Facile syntheses of all possible diastereomers of conduritol and various derivatives of inositol stereoisomers in high enantiopurity from myo-inositol

Article abstract of DOI:10.1021/jo016237a

Phosphoinositide-based signaling processes are crucially important in intracellular signal transduction events. Inositol phosphate analogues have been useful in probing the structure-activity relationships between inositol phosphates and biomacromolecules, and in studying biological functions of newly found inositol phosphates. Thus, a systematic and ready access to inositol stereoisomers is highly desirable. And practical and convenient syntheses of conduritols and related compounds are also important because of their biological activities and their synthetic utilities in the preparation of other bioactive molecules. We herein report the first syntheses of all possible diastereomers of conduritol and various derivatives of eight inositol stereoisomers in high enantiopurity from myo-inositol, which involve efficient enzymatic resolution of the intermediates conduritol B and C derivatives, followed by oxidation-reduction or the Mitsunobu reaction, and cis-dihydroxylation in stereo- and regioselective manners.

Full text of DOI:10.1021/jo016237a

J . Org. Chem. 2002, 67, 3327-3338
3327
F a cile Syn th eses of All P ossible Dia ster eom er s of Con d u r itol a n d
Va r iou s Der iva tives of In ositol Ster eoisom er s in High
En a n tiop u r ity fr om m yo-In ositol
Yong-Uk Kwon, Changgook Lee, and Sung-Kee Chung*
Department of Chemistry, Division of Molecular and Life Sciences,
Pohang University of Science & Technology, Pohang 790-784, South Korea
skchung@postech.ac.kr
Received October 25, 2001
Phosphoinositide-based signaling processes are crucially important in intracellular signal trans-
duction events. Inositol phosphate analogues have been useful in probing the structure-activity
relationships between inositol phosphates and biomacromolecules, and in studying biological
functions of newly found inositol phosphates. Thus, a systematic and ready access to inositol
stereoisomers is highly desirable. And practical and convenient syntheses of conduritols and related
compounds are also important because of their biological activities and their synthetic utilities in
the preparation of other bioactive molecules. We herein report the first syntheses of all possible
diastereomers of conduritol and various derivatives of eight inositol stereoisomers in high
enantiopurity from myo-inositol, which involve efficient enzymatic resolution of the intermediates
conduritol B and C derivatives, followed by oxidation-reduction or the Mitsunobu reaction, and
cis-dihydroxylation in stereo- and regioselective manners.
In tr od u ction
Various inositol phosphate derivatives, including D-
myo-inositol 1,4,5-trisphosphate [D-I(1,4,5)P3] and D-myo-
inositol 1,3,4,5-tetrakisphosphate [D-I(1,3,4,5)P4], and
phospholipids play pivotal roles in intracellular signal
transduction events.1 Although the scope of the phos-
phoinositide-based signaling processes is continually
widening, clear understanding of the molecular mecha-
nisms is still lacking. Thus, many research efforts are
now being directed toward the structure-activity rela-
tionship (SAR) between inositol phosphates and bio-
macromolecules, which utilizes various regio- and stereo-
isomers of inositol phosphates (IPn).2 There exist nine
stereoisomers of inositol: myo, scyllo, cis, D-chiro-(+),
L-chiro-(-), epi, allo, muco, and neo (Figure 1). Five
stereoisomers (myo, scyllo, D-chiro, L-chiro, and neo) have
been found in nature, and the other four stereoisomers
(cis, epi, allo, and muco) are unnatural synthetic prod-
F igu r e 1. Nine stereoisomeric inositols.
ucts.
cis-Inositol, with three syn-axial hydroxyl groups in
either of its chair conformations, readily forms strong
complexes with metal cations and with oxyacid anions.3
scyllo-Inositol with all equatorial hydroxyl groups has
been found in animals and plants,4 and it has been
suggested that certain human diseases are associated
with scyllo-inositol depletion.5 All inositol stereoisomers
have been synthesized in varying efficiencies from halo-
* To whom correspondence should be addressed. Phone: +82-54-
279-2103. Fax: +82-54-279-3399.
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10.1021/jo016237a CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/20/2002

3328 J . Org. Chem., Vol. 67, No. 10, 2002
Kwon et al.
benzenes,6 benzene,7 hexahydroxybenzene,8 tetrahydroxy-
quinone,9 sugars,10 inositols,11 and others.12 Yet few
reports on general and systematic approaches to all
inositol stereoisomers have been made.10a,c
Conduritols and their derivatives possess interesting
biological properties; for example, conduritol epoxides and
aminoconduritols act as inhibitors of glycosidases,13 cyclo-
phellitols have proven to be potent inhibitors of human
immunodeficiency virus (HIV) and glycosidases,14 and
conduritol A analogues modulate the release of insulin
from isolated pancreatic islets in the presence of varying
concentrations of glucose.15 A number of conduritol
derivatives have also been found to possess antibiotic,
antileukemic, and growth-regulating activities.16 In ad-
dition, conduritols have been widely used as intermedi-
ates in the chemical syntheses of inositols,6 quercitols,17
deoxyinositols,18 aminoconduritols,16,19 conduritol ep-
oxides,16 cyclophellitol,20 pseudosugars,21 amino sugar
analogues,22 sugar amino acid analogues, etc. As pointed
out in recent reviews,16 however, a number of difficulties
F igu r e 2. Six stereoisomeric conduritols.
have been encountered in the syntheses of conduritols.
Conduritols are cyclohex-5-ene-1,2,3,4-tetrols, and exist
as two meso-compounds (conduritols A and D) and four
enantiomeric pairs (conduritols B, C, E, and F) (Fig-
ure 2). Conduritols A and F are naturally occurring.
Conduritol isomers have been synthesized by several
methods: microbial oxidation of benzene23 or haloben-
zenes,19b,24 followed by epoxidation-ring opening or di-
hydroxylation, reductive elimination of inositol diols,25
and others.18,26 Although considerable progress has been
made in the synthesis of optically active conduritols from
enantiopure unsaturated cyclic cis-diols, obtained by
microbial oxidation of halobenzenes,19b,24 many other
approaches have resulted in racemic mixtures. Recently,
enantiopure conduritols have been prepared by employ-
ing chiral starting materials such as sugar alcohols27 and
diethyl L-tartrate.28 Enantiopure conduritols have also
been obtained by chemical20,25b,29 or enzymatic19a,21b,30
resolution of racemic conduritol derivatives or their
precursors.
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The ready availability of all stereoisomers of IPn would
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Syntheses of Conduritol and Derivatives of Inositol
J . Org. Chem., Vol. 67, No. 10, 2002 3329
Sch em e 1a
between inositol phosphates and various biomacro-
molecules. We previously reported the practical and
divergent synthesis of all inositol stereoisomers via
conduritol derivatives in racemic version.31 And we also
developed facile synthetic routes to all possible enantio-
meric pairs of conduritol stereoisomers.32 We herein
report the facile syntheses of all possible diastereomers
of conduritol and various derivatives of inositol stereo-
isomers in high enantiopurity via efficient enzymatic
resolution of conduritol B and C derivatives.
Resu lts a n d Discu ssion
Gen er a l Str a tegy. The major issues in our synthetic
schemes for conduritol and inositol stereoisomers are how
to efficiently prepare the key intermediates conduritol
B and C derivatives from the selectively protected myo-
inositol diols and how to enantiomerically resolve racemic
conduritol derivatives. For the conversion of vicinal diols
into olefins, two types of general procedures are known.31
Generally, the two-step methods via intermediates with
activating groups do not work well on cyclic diols,
especially cyclic trans-diols. Samuelsson et al. reported
the one-step conversion of vicinal diols into olefins using
triphenylphosphine or chlorodiphenylphosphine, imid-
azole, and iodine in toluene.33 We have previously pre-
pared conduritol derivatives from readily available myo-
inositol derivatives under the Samuelsson conditions.31
Thus, we have envisioned that conduritol B and C
derivatives, whose hydroxyl groups at C-2 and C-3 are
protected with acetonides, might easily be prepared
under the Samuelsson conditions. Nicolosi et al. and
Ba¨ckvall et al. reported the enzymatic resolution of
conduritol derivatives or analogues utilizing various
lipases.19a,21b,30 These observations prompted us to exam-
ine the enzymatic resolution of conduritol diacetates.
Stereochemical inversion of allylic hydroxyl groups in
resolved conduritol derivatives would then afford all
possible enantiomerically enriched conduritol stereo-
isomers by the Mitsunobu reaction or oxidation-reduc-
tion. The stereocontrolled dihydroxylation of each enan-
tiomerically pure conduritol isomer was expected to yield
the chiral inositol stereoisomer derivatives except cis-
inositol, which is highly symmetric and may not be
readily accessible by conduritol routes.
a
Reagents and conditions: (a) PPh3, imidazole, I2, toluene, vV,
77%; (b) NaOMe, MeOH, vV, 96%; (c) Ac2O, pyridine 97.5%; (d) see
Table 1; (e) NaOMe, MeOH, quant; (f) 80% aq AcOH, 100 °C,
quant.
(48%, 95% ee) (Scheme 1). This result was at slight
variance with Ba¨ckvall’s results, which indicated the
enzymatic resolution of the diacetate 4 by CRL produced
the unreacted diacetate (+)-4 and the diol (-)-3.30c It is
clear that the enzyme CRL shows R stereopreference and
thus recognizes and hydrolyzes preferentially the 1-acetyl
group rather than the 4-acetyl group of (-)-4. Alkaline
methanolysis and successive acid-catalyzed hydroysis of
compounds (+)-4 and (-)-5 afforded (+)-conduritol C [(+)-
6] and (-)-conduritol C [(-)-6], respectively.18b,24e,30c The
reaction catalyzed by the lipase from Pseudomonas
cepacia (PCL; Amano) also gave comparable results in
terms of products, enantioselectivity, and reaction rate.
However, the alcoholysis of the diacetate 4 with Novozym
435 (CAL, immobilized lipase from Candida antarctica;
Novo Nordisk) or Lipozyme RM IM (RML, immobilized
lipase from Rhizomucor miehei; Novo Nordisk) in tert-
butyl methyl ether (t-BME) did not work at all (Table
1).
E n zym a t ic R esolu t ion of Con d u r it ol B a n d C
Der iva tives. To obtain enantiomerically enriched con-
duritol stereoisomers, enantioselective enzyme-catalyzed
hydrolysis of conduritol B and C derivatives was explored.
First, conduritol C derivative 2 was prepared from myo-
inositol diol 134 under the Samuelsson conditions.31,33 The
corresponding diacetate 4 was derived from 2, and
exposed to lipase from Candida rugosa (CRL; Sigma) in
a phosphate buffer (pH 7) according to the Kazlauskas
procedure.35 After 3 h, the conversion reached ca. 50%
and the reaction mixture contained the unreacted di-
acetate (+)-4 (49%, 95% ee) and the monoacetate (-)-5
To obtain enantiomerically enriched conduritol B de-
rivatives, compound 7 was converted to compound 9,34
which provided the conduritol B derivative 10 when
subjected to Samuelsson’s olefination procedure (Scheme
2).33 The diacetate 12 was prepared by alkaline meth-
anolysis and subsequent acetylation of compound 10, and
then exposed to CRL and PCL in a phosphate buffer (pH
7). The desired optical resolutions were not obtained in
this experiment.
We then investigated the system with Novozym 435
and n-BuOH in t-BME at 45 °C. After 30 min, the
reaction mixture was found to contain the unreacted
diacetate (+)-12, the monoacetate (-)-13, and the diol
(-)-11. The monoacetate (-)-13 was slowly converted to
(-)-11. This reveals that this enzyme also has R stereo-
preference and can recognize both acetyl groups since the
diacetate (-)-12 has a C2 symmetry axis. After 3 h, the
reaction mixture contained (+)-12 (49.5%, 98% ee), and
(31) Chung, S. K.; Kwon, Y. U. Bioorg. Med. Chem. Lett. 1999, 9,
2135-2140.
(32) Kwon, Y. U.; Chung, S. K. Org. Lett. 2001, 3, 3013-3016.
(33) (a) Liu, Z.; Classon, B.; Samuelsson, B. J . Org. Chem. 1990,
55, 4273-4275. (b) Pakulski, Z.; Zamojski, A. Carbohydr. Res. 1990,
205, 410-414. (c) Garegg, P. J .; Samuelsson, B. Synthesis 1979, 469-
470 and 813-814.
(34) Chung, S. K.; Chang, Y. T. J . Chem. Soc., Chem. Commun.
1995, 11-12.
(35) Kazlauskas, R. J .; Weissfloch, A. N. E.; Rappaport, A. T.; Cuccia,
L. A. J . Org. Chem. 1991, 56, 2656-2665.

3330 J . Org. Chem., Vol. 67, No. 10, 2002
Kwon et al.
Sch em e 3a
Ta ble 1. Lip a se-Ca ta lyzed Resolu tion of Con d u r itol B
a n d C Der iva tives
enantioselectivity of
substrate lipase time (h)c yield (%)
products (% ee)d
4
4
4
CRLa
PCLa
CALb
RMLb
CRLa
PCLa
CALb
RMLb
3
3
48
48
95 (>99)e
95 (>99)e
no rxn.
no rxn.
no rxn.
no rxn.
