Synthesis of vicinal diketoses by using a metathesis-hydroxylation-oxidation sequence

Article abstract of DOI:10.1002/ejoc.201403140

Symmetrical vicinal diuloses were prepared from 2,3:4,5-di-O-isopropylidene-D-arabinose and-L-arabinose by using methyltriphenylphosphonium bromide to convert both enantiomers into the corresponding 1,2-dideoxy-3,4:5,6-di-O-isopropylidene-arabino-hex-1-enitols D-5 and L-5. The metathesis reactions of D-5 with itself and with L-5, respectively, by using the Hoveyda-Grubbs catalyst gave diastereomeric dec-5-enitols DD-6 and DL-6, which were dihydroxylated with osmium tetroxide to give 1,2:3,4:7,8:9,10-tetra-O-isopropylidene-protected decitols DD-7 and DL-7. Swern oxidation of the decitols afforded isopropylidene-protected deco-5,6-diuloses DD-8 and DL-8, which gave unprotected deco-5,6-diuloses DD-9 and DL-9 upon acidic cleavage of the isopropylidene groups. The structures of both diastereomers were confirmed by NMR spectroscopy and X-ray crystal structure analysis.

Full text of DOI:10.1002/ejoc.201403140

FULL PAPER
DOI: 10.1002/ejoc.201403140
Synthesis of Vicinal Diketoses by Using a Metathesis–Hydroxylation–
Oxidation Sequence
Melchior Menzel[a] and Thomas Ziegler*[a]
Keywords: Carbohydrates / Metathesis / Dihydroxylation / Oxidation / Configuration determination
Symmetrical vicinal diuloses were prepared from 2,3:4,5-di-
droxylated with osmium tetroxide to give 1,2:3,4:7,8:9,10-
O-isopropylidene- -arabinose and -arabinose by using tetra-O-isopropylidene-protected decitols DD-7 and DL-7.
D
-L
methyltriphenylphosphonium bromide to convert both
enantiomers into the corresponding 1,2-dideoxy-3,4:5,6-di-
O-isopropylidene-arabino-hex-1-enitols D-5 and L-5. The
Swern oxidation of the decitols afforded isopropylidene-pro-
tected deco-5,6-diuloses DD-8 and DL-8, which gave unpro-
tected deco-5,6-diuloses DD-9 and DL-9 upon acidic cleav-
metathesis reactions of D-5 with itself and with L-5, respec- age of the isopropylidene groups. The structures of both dia-
tively, by using the Hoveyda–Grubbs catalyst gave dia-
stereomeric dec-5-enitols DD-6 and DL-6, which were dihy-
stereomers were confirmed by NMR spectroscopy and X-ray
crystal structure analysis.
2,6:7,11-dipyranose (2b) was prepared by the coupling reac-
tion of benzyl-protected 1-tributylstannyl d-glucal with
tetra-O-benzyl-gluconolactone followed by osmoylation
and deprotection steps.[7] Although 2b is, in its open-chain
form, topologically similar to α-diulose 1 (both are C2-sym-
metric α-diketones), it was assigned the dipyranose struc-
ture that is depicted in Figure 1. Whether or not 2b exists
in a fused dipyranose form as does 1 remains unclear.
Introduction
Diketoses (α-dicarbonyl compounds) are common reac-
tive intermediates in the Maillard reaction, which is com-
prised of a number of complex reaction pathways of sugars
and amino acids that occur when food is processed. For
instance, 2-hexuloses and deoxy-2,3-hexodiuloses are
formed from the initial Amadori products of a Maillard
reaction and give rise to numerous condensation products,
which determine the flavor and color of food. Some of these
Maillard products are unwanted carcinogenic substances.[1]
Diketoses are common reactive intermediates that are pro-
duced during enzymatic redox reactions of simple aldoses.[2]
Diketoses are also versatile synthons in preparative carbo-
hydrate chemistry and lead, for example, to rare sugars. Re-
cently, the stable symmetric deco-5,6-diulose 1 (peltalosa)
was isolated from the roots of the Mexican plant Psacalium
peltatum and was attributed to the hypoglycemic activity
that can possibly be exploited to combat type 2 diabetes
mellitus.[3] Although the conformation and absolute config-
uration of 1 is hitherto unknown, it can be concluded from
its published NMR spectra and its hexa-O-acetate that pel-
talosa contains two magnetically equivalent six-membered
rings that are fused together at two vicinal hemiacetals
(anomeric centers, see Figure 1).[4] There are only two sim-
ilar symmetric diketoses that have been described in the lit-
erature (see Figure 1). d-threo-3,4-Hexodiulose (2a) was
synthesized from d-mannose[5] and by the direct oxidation
of d-isosorbide,[6] and α,α-d-gluco-l-gulo-dodeco-6,7-diulo-
Figure 1. Peltalosa (1, configuration unknown), d-threo-3,4-hexo-
diulose (2a) and α,α-d-gluco-l-gulo-dodeco-6,7-diulo-2,6:7,11-di-
pyranose (2b).
