quercitol and its pentaacetate.
e The ratio of 5d versus 5e was based on the 1H NMR integration.
The combined yield of 5f and 5g were derived from the deacetylation of a mixture of 5d and 5e.
f

T.-L. Shih et al. / Tetrahedron 61 (2005) 1919–1924
1923
however, they were still superior to the results observed in
9a in which the stereoselectivity dropped tremendously
while the acetyl group was used as a protecting group.
(br s, 1H), 5.52 (dd, JZ6.3, 3.3 Hz, 1H), 5.31 (dd, JZ10.6,
2.8 Hz, 1H), 5.23 (ddd, JZ11.3, 5.1, 2.8 Hz, 1H), 5.20 (dd,
JZ10.6, 3.3 Hz, 1H), 1.90–2.2 (mC5!CH3CO, 17H). 13
C
NMR (75.4 MHz, CDCl3): d 170.1, 170.0, 169.9, 169.6,
69.6, 69.0, 67.7, 66.8, 66.1, 28.9, 20.9, 20.7, 20.6, 20.5.
HRMS (FAB) calcd for C16H23O10 (MCCH) 375.1291.
Found 375.1289.
4. Experimental
Melting points were recorded on a polarized optical
microscopy and equipped with Mettler Toledo FP82HT
hot stage and Mettler Toledo FP90 central processor.
4.1.5. (C)-gala-Quercitol [(C)-2-deoxy-allo-inositol]
(3c).17b Recrystallization from MeOH and hexane provided
a white solid, 91% yield. [a]2D5ZC50 (c 0.6, H2O); lit.16
1
The H and 13C NMR spectra were recorded on Bruker
1
AC-300 MHz. For H and 13C NMR spectra, the internal
standards were referenced to d 7.26 and 77.0 ppm,
respectively, for CDCl3. While deuterium oxide was used,
1
C50, H2O. Mp 220–230 8C; lit.16 254–255 8C. H NMR
(300 MHz, D2O): d 3.87–3.97 (m, 2H), 3.82 (t, JZ3.3 Hz,
1H), 3.70 (ddd, JZ11.2, 9.0, 4.5 Hz, 1H), 3.58 (dd, JZ9.0,
3.3 Hz, 1H), 1.90 (dt, JZ11.6, 4.5 Hz, 1H), 1.62 (dt, JZ
11.6, 11.2 Hz, 1H). 13C NMR (75.4 MHz, D2OCCD3OD):
d 73.1, 72.9, 72.6, 68.8, 67.3, 34.4. HRMS (FAB) calcd for
C6H13O5 (MCCH) 165.0763. Found 165.0758.
1
the internal standard was referenced to 4.69 ppm for H
NMR and CD3OD at 49.0 ppm for 13C NMR. The optical
rotations were measured on a Horiba Sepa-300 spectro-
meter. Purification was employed by flash column chroma-
tography using silica gel (230–400 mesh). The purified solid
was dissolved in methanol and hexane was added to force
the recrystallization occurred.
4.1.6. (C)-gala-Quercitol pentaacetate [(C)-penta-O-
acetyl-2-deoxy-allo-inositol] (3d).4c Purification by flash
column chromatography in gradient (CH2Cl2/hexaneZ1/2–
2/1) afforded a pale yellow oil, 92% yield. [a]2D4ZC22
(c 0.5, CHCl3); lit.1 K24, CHCl3 for (K)-gala-quercitol
4.1. General procedures of dihydroxylation
1
4.1.1. KMnO4/MgSO4/EtOH condition. All of the reac-
tions were conducted in 0.1–0.2 M. To 1a, for example, in
ethyl alcohol solution at 0 8C was added slowly a mixture of
KMnO4 (1.5 equiv) and MgSO4 (1.5 equiv) in distilled
water. The reaction was completed within 3–4 h. The
resulting mixture was filtrated through celite and the solid
was washed with EtOAc and hot water several times.
The organic layer was separated, dried with MgSO4 and
concentrated. The resulting mixture was purified by flash
column chromatography.
pentaacetate. H NMR (300 MHz, CDCl3): d 5.38 (dd, JZ
5.3, 3.4 Hz, 1H), 5.20–5.30 (m, 3H), 5.11 (ddd, JZ13.4,
8.8, 4.6 Hz, 1H), 2.15–2.25 (m, 1H), 2.09 (s, 3H), 2.08 (s,
3H), 1.97–2.06 (mC3!CH3, 10H). 13C NMR (75.4 MHz,
CDCl3): d 169.8, 169.4 (!2), 69.8, 68.2, 67.7, 66.7, 29.1,
20.9, 20.8, 20.7. HRMS (FAB) calcd for C16H23O10 (MCC
H) 375.1291. Found 375.1296.
