Synthesis of both enantiomers of conduritol C tetraacetate and of meso-conduritol D tetraacetate by oxidation of benzoquinone bis(ethylene acetal)

Article abstract of DOI:10.1002/ejoc.200600764

Epoxidation of p-benzoquinone bis(ethylene acetal) (1) with m-chloroperbenzoic acid or hydrogen peroxide/benzonitrile afforded corresponding monoepoxide 2, which was converted into p-benzoquinone mono(ethylene acetal) monoepoxide 5 with perchloric acid. D

Full text of DOI:10.1002/ejoc.200600764

FULL PAPER
DOI: 10.1002/ejoc.200600764
Synthesis of Both Enantiomers of Conduritol C Tetraacetate and of meso-
Conduritol D Tetraacetate by Oxidation of Benzoquinone Bis(ethylene acetal)
Martin Lang[a] and Thomas Ziegler*[a]
Keywords: p-Benzoquinone ethylene acetal / Epoxidation / Dihydroxylation / Coduritols
Epoxidation of p-benzoquinone bis(ethylene acetal) (1) with
m-chloroperbenzoic acid or hydrogen peroxide/benzonitrile
functions in the two diastereomers 10, followed by reduction
of the second carbonyl group as described above, afforded
afforded corresponding monoepoxide 2, which was con- racemic conduritol C and meso-conduritol D tetraacetates 12
verted into p-benzoquinone mono(ethylene acetal) monoe-
poxide 5 with perchloric acid. Dihydroxylation of 1 with os-
mium tetroxide or ruthenium trichloride/sodium periodate
afforded corresponding cis-diol 6, which was subsequently
acetylated to give diacetate 7. One ethyleneacetal moiety in
7 could be selectively hydrolyzed with silica gel/ferric chlo-
ride under solvent-free conditions to give ketone 8, which,
upon reduction with sodium borohydride and subsequent
acetylation of the formed alcohol group, afforded two dia-
stereomeric triacetates 10. Hydrolysis of the remaining acetal
and 13, respectively. Enzymatic resolution of the racemic ara-
bino-configured triacetate 10 with Lipozym failed, while the
ribo-configured counterpart reacted smoothly to give enan-
tiomerically pure
D-ribo- and L-ribo-configured triacetates
10. The latter pair of enantiomerically pure triacetates were
converted into both enantiomers of conduritol C tetraacetate
13 as described for the racemic compounds.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Conduritols are tetrahydroxy-substituted cyclohexenes,
commonly denoted as conduritols A through F following
the order of their discovery or first chemical synthesis. Six
diastereomeric forms of conduritols exist: the two meso
forms A and D and the four enantiomeric pairs B, C, E,
and F (Scheme 1).[1] The only diastereomers so far found in
nature are the achiral conduritol A and (+)-conduritol F:
conduritol A was first isolated from Eagle vine (Marsdenia
condurango)[2] and is found in several other tropical plants,
whereas (+)-conduritol F is widespread in green plants.[3]
Conduritols and their derivatives display some interest-
ing biological activities, which make their chemical synthe-
sis attractive. Conduritol A derivatives, for example, exhibit
insulin-modulating activity,[4] while conduritol epoxides and
aminoconduritols are potent glycosidase inhibitors and
have been shown to inhibit human immunodeficiency virus
(HIV).[5] Furthermore, conduritols are important precur-
sors for the synthesis of a wide variety of inositol deriva-
tives,[6] cyclophellitol,[7] and pseudosugars.[8]
Scheme 1. Conduritols A–F.
groups, has been widely used for syntheses of various con-
duritols.[6d,10] None of these methods, however, has aimed
at the use of a direct epoxidation or dihydroxylation of
benzoquinone or simple derivatives thereof for the synthesis
of conduritols, although this would appear to be the most
straightforward route (Scheme 2). Despite the fact that di-
rect hydroxylation of substituted benzoquinones generated
in situ from the corresponding phenols has been reported
to proceed smoothly with dimethyl dioxirane,[11] the reac-
tion had never been performed on p-benzoquinone itself,
while osmium tetroxide hydroxylations had also only been
performed on substituted phenols and quinones.[12] A prod-
uct obtained from osmium tetroxide hydroxylation of p-
benzoquinone had been assumed to be dihydroxydihydro-
1,4-benzoquinone, but the final verification was never ad-
duced.[13] Similarly, monoepoxidation of p-benzoquinone
All stereoisomers of conduritols A–F have been chemi-
cally synthesized by various methods in recent years; the
published syntheses have been reviewed.[9] Addition of bro-
mine to benzoquinone, followed by reduction of the car-
bonyl groups and nucleophilic substitution of the bromine
[a] Institute of Organic Chemistry, University of Tuebingen,
Auf der Morgenstelle 18, 72076 Tuebingen, Germany
E-mail: thomas.Ziegler@uni-tuebingen.de
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had only been possible after temporary “blocking” of one room temperature to afford monoepoxide 2 in 81% yield,
double bond through the formation of a Diels–Alder ad- together with the crystalline, cis-configured diepoxide 4 in
duct,[14] while epoxidation of p-benzoquinone with hydro- 18% yield. Although compound 2 can be converted into
gen peroxide had resulted in a mixture of the monoepoxide 4 under harsher conditions (H2O2/PhCN, 14 d, 60 °C), the
and several hydroxylated byproducts.[15] However, diepoxid- epoxidation of 2 is still sluggish and only affords 4 in a poor
ation with hydrogen peroxide in alkaline solution has been 29% yield. We attribute the difficult epoxidation of 2 to
described to proceed smoothly with p-benzoquinone ethyl- steric and stereoelectronic factors. It has been shown from
enemonoacetal. This process is also used on an industrial measurements and calculations of the dipole moment and
scale and on p-benzoquinone mono(diphenylethylene- the Kerr constant that p-benzoquinone monoepoxide
acetal), but does not yield the monoepoxide.[16] For a suc- adopts a boat conformation with the epoxide ring in a syn
cessful monoepoxidation we anticipated that p-benzoqui- orientation,[23] and we assume a similar conformation for
none bis(ethylene acetal) (1) should be a suitable starting monoepoxide 2, whereas diepoxide 4 and starting material
material, since diepoxidation would be expected to proceed 1 had each been shown by X-ray to adopt an almost flat
slowly for steric reasons.
conformation in the six-membered ring (Figure 1).[24] Thus,
in a boat conformation, the dioxolane rings of monoepox-
ide 2 would force the epoxidation reagent to attack from
the same side as where the first epoxide ring lies, which,
in turn, should be sterically disfavored, causing the second
epoxidation to proceed slowly. Obviously, this is not the
case for monoepoxide 5 since this derivative is known to be
epoxidized rapidly [p-benzoquinone mono(ethylene acetal)
yields only the corresponding diepoxide upon treatment
with hydrogen peroxide[16]]. On the other hand, monoepox-
ide 5 can easily be prepared in 90% yield from 2 by selective
hydrolysis of one ethyleneacetal functional group with
aqueous HClO4 in acetone (Scheme 3).