3
4
12
12
12
12
48.5
48.5
>99
>99
36
a
CRL, lipase from C. rugosa (Sigma); PCL, lipase from P.
cepacia (Amano); experimental conditions, enzyme (100 mg/mmol
of substrate), 0.5 N buffer (pH 7.0, 5 mL/mmol of substrate), 0.5
b
N NaOH, rt. CAL, Novozym 435 (immobilized lipase from C.
antarctica, Novo Nordisk); RML, Lipozyme RM IM (immobilized
lipase from R. miehei, Novo Nordisk); experimental conditions,
enzyme (300 mg/mmol of substrate), n-BuOH (10 mmol/mmol of
substrate), t-BME (15 mL/mmol of substrate), 45 °C. c At ca. 50%
a
Reagents and conditions: (a) BnBr, NaH, DMF, 98.6%; (b)
OsO4, NMO, aq acetone; (c) (i) 80% aq AcOH, 100 °C, (ii) BzCl,
pyridine, 96%.
d
conversion. Determined by NMR analysis of the diacetates using
Sch em e 4a
Eu(hfc)3 as the NMR shift agent. e After recrystallization.
Sch em e 2a
a
Reagents and conditions: (a) BzCl (1.0 equiv), pyridine; (b)
SO3-pyridine complex, TEA, DMSO; (c) NaBH4, MeOH-CH2Cl2,
74.5% from (+)-19; (d) (i) NaOMe, MeOH, vV, (ii) 80% aq AcOH,
100 °C, 92%; (e) OsO4, NMO, aq acetone, 88%.
a
Reagents and conditions: (a) 80% aq AcOH, 100 °C, quant;
(b) 2-methoxypropene, TSA, DMF, 43%; (c) PPh3, imidazole, I2,
toluene, vV, 78%; (d) NaOMe, MeOH, vV, 97.4%; (e) Ac2O, pyridine
98.8%; (f) see Table 1; (g) NaOMe, MeOH, quant; (h) 80% aq AcOH,
100 °C, quant.
was derived by benzylation of (+)-3. It was expected that
the cis-dihydroxylation of (+)-15 might give the neo-
stereoisomer due to steric reasons, and it was gratifying
to find that, under the reaction conditions employing
OsO4 and NMO in aqueous acetone, D-2,3-O-(1-methyl-
ethylidene)-1,4-bis-O-(phenylmethyl)-neo-inositol [(+)-16]
was essentially the sole product (Scheme 3). To obtain
an epi-inositol derivative, we replaced the acetonide
group of (+)-15 with a benzoyl protecting group by
treatment with 80% aqueous AcOH and the subsequent
benzoylation of the crude diol with BzCl in pyridine to
give compound (+)-17; the acetonide group was thought
to be the origin of the facial selectivity observed in cis-
dihydroxylation of (+)-15. Compound (+)-17 was treated
with OsO4 and NMO in aqueous acetone to provide, as
expected, D-1,4-bis-O-(phenylmethyl)-neo-inositol 2,3-
dibenzoate [(+)-18a ] and D-3,6-bis-O-(phenylmethyl)-epi-
inositol 4,5-dibenzoate [(+)-18b] in 45% and 39% yields,
respectively.
(-)-11 (48.5%, >99% ee). Compound (+)-12 was treated
with NaOMe in MeOH to give (+)-11. The reaction
catalyzed by Lipozyme RM IM gave comparable results
in terms of products and enantioselectivity but showed
a lower reaction rate (Table 1). The enantiomerically
enriched trans-diols (+)-11 and (-)-11 were hydrolyzed
in 80% aqueous AcOH to yield (+)-conduritol B [(+)-14]
and (-)-conduritol B [(-)-14], respectively.18a,25d
Syn t h eses of All P ossib le Dia st er eom er s of
Con d u r it ol a n d Va r iou s Der iva t ives of In osit ol
Ster eoisom er s. Conversions of the enantiomeric diols
(+)-3/(-)-3 and (+)-11/(-)-11 to diastereomers of con-
duritol and inositol derivatives in high enantiopurity
follow the same procedures except that the corresponding
products involved in each route have opposite configura-
tions. Accordingly, the procedures starting from (+)-3 and
(+)-11 only are described as representative.
First, we examined cis-dihydroxylation of the enantio-
merically enriched conduritol C derivative (+)-15, which
Since our initial synthetic plan for enantiomerically
enriched conduritol stereoisomers involved the inversion

Syntheses of Conduritol and Derivatives of Inositol
J . Org. Chem., Vol. 67, No. 10, 2002 3331
Sch em e 5a
Sch em e 7a
a
Reagents and conditions: (a) BnBr, NaH, DMF, 96%; (b) OsO4,
NMO, aq acetone; (c) BzOH, Ph3P, DEAD, toluene, 80 °C, 79%.
(d) BzOH, Ph3P, DEAD, toluene, rt, 90%; (e) (i) NaOMe, MeOH,
vV, (ii) 80% aq AcOH, 100 °C, 91%; (f) (i) NaOMe, MeOH, vV, (ii)
BnBr, NaH, DMF, 92%.
a
Reagents and conditions: (a) BzOH, Ph3P, DEAD, toluene, rt.
Sch em e 6a
7aR)-rel-3a,4,7,7a-tetrahydro-4-(methoxymethoxy)-2,2-
dimethyl-1,3-be nzodioxol-7-ol and (1S,4S,5S,6R)-rel-
4,5,6-tris(methoxymethoxy)-2-cyclohexen-1-ol, derived from
the racemic 3, were subjected to the Mitsunobu conditions
(not shown), similar results were obtained, indicating
that the nature of the protecting groups made little
difference. The stereochemistry of the transformation
does not significantly depend on the steric and electronic
effects of protecting groups but rather on the substrate
structure itself.
Next, the possibility of obtaining conduritol D by way
of oxidation of (+)-19 and subsequent stereoselective
reduction was investigated (Scheme 4). Compound (+)-
19 was treated with SO3-pyridine complex and TEA in
DMSO to furnish an enone, (+)-21. Although conduritol
D itself is a meso-compound, reduction of the enone (+)-
21 with NaBH4 gave stereoselectively an enantiomeri-
cally enriched conduritol D derivative, (-)-22, in 74.5%
overall yield from (+)-19. Alkaline methanolysis and
successive acid-catalyzed hydrolysis of (-)-22 provided
achiral conduritol D (23).18b,23d,24a cis-Dihydroxylation of
(-)-22 with OsO4 and NMO in aqueous acetone gave
stereoselectively D-2,3-O-(1-methylethylidene)-allo-inosi-
tol 1-monobenzoate [(-)-24] in 88% yield. The observed
facial selectivity might again be attributed to the acet-
onide group and two neighboring functions, which block
the cis-approach to the olefinic bond.
On the other hand, the allylic alcohol (+)-29, derived
from (+)-19 by treatment with MOMCl and (i-Pr)2NEt
in CHCl3, followed by debenzoylation, was treated with
BzOH, Ph3P, and DEAD in toluene to afford in 97.1%
yield the conduritol A derivative (-)-30 with inversion
of the stereochemistry but no allylic rearrangement. All
protecting groups of (-)-30 were removed by treatment
with NaOMe and subsequent acid-catalyzed hydrolysis
to give achiral conduritol A (31) (Scheme 6).23d,26a
When compound (-)-30 was subjected to OsO4 and
NMO in aqueous acetone, inseparable multiple products
were obtained which appeared to be formed by benzoyl
migration catalyzed by 4-methylmorpholine. Thus, we
carried out benzoylation of the crude mixtures with BzCl
in pyridine to obtain D-4-O-(methoxymethyl)-5,6-O-(1-
methylethylidene)-allo-inositol tribenzoate [(-)-32a ] and
D-3-O-(methoxymethyl)-1,2-O-(1-methylethylidene)-muco-
inositol tribenzoate [(+)-32b ] in 85% and 9.3% yields,
respectively. The observed products show that the facial
selectivity is more strongly influenced by the steric bulk
a
Reagents and conditions: (a) (i) MOMCl, (i-Pr)2NEt, (ii)
NaOMe, MeOH, vV, 97.1%; (b) BzOH, Ph3P, DEAD, toluene, rt,
97.1%; (c) (i) NaOMe, MeOH, vV, (ii) 80% aq AcOH, 100 °C, 89%;
(d) (i) OsO4, NMO, aq acetone, (ii) BzCl, pyridine; (e) (i) 80% aq
AcOH, 70 °C, (ii) MOMCl, (i-Pr)2NEt, 97.1%; (f) OsO4, NMO, aq
acetone, 98%.
of the allylic alcohol stereochemistry in the selectively
protected conduritol derivatives under the Mitsunobu
conditions, the monobenzoate (+)-19 was preferentially
prepared by treatment of (+)-3 with BzCl (1.0 equiv) in
pyridine (Scheme 4). In the preliminary experiments, the
racemic monobenzoate 19 was subjected to the Mit-
sunobu conditions with BzOH, Ph3P, and DEAD in
toluene at room temperature, and it was found that the
expected conduritol D derivative 27 (8.5%) was obtained
only as the minor product together with the rearranged
conduritol C derivative 28 (73.1%) as the major product
in stereo- and regioselective fashions (Scheme 5). The
reaction proceeded predominantly with both inversion
and allylic rearrangement by an SN2′ process, presumably
via the intermediate 26. These unexpected results sug-
gest that the reaction of a carboxylate anion with an
alkoxy phosphonium salt is better described as proceed-
ing through an intimate ion pair rather than a free allylic
carbonium ion.36 When the related compounds (3aS,4S,7S,
(36) Grynkiewicz, G.; Burzynska, H. Tetrahedron 1976, 32, 2109-
2111.

3332 J . Org. Chem., Vol. 67, No. 10, 2002
Ta ble 2. Op tica l Rota tion s of Syn th etic Con d u r itol Ster eoisom er s
Kwon et al.
20
[R]D
conduritol stereoisomer
(+)-form
(-)-form
conduritol A (31)
meso
conduritol B [(+)-14/(-)-14]
conduritol C [(+)-6/(-)-6]
conduritol D (23)
conduritol E [(+)-39/(-)-39]
conduritol F [(+)-44/(-)-44]
+179.3 (c 0.80, CH3OH)25d
+218.7 (c 1.01, H2O)24e,30c
meso
-179.2 (c 1.08, CH3OH)18a
-220.0 (c 0.76, H2O)18b,24e,30c
+331.8 (c 1.20, H2O)
-331.6 (c 1.06, H2O)19b,27b
-99.7 (c 0.60, H2O)24d,25d,27b
+100.2 (c 0.77, H2O)18a
Ta ble 3. Op tica l Rota tion s of Syn th etic In ositol Ster eoisom er ic Der iva tivesa
20
[R]D
inositol
stereoisomer derivative
(+)-form
(-)-form
myo
scyllo
chirob
epi
[(+)-36/(-)-36]
[(+)-37/(-)-37]
[(+)-45/(-)-45]
[(+)-18b/(-)-18b]
[(+)-24/(-)-24]
[(+)-32a /(-)-32a ]
[(+)-41/(-)-41]
[(+)-32b/(-)-32b]
[(+)-34/(-)-34]
[(+)-16/(-)-16]
[(+)-18a /(-)-18a ]
+68.0 (c 1.08, CHCl3)
+74.7 (c 1.01, CHCl3)
+11.6 (c 2.93, CHCl3)
+16.7 (c 2.56, CHCl3)
+41.8 (c 1.16, CH3OH)
+4.82 (c 1.66, CHCl3)
+20.4 (c 1.00, CHCl3)
+89.5 (c 1.80, CHCl3)
+3.58 (c 0.43, CHCl3)
+11.7 (c 0.75, THF)
+47.7 (c 4.60, CHCl3)
-67.0 (c 1.02, CHCl3)
-74.0 (c 0.88, CHCl3)
-10.8 (c 2.10, CHCl3)
-17.2 (c 5.25, CHCl3)
-42.9 (c 1.06, CH3OH)
-4.23 (c 2.00, CHCl3)
-21.3 (c 0.57, CHCl3)
-88.2 (c 2.15, CHCl3)
-3.29 (c 1.11, CHCl3)
-11.4 (c 0.77, THF)
-46.4 (c 4.24, CHCl3)
allo
muco
neo
a
cis-Inositol, which is highly symmetric and not readily accessible by conduritol routes, was previously synthesized via myo-inositol
orthoformate as the key intermediate.31 chiro-Inositol exists as an enantiomeric pair. The (+)-form is the D-chiro-inositol derivative.
b
1
Sch em e 8a
the H NMR spectrum, indicating that the substituent
is in the equatorial orientation.
The double inversion of two allylic hydroxyl groups of
(+)-11 might be expected to give a conduritol E deriva-
tive. Treatment of (+)-11 with BzOH, Ph3P, and DEAD
in toluene at room temperature indeed provided in 90%
yield the (-)-conduritol E derivative (-)-38 without allylic
rearrangement (Scheme 7). The protecting groups of (-)-
38 were removed by successive reactions with NaOMe
in MeOH and 80% aqueous AcOH to yield (-)-conduritol
E [(-)-39].19b,27b In the direct dihydroxylation of (-)-38,
the benzoyl group migration apparently catalyzed by
4-methylmorpholine was encountered. Thus, we switched
the protecting group from benzoyl to benzyl. Compound
(-)-40, which has a symmetry axis, was treated with
OsO4 and NMO in aqueous acetone to afford D-1,6-O-(1-
methylethylidene)-2,5-bis-O-(phenylmethyl)-allo-inosi-
tol [(+)-41] in 75% yield. The dihydroxylation rate of (-)-
40 was very slow compared to that of the conduritol B
derivative (+)-35.
A conduritol F derivative might be prepared by the
inversion of one allylic hydroxyl group of the diol (+)-11.
