Organocatalytic Synthesis of Higher-Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d-Glycero-l-galacto-oct-2-ulose

Article abstract of DOI:10.1002/open.201500099

Herein we report a short and efficient protocol for the synthesis of naturally occurring higher-carbon sugars—sedoheptulose (d-altro-hept-2-ulose) and d-glycero-l-galacto-oct-2-ulose—from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn-selective aldol reaction of DHA with d-erythrose and d-xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn-selective carbon–carbon-bond-forming aldol reactions promoted by primary-based organocatalysts. For example, this methodology provided useful access to d-glycero-d-galacto-oct-2-ulose and 1-deoxy-d-glycero-d-galacto-oct-2-ulose from d-arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1).

Full text of DOI:10.1002/open.201500099

DOI: 10.1002/open.201500099
Organocatalytic Synthesis of Higher-Carbon Sugars:
Efficient Protocol for the Synthesis of Natural
Sedoheptulose and d-Glycero-l-galacto-oct-2-ulose**
[a]
[b]
[b]
[a, b]
´
Oskar Popik, Monika Pasternak-Suder, Sebastian Bas, and Jacek Mlynarski*
Herein we report a short and efficient protocol for the synthe-
sis of naturally occurring higher-carbon sugars—sedoheptulose
(d-altro-hept-2-ulose) and d-glycero-l-galacto-oct-2-ulose—
from readily available sugar aldehydes and dihydroxyacetone
(DHA). The key step includes a diastereoselective organocata-
lytic syn-selective aldol reaction of DHA with d-erythrose and
d-xylose, respectively. The methodology presented can be
expanded to the synthesis of various higher sugars by means
of syn-selective carbon–carbon-bond-forming aldol reactions
promoted by primary-based organocatalysts. For example, this
methodology provided useful access to d-glycero-d-galacto-
oct-2-ulose and 1-deoxy-d-glycero-d-galacto-oct-2-ulose from
d-arabinose in high yield (85 and 74%, respectively) and high
stereoselectivity (99:1).
Introduction
Higher-carbon sugars, with more than six carbon atoms, are
widely distributed in nature, where they have important bio-
logical functions.[1] For example, well-known members of this
family of compounds C8-KDO (3-deoxy-d-manno-oct-2-ulosonic
acid) and C9-Neu5Ac (sialic acid, neuraminic acid) possess inter-
esting biological properties with potential applications as anti-
biotics.[2] A number of lesser-known heptoses, heptitols, and
heptuloses have also been found in living organisms. For ex-
ample, l-glycero-d-manno-heptose (l,d-heptose) has been
identified as a major constituent of the lipopolysaccharides
(LPS) of Gram-negative bacteria.[3] d-altro-Heptulose (sedohep-
tulose, 1), is a naturally occurring saccharide present as an in-
termediate in the photosynthetic cycle in its phosphorylated
form and also plays a crucial role in the formation of hexoses.[4]
Similar eight-chain ketoses occur naturally in a number of
higher plants. Well-distributed d-glycero-d-manno-oct-2-ulose
and less abundant d-glycero-l-galacto-octulose (2, Scheme 1)
have been found in various plants such as Persea gratissima
and Sedum spectabile.[5]
The synthesis of sugars with carbon chains composed of
more than six carbon atoms presents an interesting chal-
lenge.[6] Typical synthetic routes for higher-carbon sugars in-
volve homologation of lower-carbon sugars and require the in-
troduction of new stereogenic centers in
a controlled
manner.[7] Interestingly, organocatalysis, which has emerged as
an important methodology for stereoselective carbon–carbon
bond formation,[8] has not been commonly applied to the syn-
thesis of carbohydrates.[9] Particularly, anti-selective aldol reac-
tion of protected hydroxyacetone (2,2-dimethyl-1,3-dioxan-5-
one) with glyceraldehyde resulted in the formation of various
isomeric hexoses.[10] Applications of organocatalysis to the syn-
thesis of higher sugars are rare and are limited to the applica-
tion of dioxanone donor. In 2006, Barbas III and co-workers
used diacetono-d-galactose (C-6-aldehyde) as an acceptor in
the reaction with 2,2-dimethyl-1,3-dioxan-5-one promoted by
(R)-proline.[11] More recently, Jarosz and colleagues demonstrat-
ed a stereoselective reaction of d-arabinose with the same pro-
tected dihydroxyacetone donor, leading stereoselectively to
protected oct-2-ulose.[12] The application of 2,2-dimethyl-1,3-
dioxan-5-one instead of hydroxyacetone, however, constitutes
a significant drawback. In both cases, the reaction proceeds
through cyclic (E)-enamine, leading exclusively to anti-selective
aldols.