Our attempts to elucidate the conformation and absolute
configuration of 1 by using the total synthesis of peltalosa
led us to a protocol that can be generally employed for the
synthesis of higher symmetrical vicinal diuloses of the pel-
talosa type. Such symmetrical diuloses are not yet well in-
vestigated, although they represent a structurally interesting
new class of naturally occurring higher carbon sugars.
Results and Discussion
We anticipated being able to establish the vicinal carb-
onyl groups of the symmetrical deco-5,6-diuloses by using
a cis-selective dihydroxylation of the related and suitably
protected dec-5-enitol followed by the oxidation of the in-
termediate diol to give the diketone. For that purpose, we
first prepared both enantiomers of 1,2-dideoxy-3,4:5,6-
[a] Institute of Organic Chemistry, University of Tübingen,
Auf der Morgenstelle 18, 72076 Tübingen, Germany
E-mail: Thomas.ziegler@uni-tuebingen.de
http://www.uni-tuebingen.de/ziegler/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403140.
7658
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Synthesis of Vicinal Diketoses
bis(O-isopropylidene)-arabino-hex-1-enitols D-5 and L-5 tions with Grubbs-type catalysts have found broad applica-
from d- and l-arabinose, respectively (see Scheme 1).
tions in carbohydrate chemistry.[11] However, problems can
be encountered for olefin metatheses that involve sugar de-
rivatives, as common protecting groups for carbohydrates
are sometimes incompatible with Grubbs-type catalysts.
Therefore, protecting groups must be chosen carefully when
a metathesis step is anticipated. In addition, because of the
instability of vicinal aliphatic diketones under basic condi-
tions, we were limited to acid-labile isopropylidene groups
to protect the hydroxy groups. Isopropylidene protecting
groups were also a good choice for the anticipated dihy-
droxylation step with osmium tetroxide. Somfai et al. re-
ported that isopropylidene-protected sugars were not suit-
able for metathesis reactions that employed second-genera-
tion Grubbs-type catalysts.[12] Indeed, the first- and second-
generation Grubbs catalysts, which we tested in the conden-
sation of hex-1-enitols 5, did not initiate any conversion
into DD-6. Fortunately, isopropylidene-protected sugars 5
and 6 were compatible with Hoveyda–Grubbs second-gen-
eration catalyst (see Supporting Information for structures
of the Grubbs catalysts that were investigated). Thus, the
dimerization of D-5 under Hoveyda–Grubbs catalysis af-
forded the protected trans-dec-5-enitol DD-6 in 91% yield.
Similarly, the cross-coupling reaction of D-5 with L-5 pro-
ceeded smoothly and gave a 3:1 diastereomeric mixture of
DL-6 and racemic DD-6 and LL-6. The separation of the
diastereomers was achieved by fractionating crystallization
to afford pure DL-6 in 59% overall yield (see Scheme 2).
The cis-selective dihydroxylation of dec-5-enitols 6 by
Scheme 1. Synthesis of 5 from diethyl thioacetals D-3 and L-3
(THF = tetrahydrofuran).