Thus, the monobenzoate (+)-42 was obtained by treat-
ment of the diol (+)-11 with BzCl (1.05 equiv) in pyridine
in 61% yield (Scheme 8). The Mitsunobu reaction of (+)-
42 with BzOH, Ph3P, and DEAD in toluene provided the
conduritol F derivative (-)-43 in 98% yield. All protecting
groups of (-)-43 were removed by alkaline methanolysis
and subsequent acid-catalyzed hydrolysis to yield con-
duritol F [(-)-44].18a,24d,25d,27b The conduritol F derivative
(-)-43 was treated with OsO4 and NMO in aqueous
acetone to afford stereoselectively L-2,3-O-(1-methyl-
ethylidene)-chiro-inositol 1,4-dibenzoate [(-)-45] in 97.4%
yield.
a
Reagents and conditions: (a) BzCl (1.05 equiv), pyridine; (b)
BzOH, Ph3P, DEAD, toluene, rt, 98%; (c) (i) NaOMe, MeOH, vV,
(ii) 80% aq AcOH, 100 °C, 90%; (d) OsO4, NMO, aq acetone, 97.4%.
of the acetonide group rather than the stereochemistry
of two neighboring groups. The acetonide group of (-)-
30, which appears to block the cis-approach to the olefinic
bond, was removed in 80% aqueous AcOH, and then the
crude mixture was treated with MOMCl and (i-Pr)2NEt
in CHCl3 to give compound (-)-33. As expected, cis-
dihydroxylation of compound (-)-33 stereoselectively
afforded D-1,2,3-tris-O-(methoxymethyl)-muco-inositol
6-monobenzoate [(-)-34] in 98% yield.
cis-Dihydroxylation of compound (+)-35,27b which was
prepared by simple benzylation of (+)-11 with BnBr and
NaH in DMF, gave exclusively D-4,5-O-(1-methylethyl-
idene)-3,6-bis-O-(phenylmethyl)-myo-inositol [(-)-36]37 in
94.4% yield (Scheme 7). The vicinal cis-diol (-)-36 was
subjected to the Mitsunobu conditions with BzOH, Ph3P,
and DEAD in toluene at 80 °C to give scyllo-inositol
derivative (-)-37 with inversion of only the axial hydroxyl
group at C-2.11d The proton on the benzoyl-bearing carbon
appears as a triplet at δ ) 5.38 ppm with J ) 8.9 Hz in
All synthetic conduritol and inositol derivatives were
fully characterized and confirmed on the basis of 1H and
1
13C NMR spectra, including H-1H homonuclear COSY
spectra, and mass spectra. Enantiomeric pairs of con-
duritol and inositol stereoisomeric derivatives derived
from the enantiomeric diols (+)-3/(-)-3 and (+)-11/(-)-
(37) Gigg, J .; Gigg, R.; Payne, S.; Conant, R. J . Chem. Soc., Perkin
Trans. 1 1987, 1757-1762.

Syntheses of Conduritol and Derivatives of Inositol
J . Org. Chem., Vol. 67, No. 10, 2002 3333
1
96 °C; H NMR (CDCl3) δ 1.39, 1.46 (2s, 6H), 2.37 (br s, 1H),
2.70 (d, J ) 4.7 Hz, 1H), 4.30-4.34 (m, 1H), 4.44-4.47 (m,
2H), 4.52 (br s, 1H), 5.98-6.07 (m, 2H); 13C NMR (CDCl3) δ
24.8, 26.7, 64.6, 68.5, 75.6, 79.4, 110.0, 132.2, 133.5; MS (FAB)
m/z 187 (M+ + H). Anal. Calcd for C9H14O4: C, 58.05; H, 7.58.
Found: C, 57.86; H, 7.55.
11 have identical spectral data except opposite optical
rotations. The optical rotations of synthetic conduritol
stereoisomers and inositol stereoisomeric derivatives are
shown in Tables 2 and 3, respectively.
Con clu sion s
(3a R,4R,7R,7a S)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zod ioxole-4,7-d iol Dia ceta te (4). To a solution of
compound 3 (4.29 g, 23.0 mmol) in pyridine (80 mL) at 0 °C
was added acetic anhydride (4.4 mL, 46.1 mmol). After 30 min,
the mixture was warmed to rt and stirred overnight. The
reaction mixture was treated with water and extracted with
EtOAc. The organic layer was washed with 1 N HCl, aq
NaHCO3, and brine. The organic layer was dried (MgSO4),
concentrated, and chromatographed to give compound 4 (6.07
g, 97.5%) as an oil: Rf 0.39 (EtOAc:Hex ) 1:4); 1H NMR
(CDCl3) δ 1.34, 1.41 (2s, 6H), 2.05, 2.15 (2s, 6H), 4.45 (dd, J )
2.3, 7.2 Hz, 1H), 4.67 (ddd, J ) 0.85, 3.9, 7.2 Hz, 1H), 5.25
(dd, J ) 2.3, 4.6 Hz, 1H), 5.50-5.53 (m, 1H), 5.98 (ddd, J )
In summary, we successfully developed synthetic routes
to all possible diastereomers of conduritol as well as
optically enriched inositol derivatives from the easily
available myo-inositol by efficient enzymatic resolution
of conduritol B and C derivatives, followed by oxidation-
reduction or the Mitsunobu reaction, and cis-dihydroxyl-
ation in stereo- and regioselective manners. The cis-
inositol derivative, which is highly symmetric and may
not be readily accessible by conduritol routes, was previ-
ously synthesized in five steps via 2-O-benzoyl-myo-
inositol orthoformate as the key intermediate.31 We are
currently examining the utilities of enantiomerically
enriched conduritol and inositol stereoisomers in the
syntheses of various biologically important cyclitols and
IPn analogues.
0.85, 2.5, 9.8 Hz, 1H), 6.06 (ddd, J ) 1.4, 4.6, 9.8 Hz, 1H); 13
C
NMR (CDCl3) δ 20.7, 20.9, 24.5, 26.0, 67.5, 68.5, 74.0, 75.7,
109.7, 127.8, 131.8, 169.7, 170.3; MS (FAB) m/z 271 (M+
H).
+
Lip a se-Ca ta lyzed Resolu tion of Com p ou n d 4. To a
solution of racemate 4 (6.65 g, 24.6 mmol) in 0.5 N sodium
phosphate buffer (120 mL, pH 7.0) was added lipase (ca. 2.5
g) from C. rugosa (Sigma) or P. cepacia (Amano). The suspen-
sion was vigorously stirred while pH 7.0 was automatically
maintained with 0.5 N NaOH by an auto pH titrator. After 3
h conversion was ca. 50%, and EtOAc (40 mL) was added. The
suspension was filtered through Celite, and the filtrate was
extracted three times with EtOAc. The combined extracts were
washed with aq NaHCO3 and brine, dried (MgSO4), concen-
trated, and chromatographed to give (+)-4 (3.26 g, 49%, 95%
ee by NMR analysis) as an oil, and (-)-5 (2.70 g, 48%, 95%
ee) as a solid whose optical purity could be improved to >99%
ee after recrystallization from CH2Cl2-Hex. The optical purity
of (+)-4 could also be improved to >99% ee after repeated
resolution. After acetylation of the monoacetate (-)-5, the
optical purities (% ee) were determined by NMR analysis of
the diacetates using europium tris[3-(heptafluoropropyl-
hydroxymethylene)-(+)-camphorate] as the NMR shift agent.
Compounds (+)-4 and (-)-5 were treated with NaOMe in
MeOH to give compounds (+)-3 and (-)-3, and their optical
purities could be improved to >99% ee upon recrystallization
from CH2Cl2-MeOH.
Exp er im en ta l Section
Gen er a l Meth od s. All nonhydrolytic reactions were carried
out in oven-dried glassware under an inert atmosphere of dry
argon or nitrogen. All commercial chemicals were used as
obtained without further purification, except for the solvents,
which were purified and dried by standard methods prior to
use. Melting points were determined on a Thomas-Hoover
apparatus and are uncorrected. Analytical TLC was performed
on a Merck 60 F254 silica gel plate (0.25 mm thickness), and
visualization was done with UV light, and/or by spraying with
a 5% solution of phosphomolybdic acid followed by charring
with a heat gun. Column chromatography was performed on
Merck 60 silica gel (70-230 mesh or 230-400 mesh). NMR
spectra were recorded on a Bruker AM 300, DPX 300, or DRX
500 spectrometer. Tetramethylsilane was used as internal
standard for 1H NMR. Mass spectra (EI or FAB) were
determined on a micromass PLATFORM II, at the Korea Basic
Science Center, Taejeon, or Inter-University Center for Natu-
ral Science Research Facilities, Seoul National University,
Seoul, Korea. Elemental analyses were carried out on an
Elementar Vario-EL system. Optical rotations were measured
with a J ASCO DIP-360 digital polarimeter.
(3a R,4R,7R,7a S)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zod ioxole-4,7-d iol Diben zoa te (2). To a stirred
solution of compound 134 (2.60 g, 6.07 mmol), imidazole (1.67
g, 24.5 mmol), and triphenylphosphine (6.49 g, 24.5 mmol) in
toluene (120 mL) at reflux was added iodine (5.08 g, 20.0
mmol) in portions. The mixture was stirred for 5.5 h. After
being cooled to rt, it was poured into excess aq sodium
thiosulfate and aq NaHCO3, and diluted with EtOAc. The
organic layer was washed with brine, dried (MgSO4), and
concentrated. The product mixture was chromatographed to
give compound 2 (1.84 g, 77%): Rf 0.25 (EtOAc:Hex ) 1:10);
mp 120.5-122 °C; 1H NMR (CDCl3) δ 1.37, 1.43 (2s, 6H), 4.68
(dd, J ) 3.1, 7.4 Hz, 1H), 4.83 (dd, J ) 4.0, 7.4 Hz, 1H), 5.69
(app t, J ) 3.3 Hz, 1H), 5.86 (dd, J ) 2.1, 4.0 Hz, 1H), 6.18-
6.26 (m, 2H), 7.43-8.14 (m, 10H); 13C NMR (CDCl3) δ 25.1,
26.6, 68.2, 70.3, 74.4, 76.5, 110.5, 128.6-133.7, 166.0, 166.5;
MS (FAB) m/z 395 (M+ + H). Anal. Calcd for C23H22O6: C,
70.04; H, 5.62. Found: C, 70.11; H, 5.72.
Da ta for (3a R,4S,7S,7a S)-3a ,4,7,7a -Tetr a h yd r o-2,2-d i-
m eth yl-1,3-ben zodioxole-4,7-diol Diacetate [(+)-4]:30c [R]D
20
+161.0 (c 4.60, CHCl3) [lit.30c [R]D +154.7 (c 1.106, CHCl3)];
20
1
Rf, H NMR, and 13C NMR data identical to those of 4.
Da t a for (3a S,4R,7R,7a R)-3a ,4,7,7a -Tet r a h yd r o-2,2-
d im eth yl-1,3-ben zod ioxole-4,7-d iol 4-Mon oa ceta te [(-)-
20
5]: Rf 0.26 (EtOAc:Hex ) 1:2); mp 63-64 °C; [R]D -206.7 (c
1
4.23, CHCl3); H NMR (CDCl3) δ 1.37, 1.41 (2s, 6H), 2.04 (s,
3H), 3.07 (br s, 1H), 4.40-4.45 (m, 2H), 4.59 (ddd, J ) 1.0,
4.3, 7.3 Hz, 1H), 5.23 (dd, J ) 2.8, 4.9 Hz, 1H), 5.97 (ddd, J )
1.4, 4.9, 9.8 Hz, 1H), 6.05 (ddd, J ) 1.0, 2.5, 9.8 Hz, 1H); 13C
NMR (CDCl3) δ 21.2, 24.8, 26.4, 65.4, 68.7, 75.9, 76.0, 109.7,
126.7, 136.5, 170.3; MS (FAB) m/z 229 (M+ + H). Anal. Calcd
for C11H16O5: C, 57.88; H, 7.07. Found: C, 57.65; H, 7.20.
Da ta for (3a R,4S,7S,7a S)- a n d (3a R,4R,7R,7a S)-3a ,4,7,
7a-Tetr ah ydr o-2,2-dim eth yl-1,3-ben zodioxole-4,7-diol [(+)-
20
3 a n d (-)-3]:30c [(+)-3] mp 122-123 °C; [R]D +88.6 (c 1.11,
1
CHCl3); Rf, H NMR, and 13C NMR data identical to those of
20
3; [(-)-3] mp 122-123 °C; [R]D -88.5 (c 1.00, CHCl3) [lit.30c
[R]D -157.2 (c 0.998, CHCl3)]; Rf, 1H NMR, and 13C NMR
20
data identical to those of 3.
(3a R,4S,7S,7a S)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zod ioxole-4,7-d iol (3). To a solution of compound 2
(9.75 g, 24.7 mmol) in MeOH (100 mL) was added sodium
methoxide (300 mg, 5.5 mmol). After being stirred for 3 h at
reflux, the mixture was filtered through a short pad of silica
gel, and the filtrate was evaporated under reduced pressure.