4.1.7. (K)-epi-Quercitol [(K)-2-deoxy-epi-inositol]
(5f).10a Recrystallization from MeOH and hexane gave a
white solid, 91% yield. [a]2D5ZK3.3 (c 0.3, H2O); lit.1 K5,
1
4.1.2. RuCl3$3H2O/NaIO4/H2SO4 condition. All of the
reactions were conducted in 0.1–0.2 M. To an aqueous
solution of NaIO4 at 0 8C was added a catalytic amount of
concentrated H2SO4 and RuCl3$3H2O (5 mol%). To this
mixture was slowly added 7a, for example, in EtOAc/
CH3CN (v/vZ1/1). The reaction was completed within
10 min and quenched with Na2S2O3 (saturated). The
aqueous layer was extracted with EtOAc. The organic
layer was separated, dried (MgSO4) and concentrated. The
resulting mixture was purified by flash column
chromatography.
H2O. Mp 180–182 8C; lit.1 194 8C. H NMR (300 MHz,
D2O): d 3.88 (dd, JZ2.9, 1.4 Hz, 1H), 3.60–3.75 (m, 1H),
3.35–3.40 (m, 2H), 3.31 (dd, JZ10.2, 2.9 Hz, 1H), 1.82–
1.92 (m, 1H), 1.64 (dt, JZ11.8, 5.9 Hz, 1H). 13C NMR
(75.4 MHz, D2OCCD3OD): d 75.2, 73.8, 72.7, 70.2, 67.4,
34.8.
4.1.8. (K)-epi-Quercitol pentaacetate [(K)-penta-O-
acetyl-2-deoxy-epi-inositol] (5d). Purification by flash
column chromatography (hexane/EtOAcZ5/1) afforded a
pale yellow oil, 90% yield. [a]2D6ZK14.5 (c 1.1, CHCl3).
1H NMR (300 MHz, CDCl3): d 5.50–5.60 (m, 1H), 5.40 (t,
JZ10.2 Hz, 1H), 4.85–5.10 (m, 3H), 2.20–2.30 (m, 1H),
2.18 (s, 3H), 2.14 (dd, JZ7.7, 6.7 Hz, 1H), 2.04 (s, 3H),
2.02 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H). 13C NMR
(75.4 MHz, CDCl3): d 170.1, 169.9, 169.8, 169.6, 169.5,
70.7, 69.3, 69.2, 68.7, 66.0, 29.4, 20.8, 20.7, 20.6, 20.5.
HRMS (FAB) calcd for C16H23O10 (MCCH) 375.1291.
Found 375.1291.
4.1.3. (K)-talo-Quercitol [(K)-1-deoxy-neo-inositol]
(1c).2 Recrystallization from MeOH and hexane afforded
a white solid, 87% yield. [a]2D4ZK64.6 (c 0.5, H2O); lit.1
C61, H2O for (C)-talo-quercitol. Mp 238–248 8C; lit.1
1
248 8C. H NMR (300 MHz, D2O): d 3.82–4.05 (m, 3H),
3.52–3.57 (br s, 2H), 1.78 (dd, JZ10.0, 3.2 Hz, 2H). 13C
NMR (75.4 MHz, D2OCCD3OD): d 73.7, 71.4, 70.8, 68.8,
66.8, 33.2. HRMS (FAB) calcd for C6H13O5 (MCCH)
165.0763. Found 165.0754.
4.1.9. neo-Quercitol pentaacetate [penta-O-acetyl-2-
deoxy-neo-inositol] (5e). Purification by flash column
chromatography (hexane/EtOAcZ4/1) gave a white solid,
93% yield. Mp 191–192 8C; lit.1 182 8C. 1H NMR
(300 MHz, CDCl3): d 5.59 (t, JZ2.9 Hz, 1H), 5.24 (ddd,
JZ11.5, 10.2, 5.1 Hz, 2H), 5.03 (dd, JZ10.2, 2.9 Hz, 2H),
2.52 (dt, JZ12.5, 5.1 Hz, 1H), 2.15 (s, 3H), 2.02 (s, 6H),
1.99 (s, 6H), 1.53 (dd, JZ12.5, 11.5 Hz, 1H). 13C NMR
4.1.4. (K)-talo-Quercitol pentaacetate [(K)-penta-O-
acetyl-1-deoxy-neo-inositol] (1d).2 Purification by flash
column chromatography (hexane/EtOAcZ5/1) afforded a
white solid, 87% yield. [a]2D4ZK25.4 (c 0.3, CHCl3); lit.1
C28, CHCl3 for (C)-talo-quercitol pentaacetate. Mp 184–
1
187 8C; lit.1 183 8C. H NMR (300 MHz, CDCl3): d 5.62

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T.-L. Shih et al. / Tetrahedron 61 (2005) 1919–1924
J. Org. Chem. 1968, 33, 4220–4227. (b) Le Drian, C.; Vogel,
P. Helv. Chim. Acta 1988, 71, 1399–1405. (c) Hudlicky, T.;
Thorpe, A. J. Synlett 1994, 899–901. (d) Gu¨ltekin, M. S.;
Celik, M.; Turkut, E.; Tanyeli, C.; Balci, M. Tetrahedron:
Asymmetry 2004, 15, 453–456.