Scheme 2. Conduritols by epoxidation of benzoquinone.
Results and Discussion
p-Benzoquinone bis(ethylene acetal) (1) can easily be pre-
pared on a large scale from the corresponding tetrameth-
ylacetal.[17] Unfortunately, the tetramethylacetal is not com-
mercially available and is difficult to prepare by electro-
chemical means[18] or by strenuous Pd-catalyzed dimeriza-
tion of cyclopropenes.[19] In our hands, diacetal 1 was best
prepared by Heller’s method,[20] starting from the inexpen-
sive 1,4-cyclohexanedione, which was first acetalized with
ethyleneglycol and then subjected to dibromination and de-
hydrobromination. Direct acetalization of p-benzoquinone
with ethyleneglycol is not possible though, as had already
been reported previously.[21]
Epoxidation of Benzoquinone Bis(ethylene acetal)
Because epoxidation of diacetal 1 had not so far been
described in the literature, we first treated 1 with 3-chloro-
perbenzoic acid in dichloromethane at ambient temperature
(Scheme 3). Inspection of the reaction mixture by TLC re-
vealed the very slow formation of two products. After 7 d,
the reaction appeared to be complete, and work up yielded
crystalline monoepoxide 2 (26%) and p-benzoquinone
mono(ethylene acetal) 3 (20%). Under more drastic condi-
tions (dichloroethane, 24 h reflux), monoepoxide 2 and
monoacetal 3 were isolated in 41% and 34% yields, respec-
tively. We next tested several other epoxidation methods
and reagents, but neither hydrogen peroxide under basic
conditions nor dimethyl dioxirane gave any reaction with 1.
This result is surprising as p-benzoquinone mono(ethylene
acetal) affords diepoxides under those conditions.[16] Fi-
nally, we found that the classical H2O2/PhCN reagent (per-
Scheme 3. Epoxidation and dihydroxylation of compound 1.
oxybenzimidic acid)[22] would react smoothly with 1 at Figure 1. X-ray structures of compounds 1 and 4.[24]
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M. Lang, T. Ziegler
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Attempts to open the epoxide rings in 2 or 5 in order solution (0.1–1.0 ), nor concentrated aqueous HCl solu-
to obtain the corresponding dihydroxy derivatives, which tion, nor HClO4 (70%) affected diacetal 7. Similarly, other
should be suitable precursors for the synthesis of conduri- reagents known to cleave acetals efficiently[30] were unable
tols, have so far failed: under various sets of acidic or basic to hydrolyze compound 7. Only treatment with ferric chlo-
aqueous conditions, extensive decomposition of the starting ride on silica gel under solvent-free conditions[31] finally re-
material was observed, and we have attributed this failure sulted in the selective cleavage of only one acetal functional
to “overcrowding” of functional groups around the six- group, so diacetal 7 was finely ground in a mortar, mixed
membered rings, which make these epoxides prone to sev- with commercially available silica gel loaded with FeCl3,
eral side reactions. Nevertheless, compound 5 must be re- and stirred in the absence of any solvent in a flask, where-
garded as quite a versatile building block since it contains upon TLC revealed the slow formation of a more slowly
a reactive epoxide group that should open regioselectively moving product. After stirring for 3 d at ambient tempera-
upon treatment with strong nucleophiles, an enone group ture, the initially yellow mixture had turned white and all
that should be usable for further modifications by selective starting material has disappeared, as shown by TLC. After
nucleophilic 1,2- or 1,4-additions or stereoselective re- chromatographic workup of the mixture, the crystalline
ductions, and a second masked carbonyl group allowing for monoacetals 8 and 9 were isolated in 61% and 5% yields,
additional derivatizations in subsequent steps. The use of respectively. It should be noted that compound 8 was prone
compound 5 as a versatile building block for the synthesis to deacetylation during chromatography on silica gel, a fact
of conduritol derivatives is currently under investigation that might be responsible for the final isolation of small
and will be published elsewhere.
amounts of monoacetylated byproduct 9, which had not
been detectable by TLC prior to workup. Since the products
were crystalline, however, enone 8 could be directly crys-
tallized from the crude reaction mixture in 87% yield, so
Dihydroxylation of Benzoquinone Bis(ethylene acetal)
We next turned our efforts to the examination of the cis- the solvent-free selective monodeacetalation of p-benzoqui-
selective dihydroxylation of 1. Surprisingly, neither the di- none diacetals with FeCl3 on silica gel proved to be the
hydroxylation of this compound nor that of any related method of choice here.
benzoquinone diacetals has yet been described in the litera-
Next, enone 8 was reduced to afford racemic dia-
ture, so we first tested various reagents and sets of condi- stereomers 10a and 10b (Scheme 5). Because the initial dia-
[25]
tions for cis-selective dihydroxylation of olefins. KMnO4
stereomeric reduction products (monoalcohols) were rather
or I2/wet AgOAc[26] gave the dihydroxylated product in very difficult to separate, due to their similar mobilities during
poor yield or not at all, respectively, but better results were chromatography on silica gel, the intermediate crude
[28]
obtained with the OsO4/NMO[27] or RuCl3/NaIO4
rea- alcohols were directly acetylated, after which chromato-
gents. Under carefully optimized conditions (Scheme 4), graphic separation could be achieved nicely. On treatment
syn-diol 6 could be obtained in 64% yield. It is noteworthy with the NaBH4/CeCl3 reagent (Luche’s reagent),[32] chosen
that dihydroxylation of 1 is rather difficult, due to the in order to avoid 1,4-reduction of the enone moiety in 8,
strongly electron-withdrawing effects of the two acetal func- and after subsequent acetylation of the crude reduction
tional groups. Furthermore, in all hydroxylation reactions products, an approximately 2:1 mixture of diastereomers
with OsO4 and RuCl3 we observed that the reactions never 10a and 10b was obtained in 89% overall yield. In its pro-
proceeded to completion: unchanged starting material ton NMR spectrum, compound 10a, isolated in 61% yield,
could even be reisolated when molar amounts of the more showed a vicinal coupling constant of 4.7 Hz between the
reactive RuCl3/NaIO4 reagent were applied.
proton at the newly formed asymmetric center and its adja-
Acetylation of diol 6 gave compound 7 in 92% yield cent proton and so was assigned the ribo configuration.