The crude product was chromatographed to give compound 3
(4.42 g, 96%) as a solid: Rf 0.12 (EtOAc:Hex ) 1:2); mp 95-
(1S,2R,3S,4S)- an d (1R,2R,3S,4R)-5-Cycloh exen e-1,2,3,4-
tetr ol [(+)- a n d (-)-Con d u r itol C, (+)-6 a n d (-)-6].18b,24e,30c
A solution of compound (+)-3 (102 mg, 0.548 mmol) in 80% aq
AcOH (5 mL) was heated at 100 °C for 3 h, and then
concentrated under reduced pressure to give a crude product,
(+)-6, quantitatively. Recrystallization from MeOH-Et2O gave
compound (+)-6 as a solid. Similarly, compound (-)-6 was
prepared from (-)-3. Data for (+)-6: mp 127-129 °C [lit.24e

3334 J . Org. Chem., Vol. 67, No. 10, 2002
Kwon et al.
mp 128-129 °C, lit.30c mp 128-129 °C]; [R]D +218.7 (c 1.01,
in tert-butyl methyl ether (150 mL) was added n-BuOH (9.3
mL). The reaction mixture was stirred at 45 °C. After 30 min,
the reaction mixture contained (+)-12, (-)-13, and (-)-11. The
monoacetate (-)-13 was slowly converted to (-)-11. After 3 h,
the enzyme was filtered off, and the filtrate was concentrated
and chromatographed to give the unreacted diacetate (+)-12
(1.34 g, 49.5%, 98% ee), whose optical purity could be improved
to >99% ee by recrystallization from EtOAc-petroleum ether,
and the diol (-)-11 (906 mg, 48.5%, >99% ee) as an oil. After
acetylation of the diol (-)-11, the optical purities (% ee) were
determined by NMR analysis of the diacetates using europium
tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphor-
ate] as the NMR shift agent. Compound (+)-12 was treated
with NaOMe in MeOH to give the diol (+)-11.
20
H2O) [lit.24e [R]D20 +212 (c 0.47, H2O), lit.30c [R]D20 +215 (c 2.008,
H2O)]; 1H NMR (CD3OD) δ 3.53 (dd, J ) 5.0, 10.5 Hz, 1H),
4.03 (m, 1H), 4.22-4.29 (m, 2H), 5.54-5.59 (m, 1H), 5.65 (td,
J ) 2.05, 2.05, 10.2 Hz, 1H); 13C NMR (CD3OD) δ 69.7, 70.8,
74.3, 76.3, 130.2, 131.0. Data for (-)-6: mp 128-129 °C [lit.18b
mp 129-130 °C, lit.24e mp 127-128 °C, lit.30c mp 128-129 °C,];
20
20
[R]D -220.0 (c 0.76, H2O) [lit.18b [R]D -209 (c 2, H2O), lit.24e
20
20
1
[R]D -207 (c 0.5, H2O), lit.30c [R]D -213 (c 1.996, H2O)]; H
NMR and 13C NMR data identical to those of (+)-6.
m yo-In ositol 1,4-Diben zoa te (8). Compound 734 (2.0 g, 4.2
mmol) in 80% aq AcOH (80 mL) was heated at reflux for 3 h,
and evaporated to dryness to give a crude product quantita-
tively. Recrystallization of the crude product from EtOH gave
compound 8: Rf 0.17 (MeOH:CH2Cl2 ) 1:20); mp 245-249 °C;
1H NMR (CD3OD) δ 3.62 (app t, J ) 9.4 Hz, 1H), 3.84 (dd, J
) 2.7, 10.0 Hz, 1H), 4.14 (app t, J ) 9.7 Hz, 1H), 4.25 (app t,
J ) 2.6 Hz, 1H), 4.97 (dd, J ) 2.6, 10.2 Hz, 1H), 5.51 (app t,
J ) 9.8 Hz, 1H), 7.45-8.16 (m, 10H); 13C NMR (CD3OD) δ 71.6,
72.1, 72.3, 74.7, 76.4, 77.1, 129.5-134.4, 168.0, 168.3; MS
(FAB) m/z 389 (M+ + H). Anal. Calcd for C20H20O8: C, 61.85;
H, 5.19. Found: C, 61.73; H, 5.49.
Da t a for (3a R,4S,7S,7a R)-3a ,4,7,7a -Tet r a h yd r o-2,2-
dim eth yl-1,3-ben zodioxole-4,7-diol Diacetate [(+)-12]: mp
20
1
94-95 °C; [R]D +180.3 (c 1.27, CHCl3); Rf, H NMR, and 13C
NMR data identical to those of 12.
Da ta for (3a R,4S,7S,7a R)- a n d (3a S,4R,7R,7a S)-3a ,4,7,
7a-Tetr ah ydr o-2,2-dim eth yl-1,3-ben zodioxole-4,7-diol [(+)-
20
1
11 a n d (-)-11]: [(+)-11] [R]D +30.4 (c 3.98, CHCl3); Rf, H
NMR, and 13C NMR data identical to those of 11; [(-)-11] [R]D
20
5,6-O-(1-Meth yleth yliden e)-myo-in ositol 1,4-Diben zoate
(9). To a solution of 8 (4.0 g, 10.3 mmol) and TSA (100 mg) in
DMF (50 mL) at 0 °C was added 2-methoxypropene (2 mL,
20.8 mmol) by syringe. The solution was stirred for 3 h in an
ice bath, poured into 1% aq NaHCO3 (350 mL) with vigorous
stirring, and extracted with CH2Cl2. The organic layer was
diluted with ether, and slow evaporation of the solvents gave
a crystalline solid precipitate, compound 9 (1.90 g, 43%). The
filtrate was evaporated under reduced pressure and boiled in
aq AcOH (80%) to give the starting material 8, quantitatively
on the basis of recovered product. Data for 9: Rf 0.4 (EtOAc:
Hex ) 1:4); mp 212-215 °C; 1H NMR (DMSO-d6) δ 1.35, 1.39
(2s, 6H), 3.87 (dd, J ) 9.2, 10.2 Hz, 1H), 3.92 (ddd, J ) 2.9,
7.3, 9.3 Hz, 1H), 4.20 (ddd, J ) 2.8, 2.9, 4.8 Hz, 1H), 4.26 (dd,
J ) 9.2, 10.7 Hz, 1H), 5.17 (d, J ) 7.3 Hz, 1H), 5.23 (dd, J )
2.8, 10.7 Hz, 1H), 5.46 (dd, J ) 9.3, 10.2 Hz, 1H), 5.59 (d, J )
4.8 Hz, 1H), 7.54-8.05 (m, 10H); 13C NMR (DMSO-d6) δ 26.6,
26.7, 70.9, 71.1, 72.3, 72.7, 75.0, 76.1, 111.3, 128.6-133.4,
165.0, 165.1; MS (FAB) m/z 429 (M+ + H). Anal. Calcd for
-30.2 (c 2.40, CHCl3); Rf, 1H NMR, and 13C NMR data identical
to those of 11.
(1S,2R,3R,4S)- an d (1R,2S,3S,4R)-5-Cycloh exen e-1,2,3,4-
tetr ol [(+)- a n d (-)-Con d u r itol B, (+)-14 a n d (-)-14].18a,25d
Compound (+)-11 (95 mg, 0.51 mmol) was hydrolyzed by the
same procedure as described for compound (+)-6 to give
compound (+)-14 as a solid. Similarly, compound (-)-14 was
prepared from compound (-)-11. Data for (+)-14: mp 169-
20
171 °C [lit.25d mp 177-178 °C]; [R]D +179.3 (c 0.80, CH3OH)
20
[lit.25d [R]D +191 (c 1.26, CH3OH)]; 1H NMR (CD3OD) δ 3.38
(dd, J ) 2.4, 5.3 Hz, 1H), 4.07 (dd, J ) 2.4, 5.3 Hz, 1H), 5.58
(s, 2H); 13C NMR (CD3OD) δ 73.8 (2C), 77.6 (2C), 130.9 (2C).
20
Data for (-)-14: mp 171-173 °C [lit.18a mp 174-175 °C]; [R]D
-179.2 (c 1.08, CH3OH) [lit.18a [R]D -179 (c 1.2, CH3OH)];
20
1H NMR and 13C NMR data identical to those of (+)-14.
(3a R,4S,7S,7a S)- a n d (3a R,4R,7R,7a S)-3a ,4,7,7a -Tetr a -
h yd r o-2,2-d im et h yl-4,7-b is(p h en ylm et h oxy)-1,3-b en zo-
d ioxole [(+)-15 a n d (-)-15]. To a solution of compound (+)-3
(1.866 g, 10.0 mmol) and NaH (1.26 g, 50.0 mmol) in DMF (50
mL) at 0 °C was added BnBr (4.9 mL, 40.4 mmol). After 30
min, the mixture was warmed to rt and stirred overnight. The
mixture was diluted with EtOAc and successively washed with
1 N HCl, aq NaHCO3, and brine. The organic phase was dried
(MgSO4), concentrated, and chromatographed to give com-
pound (+)-15 (3.61 g, 98.6%) as an oil. Similarly, compound
(-)-15 was prepared from compound (-)-3. Data for (+)-15:
C
23H24O8: C, 64.48; H, 5.65. Found: C, 64.19; H, 5.69.
(3a R,4S,7S,7a R)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zod ioxole-4,7-d iol Diben zoa te (10). Compound 9
(6.98 g, 16.3 mmol) was treated by the same procedure as
described for compound 2 to afford compound 10 (5.01 g,
1
78%): Rf 0.42 (EtOAc:Hex ) 1:4); mp 193-194 °C; H NMR
(CDCl3) δ 1.51 (s, 6H), 4.04 (dd, J ) 2.4, 5.8 Hz, 2H), 5.85-
5.90 (m, 4H), 7.26-8.11 (m, 10H); 13C NMR (CDCl3) δ 27.4
(2C), 73.3 (2C), 78.0 (2C), 112.4, 128.8-133.8, 166.4 (2C); MS
(FAB) m/z 395 (M+ + H). Anal. Calcd for C23H22O6: C, 70.04;
H, 5.62. Found: C, 70.22; H, 5.84.
20
1
Rf 0.46 (EtOAc:Hex ) 1:4); [R]D +123.5 (c 3.62, CHCl3); H
NMR (CDCl3) δ 1.32, 1.38 (2s, 6H), 4.06 (dd, J ) 2.4, 4.8 Hz,
1H), 4.29 (td, J ) 2.4, 2.4, 4.2 Hz, 1H), 4.41-4.52 (m, 3H),
4.60 (ddd, J ) 1.1, 3.7, 7.1 Hz, 1H), 4.66 (d, J ) 12.5 Hz, 1H),
4.72 (d, J ) 12.5 Hz, 1H), 6.00 (ddd, J ) 1.9, 4.6, 9.8 Hz, 1H),
6.12 (ddd, J ) 1.2, 2.4, 9.8 Hz, 1H), 7.18-7.34 (m, 10H); 13C
NMR (CDCl3) δ 25.1, 26.6, 71.1, 71.8, 72.6, 73.4, 76.0, 77.6,
109.8, 128.1-138.6; MS (FAB) m/z 367 (M+ + H). Data for (-)-
(3a R,4S,7S,7a R)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zod ioxole-4,7-d iol (11). Compound 10 (4.0 g, 12.4
mmol) was hydrolyzed by the same procedure as described for
compound 3 to afford compound 11 (1.84 g, 97.4%) as an oil:
Rf 0.23 (EtOAc:Hex ) 1:1); 1H NMR (CDCl3) δ 1.47 (s, 6H),
2.74 (br s, 2H), 3.55 (dd, J ) 2.3, 5.6 Hz, 2H), 4.50 (dd, J )
2.3, 5.6 Hz, 2H), 5.69 (s, 2H); 13C NMR (CDCl3) δ 27.4 (2C),
71.1 (2C), 81.1 (2C), 111.7, 130.9 (2C); MS (FAB) m/z 187 (M+
+ H).
(3a R,4S,7S,7a R)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zod ioxole-4,7-d iol Dia ceta te (12). Compound 11
(3.25 g, 17.4 mmol) was acetylated by the same procedure as
described for compound 4 to afford compound 12 (4.66 g,
98.8%) as a solid: Rf 0.5 (EtOAc:Hex ) 1:2); mp 153-154 °C;
1H NMR (CDCl3) δ 1.48 (s, 6H), 2.13 (s, 6H), 3.79 (dd, J ) 2.4,
5.9 Hz, 2H), 5.54 (dd, J ) 2.4, 5.9 Hz, 2H), 5.70 (s, 2H); 13C
NMR (CDCl3) δ 21.4 (2C), 27.2 (2C), 72.7 (2C), 77.7 (2C), 112.2,
128.9 (2C), 170.7 (2C); MS (FAB) m/z 271 (M+ + H). Anal.
Calcd for C13H18O6: C, 57,77; H, 6.71. Found: C, 57.39; H,
6.89.
15: [R]D -124.0 (c 3.88, CHCl3); Rf, H NMR, and 13C NMR
data identical to those of (+)-15.