First, by applying well-established procedures, we con-
verted each of the enantiomeric arabinoses into the corre-
sponding diethyl thioacetals by using ethanethiol followed
by protection of the hydroxy groups with 2,2-dimeth-
oxypropane to give arabinose derivatives D-3 and L-3.[8]
Next, both thioacetals were cleaved by oxidation to afford
the protected open-chain arabinoses D-4 and L-4. A good
alternative to the classic procedure to remove the thioacetal
group with mercuric salts is an oxidative cleavage by using
iodine,[9] and we wholeheartedly recommend this method to
avoid the use of hazardous heavy metals. The subsequent treatment with OsO4 and N-methylmorpholine N-oxide
conversion of the aldehyde group in compounds 4 by a Wit- (NMO) furnished diols 7. Dec-5-enitol DD-6 underwent the
tig olefination[10] with methyltriphenylphosphonium brom- reaction stereoselectively to give DD-7 as a single dia-
ide gave terminal hex-1-enitols D-5 and L-5 in good yields. stereomer. An explanation for the selectivity is that one face
The coupling of both enantiomers of hex-1-enitols 5 with of the double bond in DD-6 is sterically shielded, and thus
one another or with each other was effected by an olefin attack by OsO4 occurs solely from the less-hindered side
metathesis reaction. In recent years, such metathesis reac- (see Figure 2). Under identical conditions, the dihydrox-
Scheme 2. Condensation of hex-1-enitols 5, dihydroxylation of dec-5,6-enitols 6, oxidation of decitols 7, and deprotection of diuloses 8.
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ylation of DL-6 led to a racemic mixture of DL-7 and its ray structure of DD-9 shows that the diulose adopts a cis-
enantiomer ent-DL-7. Although we were not able to obtain decalin-like conformation upon double pyranose ring for-
crystals of DL-6 that were suitable for X-ray crystal struc- mation (see Figure 3). The anomeric hydroxy groups are
ture analysis, both faces of the double bond are equally both in the α-position relative to each pyranose ring, and
accessible by OsO4 and thus lead to a racemic mixture of all of the other substituents are oriented equatorially. Both
the corresponding diols.
pyranose rings are in an unstrained chair conformation.
The molecule has C2 symmetry, which results in only five
signals in the 13C NMR spectrum.
Figure 2. Crystal structure of DD-6: (A) view from the top of the
double bond and (B) view from the side of the double bond. Struc-
ture without disorder of O-4.
Problems arose when we attempted to oxidize diols 7 to
give the corresponding diketones 8. Oxidation reactions
that employed pyridinium chlorochromate (PCC)[13] or N-
bromosuccinimide (NBS)/pyridine,[14] various TEMPO-me-
diated oxidation reactions (TEMPO = 2,2,6,6-tetramethyl-
1-piperidinyloxy),[15] or those that were carried out under
Figure 3. Crystal structure of DD-9. Structure without water and
Albright–Goldman[16] or Pfitzner–Moffatt[17] conditions disorder of O-2.
failed. Only extensive decomposition of the starting mate-
rial could be detected by TLC analysis under these condi-
Deprotection of diulose DL-8 in the same manner gave,
tions. In addition, oxidation reactions with Dess–Martin after evaporation of the solvents and lyophilisation, a white
periodinane (DMP),[18] 2-iodoxybenzoic acid (IBX),[19] or amorphous solid that could not be redissolved in water or
O-(1H-benzotriazol-1-yl)-N,N,NЈ,NЈ-tetramethyluronium an organic solvent at room temperature. Thus, we con-
tetrafluoroborate (TBTU), dimethyl sulfoxide (DMSO), cluded that dipyranose DL-9 was formed upon the depro-
and Et3N[20] left the starting materials unaltered. Oxidation tection of DL-8 (see Scheme 2). However, in contrast to di-
reactions that were performed under Parikh–Doering[21] pyranose DD-9, DL-9 either forms an oligomer or polymer
conditions only yielded the corresponding hydroxy ketones, that is similar to glyoxal,[25] or it is simply less soluble in
whereas oxidations under Katzenellenbogen,[22] classical water than DD-9. The IR spectrum of the obtained material
Swern[23] conditions, or modifications thereof with tri- revealed a signal at 3433 cm–1, which indicates strong
fluoroacetic acid (TFAA), DMSO, and Et3N[24] exhibited hydrogen bonds, and acetal signals at 1121–1045 cm–1. The
an erratic reliability and often resulted in a low yield with MALDI-TOF mass spectrometry data of DL-9 showed the
many byproducts. However, the optimization of the latter presence of monomeric DL-9 and its corresponding dimer
reaction conditions was achieved by activating the DMSO in the mass range of 0–2750 Da. No higher oligomers of
with TFAA and using N,N-diisopropylethylamine (DIPEA) DL-9 were detected. The acetylation of a small analytical
as the base. Under these conditions, DD-8 and DL-8 were sample of DL-9 with an excess amount of acetic anhydride
obtained in 57 and 32% yield, respectively.