(Scheme 4). It was originally planned to subject this to a Similarly, diastereomer 10b, isolated in 28% yield, showed
selective hydrolysis of one acetal group to afford enone 8 a vicinal coupling constant of 8.4 Hz and was assigned the
for generation of the third hydroxy group through dia- arabino configuration. The structure assigned to dia-
stereoselective reduction of the carbonyl function, as it is stereomer 10a was additionally confirmed by X-ray struc-
reported in the literature that one acetal group in a p-benzo- ture determination.[24]
quinone diacetal can be selectively hydrolyzed under acidic
With NaBH4 alone, no 1,4-reduction of enone 8 was ob-
conditions,[29] but bis(ethylene acetal) 7 resisted all attempts served and the diastereomeric selectivity of the reduction
to hydrolyze it under acid conditions. Neither aqueous HCl was increased to approximately 13:1. After acetylation of
Scheme 4.
770
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Conduritol C and meso-Conduritol D Tetraacetates
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Scheme 5.
the crude reaction products, compounds 10a and 10b were it occurs only at the Si face of the carbonyl group through
thus isolated in 80% and 6% yields, respectively. Similar complexation with the pseudoaxial 4-acetoxy group to give
observations of increased diastereoselectivity during re- 12 exclusively. Compounds 12 and 13 showed analytical
duction of enones have been documented.[32c,d] Removal of data identical to those published elsewhere.[33,34]
the ethyleneacetal moieties in 10a and 10b was again
achieved by application of ferric chloride on silica gel under
solvent-free conditions to afford the crystalline enone tetra-
acetates 11a and 11b in 89% and 87% yields, respectively.
It is noteworthy that under aqueous hydrolytic conditions
(70% aqueous HClO4, ambient temp.), no hydrolysis of the
ethyleneacetals occurred at all (c.f. conversion of compound
8 to 9). The nonoccurrence of any possible rearrangement
or acetyl group migration during deprotection of 10 was
unambiguously verified by X-ray structure analysis of 11a
(Figure 2)[24] and comparison of the NMR spectroscopic
data for both diastereomers, which showed that the relative
configuration had been preserved.
Figure 3. Reduction of diastereomers 11a and 11b.
Enzymatic Resolution
For the preparation of enantiomerically pure conduritols
we used an approach based on kinetic resolution of racemic
compounds 10 with lipases, since enzymatic resolutions
have proved to be very efficient for the preparation of enan-
tiomerically pure coduritols and their precursors.[34a,35]
Here we used Lipozym exclusively. While compound 10a
was a good substrate for Lipozym, its diastereomer 10b did
Figure 2. X-ray structure of compound 11a.
not show any sign of enzymatic saponification even after
Reduction of 11a with the NaBH4/CeCl3 reagent in a month: obviously, only the ribo configuration of 10a is
methanol, followed by acetylation of the intermediate recognized by Lipozym, whereas the arabino configuration
alcohol, gave racemic conduritol tetraacetate 12 (conduri- of 10b is not, although the Kazlauskas rule predicts that
tol C) and meso-conduritol tetraacetate 13 (conduritol D) 10b should also be a substrate for Lipozym.[36] Subjection
in a ratio of approximately 1:2. In contrast, reduction and of racemic 10a to transesterification catalyzed by Lipozym
acetylation of 11b resulted exclusively in diastereomer 12. in a mixture of n-butanol and tert-butyl methyl ether left -
Similar findings had previously been described by Vogel ribo enantiomer (+)-10a untouched and afforded the par-
et al.,[33] who also found a rather unselective reduction of tially deacetylated crystalline -ribo enantiomers (–)-14,
11a. By deduction from the X-ray data for compound (–)-15, and (–)-16. After chromatographic separation,
11a[24] we explain the reduction of 11a in terms of a prefer- alcohol (–)-14 was subsequently reacetylated to provide
ential attack of the hydride nucleophile at the less hindered (–)-10a, and the enzymatic resolution of 10a thus appeared
Si face of the enone to give 13 as the main product (Fig- to be virtually quantitative, giving both enantiomers of 10a
ure 3), whereas attack at the Re face to give 12 as the minor in better than 99.5% ee. The absolute configuration of
byproduct is still possible. In contrast, 11b displays two axi- (–)-10a was unambiguously assigned by acylation with (+)-
ally oriented acetoxy groups, which steer reduction so that Mosher’s acid chloride and determination of the configura-
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M. Lang, T. Ziegler
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Scheme 6.
performed by eluting compounds with various mixtures of solvents
from glass columns of various size filled with Macherey & Nagel
silica gel S (0.032–0.063 mm). X-ray structures were recorded with
a Enraf Nonius CAD4 or a Stoe IPDS diffractometer. Enzymatic
reactions were performed by shaking the reactions mixtures on an
orbital shaker. All solvents were dried and purified by distillation
prior to use. Solutions in organic solvents were dried with Na2SO4,
filtered, and concentrated on a rotary evaporator.
tion from the X-ray structure of Mosher’s ester 17 (details
not shown here).
Finally, both enantiomers were deacetalated with the fer-
ric chloride/silica gel reagent as described above to afford
crystalline ketones (+)-11a and (–)-11a in 93% and 95%
yields, respectively. The following reduction-reacetylation
sequence as outlined above for racemic 11a gave both
enantiomers of conduritol C tetraacetate (+)-12 and (–)-12
and meso-conduritol tetraacetate 13. The diastereoselectiv-
ity of the reduction step was of the same magnitude as de-
scribed above for racemic 11a (Scheme 6).
6,7-Epoxy-1,4,9,12-tetraoxadispiro[4.2.4.2]tetradec-13-ene (2), 1,4-
Dioxaspiro[4.5]deca-6,9-dien-8-one (3) and cis-6,7,13,14-Diepoxy-
1,4,9,12-tetraoxadispiro[4.2.4.2]tetradecane (4)
Method a: A solution of p-benzoquinone bis(ethylene actal) (1,[20]
1.36 g, 6.94 mmol) and m-chloroperbenzoic acid (3.54 g,
20.83 mmol) in C2H4Cl2 (80 mL) was heated at reflux for 22 h,
washed with ice-cold aqueous NaOH solution (20%), dried, and
the solvents were evaporated. Chromatography of the residue with
toluene/acetone (10:1) first afforded impure compound 3, which
was further purified by microdistillation to give pure 3 (359 mg,
34%), showing physical data identical to those published pre-
viously.[37] Eluted next was crystalline 2 (604 mg, 41%). M.p.
Experimental Section
General Remarks: NMR spectra were recorded with a Bruker
Avance 400 spectrometer at 400 MHz for 1H and 100.6 MHz for
13C NMR spectra, respectively. Chemical shifts in CDCl3 are re-
ported in δ (ppm) relative to tetramethylsilane (TMS) as internal
standard. Coupling constants J are reported in Hz. Assignment of
signals was achieved by first-order inspection of the spectra and by
1H,1H-, 13C,1H-COSY, HMQC, or NOESY experiments performed
with a Bruker DRX 600 spectrometer. MS spectra were recorded
with Finnigan TSQ 70 MAT (EI) and Bruker Apex II FT-ICR
(FAB) instruments. Specific optical rotations [α] were recorded with
a Perkin–Elmer polarimeter Model 341 at 589 nm (Na-D) for solu-
tions in CHCl3 at 20 °C if not stated otherwise. Elemental analyses
were performed with a Hekatech CHNS analyzer Euro EA 300.