20
1
D-2,3-O-(1-Meth yleth yliden e)-1,4-bis-O-(ph en ylm eth yl)-
n eo-in osit ol [(+)-16] a n d D-1,2-O-(1-Met h ylet h ylid en e)-
3,6-bis-O-(p h en ylm eth yl)-n eo-in ositol [(-)-16]. To a solu-
tion of compound (+)-15 (450 mg, 1.23 mmol) in a mixture of
acetone and water (8:1, 4.5 mL) were added 4-methylmorpho-
line N-oxide (NMO) (690 mg, 5.71 mmol) and then OsO4 (∼25
mg). After being stirred for 12 h at rt, the reaction mixture
was quenched with a few drops of 10% NaHSO3, and the
solvents were evaporated under reduced pressure. The crude
material was dissolved in MeOH and filtered through a short
pad of silica gel. After removal of the solvent by evaporation,
flash column chromatography on silica gel gave compound (+)-
16 (467 mg, 95%) as a solid. Similarly, compound (-)-16 was
prepared from compound (-)-15. Data for (+)-16: Rf 0.24
(EtOAc:Hex ) 1:1); mp 116-117 °C; [R]D20 +11.7 (c 0.75, THF);
1H NMR (CDCl3) δ 1.30, 1.35 (2s, 6H), 2.84 (d, J ) 4.3 Hz,
1H), 2.88 (d, J ) 2.5 Hz, 1H), 3.43 (dd, J ) 2.5, 6.8 Hz, 1H),
Lip a se-Ca ta lyzed Resolu tion of Com p ou n d 12. To a
solution of racemate 12 (2.71 g, 10.0 mmol) and Novozym 435
(immobilized lipase from C. antarctica, Novo Nordisk, 3.0 g)

Syntheses of Conduritol and Derivatives of Inositol
J . Org. Chem., Vol. 67, No. 10, 2002 3335
3.88 (ddd, J ) 3.0, 4.3, 9.4 Hz, 1H), 3.96 (dd, J ) 3.7, 9.4 Hz,
1H), 4.14 (app q, J ) 2.5 Hz, 1H), 4.25 (app t, J ) 6.0 Hz, 1H),
4.31 (dd, J ) 3.7, 5.1 Hz, 1H), 4.64-4.77 (m, 4H), 7.28-7.40
(m, 10H); 13C NMR (CDCl3) δ 26.3, 28.4, 70.4, 70.6, 72.4, 73.2,
73.8, 76.8, 78.5, 79.1, 110.0, 128.3-138.5; MS (FAB) m/z 401
(M+ + H). Anal. Calcd for C23H28O6: C, 68.98; H, 7.05. Found:
(211 mg, 7.3%), (+)-2 (448 mg, 11.3%), and the starting
material (+)-3 (345 mg, 18.5%). A similar reaction with
compound (-)-3 afforded compounds (-)-19, (-)-20, (-)-2, and
the starting material (-)-3. Data for (+)-19: Rf 0.25 (EtOAc:
Hex ) 1:2); mp 128-129 °C; [R]D +190.5 (c 2.07, CHCl3); 1H
20
NMR (CDCl3) δ 1.34, 1.36 (2s, 6H), 2.77 (br s, 1H), 4.37 (dd, J
) 4.3, 8.0 Hz, 1H), 4.53 (dd, J ) 4.2, 8.0 Hz, 1H), 4.65 (br s,
1H), 5.75 (app t, J ) 4.3 Hz, 1H), 6.06 (ddd, J ) 1.4, 4.4, 9.4
20
C, 68.62; H, 7.09. Data for (-)-16: mp 116-117 °C; [R]D
-11.4 (c 0.77, THF); Rf, 1H NMR, and 13C NMR data identical
to those of (+)-16.
Hz, 1H), 6.13 (dd, J ) 2.8, 9.4 Hz, 1H), 7.37-8.04 (m, 5H); 13
C
(1R,2S,3S,6S)- a n d (1S,2R,3R,6R)-3,6-Bis(p h en ylm eth -
oxy)-4-cycloh exen e-1,2-d iol Diben zoa te [(+)-17 a n d (-)-
17]. A solution of compound (+)-15 (3.09 g, 8.43 mmol) in 80%
aq AcOH (70 mL) was heated at 100 °C for 3 h, and then
concentrated under reduced pressure to give a crude product
quantitatively. To a solution of the crude product and DMAP
(108 mg) in pyridine (60 mL) at 0 °C was added BzCl (4 mL,
34.1 mmol) dropwise. After being stirred for 10 h at rt, the
mixture was treated with water (5 mL) for 30 min, diluted
with EtOAc, and washed with 1 N HCl, aq NaHCO3, and brine.
The organic layer was separated, dried (MgSO4), concentrated,
and chromatographed to afford compound (+)-17 (4.33 g, 96%)
as an oil. Similarly, compound (-)-17 was prepared from
compound (-)-15. Data for (+)-17: Rf 0.35 (EtOAc:Hex ) 1:4);
NMR (CDCl3) δ 24.9, 26.7, 67.3, 69.7, 74.3, 79.9, 110.5, 127.8-
136.4, 166.4; MS (FAB) m/z 291 (M+ + H). Anal. Calcd for
C16H18O5: C, 66.19; H, 6.25. Found: C, 65.79; H, 6.28. Data
20
for (-)-19: mp 128-129 °C; [R]D -190.2 (c 2.15, CHCl3); Rf,
1H NMR, and 13C NMR data identical to those of (+)-19. Data
20
for (+)-20: Rf 0.32 (EtOAc:Hex ) 1:2); mp 124-125 °C; [R]D
+205.6 (c 1.04, CHCl3); 1H NMR (CDCl3) δ 1.39, 1.45 (2s, 6H),
2.67 (br s, 1H), 4.50 (br s, 1H), 4.61 (dd, J ) 2.8, 7.3 Hz, 1H),
4.68 (dd, J ) 4.4, 7.3 Hz, 1H), 5.53 (app q, J ) 2.7 Hz, 1H),
6.11 (m, 2H), 7.41-8.00 (m, 5H); 13C NMR (CDCl3) δ 25.0, 26.6,
65.7, 69.0, 75.9, 76.0, 110.0, 126.9-136.8, 165.9 (COPh); MS
(FAB) m/z 291 (M+ + H). Anal. Calcd for C16H18O5: C, 66.19;
H, 6.25. Found: C, 65.89; H, 6.42. Data for (-)-20: mp 124-
125 °C; [R]D -205.5 (c 1.05, CHCl3); Rf, 1H NMR, and 13C
20
[R]D +190.5 (c 1.91, CHCl3); 1H NMR (CDCl3) δ 4.46 (td, J )
NMR data identical to those of (+)-20. Data for (+)-2: mp 140-
20
141 °C; [R]D +175.3 (c 1.66, CHCl3); Rf, 1H NMR, and 13C
20
2.6, 5.5 Hz, 1H), 4.52 (d, J ) 11.7 Hz, 1H), 4.64-4.73 (m, 3H),
4.74 (d, J ) 11.7 Hz, 1H), 5.59 (dd, J ) 2.0, 8.0 Hz, 1H), 5.84
(m, 1H), 6.00 (td, J ) 2.3, 2.3, 10.4 Hz, 1H), 6.17 (td, J ) 1.6,
1.6, 3.3 Hz, 1H), 7.21-8.00 (m, 20H); 13C NMR (CDCl3) δ 70.6,
71.7, 72.4, 73.9, 74.0, 75.0, 128.0-138.3, 166.3, 166.4; MS
NMR data identical to those of 2. Data for (-)-2: mp 140-
20
141 °C; [R]D -175.3 (c 1.62, CHCl3); Rf, 1H NMR, and 13C
NMR data identical to those of 2.
(3a S,7S,7a S)- a n d (3a R,7R,7a R)-7-(Ben zoyloxy)-7,7a -
d ih yd r o-2,2-d im eth yl-1,3-ben zod ioxol-4(3a H)-on e [(+)-21
a n d (-)-21]. To a solution of compound (+)-19 (581 mg, 2
mmol) and TEA (3 mL, 21.4 mmol) in DMSO (6 mL) at -15
°C, was added sulfur trioxide-pyridine complex (1.136 g, 7
mmol) in DMSO (4 mL). After being stirred for 3 h at rt, the
mixture was poured into cold brine, and extracted with EtOAc
three times. The organic extracts were washed with 0.1 N HCl
and brine, dried (MgSO4), and concentrated to afford the enone
(+)-21, which was used in the next step without further
purification. Similarly, compound (-)-21 was prepared from
compound (-)-19. Data for (+)-21: Rf 0.41 (EtOAc:Hex ) 1:2);
1H NMR (CDCl3) δ 1.38, 1.40 (2s, 6H), 4.44 (d, J ) 4.7 Hz,
1H), 4.91 (dt, J ) 2.2, 4.4, 4.4 Hz, 1H), 6.16 (td, J ) 2.4, 2.4,
4.1 Hz, 1H), 6.22 (dd, J ) 2.5, 10.4 Hz, 1H), 6.90 (td, J ) 2.2,
2.2, 10.4, 9.4 Hz, 1H), 7.45-8.15 (m, 5H); 13C NMR (CDCl3) δ
26.4, 27.8, 67.7, 74.9, 75.8, 111.6, 128.8-146.4, 166.1, 195.6.
20
(FAB) m/z 535 (M+ + H). Data for (-)-17: [R]D -192.6 (c
2.34, CHCl3); Rf, 1H NMR, and 13C NMR data identical to those
of (+)-17.
D-1,4-Bis-O-(ph en ylm eth yl)-n eo-in ositol 2,3-Diben zoate
[(+)-18a ], D-3,6-Bis-O-(p h en ylm et h yl)-n eo-in osit ol 1,2-
Dib en zoa t e [(-)-18a ], D-3,6-Bis-O-(p h en ylm et h yl)-ep i-
in ositol 4,5-Diben zoa te [(+)-18b], a n d D-3,6-Bis-O-(p h en -
ylm et h yl)-ep i-in osit ol 1,2-Dib en zoa t e [(-)-18b ]. Com-
pound (+)-17 (4.29 g, 8.02 mmol) was dihydroxylated by the
same procedure as described for compound (+)-16 to give
compounds (+)-18a (2.01 g, 45%) and (+)-18b (1.73 g, 39%).
A similar reaction with compound (-)-17 gave compounds (-)-
18a and (-)-18b. Data for (+)-18a : oil; Rf 0.25 (EtOAc:Hex )
20
1
1:1); [R]D +47.7 (c 4.60, CHCl3); H NMR (CDCl3) δ 2.73 (br
s, 1H), 2.84 (br s, 1H, 4.03-4.08 (m, 3H, H-3), 4.44 (br s, 1H),
4.48 (d, J ) 10.8 Hz, 1H), 4.63 (d, J ) 12.0 Hz, 1H), 4.71(d, J
) 12.0 Hz, 1H), 4.82 (d, J ) 10.8 Hz, 1H), 5.70 (dd, J ) 2.4,
10.0 Hz, 1H), 6.13 (br s, 1H), 7.23-7.91 (m, 20H); 13C NMR
(CDCl3) δ 68.6, 69.1, 70.3, 71.1, 72.5, 72.8, 76.1, 76.8, 128.4-
137.8, 166.0, 166.1; HRMS (FAB) m/z calcd for C34H33O8
1
Data for (-)-21: Rf, H NMR, and 13C NMR data identical to
those of (+)-21.
(3a S,4S,7R,7a R)- a n d (3a R,4R,7S,7a S)-3a ,4,7,7a -Tetr a -
h ydr o-2,2-dim eth yl-1,3-ben zodioxole-4,7-d iol 4-Mon oben -
zoa te [(-)-22 a n d (+)-22]. To a solution of the crude enone
(+)-21 in MeOH-CH2Cl2 (1:5, 12 mL) at 0 °C was added
NaBH4 (193 mg, 5 mmol). After being stirred at rt for 2.5 h,
the mixture was treated with water (2 mL), evaporated, and
diluted with EtOAc. The organic layer was washed with water
and brine, dried (MgSO4), concentrated, and chromatographed
to afford compound (-)-22 (433 mg, 74.5% from (+)-19).
Similarly, compound (+)-22 was prepared from compound (-)-
19 via compound (-)-21. Data for (-)-22: Rf 0.24 (EtOAc:Hex
569.2175, found 569.2171 (M+ + H). Data for (-)-18a : [R]D
20
-46.4 (c 4.24, CHCl3); Rf, 1H NMR, and 13C NMR data identical
to those of (+)-18a . Data for (+)-18b: oil; Rf 0.4 (EtOAc:Hex
) 1:1); [R]D20 +16.7 (c 2.56, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 2.97 (br s, 1H), 3.10 (br s, 1H), 3.86 (dd, J ) 3.0, 6.3 Hz,
1H), 4.02 (br s, 1H), 4.29-4.32 (m, 2H), 4.67-4.84 (m, 4H),
5.52 (dd, J ) 3.1, 6.9 Hz, 1H), 5.96 (br s, 1H), 7.27-8.06 (m,
20H); 13C NMR (CDCl3) δ 70.5, 70.6, 71.7, 73.0, 74.1, 75.0, 77.1,
77.6, 128.5-138.4, 166.1, 166.2; HRMS (FAB) m/z calcd for
20
20
C
34H33O8 569.2175, found 569.2178 (M+ + H). (-)-18b: [R]D
) 1:2); mp 108-109 °C; [R]D -42.6 (c 1.03, CHCl3); 1H NMR
-17.2 (c 5.25, CHCl3); Rf, 1H NMR, and 13C NMR data identical
to those of (+)-18b.
(CDCl3) δ 1.35, 1.42 (2s, 6H), 2.66 (br s, 1H), 4.10 (br s, 1H),
4.60 (ddd, J ) 1.6, 4.8, 7.4 Hz, 1H), 4.82 (ddd, J ) 1.7, 3.7, 7.4
Hz, 1H), 5.33-5.36 (m, 1H), 5.76-5.81 (m, 1H), 5.83-5.88 (m,
1H), 7.44-8.14 (m, 5H); 13C NMR (CDCl3) δ 25.2, 26.2, 67.0,
70.0, 74.1, 75.7, 110.6, 126.7-133.7, 166.6; MS (FAB) m/z 291
(M+ + H). Anal. Calcd for C16H18O5: C, 66.19; H, 6.25. Found:
(3a S,4S,7S,7a R)- a n d (3a R,4R,7R,7a S)-3a ,4,7,7a -Tetr a -
h ydr o-2,2-dim eth yl-1,3-ben zod ioxole-4,7-d iol 4-Mon oben -
zoate [(+)-19 an d (-)-19], (3aR,4S,7S,7aS)- an d (3aS,4R,7R,
7aR)-3a,4,7,7a-Tetr ah ydr o-2,2-dim eth yl-1,3-ben zodioxole-
4,7-d iol 4-Mon oben zoa te [(+)-20 a n d (-)-20], a n d (3a R,
4S,7S,7a S)- a n d (3a R,4R,7R,7a S)-3a ,4,7,7a -Tet r a h yd r o-
2,2-d im eth yl-1,3-ben zod ioxole-4,7-d iol Diben zoa te [(+)-
2 a n d (-)-2]. To a solution of compound (+)-3 (1.865 g, 10
mmol) in pyridine (50 mL) at 0 °C was added BzCl (1.2 mL,
10.2 mmol) dropwise. After being stirrred for 5 h at 0-10 °C,
the mixture was treated with water (3 mL) for 30 min, diluted
with EtOAc, and washed with 1 N HCl, aq NaHCO3, and brine.