in pyridine at room temperature resulted in material that
Deprotection of diulose DD-8 was effected with TFA in was identified by mass spectrometry as the hexaacetate of
aqueous THF at room temperature until TLC analysis DL-9. Thus, it can be concluded that DL-9 does not form
showed the complete hydrolysis of all of the acetonide oligo- or polymers but is simply insoluble in water at room
groups. Removal of the organic solvents in vacuo and temperature. The insolubility of DL-9 in virtually all sol-
lyophilisation of the remaining aqueous solution afforded vents initially hindered us from recording its NMR spectro-
deco-5,6-diulose DD-9 in 74% yield (see Scheme 2). The X- scopic data. However, it was possible to dissolve DL-9 in
7660
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Synthesis of Vicinal Diketoses
hot water or pyridine. The 13C NMR spectrum of DL-9 in
hot D2O displayed only five signals, as was found for di-
ulose DD-9, and proved the symmetric conformation for
DL-9 as well. Furthermore, diulose DL-9 is achiral and thus
had no specific rotation (measured by dissolving DL-9 in
hot water, quickly cooling the solution to room tempera-
ture, and immediately measuring the optical rotation before
DL-9 precipitated). This is in accordance with the trans-
decalin-like conformation of the two pyranose rings. Both
stirred for 2 h.
A solution of 2,3:4,5-di-O-isopropylidene-d-
arabinose[9] (1.5 g, 6.5 mmol) in dry THF (25 mL) was added, and
the mixture was stirred for 10 min. The reaction mixture was
poured into diethyl ether (150 mL) and then quenched by the ad-
dition of saturated aqueous NH4Cl solution (5 mL) at room tem-
perature. Water was removed from the mixture by the addition of
solid Na2SO4 with stirring followed by filtration. The filtrate was
concentrated in vacuo, and the crude product was redissolved in
diethyl ether (100 mL). The resulting solution was washed with
brine (3ϫ), dried with Na2SO4, filtered, and concentrated in vacuo.
anomeric hydroxy groups adopt the thermodynamically Chromatography (petroleum ether/ethyl acetate, 9:1) of the residue
gave D-5 (1.15 g, 77%). The spectral data are in accordance with
preferred α-position, and all of the other substituents are
equatorially oriented. Although we were unable to obtain
suitable crystals of DL-9 for an X-ray crystal structure
analysis, it is evident from the NMR spectroscopic data that
it adopts the structure depicted in Scheme 2.
that in the literature.[26]
3,4:5,6-Di-O-isopropylidene-1,2-dideoxy-L-gluc-1-enitol (L-5): As
described for the synthesis of D-5, 2,3:4,5-di-O-isopropylidene-l-
arabinose[27] (1.5 g, 6.5 mmol) was employed to give L-5 (1.22 g,
82%). Spectral data are in accordance with the literature data.[28]
(E)-1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-5,6-dideoxy-L-gulo-D-
erythro-dec-5-enitol (DD-6): Compound D-5 (0.75 g, 3.28 mmol)
was dissolved in dichloromethane (75 mL) under N2, and a cata-
lytic amount of Grubbs–Hoveyda II catalyst (25 mg, 0.04 mmol)
was added. The resulting mixture was stirred at room temperature
until TLC analysis showed the complete consumption of the start-
ing material (20 h). The mixture was then concentrated in vacuo,
and the residue was purified by chromatography (petroleum ether/
ethyl acetate, 8:1) to give DD-6 (0.64 g, 91%) as colorless crystals.
Crystals for X-ray analysis were obtained by slow crystallization of
D D - 6 f r o m n - h e x a n e ; m . p . 7 2 . 3 ° C ( n - h e x a n e ) .
Conclusions
We have developed a concise and general synthetic route
to deco-5,6-diuloses that are structurally similar to pelta-
losa. Although the NMR spectroscopic data and the spe-
cific optical rotations of the deco-5,6-diuloses in the arabino
series (i.e., DD-9 and DL-9), as prepared here, do not mir-
ror the reported data for peltalosa and, thus, do not allow
for the unambiguous determination of the absolute configu-
ration of peltalosa, diastereomeric uloses of this type in the
ribo, lyxo, and xylo series, respectively, should reveal the
correct structure. The preparations of these missing dia-
stereomers of deco-5,6-diulose and similar α-diuloses by ap-
plying the synthetic route herein are now underway.