Melting points were determined with a Büchi SMP-20 instrument.
GC was performed with Varian/Chrompack CP 9000 and CP 9001
instruments with the use of Chirasil-β-cyclodextrin columns. TLC
was performed on Macherey & Nagel silica gel (SIL G/UV254)
plates. Spots were detected by visual inspection of the plates under
1
162 °C (EtOH). H NMR (CDCl3): δ = 5.62 (s, 2 H, 13-H, 14-H),
4.11 (m, 8 H, 2-H, 2-HЈ, 3-H, 3-HЈ, 10-H, 10-HЈ, 11-H, 11-HЈ),
3.31 (s, 2 H, 6-H, 7-H) ppm. 13C NMR (CDCl3): δ = 128.4 (2 C,
C-13, C-14), 103.4 (2 C, C-5, C-8), 65.7a (2 C, C-2, C-10), 65.6a
(2 C, C-3, C-11), 52.3 (2 C, C-6, C-7) ppm (a assignment may be
exchanged). FAB-MS: m/z = 235 [M + Na]+, 213 [M + H]+.
C10H12O5 (212.20): calcd. C 56.60, H 5.70; found C 56.75, H 5.61.
Method b:
A mixture of compound 1 (2.00 g, 10.19 mmol),
NaHCO3 (2 g), and aqueous H2O2 solution (30%, 50 mL) in ben-
zonitrile (40 mL), CH2Cl2 (40 mL), and MeOH (200 mL) was vig-
orously stirred at ambient temp. for 24 h, washed with ice-cold
aqueous NaHCO3 solution, dried, and concentrated. Chromatog-
raphy of the residue first afforded 2 (1.75 g, 81%). Eluted next was
1
UV light, by charring with H2SO4 (5% in EtOH), with KMnO4 4 (418 mg, 18%). M.p. 162–163 °C (EtOH). H NMR (CDCl3): δ
(5% in H2O), and with I2. Preparative column chromatography was
= 4.22a (m, 4 H, 2-H, 2-HЈ, 10-H, 10-HЈ), 4.12a (m, 4 H, 3-H, 3-
772
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HЈ, 11-H, 11-HЈ), 3.17 (s, 4 H, 6-H, 7-H, 13-H, 14-H) ppm. 13C
NMR (CDCl3): δ = 102.1a (C-5), 101.4a (C-8), 66.5b (2 C, C-2, C-
C, C-6, C-7), 66.2a (2 C, C-2, C-10), 65.2a (2 C, C-3, C-11), 21.0 [2
C, C{O}CH3] ppm (a assignment may be exchanged). FAB-MS:
10), 65.9b (2 C, C-3, C-11), 55.0 (4 C, C-6, C-7, C-13, C-14) ppm m/z = 337 [M + Na]+, 315 [M + H]+. C14H18O8 (314.29): calcd. C
(
a,b assignment may be exchanged). FAB-MS: m/z = 251 [M + Na]+, 53.50, H 5.77; found C 53.65, H 5.77.
229 [M + H]+, 211 [M + H – H2O]+. C10H12O6 (228.20): calcd. C
cis-6,7-Diacetoxy-8-oxo-1,4-dioxaspiro[4.5]dec-9-ene (8) and cis-6-
Acetoxy-7-hydroxy-8-oxo-1,4-dioxaspiro[4.5]dec-9-ene (9)
52.63, H 5.30; found C 52.47, H 5.32.
Method c: Treatment of compound 2 (1.07 g, 5.03 mmol) at 60 °C
for 14 d as described under method b) afforded 4 (333 mg, 29%),
together with unchanged 2 (757 mg, 71%).
Method a: Finely ground compound 7 (3.20 g, 10.17 mmol) was
mixed with silica gel/FeCl3 (30 g, containing 0.4 mmol FeCl3/g sil-
ica gel), the mixture was stirred at ambient temp. for 3 d until the
initial yellow color had disappeared, and the silica gel was then
extracted several times with diethyl ether. The combined extracts
were washed with saturated aqueous NaHCO3 solution, dried, and
concentrated, and chromatography of the residue with toluene/ace-
tone 5:1 first afforded 8 (1.676 g, 61%). M.p. 110–111 °C (EtOH).
1H NMR (CDCl3): δ = 6.52 (dd, J9,10 = 10.4 Hz, J6,10 = 2.3 Hz, 1
H, 10-H), 6.20 (d, J9,10 = 10.4 Hz, 1 H, 9-H), 5.81 (d, J6,7 = 2.8 Hz,
1 H, 7-H), 5.51 (t, J6,7 = 2.5 Hz, 1 H, 6-H), 4.14 (m, 4 H, 2-H, 2-
HЈ, 3-H, 3-HЈ), 2.18, 2.09 [2ϫs, 6 H, C{O}CH3] ppm. 13C NMR
(CDCl3): δ = 190.2 (C-8), 170.1, 169.5 [2 C, C{O}CH3], 143.8 (C-
10), 130.0 (C-9), 103.3 (C-5), 72.7 (C-6), 72.5 (C-7), 66.0a (C-2),
65.9a (C-3), 20.8, 20.5 [2 C, C{O}CH3] ppm (a assignment may be
exchanged). FAB-MS: m/z = 293 [M + Na]+, 271 [M + H]+.
C12H14O7 (270.24): calcd. C 53.33, H 5.22; found C 53.05, H 5.19.
Eluted next was 9 (116 mg, 5%). M.p. 126–127 °C (EtOH). 1H
NMR (CDCl3): δ = 6.53 (dd, J9,10 = 10.2 Hz, J6,10 = 2.5 Hz, 1 H,
10-H), 6.26 (d, J9,10 = 10.4 Hz, 1 H, 9-H), 5.55 (t, J6,7 = 3.0 Hz, 1
H, 6-H), 4.66 (t, J6,7 = 3.3 Hz, 1 H, 7-H), 4.14 (m, 4 H, 2-H, 2-
HЈ, 3-H, 3-HЈ), 3.41 (d, J7,OH = 3.3 Hz, 1 H, 7-OH), 2.05 [s, 3 H,
C{O}CH3] ppm. 13C NMR (CDCl3): δ = 196.6 (C-8), 170.1
[C{O}CH3], 145.1 (C-10), 128.7 (C-9), 103.3 (C-5), 73.9 (C-6), 72.3
(C-7), 66.0a (C-2), 65.9a (C-3), 20.7 [C{O}CH3] ppm (a assignment
may be exchanged). FAB-MS: m/z = 251 [M + Na]+, 229 [M +
H]+, 211 [M + H – H2O]+. C10H12O6 (228.20): calcd. C 52.63, H
5.20; found C 52.34, H 5.30.