The organic layer was separated, dried (MgSO4), concentrated,
and chromatographed to afford (+)-19 (1.69 g, 58.3%), (+)-20
20
C, 65.87; H, 6.34. Data for (+)-22: mp 108-109 °C; [R]D
+42.5 (c 0.74, CHCl3); Rf, 1H NMR, and 13C NMR data identical
to those of (-)-22.
(1R,2R,3S,4S)-r el-5-Cycloh exen e-1,2,3,4-tetr ol (Con d u -
r itol D, 23).18b,23d,24a To a solution of compound (+)-22 or (-)-
22 (145 mg, 0.50 mmol) in MeOH (3 mL) was added 25 wt %
sodium methoxide (in MeOH, 3 drops). After being stirred for
1.5 h at reflux, the mixture was filtered through a short pad
of silica gel, and the solvent was evaporated under reduced
pressure. The crude product in 80% aq AcOH (5 mL) was

3336 J . Org. Chem., Vol. 67, No. 10, 2002
Kwon et al.
heated at 100 °C for 3 h, and then concentrated under reduced
pressure to give a crude product which was chromatographed
(MeOH:CH2Cl2 ) 1:15) to give the pure conduritol D (23)18b,23d,24a
(67 mg, 92%) as an oil: 1H NMR (CD3OD) δ 3.77 (d, J ) 4.6
(3a S,4R,7S,7a R)- a n d (3a R,4S,7R,7a S)-3a ,4,7,7a -Tetr a -
h ydr o-7-(m eth oxym eth oxy)-2,2-dim eth yl-1,3-ben zodioxol-
4-ol Mon oben zoa te [(-)-30 a n d (+)-30]. Mitsunobu reaction
of compound (+)-29 (665 mg, 2.89 mmol) was accomplished
by the same procedure as described for compound 19 to give
compound (-)-30 (938 mg, 97.1%) as an oil. Similarly, com-
pound (+)-30 was prepared from compound (-)-29. Data for
(-)-30: Rf 0.55 (EtOAc:Hex ) 1:4); [R]D20 -91.7 (c 4.37, CHCl3);
1H NMR (CDCl3) δ 1.39, 1.51 (2s, 6H), 3.34 (s, 3H), 4.26-4.31
(m, 2H), 4.39-4.44 (m, 1H), 4.79 (d, J ) 6.7 Hz, 1H), 4.90 (d,
J ) 6.7 Hz, 1H), 5.47-5.51 (m, 1H), 5.78 (td, J ) 2.1, 2.1, 10.0
Hz, 1H), 5.91 (td, J ) 2.2, 2.2, 10.0 Hz, 1H), 7.42-8.11 (m,
5H); 13C NMR (CDCl3) δ 25.5, 27.6, 56.0, 73.3, 74.9, 76.4, 77.9,
96.2, 110.0, 128.0-133.6, 166.3; HRMS (FAB) m/z calcd for
Hz, 2H), 4.06 (d, J ) 3.4 Hz, 2H), 5.76 (d, J ) 1.5 Hz, 2H); 13
NMR (CD3OD) δ 69.2 (2C), 71.1 (2C), 130.5 (2C).
C
D-2,3-O-(1-Meth yleth ylid en e)-a llo-in ositol 1-Mon oben -
zoa t e [(-)-24] a n d D-2,3-O-(1-Met h ylet h ylid en e)-a llo-
in ositol 4-Mon oben zoa te [(+)-24]. Compound (-)-22 (290
mg, 1.0 mmol) was dihydroxylated by the same procedure as
described for compound (+)-16 to give compound (-)-24 (285
mg, 88%) as a solid. A similar reaction with compound (+)-22
gave compound (+)-24. Data for (-)-24: Rf 0.22 (MeOH:CH2Cl2
) 1:20); mp 173-175 °C; [R]2D0 -42.9 (c 1.06, CH3OH); 1H
NMR (CD3OD) δ 1.32, 1.43 (2s, 6H), 3.92 (dd, J ) 4.1, 8.4 Hz,
1H), 4.09 (dd, J ) 5.1, 8.4 Hz, 1H), 4.25 (dd, J ) 5.1, 8.2 Hz,
1H), 4.55 (dd, J ) 4.1, 6.8 Hz, 1H), 4.67 (dd, J ) 4.2, 6.8 Hz,
1H), 5.30 (dd, J ) 4.2, 8.2 Hz, 1H), 7.45-8.10 (m, 5H); 13C
NMR (CD3OD) δ 24.9, 26.3, 69.1, 70.4, 71.1, 73.4, 74.5, 77.0,
111.1, 129.6, 130.9, 131.4, 134.5, 167.7; MS (FAB) m/z 325 (M+
+ H). Anal. Calcd for C16H20O7: C, 59.25; H, 6.22. Found: C,
C
18H23O6 335.1495, found 335.1511 (M+ + H). Data for (+)-
20 1
30: [R]D +91.3 (c 4.16, CHCl3); Rf, H NMR, and 13C NMR
data identical to those of (-)-30.
(1R,2S,3R,4S)-r el-5-Cycloh exen e-1,2,3,4-tetr ol (Con d u -
r itol A, 31).23d,26a Compound (-)-30 or (+)-30 (151 mg, 0.45
mmol) was hydrolyzed by the same procedure as described for
compound 23 to give conduritol A (31) (40 mg, 89%) as a
solid: mp 140-142 °C [lit.23d mp 141-143 °C, lit.26a mp 140-
141 °C]; 1H NMR (CD3OD) δ 3.64 (d, J ) 4.6 Hz, 2H), 3.99 (d,
J ) 4.1 Hz, 2H), 5.56 (d, J ) 1.2 Hz, 2H); 13C NMR (CD3OD)
δ 70.6 (2C), 74.2 (2C), 130.7 (2C).
20
58.99; H, 6.42. Data for (+)-24: mp 174-175 °C; [R]D +41.8
1
(c 1.16, CH3OH); Rf, H NMR, and 13C NMR data identical to
those of (-)-24.
(3a R,4R,7S,7a S)-r el-3a ,4,7,7a -Tetr a h yd r o-2,2-d im eth yl-
1,3-ben zodioxole-4, 7-diol Diben zoate (27) an d (3aR,4S,5R,
7aR)-r el-3a,4,5,7a-Tetr ah ydr o-2,2-dim eth yl-1,3-ben zodiox-
ole-4,5-d iol Diben zoa te (28). To a solution of the racemate
19 (mp 132-133 °C; 790 mg, 2.72 mmol), which was prepared
from racemate 3 by the same procedure as described for
compound (+)-19, Ph3P (1.80 g, 6.79 mmol), and benzoic acid
(839 mg, 6.79 mmol) in toluene (25 mL) was added dropwise
diethyl azodicarboxylate (1.1 mL, 6.79 mmol). After being
stirred at rt for 3 h, the mixture was filtered through silica
gel (EtOAc:Hex ) 1:4), concentrated, and chromatographed
to afford compounds 27 (91 mg, 8.5%) and 28 (785 mg, 73.1%).
D-4-O-(Meth oxym eth yl)-5,6-O-(1-m eth yleth yliden e)-a llo-
in ositol Tr iben zoa te [(-)-32a ], D-1-O-(Meth oxym eth yl)-
5,6-O-(1-m eth yleth yliden e)-a llo-in ositol Tr iben zoate [(+)-
32a ], D-3-O-(Meth oxym eth yl)-1,2-O-(1-m eth yleth ylid en e)-
m u co-in osit ol Tr ib en zoa t e [(+)-32b ], a n d D-6-O-(Met h -
oxym eth yl)-1,2-O-(1-m eth yleth yliden e)-mu co-in ositol Tr i-
ben zoa te [(-)-32b]. To a solution of compound (-)-30 (418
mg, 1.25 mmol) in a mixture of acetone and water (8:1, 9 mL)
were added NMO (630 mg, 5.22 mmol) and then OsO4 (∼30
mg). After being stirred for 15 h at rt, the reaction mixture
was quenched with a few drops of 10% NaHSO3, and the
solvents were evaporated under reduced pressure. The crude
mixture was diluted with MeOH-CH2Cl2 (1:20) and filtered
through a short pad of silica gel. After removal of the solvent
by evaporation, TLC showed 3-4 products which were thought
to be benzoyl-migrated products. Direct benzoylation of the
crude mixture was carried out with BzCl (0.7 mL, 5.97 mmol)
and DMAP (25 mL) in pyridine (7 mL). After being stirred at
rt overnight, the mixture was treated with water (2 mL) for
20 min, diluted with EtOAc, and washed with 1 N HCl, aq
NaHCO3, and brine. The organic layer was separated, dried
(MgSO4), concentrated, and chromatographed to afford com-
pounds (-)-32a (613 mg, 85%) and (+)-32b (75 mg, 9.3%). A
similar reaction with compound (+)-30 was carried out to give
compounds (+)-32a and (-)-32b. Data for (-)-32a : oil; Rf 0.16
(CH2Cl2); [R]D20 -4.23 (c 2.00, CHCl3); 1H NMR (CDCl3) δ 1.44,
1.62 (2s, 6H), 3.37 (s, 3H), 4.25 (dd, J ) 3.0, 6.7 Hz, 1H), 4.58-
4.66 (m, 2H), 4.74 (d, J ) 6.9 Hz, 1H), 4.80 (d, J ) 6.9 Hz,
1H), 5.76 (dd, J ) 2.8, 4.2 Hz, 1H), 5.95-5.97 (m, 2H), 7.13-
8.06 (m, 15H); 13C NMR (CDCl3) δ 26.7, 28.5, 56.2, 68.8, 69.4,
70.4, 74.1, 76.1, 76.4, 96.0, 110.1, 128.6-133.6, 165.6, 166.1,
166.2; HRMS (FAB) m/z calcd for C32H33O10 577.2074, found
1
Data for 27: Rf 0.6 (EtOAc:Hex ) 1:2); mp 201-202 °C; H
NMR (CDCl3) δ 1.33, 1.44 (2s, 6H), 4.88 (app t, J ) 1.2 Hz,
2H), 5.42 (dd, J ) 2.4 Hz, 2H), 5.96 (s, 2H), 7.45-8.16 (m,
10H); 13C NMR (CDCl3) δ 24.9, 25.9, 69.8 (2C), 73.9 (2C), 110.7,
127.6-133.5, 166.3 (2C); MS (FAB) m/z 395 (M+ + H). Anal.
Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 69.83; H,
5.66. Data for 28: Rf 0.61 (EtOAc:Hex ) 1:2); mp 108-110
1
°C; H NMR (CDCl3) δ 1.36, 1.45 (2s, 6H), 4.71 (dd, J ) 2.3,
8.4 Hz, 1H), 4.78-4.80 (m, 1H), 5.58 (dd, J ) 2.3, 8.9 Hz, 1H),
5.83 (m, 2H), 6.13 (br d, J ) 8.9 Hz, 1H), 7.33-8.06 (m, 10H);
13C NMR (CDCl3) δ 27.2, 28.2, 69.4, 72.8, 74.0, 74.9, 111.1,
127.2-133.7, 166.4, 166.6; MS (FAB) m/z 395 (M+ + H). Anal.
Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 69.79; H,
5.84.
(3a S,4S,7S,7a R)- a n d (3a R,4R,7R,7a S)-3a ,4,7,7a -Tetr a -
h ydr o-7-(m eth oxym eth oxy)-2,2-dim eth yl-1,3- ben zodioxol-
4-ol [(+)-29 a n d (-)-29]. To a solution of compound (+)-19
(900 mg, 3.10 mmol) in chloroform (12 mL) were added N,N-
diisopropylethylamine (2.2 mL, 12.6 mmol) and chloromethyl
methyl ether (0.71 mL, 9.35 mmol). After being stirred at rt
overnight, the reaction mixture was diluted with CH2Cl2. The
organic layer was washed with aq NaHCO3 and brine, dried,
and concentrated to dryness. The crude mixture was treated
with 25 wt % sodium methoxide (in MeOH, 0.2 mL) in MeOH
(12 mL). The resulting mixture was stirred under reflux for 3
h and filtered through a short pad of silica gel, and the solvent
was evaporated under reduced pressure. Column chromatog-
raphy gave compound (+)-29 (693 mg, 97.1%) as an oil.