(75.4 MHz, CDCl3): d 169.8, 169.7, 70.8, 68.9, 67.2, 31.6,
20.8, 20.7, 20.5. HRMS (FAB) calcd for C16H23O10 (MCC
H) 375.1291. Found 375.1295.
4.1.10. neo-Quercitol [2-deoxy-neo-inositol] (5g). Recrys-
tallization from MeOH and hexane gave a white solid, 89%
6. For representative syntheses of (K)-proto-quercitol, see
Ref. 5a and 5d.
1
yield. Mp 237–242 8C; lit.1 239 8C. H NMR (300 MHz,
D2O): d 3.94 (t, JZ2.8 Hz, 1H), 3.69 (ddd, JZ14.4, 11.5,
4.8 Hz, 2H), 3.35 (dd, JZ9.7, 2.8 Hz, 2H), 2.08 (dt, JZ
12.3, 4.8 Hz, 1H), 1.22 (dd, JZ12.3, 11.9 Hz, 1H). 13C
NMR (75.4 MHz, D2OCCD3OD): d 75.2 (!2), 73.6, 68.4
(!2), 37.7. HRMS (FAB) calcd for C6H13O5 (MCCH)
165.0763. Found 165.0768.
7. For representative synthesis of (G)-allo-quercitol, see:
Shoolery, J. N.; Johnson, L. F.; Furuta, S.; McCasland, G. E.
J. Am. Chem. Soc. 1961, 83, 4243–4248.
8. For representative synthesis of (C)-allo-quercitol, see: Yadav,
J. S.; Maiti, A.; Sankar, A. R.; Kunwar, A. C. J. Org. Chem.
2001, 66, 8370–8378.
9. For representative synthesis of (G)-talo-quercitol, see Ref. 2.
10. For representative syntheses of (C)-talo-quercitol, see:
(a) McCasland, G. E.; Furuta, S.; Bartuska, V. J. Org. Chem.
1963, 28, 2096–2101. (b) Angelaud, R.; Babot, O.; Charvat,
T.; Landais, Y. J. Org. Chem. 1999, 64, 9613–9624 and Refs. 1
and 8.
4.1.11. (K)-allo-Quercitol pentaacetate [(K)-penta-O-
acetyl-5-deoxy-allo-inositol] (7d).8 Purification by flash
column chromatography in gradient (EtOAc/hexaneZ
1/10–1/4) gave a white solid, 35% yield. [a]2D4ZK15
(c 0.5, CHCl3); lit.8 C11.6, CHCl3 for (C)-allo-quercitol
pentaacetate. Mp 103–110 8C; lit.8 114 8C. 1H NMR
(300 MHz, CDCl3): d 5.38 (t, JZ3.4 Hz, 1H), 5.22–5.32
(m, 3H), 5.10 (dd, JZ7.0, 3.5 Hz, 1H), 2.27 (ddd, JZ14.4,
7.6, 4.0 Hz, 1H), 1.97–2.15 (m, 15H), 1.75–1.89 (m, 1H).
13C NMR (75.4 MHz, CDCl3): d 169.8, 169.6, 169.5, 69.0,
68.3, 67.9, 67.2, 66.7, 28.6, 20.9, 20.8, 20.6.
11. For representative syntheses of (C)-epi-quercitol, see:
(a) Dubreuil, D.; Cleophax, J.; de Almeida, M. V.; Verre-
´
Sebrie, C.; Liaigre, J.; Vass, G.; Gero, S. D. Tetrahedron 1997,
53, 16747–16766. (b) Ogawa, S.; Uetsuki, S.; Tezuka, Y.;
Morikawa, T.; Takahashi, A.; Sato, K. Bioorg. Med. Chem.
Lett. 1999, 9, 1493–1498.
12. For representative syntheses of (G)-vibo-quercitol, see:
McCasland, G. E.; Horswill, E. C. J. Am. Chem. Soc. 1953,
75, 4020–4026 and Refs. 2 and 4c.