[a] O. Popik, Prof. J. Mlynarski
Institute of Organic Chemistry, Polish Academy of Sciences
Kasprzaka 44/52, 01-224 Warsaw (Poland)
E-mail: jacek.mlynarski@gmail.com
Homepage: http://www.jacekmlynarski.pl
´
[b] Dr. M. Pasternak-Suder, Dr. S. Bas, Prof. J. Mlynarski
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow
(Poland)
Previously, we showed that an organocatalytic aldol reaction
of unprotected hydroxyacetone with glyceraldehyde may be
an alternative tool for the biomimetic synthesis of d- and l-ke-
tohexoses.[13] To realize such goal, we used organocatalysts
with proline and serine motifs resulting in either an anti- or—
more importantly—an elusive syn-selective aldol reaction.
Herein we demonstrate that the efficient and highly stereose-
lective preparation of various higher-carbon sugars may also
become facile via syn-selective organocatalytic aldol reaction
[**] This article is part of the Virtual Special Issue “Carbohydrates in the 21st
Century: Synthesis and Applications”.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/open.201500099.
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This is an open access article under the terms of the Creative Commons
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hydroxyacetone attacks alde-
hyde enantioselectively.[13]
To prove our expectations, we
tested the stereoselective aldol
reaction of dihydroxyacetone
and erythrose promoted by or-
ganocatalyst 6 (Scheme 3). The
necessary chiral building block,
protected d-erythrose 3, can be
synthesized in a few steps from
readily available d-mannose.[14]
Scheme 1. Natural higher-carbon heptose and octose.
As expected, the crucial aldol re-
of dihydroxyacetone with the appropriate chiral aldehyde ac-
ceptor, complementary to previously demonstrated attempts
at anti-selective reactions.
action promoted by (R)-siloxyserine organocatalysts 6 gave
hept-2-ulose 7 in 78% yield and high diastereoselectivity, fa-
voring the expected syn-aldol (Scheme 3). Application of un-
matched catalysts with S-configured serine resulted in unselec-
tive formation of three isomeric aldols, thus confirming our
assumptions.
Results and Discussion
The absolute stereochemistry of the aldol product is be-
lieved to be the same as that of natural sedoheptulose, and
this was proven after reduction of the aldol carbonyl group
Our retrosynthetic analysis of the sedoheptulose (1) and d-
glycero-l-galacto-oct-2-ulose (2) skeletons revealed that both
structures could be reduced to simple starting materials such
as dihydroxyacetone (C3) and te-
trose 3/pentose 4 through a syn-
selective aldol reaction. Thinking
in the forward direction, such
a scenario seemed possible by
using a primary-amine-based or-
ganocatalyst. It was envisaged
that stereochemical control in
the synthesis of 1 might be
achieved by (R)-serine-based or-
ganocatalysts with the use of d-
erythrose aldehyde
3 as the
chiral aldehyde building block
(Scheme 2). In this case, the R-
configured stereocenter at C2 of
3 should match the R-configured
amino acid resulting in a con-
trolled synthesis of (3S,4S)-con-
figured stereocenters based on
previously deduced principles
that (Z)-enamine formed from
Scheme 3. Stereoselective synthesis of sedoheptulose. Reagents and conditions: a) BnBr, NaH, imidazole, Bu4NI,
DMF, 08C, 2 h, 79%; b) Amberlyst 15 hydrogen form, MeOH, RT, 24 h, 82%; c) H2, Pd/C, MeOH, RT, 20 h, 98%. Over-
all yield: 63%.