Similarly, compound (-)-29 was prepared from (-)-19. Data
20
577.2101 (M+ + H). Data for (+)-32a : [R]D +4.82 (c 1.66,
1
CHCl3); Rf, H NMR, and 13C NMR data identical to those of
20
(-)-32a . Data for (+)-32b: oil; Rf 0.25 (CH2Cl2); [R]D +89.5
1
(c 1.80, CHCl3); H NMR (500 MHz, CDCl3) δ 1.42, 1.72 (2s,
6H), 3.50 (s, 3H), 4.46 (dd, J ) 3.2, 5.0 Hz, 1H), 4.53 (app. t,
J ) 3.9 Hz, 1H), 4.57 (app t, J ) 6.0 Hz, 1H), 4.89 (s, 2H),
5.76 (dd, J ) 2.8, 9.3 Hz, 1H), 5.80 (app t, J ) 3.5 Hz, 1H),
6.14 (dd, J ) 6.8, 9.3 Hz, 1H), 7.28-8.12 (m, 15H); 13C NMR
(CDCl3) δ 26.5, 28.3, 56.6, 69.7, 71.2, 71.4, 72.8, 77.3, 77.8,
97.3, 110.4, 128.8-133.8, 166.0 (2C), 166.1; HRMS (FAB) m/z
calcd for C32H32O10Na 599.1893, found 599.1901 (M+ + Na).
20
for (+)-29: Rf 0.22 (EtOAc:Hex ) 1:2); [R]D +111.3 (c 1.21,
CHCl3); 1H NMR (CDCl3) δ 1.37, 1.41 (2s, 6H), 2.99 (br s, 1H),
3.36 (s, 3H), 4.29 (app t, J ) 3.4 Hz, 1H), 4.38-4.44 (m, 2H),
4.51 (dd, J ) 4.1, 7.5 Hz, 1H), 4.65 (d, J ) 6.7 Hz, 1H), 4.68
(d, J ) 6.7 Hz, 1H), 5.97-6.03 (m, 2H); 13C NMR (CDCl3) δ
24.8, 26.5, 55.7, 65.3, 71.4, 76.1, 77.5, 95.3, 109.5, 129.4, 134.7;
Data for (-)-32b: [R]D -88.2 (c 2.15, CHCl3); Rf, 1H NMR,
20
and 13C NMR data identical to those of (+)-32b.
(1R,4S,5R,6S)- a n d (1S,4R,5S,6R)-4,5,6-Tr is(m eth oxy-
m eth oxy)-2-cycloh exen -1-ol Mon oben zoa te [(-)-33 a n d
(+)-33]. Compound (-)-30 (475 mg, 1.42 mmol) in 80% aq
AcOH (8 mL) was heated at 70 °C for 3 h, and then
concentrated to dryness. To a solution of the crude mixture in
20
MS (FAB) m/z 231 (M+ + H). Data for (-)-29: [R]D -111.5
1
(c 2.25, CHCl3); Rf, H NMR, and 13C NMR data identical to
those of (+)-29.

Syntheses of Conduritol and Derivatives of Inositol
J . Org. Chem., Vol. 67, No. 10, 2002 3337
chloroform (10 mL) were added N,N-diisopropylethylamine (4.5
mL, 25.8 mmol) and chloromethyl methyl ether (1.8 mL, 23.5
mmol). After being stirred at rt overnight, the reaction mixture
was diluted with CH2Cl2, washed with aq NaHCO3 and brine,
dried, and concentrated. Column chromatography afforded
compound (-)-33 (474 mg, 97.1%) as an oil. Similarly, com-
pound (+)-33 was prepared from compound (+)-30. Data for
(-)-33: Rf 0.4 (EtOAc:Hex ) 1:2); [R]D20 -132.3 (c 1.75, CHCl3);
1H NMR (CDCl3) δ 3.36, 3.42, 3.44 (3s, 9H), 4.14 (dd, J ) 2.2,
5.0 Hz, 1H), 4.23 (dd, J ) 2.2, 6.0 Hz, 1H), 4.32 (app t, J ) 4.0
Hz, 1H), 4.75-4.84 (m, 6H), 5.77 (dd, J ) 2.8, 6.0 Hz, 1H),
5.90 (dd, J ) 2.8, 10.0 Hz, 1H), 5.96 (dd, J ) 3.1, 10.0 Hz,
1H), 7.42-8.07 (m, 5H); 13C NMR (CDCl3) δ 56.0 (3C), 71.3,
74.3, 74.8, 76.1, 96.5, 96.9, 97.2, 128.8-133.5, 166.3; MS (FAB)
being stirred at 80 °C overnight, the mixture was filtered
through silica gel (EtOAc:Hex ) 1:2), concentrated, and
chromatographed to afford compound (-)-37 (399 mg, 79%)
as a solid. Similarly, compound (+)-37 was prepared from
compound (+)-36. Data for (-)-37: Rf 0.5 (EtOAc:Hex ) 1:2);
mp 199-201 °C; [R]D20 -74.0 (c 0.88, CHCl3); 1H NMR (CDCl3)
δ 1.50, 1.51 (2s, 6H), 2.55 (br s, 1H), 3.59 (app t, J ) 9.3 Hz,
1H), 3.65 (app t, J ) 7.5 Hz, 1H), 3.71 (app t, J ) 8.0 Hz, 1H),
3.75 (m, 2H), 4.64-4.98 (m, 4H), 5.38 (app t, J ) 8.9 Hz, 1H),
7.14-8.02 (m, 15H); 13C NMR (CDCl3) δ 27.4 (2C), 72.6, 73.3,
75.0, 76.5, 76.7, 79.1, 79.3, 79.5, 113.3, 127.8-138.5, 166.5;
MS (FAB) m/z 505 (M+ + H). Anal. Calcd for C30H32O7: C,
71.41; H, 6.39. Found: C, 71.28; H, 6.59. Data for (+)-37: mp
200-202 °C; [R]D +74.7 (c 1.01, CHCl3); Rf, 1H NMR, and
20
m/z 383 (M+ + H). Data for (+)-33: [R]D +131.9 (c 3.43,
13C NMR data identical to those of (-)-37.
20
1
CHCl3); Rf, H NMR, and 13C NMR data identical to those of
(3a R,4R,7R,7a R)- a n d (3a S,4S,7S,7a S)-3a ,4,7,7a -Tetr a -
h yd r o-2,2-d im eth yl-1,3-ben zod ioxole-4,7-d iol Diben zoa te
[(-)-38 a n d (+)-38]. To a solution of compound (+)-11 (295
mg, 1.58 mmol), Ph3P (2.91 g, 11.0 mmol), and benzoic acid
(1.35 g, 10.9 mmol) in toluene (20 mL) was added dropwise
diethyl azodicarboxylate (1.9 mL, 11.7 mmol). After being
stirred for 6 h at rt, the mixture was filtered through silica
gel (EtOAc:Hex ) 1:2), concentrated, and chromatographed
to afford compound (-)-38 (562 mg, 90%) as a solid. Similarly,
compound (+)-38 was prepared from compound (-)-11. Data
(-)-33.
D-1,2,3-Tr is-O-(m eth oxym eth yl)-m u co-in ositol 6-Mon o-
ben zoa te [(-)-34] a n d D-1,2,6-Tr is-O-(m eth oxym eth yl)-
m u co-in ositol 3-Mon oben zoa te [(+)-34]. Compound (-)-33
(285 mg, 0.745 mmol) was dihydroxylated by the same
procedure as described for compound (+)-16 to give compound
(-)-34 (304 mg, 98%) as an oil. Similarly, compound (+)-34
was prepared from compound (+)-33. Data for (-)-34: Rf 0.21
(EtOAc:Hex ) 1:1); [R]D -3.29 (c 1.11, CHCl3); 1H NMR
20
20
(CDCl3) δ 2.86 (br s, 1H), 3.31, 3.44, 3.45 (3s, 9H), 3.61 (br s,
1H), 3.95-4.00 (m, 2H), 4.07 (app t, J ) 4.6 Hz, 1H), 4.16 (dd,
J ) 2.8, 8.7 Hz, 1H), 4.20 (app t, J ) 3.4 Hz, 1H), 4.67-4.84
(m, 6H), 5.63 (app t, J ) 8.3 Hz, 1H), 7.42-8.09 (m, 5H); 13C
NMR (CDCl3) δ 56.3, 56.4, 56.6, 71.9, 72.8, 73.1, 75.1, 76.1,
76.9, 96.9, 97.7, 97.8, 128.8, 129.1, 130.2, 133.5, 166.2; HRMS
(FAB) m/z calcd for C19H28O10Na 439.1580, found 439.1587 (M+
for (-)-38: Rf 0.59 (EtOAc:Hex ) 1:2); mp 119-120 °C; [R]D
1
-452.3 (c 1.17, CHCl3); H NMR (CDCl3) δ 1.41 (s, 6H), 4.33
(d, J ) 1.1 Hz, 2H), 5.96 (d, J ) 1.1 Hz, 2H), 6.26 (m, 2H),
7.43-8.07 (m, 10H); 13C NMR (CDCl3) δ 27.1 (2C), 66.7 (2C),
72.9 (2C), 111.5, 126.3-133.6, 166.3 (2C); MS (FAB) m/z 395
(M+ + H). Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found:
20
C, 69.74; H, 5.73. Data for (+)-38: mp 119-120 °C; [R]D
+ Na). Data for (+)-34: [R]D +3.58 (c 0.43, CHCl3); Rf, 1H
+453.2 (c 1.24, CHCl3); Rf, 1H NMR, and 13C NMR data
identical to those of (-)-38.
20
NMR, and 13C NMR data identical to those of (-)-34.
(3a R,4S,7S,7a R)- a n d (3a S,4R,7R,7a S)-3a ,4,7,7a -Tetr a -
h yd r o-2,2-d im eth yl-4,7-bis(p h en ylm eth oxy)-1, 3-ben zo-
d ioxole [(+)-35 a n d (-)-35].27b Compound (+)-11 (345 mg,
1.85 mmol) was benzylated by the same procedure as described
for compound (+)-15 to give compound (+)-35 (651 mg, 96%)
as an oil. Similarly, compound (-)-35 was prepared from
compound (-)-11. Data for (+)-35: Rf 0.54 (EtOAc:Hex ) 1:6);
[R]D20 +19.0 (c 2.29, CHCl3) [lit.27b [R]D20 +6.1 (c 1.46, CHCl3)];
1H NMR (CDCl3) δ 1.48 (s, 6H), 3.64 (dd, J ) 2.2, 5.3 Hz, 2H),
4.25 (dd, J ) 2.2, 5.3 Hz, 2H), 4.66 (d, J ) 11.8 Hz, 2H), 4.84
(d, J ) 11.8 Hz, 2H), 5.70 (s, 2H), 7.27-7.39 (m, 10H); 13C
NMR (CDCl3) δ 27.6 (2C), 72.2 (2C), 77.6 (2C), 80.8 (2C), 111.4,
(1R,2R,3R,4R)- an d (1S,2S,3S,4S)-5-Cycloh exen e-1,2,3,4-
tetr ol [(-)- a n d (+)-Con d u r itol E, (-)-39 a n d (+)-39].19b,27b
Compound (-)-38 (146 mg, 0.37 mmol) was hydrolyzed by the
same procedure as described for compound 23 to give com-
pound (-)-39 (49 mg, 91%) as a solid. Similarly, compound
(+)-39 was prepared from compound (+)-38. Data for (-)-39:
mp 190-192 °C [lit.27b mp 191-193 °C, lit.19b mp 192-193 °C];
[R]D -331.6 (c 1.06, H2O) [lit.27b [R]D -330.0 (c 1.90, H2O),
20
20
lit.19b [R]D -330 (c 4.5, H2O)]; H NMR (D2O) δ 3.93 (s, 2H),
4.31 (s, 2H), 5.88 (d, J ) 2.3 Hz, 2H); 13C NMR (D2O) δ 66.8
(2C), 69.3 (2C), 129.9 (2C). Data for (+)-39: mp 191-193 °C;
20
1
[R]D +331.8 (c 1.20, H2O); 1H NMR and 13C NMR data
identical to those of (-)-39.
20
128.0, 128.2, 128.8, 129.5, 138.7; MS (FAB) m/z 367 (M+
+
H). Data for (-)-35: [R]D20 -18.9 (c 1.61, CHCl3); Rf, 1H NMR,
(3a R,4R,7R,7a R)- a n d (3a S,4S,7S,7a S)-3a ,4,7,7a -Tetr a -
h yd r o-2,2-d im et h yl-4,7-b is(p h en ylm et h oxy)-1,3-b en zo-
d ioxole [(-)-40 a n d (+)-40].27b To a solution of compound
(-)-38 (382 mg, 0.97 mmol) in MeOH (6 mL) was added 25 wt
% sodium methoxide (in MeOH, 0.05 mL). The resulting
mixture was stirred under reflux. After 4 h, the solvent was
evaporated under reduced pressure. To a solution of the crude
mixture and NaH (150 mg, 5.9 mmol) in DMF (5 mL) at 0 °C
was added BnBr (0.5 mL, 4.05 mmol). After 30 min, the
mixture was warmed to rt and stirred overnight. The mixture
was diluted with EtOAc and successively washed with 1 N
HCl, aq NaHCO3, and brine. The organic layer was separated,
dried (MgSO4), and concentrated. Column chromatography
gave compound (-)-40 (327 mg, 92%) as a solid. Similarly,
compound (+)-40 was prepared from compound (+)-38. Data
for (-)-40: Rf 0.35 (EtOAc:Hex ) 1:10); mp 49-50 °C [lit.27b
and 13C NMR data identical to those of (+)-35.