4.1.12. (K)-allo-Quercitol [(K)-5-deoxy-allo-inositol]
(7e).8 Recrystalization from MeOH and hexane gave a
white solid, 96% yield. [a]2D4ZK23 (c 0.4, H2O); lit.8
C23.3, H2O for (C)-allo-quercitol. Mp 237–258 8C; lit.8
13. For representative synthesis of (C)-vibo-quercitol, see:
Posternak, T. Helv. Chim. Acta 1950, 33, 1594–1597.
14. For representative syntheses of (K)-vibo-quercitol, see:
Ogawa, S.; Ohishi, Y.; Asada, M.; Tomoda, A.; Takahashi,
A.; Ooki, Y.; Mori, M.; Itoh, M.; Korenaga, T. Org. Biomol.
Chem. 2004, 2, 884–889 and Refs. 5b and 10b.
1
262 8C. H NMR (300 MHz, D2O): d 3.93 (ddd, JZ13.5,
4.2, 2.5 Hz, 3H), 3.69 (t, JZ4.2 Hz, 1H), 3.45 (dd, JZ8.1,
3.1 Hz, 1H), 2.02 (ddd, JZ14.1, 6.0, 4.6 Hz, 1H), 1.49 (ddd,
JZ14.1, 9.4, 3.2 Hz, 1H). 13C NMR (75.4 MHz, D2OC
CD3OD): d 74.7, 73.3, 71.5, 70.4, 67.3, 34.5.
15. For representative synthesis of (G)-gala-quercitol, see: Baran,
A.; Secen, H.; Balci, M. Synthesis 2003, 1500–1502.
16. For representative synthesis of (C)-gala-quercitol, see:
Angyal, S. J.; Odier, L. Carbohydr. Res. 1982, 101, 209–219.
17. For representative syntheses of (K)-gala-quercitol, see:
(a) Angelaud, R.; Landais, Y. J. Org. Chem. 1996, 61,
5202–5203. (b) Maezaki, N.; Nagahashi, N.; Yoshigami, R.;
Iwata, C.; Tanaka, T. Tetrahedron Lett. 1999, 40, 3781–3784
and Refs. 1, 9b and 10a.
Acknowledgements
This work was financially supported from the National
Science Council (NSC92-2113-M-032-004) and Tamkang
University.
18. McCasland, G. E.; Naumann, M. O.; Durham, L. J. J. Org.
Chem. 1969, 34, 1382–1385.
References and notes
19. McCasland, G. E.; Furuta, S.; Furst, A. J. Org. Chem. 1964,
29, 724–727.
1. McCasland, G. E.; Furuta, S.; Johnson, L. F.; Shoolery, J. N.
J. Am. Chem. Soc. 1961, 83, 2335–2343.
20. Kim, K. S.; Park, J. I.; Moon, H. K.; Yi, H. Chem. Commun.
1998, 1945–1946.
2. Maras, A.; Secen, H.; Su¨tbeyaz, Y.; Balci, M. J. Org. Chem.
1998, 63, 2039–2041 and references cited therein.
21. Shih, T.-L.; Kuo, W.-S.; Lin, Y.-L. Tetrahedron Lett. 2004, 45,
5751–5754.
3. Hudlicky, T.; Cebulak, M. Cyclitols and their Derivatives;
VCH: New York, 1993.
22. Kee, A.; O’Brien, P.; Pilgram, C. D.; Watson, S. T. Chem.
Commun. 2000, 1521–1522.
4. For representative syntheses of (G)-proto-quercitol, see:
(a) Cambie, R. C.; Renner, N. D.; Rutledge, P. S.; Woodgate,
P. D. Aust. J. Chem. 1990, 43, 1597–1602. (b) Secen, H.;
Salamci, E.; Su¨tbeyaz, Y.; Balci, M. Synlett 1993, 609–610.
(c) Salamci, E.; Secen, H.; Su¨tbeyaz, Y.; Balci, M. J. Org.
Chem. 1997, 62, 2453–2457. (d) Gu¨ltekin, M. S.; Salamci, E.;
Balci, M. Carbohydr. Res. 2003, 338, 1615–1619.
23. The spectroscopic data are in agreement with the reported
values of Refs. 16 and 17.
24. (a) Shing, T. K. M.; Tam, E. K. W. J. Org. Chem. 1998, 63,
1547–1554. (b) Plietker, B.; Niggemann, M.; Pollrich, A. Org.
Biomol. Chem. 2004, 2, 1116–1124. (c) Plietker, B.;
Niggemann, M. Org. Biomol. Chem. 2004, 2, 2403–2407.
25. The spectroscopic data are referenced to the (C)-allo-
quercitol, see Ref. 8.
5. For representative syntheses of (C)-proto-quercitol, see:
(a) McCasland, G. E.; Naumann, M. O.; Durham, L. J.