1
[α]2D0 = +12.0 (c = 1.0, CHCl3). H NMR (400 MHz, CDCl3): δ =
5.94 (dd, J = 2.9, 1.4 Hz, 2 H, 5-H, 6-H), 4.40 (ddd, J = 7.6, 3.0,
1.3 Hz, 2 H, 4-H, 7-H), 4.04–4.18 (m, 4 H, 1-Ha, 2-H, 9-H, 10-
Ha), 3.86–3.97 (m, 2 H, 1-Hb, 10-Hb), 3.65–3.74 (m, 2 H, 3-H, 8-
H), 1.39–1.48 (s, 18 H, CH3), 1.35 (s, 6 H, CH3) ppm. 13C NMR
(400 MHz, CDCl3): δ = 130.4 (C-5, C-6), 110.1, 109.9 (4 C, C-
quaternary), 81.7 (C-3, C-8), 79.9 (C-4, C-7), 77.0 (C-2, C-9), 67.5
(C-1, C-10), 27.4, 27.3, 27.1, 25.7 (8 C, CH3) ppm. C22H36O8
(428.52): calcd. C 61.66, H 8.47; found C 61.59, H 8.53.
Experimental Section
General Methods: Optical rotations were measured in CHCl3 and
H2O with a Perkin–Elmer type 341 polarimeter. Melting points
were measured with a Büchi M-560 apparatus. TLC analysis was
performed with Macherey–Nagel Polygram SIL G/UV plates. De-
tection of the developed TLC plates was effected by charring with
5% H2SO4 in methanol. Elemental analyses were performed with
a HEKAtech Euro EA Analyzer. The NMR spectroscopic data
were recorded with Bruker Avance 400 MHz and 600 MHz specto-
meters. The NMR signals were assigned by using homonuclear and
heteronuclear 1D and 2D spectroscopy. The NMR spectroscopic
data for compounds 9 were reported according to the numeration
of the corresponding open-chain compounds. ESI mass spectra
were recorded with a Bruker Apex II FT-ICR-MS spectrometer,
and MALDI-TOF mass spectra were recorded with a Bruker Auto-
flex spectrometer. X-ray diffraction was conducted with a Bruker
Apex Duo diffractometer. The Hoveyda–Grubbs II catalyst was
purchased from Aldrich.
(E)-1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-1,2-dideoxy-L-manno-D-
erythro-dec-5-enitol (DL-6): As described for the preparation of
DD-6, a mixture of D-5 (0.5 g, 2.2 mmol) and L-5 (0.5 g, 2.2 mmol)
in dichloromethane (50 mL) was treated with a catalytic amount of
Grubbs–Hoveyda II catalyst (25 mg, 0.04 mmol). The workup and
chromatography afforded a 1:1:6 diastereomeric mixture of racemic
DD-6/LL-6/DL-6. Crystallization of the mixture from n-hexane
first afforded pure DL-6 (0.28 g, 59%), and then the concentration
of the mother liquor gave racemic DD-6/LL-6 (0.13 g, 28%) that
was contaminated by impurities of DL-6. Data for DL-6: M.p.
92.2 °C (n-hexane). [α]2D0 = +0.0 (c = 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 5.59–6.21 (m, 2 H, 5-H, 6-H), 4.40 (ddd,
J = 7.6, 3.0, 1.3 Hz, 2 H, 4-H, 7-H), 4.06–4.16 (m, 4 H, 1-Ha, 2-
H, 9-H, 10-Ha), 3.89–3.98 (m, 2 H, 1-Hb, 10-Hb), 3.66–3.73 (m, 2
H, 3-H, 8-H), 1.41 (s, 18 H, CH3), 1.34 (s, 6 H, CH3) ppm. 13C
NMR (400 MHz, CDCl3): δ = 130.4 (C-5, C-6), 109.6 and 109.5
(C-quaternary), 81.2 (C-3, C-8), 79.5 (C-4, C-7), 77.3 (C-2, C-9),
67.1 (C-1, C-5), 26.9, 26.8, 26.7, 25.2 (8 C, CH3) ppm. C22H36O8
(428.52): calcd. C 61.66, H 8.47; found C 61.91, H 8.49.