with sodium borohydride and deprotection of the resulting
heptitol 8. Reduction of aldol 7 afforded two possible C2-epi-
meric heptitols: d-glycero-d-manno-heptitol (9a) and d-glycero-
1
d-gluco-heptitol (9b) in a 7:3 ratio. H and 13C NMR spectra of
both compounds and their peracetylated forms agree with
data published previously for the same heptitols,[15] thus ulti-
mately providing evidence for the configuration of sedoheptu-
lose 7.
Highly stereoselective synthesis of sedoheptulose encour-
aged us in the synthesis of d-glycero-l-galacto-oct-2-ulose
from protected d-xylose 5[16] (Scheme 4). In this case, the
R-configured stereocenter at C2 of the substrate required ap-
plication of the same catalyst as previously used. Indeed, the
Scheme 2. Retrosynthetic analysis of hept-2-ulose and oct-2-ulose.
reaction of 4 and 5 in the presence of (R,R,R,R)-6 in aqueous
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d-glycero-d-galacto-oct-2-ulose (12). Moreover, appli-
cation of the same catalyst to the reaction between
d-arabinose and hydroxyacetone 13 gave the expect-
ed 1-deoxy-d-glycero-d-galacto-oct-2-ulose (14) in
high yield (74%) and impressive stereoselectivity
(Scheme 5).
In all presented aldol reactions, proper selection of
the chiral substrate and aldehyde was decisive,
giving us full control over the created stereocenters
despite the substrate configuration. When used with
chiral R- and S-configured aldehydes at the a-carbon
atom, in the presence of the optional use of (R,R,R,R)-
6 and (S,S,S,S)-ent-6 catalysts, a matched/mismatched
situation becomes apparent. We confirmed the for-
mation of 4,5-anti-3,4-syn-aldols exclusively. Application of d-
serine-based catalyst (R,R,R,R)-6 was privileged for 2R-config-
ured aldehydes and resulted in a predictable formation of
3S,4S-configured aldols. Such a concept can be useful for the
flexible synthesis of various higher sugars by using elaborated
catalysts and methodology.
Scheme 4. Stereoselective synthesis of d-glycero-l-galacto-oct-2-ulose.
DMF afforded 10 as a single diastereomer in high yield (89%).
In the case of d-xylose, application of catalyst 6 resulted in the
formation of d-glycero-l-galacto-oct-2-ulose in high yield and
diastereomeric ratio. In contrast, enantiomeric catalyst (S,S,S,S)-
ent-6 delivered a 1:1 mixture of 3,4-syn aldols.
The presented short and stereoselective syntheses of hept-
and oct-2-uloses surpass all previously presented routes to
such higher-carbon sugars in terms of efficiency; for this
reason we decided to test the flexibility of this methodology
for substrates with S configurations at the a-position to the
carbonyl group. In our opinion, the best candidate for such
a study was d-arabinose (11) with an S-configured stereocenter
at the a-position to carbonyl group.
Conclusion
In summary, we report a short and efficient one-step protocol
for the synthesis of naturally occurring higher-carbon sedohep-
tulose (d-altro-hept-2-ulose) and d-glycero-l-galacto-oct-2-
ulose, from the readily available sugar aldehydes and dihydrox-
yacetone (DHA). The key step includes diastereoselective orga-
nocatalytic syn-aldol reaction of DHA with d-erythrose and d-
xylose, respectively. This methodology can be used for the syn-
thesis of various higher sugars by using predictable stereo-
chemistry rules, correlating the absolute configurations of the
substrate and catalyst.