rac-6,7-Epoxy-1,4-dioxaspiro[4.5]deca-9-en-8-one (5): A solution of
compound 2 (2.56 g, 12.06 mmol) and HClO4 (70%, 0.1 mL) in
acetone (300 mL) was stirred at ambient temp. for 1 h, diluted with
CH2Cl2 (200 mL), washed with aqueous NaHCO3 solution, dried,
and concentrated. The oily residue was triturated with boiling di-
isopropyl ether and the solvent was decanted while warm from a
sticky brown residue. Evaporation of the solvent and recrystalli-
zation of the residue from EtOH gave 5 (1.82 g, 90%). M.p. 58–
59 °C (EtOH). 1H NMR (CDCl3): δ = 6.32 (dd, J9,10 = 10.6 Hz,
J6,10 = 2.8 Hz, 1 H, 10-H), 5.98 (dd, J9,10 = 10.6 Hz, J7,9 = 2.0 Hz,
1 H, 9-H), 4.19 (m, 4 H, 2-H, 2-HЈ, 3-H, 3-HЈ), 3.59 (dd, J6,7
3.5 Hz, J6,10 = 3.0 Hz, 1 H, 6-H), 3.48 (dd, J6,7 = 3.7 Hz, J7,9
=
=
2.0 Hz, 1 H, 7-H) ppm. 13C NMR (CDCl3): δ = 192.5 (C-8), 141.8
(C-10), 127.6 (C-9), 101.3 (C-5), 66.2a (C-2), 66.0a (C-3), 55.1 (C-
6), 52.1 (C-7) ppm (a assignment may be exchanged). FAB-MS :
m/z = 169 [M + H]+, 154 [M – O + H2]+, 136 [m/z 154 – H2O]+.
C8H8O4 (168.15): calcd. C 57.14, H 4.80; found C 57.43, H 4.87.
cis-1,4,9,12-Tetraoxadispiro[4.2.4.2]tetradec-13-ene-6,7-diol (6)
Method a: A mixture of compound 1 (1.00 g, 5.10 mmol), NMO
monohydrate (1.10 g, 8.10 mmol), and an aqueous solution of
OsO4 (4%, 5 mL) in acetone (60 mL) and H2O (10 mL) was stirred
at 40 °C for 4 d. After addition of a small amount of Na2SO3 the
mixture was concentrated. Chromatography of the residue with tol-
uene/acetone 1:1 and crystallization from toluene afforded 6
(751 mg, 64%). M.p. 124 °C (toluene). 1H NMR ([D4]-
MeOH): δ = 5.71 (s, 2 H, 13-H, 14-H), 4.06 (m, 8 H, 2-H, 2-HЈ, 3-
H, 3-HЈ, 10-H, 10-HЈ, 11-H, 11-HЈ), 3.91 (s, 2 H, 6-H, 7-H) ppm.
13C NMR ([D4]MeOH): δ = 131.2 (2 C, C-13, C-14), 106.6 (2 C,
C-5, C-8), 73.9 (2 C, C-6, C-7), 67.3a (2 C, C-2, C-10), 66.4a (2
C, C-3, C-11) ppm (a assignment may be exchanged). FAB-MS for
C10H14O6 (m/z 230): 253 [M + Na]+, 231 [M + H]+, 213 [M + H –
H2O]+. C10H14O6 (230.22): calcd. C 52.17, H 6.13; found: C 52.46,
H 6.13.
Method b: Treatment of compound 7 (1.95 g, 6.21 mmol) with silica
gel/FeCl3 (20 g) as described above, without chromatography but
with direct crystallization from EtOH, instead afforded 8 (1.46 g,
87%).
rac-(8RS,9RS,10RS)- (10a) and rac-(8RS,9SR,10SR)-8,9,10-Tri-
acetoxy-1,4-dioxaspiro[4.5]dec-6-ene (10b)
Method a: NaBH4 (193 mg, 5.09 mmol) was added in small por-
tions at –10 °C to a solution of compound 8 (917 mg, 3.39 mmol)
and CeCl3·7H2O (0.4  in MeOH, 30 mL) in CH2Cl2 (30 mL), and
the mixture was stirred for 30 min at –10 °C, allowed to warm to
ambient temp. over 30 min, diluted with H2O (20 mL), and poured
into saturated aqueous NaCl solution (50 mL). The resulting mix-
ture was extracted with ethyl acetate (3ϫ50 mL), the combined
extracts were dried and concentrated, the residue was dissolved in
pyridine (20 mL), and acetic anhydride (20 mL) was added with
cooling with an ice bath. The mixture was stirred at ambient temp.
for 5 h and worked up as described for the preparation of com-
Method b: A mixture of compound 1 (712 mg, 3.63 mmol), NaIO4
(1.16 g, 5.44 mmol), and RuCl3·3H2O (122 mg, 0.47 mmol) in ethyl
acetate (15 mL), MeCN (15 mL), and H2O (5 mL) was vigorously
shaken at ambient temp. for 3 min, poured into saturated aqueous
Na2SO3 solution, and extracted with CH2Cl2. Concentration of the
extracts and chromatography of the residue with toluene/acetone
1:1 first afforded reisolated 1 (71 mg, 10%). Eluted next was 6
(535 mg, 64%).