CCDC-1020014 (for DD-6) and -1020015 (for DD-9) contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-D-manno-L-manno-decositol
(DD-7): Enitol DD-6 (0.20 g, 0.47 mmol) was dissolved in a mixture
of water (1 mL) and acetone (5 mL). To this solution were added
NMO (0.3 g, 2.5 mmol) and a solution of OsO4 (4 % in water,
0.5 mL), and the mixture was stirred at room temperature for 16 h.
An additional portion of NMO (0.3 g, 2.5 mmol) was added when
3,4:5,6-Di-O-isopropylidene-5,6-dideoxy-
D-gluc-1-enitol
(D-5):
MePh3PBr (4.65 g, 13.0 mmol) was suspended in dry THF (75 mL)
under N2, and the resulting mixture was cooled to 0 °C. Potassium
tert-butoxide (1.46 g, 9.7 mmol) was added, and the mixture was
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M. Menzel, T. Ziegler
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the TLC analysis showed incomplete conversion of the starting ma-
terial. Ethyl acetate (25 mL) and a saturated aqueous solution of
Na2S2O3 (1 mL) were added, and the mixture was stirred for
20 min. NaCl was added, and the organic phase was separated and
then washed with a saturated aqueous solution of Na2S2O3 (3ϫ)
and brine (2ϫ). The organic phase was then dried with MgSO4,
filtered, and concentrated. Purification by chromatography (ethyl
acetate/petroleum ether, 1:2) gave DD-7 (0.15 g, 72%) as colorless
racemic mixture of DL-7 and ent-DL-7 (250 mg, 0.54 mmol) gave
DL-8 (79 mg, 32%) as yellow crystals; m.p. 147.8 °C. [α]2D0 = 0 (c =
1.0, CHCl3). FT-ICR-MS: calcd. for [M + MeOH + Na]+
1
513.2306; found 513.2311. H NMR (400 MHz, CDCl3): δ = 4.92
(d, J = 6.1 Hz, 2 H, 4-H, 7-H), 4.25–4.34 (m, 2 H, 3-H, 8-H), 4.17–
4.25 (m, 2 H, 2-H, 9-H), 4.08–4.17 (m, 2 H, 1-Ha, 10-Ha), 3.97
(dd, J = 8.6, 4.8 Hz, 2 H, 1-Hb, 10-Hb), 1.46, 1.39, 1.39, 1.34 (4 s,
24 H, CH3) ppm. 13C NMR (400 MHz, CDCl3): δ = 198.9 (C-5,
C-6), 112.4, 110.1 (4 C, C-quaternary), 80.0 (C-4, C7), 78.7 (C-3,
C-8), 76.2 (C-2, C-9), 66.7 (C-1, C-10), 27.1, 26.4, 26.1, 25.3 (8 C,
crystals; m.p. 139.0 °C. [α]2D0 = +13.9 (c = 1.0, CHCl3). H NMR
1
(400 MHz, CDCl3): δ = 4.16–4.22 (m, 2 H, 1-Ha, 10-Ha), 4.03–
4.15 (m, 4 H, 2-H, 4-H, 7-H, 9-H), 3.99 (dd, J = 8.3, 5.6 Hz, 2 H, CH3) ppm.
1-Hb, 10-Hb), 3.91 (dd, J = 8.1, 6.8 Hz, 2 H, 3-H, 8-H), 3.83 (d, J
α,α-L-gulo-D-erythro-Deco-5,6-diulo-1,5:6,10-dipyranose (DD-9): A
= 8.6 Hz, 2 H, 5-H, 6-H), 3.39 (br. s, 2 H, OH), 1.45 (6 H, CH3),
1.40 (s, 6 H, CH3), 1.38 (s, 6 H, CH3), 1.36 (s, 6 H, CH3) ppm. 13
NMR (400 MHz, CDCl3): δ = 110.1, 109.8 (4 C, C-quaternary),
81.2 (C-3, C-8), 78.9 (C-4, C-7), 76.7 (C-2, C-9), 71.3 (C-5, C-6),
67.6 (C-1, C-10), 27.2, 27.0, 26.4, 25.2 (8 C, CH3) ppm. C22H38O10
(462.53): calcd. C 57.13, H 8.29; found C 57.18, H 8.38.