The first experiment confirmed our assumptions: the
(S,S,S,S)-ent-6-catalyzed aldol reaction of this substrate with di-
hydroxyacetone gave the 3,4-syn aldol 12 in 85% yield and
with high diastereoselectivity (Scheme 5). In this case, the
application of catalyst composed of l-serine motifs resulted in
the formation of the 3R,4R-configured aldol. This demonstrated
efficient methodology provided synthetically useful access to
Experimental Section
General Information: All starting
materials and reagents were ob-
tained from commercial sources
and used as received unless other-
wise noted. All solvents used were
freshly distilled prior to use. Opti-
cal rotations were measured at
room temperature with a polarime-
ter. High-resolution mass spectra
were acquired using electrospray
ionization mode with a time-of-
flight detector. Infrared (IR) spectra
were recorded on a Fourier trans-
form infrared (FT-IR) spectrometer
as either a thin film on a NaCl
plate (film) or as a KBr pellet (KBr).
1H NMR spectra were recorded on
spectrometers operating at 300,
400, 500, and 600 MHz in CDCl3,
D2O, or CD3OD. Data are reported
as follows: chemical shifts (d) in
Scheme 5. Stereoselective synthesis of d-glycero-d-galacto-oct-2-ulose and 1-deoxy-d-glycero-d-galacto-oct-2-
ulose.
parts per million from tetramethyl-
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silane as an internal standard, integration, multiplicity (s=singlet,
d=doublet, t=triplet, q=quartet, dd=double-doublet, m=mul-
tiplet, br=broad), coupling constants (in Hz), and assignment.
13C NMR spectra were measured at 75, 100, 125, or 150 MHz with
complete proton decoupling. Chemical shifts are reported in ppm
from the residual solvent as an internal standard. Reactions were
monitored by TLC on silica [alu-plates (0.2 mm)]. Plates were visual-
ized with UV light (l 254 nm) and by treatment with ethanolic p-
anisaldehyde with sulfuric and glacial acetic acid followed by heat-
ing, aqueous cerium(IV) sulfate solution with molybdic and sulfuric
acid followed by heating, or ethanolic ninhydrin solution followed
by heating. All organic solutions were dried over anhydrous
sodium sulfate. Reaction products were purified by flash chroma-
tography using silica gel 60 (240–400 mesh). HPLC analyses were
performed on an HPLC system equipped with chiral stationary
phase columns, detection at l 254 nm.
argon. A mixture of protected heptitols 8 (45 mg, 0.13 mmol) was
dissolved in anhydrous DMF, and imidazole (10 mol%) was added.
The reaction mixture was cooled to 08C, and NaH (60% dispersion
in mineral oil, 4”1.3 equiv) was added. After 30 min BnBr (4”
1.2 equiv) and Bu4NI (4”0.12 equiv) were added, and the reaction
was monitored by TLC. After 2 h H2O was added to the reaction
mixture and the aqueous phase was washed with EtOAc. The or-
ganic phase was washed with brine, dried, concentrated, purified
by flash column chromatography (hexane/EtOAc 9:1) and submit-
ted to the next step. After the substrate was dissolved in MeOH,
Amberlyst 15 hydrogen form was added, and the vial with the mix-
ture was placed on a laboratory shaker. After 24 h the reaction mix-
ture was filtered, concentrated, purified by flash column chroma-
tography (hexane/EtOAc 3:1), and submitted to the next step. Re-
moval of benzyl groups was performed by hydrogenation in the
presence of palladium on charcoal. The substrate was dissolved in
MeOH, and Pd/C was added. After 20 h of stirring under hydrogen
atmosphere the reaction mixture was filtered through a Celite plug
d-Erythrose (3),[14] d-xylose (5),[16] and d-arabinose (11)[17] aceto-
nides were prepared according to published procedures. Synthesis
and spectroscopic data for organocatalysts 6 and ent-6 were
described previously.[18]
1
and concentrated. Yield 16 mg, 63%; H NMR (400 MHz, D2O): d=
3.91–3.86 (m, 2H), 3.86–3.83 (m, 1H), 3.83–3.80 (m, 1H), 3.80–3.77
(m, 2H), 3.77–3.75 (m, 2H), 3.75–3.73 (m, 2H), 3.72–3.68 (m, 2H),
3.68–3.65 (m, 1H), 3.65–3.61 (m, 2H), 3.61–3.54 (m, 1H); 13C NMR
(100 MHz, D2O): d=74.3, 74.2, 73.9, 73.0, 72.8, 72.1, 71.2, 71.0, 70.9,
64.5, 63.8, 63.5, 63.4; IR (ATR, ZnSe): 3364, 2938, 1648, 1598, 1418,
General procedure for the aldol reaction of dihydroxyacetone
(Schemes 3–5): To a solution of aldehyde (0.5 mmol) in DMF/H2O
(9:1, 0.5 mL), 1,3-dihydroxyacetone dimer 4 (180 mg, 1 mmol;
2 mmol as a monomer) was added. After the substrates dissolved,
organocatalyst 6 or ent-6 (20 mol%) was added to the reaction
mixture. The reaction was stirred at room temperature and moni-
tored by TLC. The reaction mixture was poured directly on silica
gel. The aldol product was purified by flash column chromatogra-
phy (CHCl3/MeOH, 97:3).