D-4,5-O-(1-Meth yleth yliden e)-3,6-bis-O-(ph en ylm eth yl)-
m yo-in ositol [(-)-36] a n d D-5,6-O-(1-Meth yleth ylid en e)-
1,4-b is-O-(p h en ylm et h yl)-m yo-in osit ol [(+)-36].37 Com-
pound (+)-35 (602 mg, 1.64 mmol) was dihydroxylated by the
same procedure as described for compound (+)-16 to give
compound (-)-36 (621 mg, 94.4%) as a solid. Similarly,
compound (+)-36 was prepared from compound (-)-35. Data
for (-)-36: Rf 0.2 (EtOAc:Hex ) 1:2); mp 125-126 °C [lit.37
20
1
mp 149-151 °C (racemate)]; [R]D -67.0 (c 1.02, CHCl3); H
NMR (CDCl3) δ 1.47, 1.49 (2s, 6H), 2.60 (br s, 2H), 3.39 (app
t, J ) 9.6 Hz, 1H), 3.55 (dd, J ) 3.1, 8.7 Hz, 1H), 3.60 (dd, J
) 3.0, 10.1 Hz, 1H), 3.82 (app t, J ) 9.2 Hz, 1H), 4.05 (app t,
J ) 9.9 Hz, 1H), 4.22 (app t, J ) 3.1 Hz, 1H), 4.68-4.97 (m,
4H), 7.27-7.40 (m, 10H); 13C NMR (CDCl3) δ 27.4 (2C), 71.7,
72.2, 73.4, 74.0, 76.6, 78.0, 78.6, 79.7, 112.3, 128.1-138.4; MS
(FAB) m/z 401 (M+ + H). Anal. Calcd for C23H28O6: C, 68.98;
H, 7.05. Found: C, 68.65; H, 7.21. Data for (+)-36: mp 125-
126 °C; [R]D20 +68.0 (c 1.08, CHCl3); Rf, 1H NMR, and 13C NMR
data identical to those of (-)-36.
20
20
mp 66-68 °C]; [R]D -206.7 (c 1.21, CHCl3) [lit.27b [R]D
1
-192.3 (c 0.87, CHCl3)]; H NMR (CDCl3) δ 1.54 (s, 6H), 4.20
(s, 2H), 4.33 (m, 2H), 4.63 (d, J ) 11.6 Hz, 2H), 4.97 (d, J )
11.6 Hz, 2H), 5.90 (dd, J ) 1.2, 3.0 Hz, 2H), 7.27-7.38 (m,
10H); 13C NMR (CDCl3) δ 27.3 (2C), 72.4 (2C), 73.9 (2C), 75.3
(2C), 110.5, 127.9, 128.1, 128.7, 129.8, 139.2; MS (FAB) m/z
367 (M+ + H). Data for (+)-40: mp 48-49 °C; [R]D20 +206.0 (c
1.52, CHCl3); Rf, 1H NMR, and 13C NMR data identical to those
of (-)-40.
D-4,5-O-(1-Meth yleth yliden e)-3,6-bis-O-(ph en ylm eth yl)-
scyllo-in ositol 1-Mon oben zoa te [(-)-37] a n d D-3,4-O-(1-
Meth yleth ylid en e)-2,5-bis-O-(p h en ylm eth yl)-scyllo-in os-
itol 1-Mon oben zoa te [(+)-37]. To a solution of compound (-)-
36 (401 mg, 1.0 mmol), Ph3P (477 mg, 1.8 mmol), and benzoic
acid (222 mg, 1.8 mmol) in toluene (12 mL) was added
dropwise diethyl azodicarboxylate (0.30 mL, 1.85 mmol). After
D-1,6-O-(1-Meth yleth yliden e)-2,5-bis-O-(ph en ylm eth yl)-
a llo-in ositol [(+)-41] a n d D-4,5-O-(1-Meth yleth ylid en e)-
3,6-bis-O-(p h en ylm eth yl)-a llo-in ositol [(-)-41]. Compound

3338 J . Org. Chem., Vol. 67, No. 10, 2002
Kwon et al.
(-)-40 (240 mg, 0.655 mmol) was dihydroxylated by the same
procedure as described for compound (+)-16 to give compound
(+)-41 (197 mg, 75%) as a solid. Similarly, compound (-)-41
was prepared from compound (+)-40. Data for (+)-41: Rf 0.38
(EtOAc:Hex ) 1:2); mp 87-88 °C; [R]D20 +20.4 (c 1.00, CHCl3);
1H NMR (CDCl3) δ 1.53, 1.55 (2s, 6H), 3.04 (d, J ) 9.6 Hz,
1H), 3.11 (d, J ) 10.0 Hz, 1H), 3.87-3.90 (m, 1H), 3.99-4.02
(m, 1H), 4.08 (dd, J ) 1.8, 10.1 Hz, 1H), 4.19 (app t, J ) 2.9
Hz, 1H), 4.32 (dd, J ) 2.4, 10.1 Hz, 1H), 4.36 (br s, 1H), 4.64
(d, J ) 11.2 Hz, 1H), 4.65 (d, J ) 11.8 Hz, 1H), 4.88 (d, J )
11.8 Hz, 1H), 4.50 (d, J ) 11.2 Hz, 1H), 7.28-7.39 (m, 10H);
13C NMR (CDCl3) δ 27.23 (2C), 68.4, 73.8, 73.9, 74.7, 75.5, 75.6,
75.7, 79.7, 111.24, 127.9-138.8; MS (FAB) m/z 401 (M+ + H).
Anal. Calcd for C23H28O6: C, 68.98; H, 7.05. Found: C, 68.70;
1H), 5.79 (br d, J ) 9.1 Hz, 1H), 5.93 (app t, J ) 4.3 Hz, 1H),
6.00 (dd, J ) 1.8, 10.0 Hz, 1H), 6.13 (ddd, J ) 1.8, 5.0, 10.0
Hz, 1H), 7.44-8.13 (m, 10H); 13C NMR (CDCl3) δ 27.0, 27.4,
66.4, 73.7, 74.6, 75.7, 112.0, 126.6-133.7, 166.2, 166.3; HRMS
(FAB) m/z calcd for C23H22O6Na 417.1314, found 417.1294 (M+
+ Na). Data for (+)-43: [R]D +55.0 (c 3.10, CHCl3); Rf, 1H
20
NMR, and 13C NMR data identical to those of (-)-43.
(1R,2R,3R,4S)- an d (1R,2S,3S,4S)-5-Cycloh exen e-1,2,3,4-
tetr ol [(-)- a n d (+)-Con d u r itol F , (-)-44 a n d (+)-
44].18a,24d,25d,27b Compound (-)-43 (140 mg, 0. 35 mmol) was
hydrolyzed by the same procedure as described for compound
23 to give compound (-)-44 (46.5 mg, 90%) as a solid.
Similarly, compound (+)-44 was prepared from compound (+)-
43. Data for (-)-44: mp 129-130 °C [lit. mp24d 126 °C, lit.25d
mp 131-132 °C, lit.27b mp 128-130 °C]; [R]D -99.7 (c 0.60,
20
20
H, 7.22. Data for (-)-41: mp 87-88 °C; [R]D -21.3 (c 0.57,
1
20
20
CHCl3); Rf, H NMR, and 13C NMR data identical to those of
H2O) [lit.24d [R]D -102 (c 1.5, H2O), lit.25d [R]D -71 (c 0.75,
CH3OH), lit.27b [R]D -84.0 (c 0.71, CH3OH)]; 1H NMR
20
(+)-41.
(3a R,4S,7S,7a R)- a n d (3a S,4R,7R,7a S)-3a ,4,7,7a -Tetr a -
h yd r o-2,2-d im et h yl-1,3-b en zod ioxole-4,7-d iol 4-Mon o-
ben zoa te [(+)-42 a n d (-)-42] a n d (3a S,4R,7R,7a S)- a n d
(3a R,4S,7S,7a R)-3a ,4,7,7a -Tet r a h yd r o-2,2-d im et h yl-1,3-
ben zod ioxole-4,7-d iol Diben zoa te [(+)-10 a n d (-)-10]. To
a solution of (+)-11 (620 mg, 3.3 mmol) in pyridine (15 mL) at
0 °C was added BzCl (0.41 mL, 3.50 mmol) dropwise. After
being stirred for 5 h at 0-5 °C, the mixture was treated with
water (2 mL) for 20 min, diluted with EtOAc, and washed with
1 N HCl, aq NaHCO3, and brine. The organic layer was
separated, dried (MgSO4), concentrated, and chromatographed
to afford the monobenzoate (+)-42 (590 mg, 61%), the diben-
zoate (+)-10 (184 mg, 14%), and the starting material (+)-11
(58 mg, 9.4%). A similar reaction with compound (-)-11 was
carried out to afford the monobenzoate (-)-42, the dibenzoate
(-)-10, and the starting material (-)-11. Data for (+)-42: Rf
0.27 (EtOAc:Hex ) 1:2); mp 123-124 °C; [R]D20 +172.1 (c 1.71,
(CD3OD) δ 3.44 (dd, J ) 4.3, 10.3 Hz, 1H), 3.64 (dd, J ) 7.6,
10.3 Hz, 1H), 3.95 (br d, J ) 7.5 Hz, 1H), 4.18 (app t, J ) 4.4
Hz, 1H), 5.73 (dd, J ) 1.8, 10.0 Hz, 1H), 5.81 (ddd, J ) 1.8,
4.7, 10.0 Hz, 1H); 13C NMR (CD3OD) δ 67.1, 71.7, 72.9, 73.1,
127.1, 132.9. Data for (+)-44: mp 128-129 °C [lit.18a mp 129-
130 °C]; [R]D +100.2 (c 0.77, H2O) [lit.18a [R]D +97.4 (c 0.7,
20
20
1
H2O)]; H NMR and 13C NMR data identical to those of (-)-
44.
L-2,3-O-(1-Meth yleth ylid en e)-ch ir o-in ositol 1,4-Diben -
zoa te [(-)-45] a n d D-2,3-O-(1-Meth yleth ylid en e)-ch ir o-
in ositol 1,4-Diben zoa te [(+)-45]. Compound (-)-43 (395 mg,
1.0 mmol) was dihydroxylated by the same procedure as
described for compound (+)-16 to give compound (-)-45 (418
mg, 97.4%) as an oil. A similar reaction with compound (+)-
43 was carried out to give compound (+)-45. Data for (-)-45:
Rf 0.31 (EtOAc:Hex ) 1:2); [R]D -10.8 (c 2.10, CHCl3); 1H
20
NMR (CDCl3) δ 1.39, 1.47 (2s, 6H), 3.64 (d, J ) 6.7 Hz, 1H),
3.78 (d, J ) 3.3 Hz, 1H), 4.00-4.07 (m, 1H), 4.18-4.31 (m,
3H), 5.56 (app t, J ) 9.3 Hz, 1H), 5.75 (app t, J ) 2.3 Hz, 1H),
7.41-8.13 (m, 10H); 13C NMR (CDCl3) δ 27.0, 27.3, 69.5, 71.9,
73.3, 74.5, 75.5, 75.6, 112.6, 128.8-133.9, 165.8, 168.0; HRMS
1
CHCl3); H NMR (CDCl3) δ 1.50 (s, 6H), 3.46 (br s, 1H), 3.71
(dd, J ) 8.3, 9.8 Hz, 1H), 3.88 (app t, J ) 9.2 Hz, 1H), 4.55 (br
d, J ) 7.1 Hz, 1H), 5.71-5.83 (m, 3H), 7.41-8.09 (m, 5H); 13
C
NMR (CDCl3) δ 27.3, 27.4, 70.9, 73.7, 77.8, 81.3, 112.0, 127.2,
128.8, 130.1, 130.3, 132.9, 133.7, 166.4; MS (FAB) m/z 291 (M+
+ H). Anal. Calcd for C16H18O5: C, 66.19; H, 6.25. Found: C,
65.94; H, 6.54. Data for (-)-42: mp 123-124 °C; [R]D20 -172.9
(FAB) m/z calcd for C23H25O8 429.1549, found 429.1573 (M+
+
H). Data for (+)-45: [R]D20 +11.6 (c 2.93, CHCl3); Rf, 1H NMR,
and 13C NMR data identical to those of (-)-45.
1
(c 1.41, CHCl3); Rf, H NMR, and 13C NMR data identical to
those of (+)-42. Data for (+)-10: mp 182-184 °C; [R]D20 +208.2
Ack n ow led gm en t. This work was financially sup-
ported by POSTECH/POSCO and the Ministry of Edu-
cation/Basic Science Research Institute fund. We also
thank Novo Nordisk Co. for kindly providing Novozym
435 and Lipozyme RM IM and Amano Co. for a generous
gift of PCL.
1
(c 1.12, CHCl3); Rf, H NMR, and 13C NMR data identical to
20
those of 10. Data for (-)-10: mp 182-184 °C; [R]D -207.8 (c
1.13, CHCl3); Rf, 1H NMR, and 13C NMR data identical to those
of 10.
(3a R,4R,7S,7a R)- a n d (3a S,4S,7R,7a S)-3a ,4,5,7a -Tetr a -
h yd r o-2,2-d im eth yl-1,3-ben zod ioxole-4,7-d iol Diben zoa te
[(-)-43 a n d (+)-43]. Mitsunobu reaction of compound (+)-42
(420 mg, 1.45 mmol) was carried out by the same procedure
as described for compound 19 to give compound (-)-43 (560
mg, 98%) as an oil. Similarly, compound (+)-43 was prepared
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds (+)-11, (+)-15, (+)-17, (+)-18a , (+)-18b,
(+)-29, (-)-30, (-)-32a , (+)-32b, (-)-33, (-)-34, (-)-43, and
(-)-45. This material is available free of charge via the
Internet at http://pubs.acs.org.
20
from (-)-42. Data for (-)-43: Rf 0.55 (EtOAc:Hex ) 1:2); [R]D
1
-56.3 (c 3.29, CHCl3); H NMR (CDCl3) δ 1.43, 1.50 (2s, 6H),
3.86 (dd, J ) 3.7, 10.0 Hz, 1H), 4.39 (dd, J ) 8.9, 10.0 Hz,
J O016237A