solution of DD-8 (60 mg, 0.13 mmol) and trifluoroacetic acid
(0.1 mL) in 50% aqueous THF (5 mL) was stirred at room tem-
perature until TLC analysis showed the complete conversion of the
starting material (approximately 4 h). The solution was concen-
trated in vacuo, and the remaining aqueous solution was lyophi-
lized to give crude DD-9. Recrystallization (methanol/water, 100:1)
by slowly diffusing diethyl ether into the aqueous methanol solu-
tion gave pure DD-9 (28 mg, 74%) as colorless crystals; m.p. 202 °C
(decomp). [α]2D0 = +36.6 (c = 1.0, H2O). FT-ICR-MS: calcd. for [M
+ Na]+ 321.0792; found 321.0792. 1H NMR (400 MHz, [D6]-
DMSO): δ = 3.60 (d, J = 10.4 Hz, 1 H, 1-Ha, 10-Ha), 3.47–3.55
(m, 1 H, 2-H, 9-H), 3.43 (d, J = 9.1 Hz, 1 H, 4-H, 7-H), 3.30–3.36
(m, 1 H, 1-Hb, 10-Hb), 3.17 (d, J = 9.1 Hz, 1 H, 3-H, 8-H) ppm.
13C NMR (400 MHz, [D6]DMSO): δ = 95.8 (C-5, C-6), 74.8 (C-4,
C-7), 73.5 (C-2, C-9), 70.1 (C-3, C-8), 62.6 (C-1, C-10) ppm.
C10H18O10 (298.24): calcd. C 40.27, H 6.08; found C 39.43, H 6.42.
C
1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-
(DL-7) and 1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-
D
-gluco-
L
-manno-decositol
-gluco-D-
L
manno-decositol (ent-DL-7): As described for the preparation of
DD-7, DL-6 (1.5 g, 3.3 mmol) was treated with NMO and OsO4 to
give a racemic mixture of DL-7 and ent-DL-7 (1.4 g, 88%) as color-
less crystals; m.p. 82.6 °C. [α]2D0 = 0 (c = 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 3.89–4.18 (m, 11 H, 1-Ha, 1-Hb, 2-H, 3-
H, 4-H, 6-H, 7-H, 8-H, 9-H, 10-Ha, 10Hb), 3.77 (d, J = 7.8 Hz, 1
H, 5-H), 3.58 (br. s, 1 H, OH), 2.89 (br. s, 1 H, OH), 1.43 (s, 3 H,
CH3), 1.41 (s, 6 H, CH3), 1.39 (s, 3 H, CH3), 1.36 (s, 6 H, CH3),
1.34 (s, 3 H, CH3), 1.32 (s, 3 H, CH3) ppm. 13C NMR (400 MHz,
CDCl3): δ = 110.0, 109.9, 109.7, 109.6, (4 c, C-quaternary), 82.0,
80.7, 79.7, 77.8, 77.2, 76.4, 73.3, 69.1, 67.7, 67.2 (10 C, C-1 to C-
10), 27.2, 27.1, 27.0, 26.7, 26.5, 26.4, 25.2, 25.1 (8 C, CH3) ppm.
C22H38O10 (462.53): calcd. C 57.13, H 8.29; found C 56.95, H 8.20.
α,α-L-manno-D-erythro-Deco-5,6-diulo-1,5:6,10-dipyranose (DL-9):
As described for the preparation of DD-9, DL-8 (71 mg,
0.65 mmol) was treated with trifluoroacetic acid in aqueous THF
to give DL-9 (30 mg, 65%) as a white amorphous solid, which was
insoluble in water at room temperature. The amorphous material
dissolved in hot water or pyridine. Decomposition occurred at
1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-L-gulo-D-erythro-deco-5,6-di-
ulose (DD-8): Trifluoroacetic acid (0.11 mL, 0.8 mmol) was added
at –75 °C to a solution of DMSO (0.07 mL, 1.0 mmol) in dichloro-
methane (5 mL), and the mixture was stirred at that temperature
for 30 min. To this solution was added a solution of DD-7 (150 mg,
0.32 mmol) in dichloromethane (3 mL) over 15 min, and stirring
was continued at –75 °C for an additional 30 min. N,N-Diisoprop-
ylethylamine (0.2 mL, 1.2 mmol) was slowly added, and the mix-
ture was warmed to room temperature in the course of 2 h, where-
upon TLC analysis (ethyl acetate/petroleum ether, 1:2 containing
1% Et3N) showed complete consumption of the starting material.