1311 cmÀ1
; HRMS (ESI) exact mass calcd for C7H16O7Na m/z
235.0794 [M+Na]+, found m/z 235.0796 [M+Na]+.
1H and 13C NMR spectra of the mixture of peracetylated heptitols
9a/9b also match previously published data.[15] The peracetylation
reaction was performed under argon. The mixture of heptitols 9a
and 9b (12 mg, 0.05 mmol) was dissolved in dry pyridine, Ac2O
(30 equiv) and DMAP (10 mol%) were added, and the reaction was
kept at room temperature for 24 h. MeOH was added, and the mix-
ture was concentrated under reduced pressure. The residue was
partitioned between CH2Cl2 and 5% aqueous HCl. The organic
layer was washed with 5% aqueous NaHCO3, dried, concentrated,
and purified by flash column chromatography (hexane/EtOAc, 3:2).
d-Altro-hept-2-ulose (7, Scheme 3): Yield 132 mg, 78%; [a]22
=
D
1
À12.9 (c=2.38, CHCl3); H NMR (400 MHz, CDCl3): d=7.38–7.27 (m,
5H), 4.57 (d, J=5.3 Hz, 2H), 4.55–4.50 (m, 1H), 4.48–4.37 (m, 3H),
4.34 (dd, J=9.2, 5.7 Hz, 1H), 4.06 (ddd, J=9.2, 3.5, 1.5 Hz, 1H), 3.93
(d, J=3.9 Hz, 1H), 3.72 (t, J=9.5 Hz, 1H), 3.58 (dd, J=9.8, 3.9 Hz,
1H), 3.19 (d, J=8.3 Hz, 1H), 3.01 (brs, 1H), 1.39 (s, 3H), 1.35 (s,
3H); 13C NMR (100 MHz, CDCl3): d=211.7, 136.4, 128.9, 128.7, 128.3,
109.2, 76.2, 75.8, 75.1, 74.4, 70.0, 68.3, 67.1, 28.0, 25.4; IR (film,
CHCl3): 3412, 2986, 2932, 2872, 1726, 1455, 1382, 1375 cmÀ1; HRMS
(ESI) exact mass calcd for C17H24O7Na m/z 363.1420 [M+Na]+,
found m/z 363.1429 [M+Na]+.