cis-6,7-Diacetoxy-1,4,9,12-tetraoxadispiro[4.2.4.2]tetradec-13-ene pound 7, and chromatography of the residue with toluene/acetone
(7): A solution of compound 6 (2.04 g, 8.87 mmol) in a mixture of
acetic anhydride (25 mL) and pyridine (25 mL) was stirred at ambi-
ent temp. for 5 h, diluted with CH2Cl2 (200 mL), washed with ice-
cold aqueous HCl solution and saturated aqueous NaHCO3 solu-
tion, dried, and concentrated. Crystallization of the residue from
EtOH afforded 7 (2.566 g, 92%). M.p. 164 °C (EtOH). 1H NMR
(CDCl3): δ = 5.74 (s, 2 H, 13-H, 14-H), 5.38 (s, 2 H, 6-H, 7-H),
10:1 and crystallization from EtOH first afforded 10b (299 mg,
28%). M.p. 87–88 °C (EtOH). 1H NMR (CDCl3): δ = 5.86 (dd, J6,7
= 10.2 Hz, J6,10 = 2.3 Hz, 1 H, 6-H), 5.64 (m, J8,9 = 8.3 Hz, 2 H,
7-H, 8-H), 5.37 (dd, J8,9 = 8.5 Hz, J9,10 = 2.3 Hz, 1 H, 9-H), 5.30
(t, J9,10 = 2.0 Hz, 1 H, 10-H), 4.05 (m, 4 H, 2-H, 2-HЈ, 3-H, 3-HЈ),
2.13, 2.08, 2.04 [3ϫs, 9 H, C{O}CH3] ppm. 13C NMR (CDCl3): δ
= 170.5, 170.4, 169.9 [3 C, C{O}CH3], 130.1 (C-6), 128.2 (C-7),
4.02 (m, 8 H, 2-H, 2-HЈ, 3-H, 3-HЈ, 10-H, 10-HЈ, 11-H, 11-HЈ), 103.8 (C-5), 70.9 (C-8), 70.7 (C-10), 68.8 (C-9), 65.6a (C-2), 65.5a
2.12 [s, 6 H, C{O}CH3] ppm. 13C NMR (CDCl3): δ = 170.3 [2 C, (C-3), 20.9, 20.8, 20.7 [3 C, C{O}CH3] ppm (a assignment may be
C{O}CH3], 130.2 (2 C, C-13, C-14), 103.4 (2 C, C-5, C-8), 70.8 (2 exchanged). FAB-MS: m/z = 337 [M + Na]+, 315 [M + H]+, 255
Eur. J. Org. Chem. 2007, 768–776
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
773

M. Lang, T. Ziegler
FULL PAPER
[M + H – HOAc]+. C14H18O8 (314.29): calcd. C 53.50, H 5.77;
found C 53.56, H 5.84. Eluted next and crystallized from EtOH
was 10a (651 mg, 61%). M.p. 95–96 °C (EtOH). 1H NMR (CDCl3):
[4.5]dec-9-ene [(–)-14], (–)-(8R,9R,10R)-8,10-Diacetoxy-9-hydroxy-
1,4-dioxaspiro[4.5]dec-6-ene [(–)-15], and (–)-(6R,7R,8R)-6-Acetoxy-
7,8-dihydroxy-1,4-dioxaspiro[4.5]dec-9-ene [(–)-16]: A mixture of ra-
δ = 5.93 (dd, J9,10 = 10.2 Hz, J6,10 = 3.9 Hz, 1 H, 10-H), 5.79 (d, cemic 10a (1.42 g, 4.52 mmol), Lipozym (4 g), and n-butanol
J9,10 = 10.1 Hz, 1 H, 9-H), 5.61 (m, J7,8 = 4.7 Hz, 1 H, 7-H), 5.47
(dd, J6,7 = 2.3 Hz, J7,8 = 4.7 Hz, 1 H, 8-H), 5.22 (d, J6,7 = 1.8 Hz,
(4 mL) in tert-butyl methyl ether (150 mL) was shaken at ambient
temp. for 3 d on an orbital shaker, filtered through a layer of Celite,
1 H, 6-H), 4.04 (m, 4 H, 2-H, 2-HЈ, 3-H, 3-HЈ), 2.12, 2.08, 2.07 [3 and concentrated. Chromatography of the residue with toluene/ace-
s, 9 H, C{O}CH3] ppm. 13C NMR (CDCl3): δ = 170.1, 170.0, 169.9 tone 5:1 and crystallization from EtOH first afforded (+)-10a
[3 C, C{O}CH3], 130.5 (C-9), 127.7 (C-10), 103.7 (C-5), 69.9 (C-
6), 67.8 (C-8), 66.2a (C-2), 65.2a (C-3), 64.8 (C-7), 20.9, 20.8, 20.7
[3 C, C{O}CH3] ppm (a assignment may be exchanged). FAB-MS:
(710 mg, 50%). M.p. 95–96 °C (EtOH). ee Ͼ 99.5%. [α]D = +109.6
1
(c = 1.0, CHCl3). H and 13C NMR data were identical to those
of racemic 10a. FAB-MS: m/z = 337 [M + Na]+, 315 [M + H]+,
m/z = 337 [M + Na]+, 315 [M + H]+, 255 [M + H – HOAc]+. 255 [M + H – HOAc]+. C14H18O8 (314.29): calcd. C 53.50, H 5.77;
C14H18O8 (314.29): calcd. C 53.50, H 5.77; found C 53.70, H 5.73.
found C 53.55, H 5.76. Eluted next and crystallized from EtOH
was (–)-14 (455 mg, 37%). M.p. 91–92 °C (EtOH). [α]D = –130.2 (c
= 1.0, CHCl3). H NMR (CDCl3): δ = 5.87 (dd, J9,10 = 10.4 Hz, 1
H, 10-H), 5.74 (dd, J9,10 = 10.4 Hz, 1 H, 9-H), 5.43 (m, 1 H, 6-H),
5.18 (d, 1 H, 8-H), 4.34 (m, 1 H, 7-H), 4.04 (m, 4 H, 2-H, 2-HЈ, 3-
Method b: Treatment of compound 8 (923 mg, 3.42 mmol) in
CH2Cl2 (30 mL) with NaBH4 (195 mg, 5.12 mmol), followed by
workup, acetylation, and chromatography as described under
method a first afforded 10b (64 mg, 6%). Eluted next was 10a
(859 mg, 80%).
1
H, 3-HЈ), 3.00 (d,
1 H, 8-OH), 2.15, 2.14 [2ϫs, 6 H,
C{O}CH3] ppm. 13C NMR (CDCl3): δ = 170.3, 170.2 [2 C,
C{O}CH3], 129.7 (C-9), 128.0 (C-10), 104.1 (C-5), 71.9 (C-8), 69.1
(C-6), 68.6 (C-7), 66.5a (C-2), 65.3a (C-3), 21.0, 20.9 [2 C,
C{O}CH3] ppm (a assignment may be exchanged). FAB-MS: m/z =
295 [M + Na]+. C12H16O7 (272.26): calcd. C 52.94, H 5.92; found
C 52.85, H 5.87. Eluted next was (–)-15 (12 mg, 1%). 1H NMR
(CDCl3): δ = 5.80 (m, 2 H, 6-H, 7-H), 5.57 (d, 1 H, 10-H), 5.47
(m, 1 H, 8-H), 4.09 (m, 4 H, 2-H, 2-HЈ, 3-H, 3-HЈ), 3.96 (d, 1 H,
9-H), 1.81 (d, 1 H, 9-OH), 2.13, 2.08 [2ϫs, 6 H, C{O}CH3] ppm.
13C NMR (CDCl3): δ = 170.9, 170.0 [2 C, C{O}CH3], 129.4a (C-
6), 127.5a (C-7), 104.5 (C-5), 71.7 (C-8), 70.8 (C-9), 66.9 (C-10),
66.5b (C-2), 65.3b (C-3), 21.0, 20.9 [2 C, C{O}CH3] ppm (a,b assign-
ment may be exchanged). Eluted next and crystallized from EtOH
was (–)-16 (125 mg, 12%). M.p. 102–103 °C (EtOH). [α]D = –120.8
rac-(1RS,5RS,6RS)-1,5,6-Triacetoxy-4-oxocyclohex-2-ene
(11a):
Treatment of compound 10a (908 mg, 2.89 mmol) with silica gel/
FeCl3 (12 g, containing 0.4 mmol FeCl3/g silica gel) at ambient
temp. for 3 d and crystallization of the crude product as described
for the preparation of compound 9 gave 11a (695 mg, 89%). M.p.