The mixture was poured into dichloromethane (50 mL), and the
resulting mixture was washed with water, saturated aqueous
NaHCO3 solution, HCl (0.3 n aqueous solution), and water. The
organic phase was dried with MgSO4, filtered, and concentrated to
give crude DD-8. Recrystallization from n-hexane afforded pure
DD-8 (40 mg, 57%) as yellow crystals (DD-8 rapidly decomposed
under slightly basic conditions); m.p. 108.9 °C. [α]2D0 = –2.2 (c =
1.0, CHCl3). FT-ICR-MS (Fourier transform ion cyclotron reso-
nance mass spectrometry): calcd. for [M + MeOH + Na]+
230 °C. IR (KBr): ν = 3433, 3257, 2932, 2360, 1438, 1359, 1322,
˜
1243, 1187, 1121, 1092, 1045, 998, 886, 788 cm–1. MS (ESI, nega-
tive ion mode): m/z = 297.0833 [M – H+]–, 595.1726 [2 M – H+]–.
1H NMR (600 MHz, D2O, 80 °C): δ = 3.95 (d, J = 8.7 Hz, 1 H, 3-
H, 8-H), 3.93–3.86 (m, 2 H, 2-H, 9-H, 1-Ha, 10-Ha), 3.71 (dd, J =
6.4, 12.1 Hz, 1 H, 1-Hb, 10-Hb), 3.55 (t, J = 9.5 Hz, 1 H, 4-H, 7-
H) ppm. 13C NMR (600 MHz, D2O): δ = 95.8 (C-5, C-6), 74.7 (C-
2, C-9), 72.8 (C-3, C-8), 69.7 (C-4, C-7), 61.6 (C-1, C-10) ppm.
C10H18O10 (298.24): calcd. C 40.27, H 6.08; found C 39.92, H 6.25.
An analytical sample of DL-9 (approximately 0.5 mg) was treated
with a mixture of acetic anhydride (0.15 mL) and pyridine (0.6 mL)
at room temperature for 6 h followed by the coevaporation with
toluene (3ϫ 5 mL) and final concentration to dryness to give the
crude hexaacetate of DL-9. FAB-MS: m/z = 573.1 [M + Na]+,
1122.9 [2 M + Na]+.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra of all new compounds and molecular structures
of the Grubbs-type catalysts.
1
513.2306; found 513.2309. H NMR (400 MHz, CDCl3): δ = 4.91
(d, J = 6.1 Hz, 2 H, 5-H, 6-H), 4.31–4.40 (m, 2 H, 4-H, 7-H), 4.20
(td, J = 6.7, 4.8 Hz, 2 H, 3-H, 8-H), 4.11–4.17 (m, 4 H, 1-Ha, 2-
H, 9-H, 10-Ha), 3.98 (dd, J = 8.7, 4.7 Hz, 2 H, 1-Hb, 10-Hb), 1.46
(s, 6 H, CH3), 1.42 (s, 6 H, CH3), 1.35 (s, 12 H, CH3) ppm. 13C
NMR (400 MHz, CDCl3): δ = 199.3 (C-5, C-6), 112.3, 110.0, (4 C,
C-quaternary), 80.1 (C-4, C-7), 78.2 (C-3, C-8), 76.2 (C-2, C-9),
66.7 (C-1, C-10), 27.1, 26.4, 26.0, 25.1 (8 C, CH3) ppm.
Acknowledgments
We would like to express our gratitude towards Petra Krüger for
the elemental analysis (EA) measurements, Dr. Dorothee Wistuba
for the mass spectrometry analysis, and Dr. Cäcilia Maichle-
Mössmer for the crystal structure analysis.
1,2:3,4:7,8:9,10-Tetra-O-isopropylidene-
5,6-diulose (DL-8): As described for the preparation of DD-8, the
L-manno-D-erythro-deco-
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Published Online: October 24, 2014
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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