1
Yield 20 mg, 79%; H NMR (400 MHz, CDCl3): d=5.47–5.40 (m, 1H),
5.40–5.36 (m, 1H), 5.27–5.18 (m, 1H), 5.16–5.10 (m, 1H), 5.09–5.02
(m, 1H), 4.38–4.28 (m, 1H), 4.25–4.15 (m, 2H), 4.04 (dd, J=12.5,
5.3 Hz, 0.7”1H), 3.96 (dd, J=11.7, 6.3 Hz, 0.3”1H), 2.15 (s, 0.9H),
2.14 (s, 0.9H), 2.13 (s, 2.1H), 2.10 (s, 0.9H), 2.07 (s, 0.9H), 2.06 (s,
2.1H), 2.06 (s, 4H), 2.04 (s, 5H), 2.04 (s, 2.1H), 2.03 (s, 0.9H), 2.02 (s,
0.9H); 13C NMR (100 MHz, CDCl3): d=170.8, 170.7, 170.7, 170.4,
170.4, 170.1, 170.1, 170.1, 170.0, 169.9, 169.9, 169.7, 169.7, 169.4,
70.3, 70.1, 69.4, 69.2, 68.8, 68.7, 68.5, 68.2, 67.9, 67.6, 61.9, 61.7,
61.6, 61.5, 21.0, 21.0, 20.9, 20.9, 20.9, 20.8, 20.8, 20.8, 20.8, 20.7,
20.7, 20.6; IR (film, CHCl3): 1749, 1434, 1372, 1217 cmÀ1; HRMS (ESI)
exact mass calcd for C21H30O14Na m/z 529.1533 [M+Na]+, found
m/z 529.1536 [M+Na]+.
7-O-Benzyl-5,6-O-isopropylidene-d-glycero-d-mannoheptitol and
7-O-benzyl-5,6-O-isopropylidene-d-glycero-d-glucoheptitol
(8,
Scheme 3): After the aldol product 7 was dissolved in CH2Cl2/
MeOH (9:1) and cooled to 08C, NaBH4 (1.2 equiv) was added, and
the reaction mixture was stirred for 2 h. Next the mixture was dilut-
ed with CH2Cl2 and washed with saturated solution of sodium hy-
drogen carbonate. The aqueous phase was extracted with CH2Cl2,
and the combined organic layer was dried, concentrated, and puri-
fied by flash column chromatography (CH2Cl2/MeOH, 93:7). Yield
49 mg, 72%; 1H NMR (400 MHz, CD3OD): d=7.41–7.29 (m, 4H),
7.32–7.23 (m, 1H), 4.59 (s, 2H), 4.44–4.36 (m, 1H), 4.31–4.24 (m,
1H), 3.96 (d, J=9.8 Hz, 1H), 3.89–3.80 (m, 1H), 3.81–3.74 (m, 1H),
3.72–3.64 (m, 2H), 3.64–3.56 (m, 2H), 1.38 (s, 3H), 1.34 (s, 3H);
13C NMR (100 MHz, CD3OD): d=139.3, 139.3, 129.4, 129.0, 129.0,
128.8, 128.8, 109.9, 109.8, 78.0, 77.9, 77.2, 76.9, 75.0, 74.5, 74.5,
72.4, 71.8, 71.2, 71.0, 70.4, 70.3, 68.7, 65.2, 64.0, 28.3, 28.3, 25.9,
5,6:7,8-Di-O-isopropylidene-d-glycero-l-galactooct-2-ulose (10,
Scheme 4): Yield 142 mg, 89%; [a]21D =À9.4 (c=1.85, CHCl3);
1H NMR (400 MHz, CDCl3): d=4.59 (d, J=19.5 Hz, 1H), 4.54–4.42
(m, 2H), 4.36 (td, J=6.9, 4.2 Hz, 1H), 4.16 (dd, J=7.1, 4.2 Hz, 1H),
4.06 (td, J=8.5, 7.1 Hz, 2H), 3.94 (dd, J=8.5, 7.1 Hz, 2H), 3.48 (d,
J=6.4 Hz, 1H), 3.21 (d, J=5.9 Hz, 1H), 3.08 (brs, 1H), 1.45 (s, 3H),
1.43 (s, 3H), 1.41 (s, 3H), 1.37 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=211.2, 110.5, 110.2, 79.6, 76.1, 75.7, 74.9, 73.9, 66.8, 65.8, 27.2,
27.2, 26.1, 25.2; IR (film, CHCl3): 3410, 2987, 2935, 1727, 1641, 1456,
1382, 1372 cmÀ1; HRMS (ESI) exact mass calcd for C14H24O8Na m/z
343.1369 [M+Na]+, found m/z 343.1378 [M+Na]+.