1
110–111 °C (dec.) (EtOH). H NMR (CDCl3): δ = 6.67 (dt, J2,3
=
10.6 Hz, 1 H, 2-H), 6.24 (dd, J2,3 = 10.5 Hz, 1 H, 3-H), 5.96 (m, 1
H, 1-H), 5.87 (m, 1 H, 6-H), 5.61 (d, 1 H, 5-H), 2.19, 2.09, 2.08
[3ϫs, 9 H, C{O}CH3] ppm. 13C NMR (CDCl3): δ = 189.8 (C-4),
170.0, 169.4, 169.3 [3 C, C{O}CH3], 144.3 (C-2), 128.9 (C-3), 72.6
(C-5), 72.5 (C-6), 68.1 (C-1), 20.6, 20.4, 20.3 [3 C, C{O}CH3] ppm.
FAB-MS: m/z = 293 [M + Na]+, 271 [M + H]+. C12H14O7 (270.24):
calcd. C 53.33, H 5.22; found C 53.34, H 5.23.
(c = 1.0, MeOH). 1H NMR ([D6]acetone): δ = 5.98 (dd, J9,10
=
rac-(1SR,5RS,6RS)-1,5,6-Triacetoxy-4-oxocyclohex-2-ene
(11b):
Treatment of compound 10b (445 mg, 1.42 mmol) with silica gel/
FeCl3 (8 g, containing 0.4 mmol FeCl3/g silica gel) at ambient temp.
for 3 d and crystallization of the crude product as described for the
preparation of compound 9 gave 11b (333 mg, 87%). M.p. 106–
10.1 Hz, 1 H, 10-H), 5.57 (d, J9,10 = 10.1 Hz, 1 H, 9-H), 5.10 (d, 1
H, 6-H), 4.12 (m, 1 H, 7-H), 4.03 (m, 4 H, 2-H, 2-HЈ, 3-H, 3-HЈ),
3.94 (m, 1 H, 8-H), 3.79 (d, 1 H, 8-OH), 3.30 (d, 1 H, 7-OH),
2.06 [s, 3 H, C{O}CH3] ppm. 13C NMR ([D6]acetone): δ = 171.3
[C{O}CH3], 134.3 (C-10), 129.4 (C-9), 106.0 (C-5), 74.3 (C-6), 69.7
(C-8), 67.6 (C-7), 67.4a (C-2), 66.7a (C-3), 21.8 [C{O}CH3] ppm
(a assignment may be exchanged). FAB-MS: m/z = 253 [M + Na]+,
231 [M + H]+. C10H14O6 (230.22): calcd. C 52.17, H 6.13; found C
52.25, H 6.15.
107 °C dec. (EtOH). 1H NMR (CDCl3): δ = 6.56 (dd, J3,4
=
10.3 Hz, 1 H, 4-H), 6.28 (d, J3,4 = 10.3 Hz, 1 H, 3-H), 6.01 (m, 1
H, 2-H), 5.87 (m, 1 H, 1-H), 5.72 (d, 1 H, 6-H), 2.12, 2.10, 2.07 [3
s, 9 H, C{O}CH3] ppm. 13C NMR (CDCl3): δ = 190.4 (C-5), 170.5,
170.4, 169.9 [3 C, C{O}CH3], 141.3 (C-4), 129.8 (C-3), 72.7 (C-2),
72.1 (C-6), 69.9 (C-1), 20.6, 20.5, 20.2 [3 C, C{O}CH3] ppm. FAB-
MS: m/z = 293 [M + Na]+, 271 [M + H]+. C12H14O7 (270.24):
calcd. C 53.33, H 5.22; found C 53.44, H 5.15.
(6R,7R,8R)-6,7-Diacetoxy-8-[(S)-(methoxy)(phenyl)(trifluorometh-
yl)acetoxy]-1,4-dioxaspiro[4.5]dec-9-ene (17): A solution of (–)-14
(39 mg, 0.14 mmol) and (S)-methoxyphenyltrifluoromethylacetyl
chloride (77 mg, 0.16 mmol) in pyridine (5 mL) was stirred at ambi-
ent temp. for 12 h, concentrated, and crystallized from EtOH to
afford 17 (70 mg, 100%). M.p. 100–101 °C (EtOH). [α]D = –70.0 (c
= 1.0, CHCl3). A suitable crystal was selected for determination of
the X-ray structure.[24]
rac-Conduritol C Tetraacetate (12) and meso-Conduritol D Tetraace-
tate (13)
Method a: Treatment of compound 11a (717 mg, 2.28 mmol) and
CeCl3·7H2O (30 mL, 0.4  in MeOH) in CH2Cl2 (20 mL) with
NaBH4 (132 mg, 3.42 mmol), followed by acetylation of the crude
product and chromatography as described for the preparation of
10 under method a, first afforded 12 (201 mg, 28%) as a colorless
oil. Physical data were identical to those published previously.[6d]
Eluted next was crystalline 13 (380 mg, 53%). M.p. 105 °C (EtOH);
M.p.[38] 105 °C (EtOH). Spectroscopic data were identical to those
published previously.[33,34b]
(–)-(8R,9R,10R)-8,9,10-Triacetoxy-1,4-dioxaspiro[4.5]dec-6-ene
[(–)-10a]: Treatment of compound (–)-14 (100 mg, 0.37 mmol) with
acetic anhydride (5 mL) in pyridine (5 mL) at ambient temp. for
2 h, followed by work up as described for the preparation of com-
pound 7, afforded (–)-10a (115 mg, 100%). M.p. 95–96 °C (EtOH).
ee Ͼ 99.5%. [α]D = –110.7 (c = 1.0, CHCl3). 1H and 13C NMR
data were identical to those of racemic 10a. FAB-MS: m/z = 337
[M + Na]+, 315 [M + H]+, 255 [M + H – HOAc]+. C14H18O8
(314.29): calcd. C 53.50, H 5.77; found C 53.73, H 5.80.
Method b: Treatment of compound 11b (333 mg, 1.23 mmol) and
CeCl3·7H2O (0.4  in MeOH, 15 mL) in CH2Cl2 (15 mL) with
NaBH4 (70 mg, 1.85 mmol), followed by acetylation of the crude
product and chromatography as described for the preparation of
10 under method a, first afforded 12 (275 mg, 71%).
(+)-(1S,5S,6S)-1,5,6-Triacetoxy-4-oxocyclohex-2-ene [(+)-11a]:
(+)-(8S,9S,10S)-8,9,10-Triacetoxy-1,4-dioxaspiro[4.5]dec-6-ene Treatment of compound (+)-10a (301 mg, 0.96 mmol) with silica
[(+)-10a], (–)-(6R,7R,8R)-6,7-Diacetoxy-8-hydroxy-1,4-dioxaspiro- gel/FeCl3 (8 g, containing 0.4 mmol FeCl3/g silica gel) as described
774
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 768–776

Conduritol C and meso-Conduritol D Tetraacetates
FULL PAPER
Dalko, S. D. Géro, B. Quidet-Sire, P. Stütz, J. Org. Chem. 1989,
54, 3764–3766.
for the preparation of compound 9 under method b afforded (+)-
11a (240 mg, 93%). M.p. 110–111 °C (dec.) (EtOH). [α]D = +116.4
1
(c = 1.0, CHCl3). H and 13C NMR data were identical to those
[6]
a) L. E. Brammer, T. Hudlicky, Tetrahedron: Asymmetry 1998,
9, 2011–2014; b) S. Saito, R. Shimazawa, R. Shirai, Chem.
Pharm. Bull. 2004, 52, 727–732; c) M. E. L. Podeschwa, O.
Plettenburg, H.-J. Altenbach, Eur. J. Org. Chem. 2005, 14,
3116–3127; d) M. Podeschewa, O. Plettenburg, J. von Brocke,
O. Block, S. Adelt, H.-J. Altenbach, Eur. J. Org. Chem. 2003,
10, 1958–1972.
of racemic 11a. FAB-MS: m/z = 293 [M + Na]+, 271 [M + H]+.
C12H14O7 (270.24): calcd. C 53.33, H 5.22; found C 53.39, H 5.27.
(–)-(1R,5R,6R)-1,5,6-Triacetoxy-4-oxocyclohex-2-ene [(–)-11a]:
Treatment of compound (–)-10a (246 mg, 0.78 mmol) with silica
gel/FeCl3 (8 g, containing 0.4 mmol FeCl3/g silica gel) as described
for the preparation of compound 9 under method b afforded (–)-
11a (201 mg, 95%). M.p. 110–111 °C (dec.) (EtOH). [α]D = –116.5
[7]
[8]
B. M. Trost, E. J. Hembre, Tetrahedron Lett. 1999, 40, 219–222.
a) D. A. Entwistle, T. Hudlicky, Tetrahedron Lett. 1995, 36,
2591–2594; b) L. Pingli, M. Vandewalle, Tetrahedron 1994, 50,
7061–7074.
a) M. Balci, Pure Appl. Chem. 1997, 69, 97–104; b) M. S.
Gültekin, M. Celik, M. Balci, Curr. Org. Chem. 2004, 8, 1159–
1186.
a) T. Hudlicky, D. A. Entwistle, K. K. Pitzer, A. J. Thorpe,
Chem. Rev. 1996, 96, 1195–1220; b) D. C. Billington in Carbo-
hydrate Mimics (Ed.: Y. Chapleur), Wiley-VCH, Weinheim,
1998, pp. 433–441; c) H.-J. Altenbach, H. Stegelmeier, E. Vogel,
Tetrahedron Lett. 1978, 19, 3333–3336; d) A. E. Gal, J. P. Voor-
stad, J. Labelled Compd. Radiopharm. 1987, 24, 397–407; e) Z.-
X. Guo, A. H. Haines, S. M. Pyke, S. G. Pyke, R. J. K. Taylor,
Carbohydr. Res. 1994, 264, 147–153.
a) J. K. Crandall, M. Zucco, R. S. Kirsch, D. M. Coppert, Tet-
rahedron Lett. 1991, 32, 5441–5442; b) A. Altamura, C. Fusco,
L. DЈAccolti, R. Mello, T. Prencipe, R. Curci, Tetrahedron
Lett. 1991, 32, 5445–5448; c) W. Adam, A. Schönberger, Tetra-
hedron Lett. 1992, 33, 53–56; d) W. Adam, L. Hadjiarapoglou,
K. Mielke, A. Treiber, Tetrahedron Lett. 1994, 35, 5625–5628.
1
(c = 1.0, CHCl3). H and 13C NMR data were identical to those
of racemic 11a. FAB-MS: m/z = 293 [M + Na]+, 271 [M + H]+.
[9]
C12H14O7 (270.24): calcd. C 53.33, H 5.22; found C 53.56, H 5.14.
(+)-Conduritol C Tetraacetate [(+)-12], (–)-Conduritol C Tetraace-
tate [(–)-12], and meso-Conduritol D Tetraacetate (13)
[10]
Method a: Treatment of compound (+)-11a (190 mg, 0.70 mmol)
and CeCl3·7H2O (0.4  in MeOH, 5 mL) in CH2Cl2 (20 mL) with
NaBH4 (40 mg, 1.06 mmol), followed by acetylation of the crude
product and chromatography as described for the preparation of
10 under method a, first afforded (+)-12 (57 mg, 26%) as a color-
less oil. [α]D = +194.8 (c = 1.0, CHCl3); ref.[39] [α]D = +194.0 (c =
1
1.1, CHCl3). H and 13C NMR data were identical to those pub-
[11]
lished previously.[6d,33,40] Eluted next was crystalline 13 (119 mg,
54%).
Method b: Treatment of compound (–)-11a (170 mg, 0.63 mmol)
and CeCl3·7H2O (0.4  in MeOH, 5 mL) in CH2Cl2 (5 mL) with
NaBH4 (36 mg, 0.94 mmol), followed by acetylation of the crude
product and chromatography as described for the preparation of
10 under method a, first afforded (–)-12 (57 mg, 29%) as a colorless
oil. [α]D = –194.3 (c = 1.0, CHCl3); ref.[33] [α]2D5 = –186.0 (c = 2.0,
[12]
[13]
J. Y. Savoie, P. Brassard, Can. J. Chem. 1971, 49, 3515–3523.
To our surprise this work has never been cited before: E. M.
Terry, N. A. Milas, J. Am. Chem. Soc. 1926, 48, 2647–2652.
a) K. Alder, F. H. Flock, H. Beumling, Chem. Ber. 1960, 93,
1896–1899; b) A. Ichihara, M. Kobayashi, K. Oda, S. Saka-
mura, Tetrahedron 1979, 35, 2861–2866.
[14]
1
CHCl3). H and 13C NMR data were identical to those published
previously.[6d,33,40] Eluted next was crystalline 13 (111 mg, 56%).
[15]
[16]
A. Brunmark, J. Biolumin. Chemilumin. 1989, 4, 219–225.
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Acknowledgments
We thank the following colleagues for their support of this work:
K. Albert and his crew for recording the NMR spectra, K.-P. Zeller
and his crew for performing the mass spectroscopy, A. Just for
performing the elemental analyses, and C. Maichle-Moessmer for
determining the X-ray structures. This work was financially sup-
ported by the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie.
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