25.8; IR (ATR, ZnSe): 3301, 2986, 2941, 2878, 1455, 1434, 1382 cmÀ1
;
HRMS (ESI) exact mass calcd for C17H26O7Na m/z 365.1576 [M+
Na]+, found m/z 365.1582 [M+Na]+.
5,6:7,8-Di-O-isopropylidene-d-glycero-d-galactooct-2-ulose (12,
Scheme 5): Yield 136 mg, 85%; [a]24D = +5.4 (c=1.01, CHCl3);
d-Glycero-d-mannoheptitol (9b, Scheme 3) and d-glycero-d-glu-
coheptitol (9b, Scheme 3): The reaction was performed under
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1H NMR (400 MHz, CDCl3): d=4.63 (dd, J=19.6, 4.4 Hz, 1H), 4.54–
4.42 (m, 2H), 4.26–4.18 (m, 1H), 4.08–4.00 (m, 3H), 3.97 (d, J=
4.4 Hz, 2H), 3.77–3.70 (m, 1H), 3.28 (d, J=8.3 Hz, 1H), 3.01 (t, J=
4.8 Hz, 1H), 1.44 (s, 3H), 1.39 (s, 3H), 1.38 (s, 3H), 1.36 (s, 3H);
13C NMR (100 MHz, CDCl3): d=211.5, 110.7, 110.2, 81.3, 79.3, 76.3,
75.9, 73.4, 68.2, 67.1, 26.9, 26.5, 25.1; IR (film, CHCl3): 3424, 2987,
2935, 2898, 1726, 1374 cmÀ1; HRMS (ESI) exact mass calcd for
C14H24O8Na m/z 343.1369 [M+Na]+, found m/z 343.1366 [M+Na]+.
c) G. Haustveit, E. A. McComb, V. V. Rendig, Carbohydr. Res. 1975, 39,
125–129.
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5,6:7,8-Di-O-isopropylidene-1-deoxy-d-glycero-d-galactooct-2-
ulose (14, Scheme 5): A solution of d-arabinose acetonide 11
(115 mg, 0.5 mmol) in THF/H2O (1:1, 0.2 mL) and hydroxyacetone
(HA, 0.9 mL, 13.1 mmol) and catalyst ent-6 (20 mol%) was stirred
at room temperature for 24 h and then directly purified by flash
column chromatography on silica gel (toluene/EtOH, 20:1) to
afford pure aldol 14. Yield 113 mg, 74%; [a]22D =À44.6 (c=1.00,
1
CHCl3); H NMR (600 MHz, CDCl3): d=4.37 (d, J=4.5 Hz, 1H), 4.22
(dd, J=8.8, 6.2 Hz, 1H), 4.10–4.05 (m, 2H), 4.02 (dd, J=8.8, 5.2 Hz,
1H), 3.98 (ddd, J=8.7, 2.7, 1.5 Hz, 1H), 3.80 (dd, J=8.7, 7.3 Hz, 1H),
3.74 (d, J=1.9 Hz, 1H), 3.60 (d, J=5.9 Hz, 1H), 2.31 (s, 3H), 1.44 (s,
3H), 1.42 (s, 3H), 1.41 (s, 3H), 1.35 (s, 3H); 13C NMR (150 MHz,
CDCl3): d=208.2, 110.5, 110.1, 81.4, 79.3, 77.4, 76.5, 73.2, 68.1, 27.1,
27.0, 26.4, 25.7, 25.1; IR (neat): 3490, 3456, 2994, 2938, 1706, 1373,
1247, 1219, 1155, 1133, 1078, 1066, 848 cmÀ1; HRMS (ESI): exact
mass calcd for C14H24O7Na m/z 327.1420 [M+Na]+, found m/z
327.1422 [M+Na]+.
Acknowledgements
Financial support from the Polish National Science Centre (grant
number NCN 2011/03/B/ST5/03126) is gratefully acknowledged.
This publication was co-financed with European Union funds by
the European Social Fund.
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Keywords: aldol reaction
carbohydrates · natural products · organocatalysis
·
asymmetric synthesis
·
´
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