Studies on indium-mediated additions to lactones: Synthesis of 2-deoxy-2-substituted-3-ulosonic acids

Article abstract of DOI:10.1016/j.tetasy.2010.07.011

The indium-mediated Reformatsky reaction of a mannose-derived lactone with α,α-disubstituted-α-bromo esters yielded the corresponding ulosonic acid esters as mixtures of anomers. In contrast, the reaction with α-monosubstituted-α-bromo esters is highly stereoselective and afforded a single anomer of the corresponding (2S)-ulosonic acid esters. A mechanistic proposal for the reaction and an explanation of its outcome is discussed. The indium-mediated Reformatsky reaction of the mannose-derived lactone with 2-bromo-lactones was also achieved and the products obtained were consistent with those of our proposed mechanism in all cases. Moreover, indium-mediated allylation of the model sugar lactone was also investigated.

Full text of DOI:10.1016/j.tetasy.2010.07.011

Tetrahedron: Asymmetry 21 (2010) 2249–2253
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Studies on indium-mediated additions to lactones: synthesis of
2-deoxy-2-substituted-3-ulosonic acids
Raquel G. Soengas
Departamento de Química Fundamental, Universidade de A Coruña, 15071 A Coruña, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The indium-mediated Reformatsky reaction of a mannose-derived lactone with
a,a-disubstituted-a-
Received 29 June 2010
Accepted 13 July 2010
Available online 11 August 2010
bromo esters yielded the corresponding ulosonic acid esters as mixtures of anomers. In contrast, the reac-
tion with -monosubstituted- -bromo esters is highly stereoselective and afforded a single anomer of
a
a
the corresponding (2S)-ulosonic acid esters. A mechanistic proposal for the reaction and an explanation
of its outcome is discussed. The indium-mediated Reformatsky reaction of the mannose-derived lactone
with 2-bromo-lactones was also achieved and the products obtained were consistent with those of our
proposed mechanism in all cases. Moreover, indium-mediated allylation of the model sugar lactone
was also investigated.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
sobutyrate and aldonolactones.8 Previously reported examples of
the Reformatsky reaction on aldonolactones proved to be experi-
Carbohydrates have been widely used as starting materials for
the synthesis of important small biological molecules and for
new biopolymeric materials. In particular, sugar lactones provide
short syntheses of novel nucleosides,1 imino sugars2 and sugar-
derived amino acids.3 All these targets have unbranched carbon
chains, but recent results have indicated that all three classes of
such carbon-branched materials give rise to promising biologically
active compounds and novel biopolymers. In particular, alkyl-
branched sugars could be of great biological interest because the
presence of a highly lipophilic region in their sugar skeleton could
modify binding to certain enzymes and thus alter their biological
activity.
mentally complex and suffered from low yields, functional group
incompatibility and low regio- and/or stereoselectivity.9 However,
the indium-mediated Reformatsky reaction of aldonolactones with
a-bromoisobutyrate proved to be experimentally very simple. This
reaction takes place under very mild conditions and provides ac-
cess to 2-deoxy-2,20-dimethyl-3-ulosonates with remarkably high
levels of stereoselectivity. As a continuation of this work, we herein
report an extension of this method to a number of 2-bromo esters
and 2-bromo-lactones, which also allowed us to propose a mecha-
nism that could prove useful for predicting the stereochemical out-
come of this reaction.
Ulosonic acids, including KDO (3-deoxy-D-manno-2-octulosonic
2. Results and discussion
acid) and NANA (N-acetylneuraminic or sialic acid), are a family of
natural sugar derivatives that are the constituents of cellular and
bacterial membranes and are involved in a number of biological
functions.4 Some analogues have shown inhibitory activity in the
The reaction of the
D-mannose-derived lactone 1 with ethyl
2-bromo-alkanoates 2–7 in the presence of indium powder and
under ultrasonic waves gave the respective chain-elongated prod-
ucts 8a,b, 9, 10, 11, 12 and 13 (Scheme 1, Table 1). When tertiary
bromo-alkanoate 2 was used as the substrate, an anomeric mixture
biosynthesis of membrane lipopolysaccharides of bacteria.5,6
A
family of homologated derivatives of 2-ulosonic acids, known as
3-ulosonic acids, has recently attracted some synthetic interest.7
Accordingly, it would be of great interest to have easy access to
branched 3-ulosonic acids in order to study their biological activity
and use them as synthetic precursors of additional branched sugar
derivatives of potential biological interest.
R2
CO2Et
O
O
O
R1
O
O
O
R1 R2
Br CO2Et
O
In
O
+
OH
THF
As part of our studies on the synthetic usefulness of indium in
carbohydrate chemistry, we recently reported a highly efficient in-
O
O
O
dium-mediated Reformatsky reaction between ethyl
a-bromoi-
1
2-7
8-13
E-mail address: rsoengas@udc.es
Scheme 1.
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.07.011

2250
R. G. Soengas / Tetrahedron: Asymmetry 21 (2010) 2249–2253
Table 1
Indium-mediated Reformatsky reaction of lactone 1 with ethyl 2-bromo-alkanoates
O
Ester
R1
R2
Product
Yield (%)
a
/b
O
O
In
2
3
4
5
6
7
–CH3
–CH3
–Ph
–Br
–Pr
–F
–CH3
–H
–H
–H
–H
–F
8
9
10
11
12
13
87
51
52
26
51
49
80:20
100:0
100:0
100:0
100:0
100:0
O
O
O
O
O
Figure 2.
was obtained in which the major component was the thermody-
namically most stable anomer. Interestingly, when bromo-alkano-
ates 3–7 were used, a single isomer was obtained in all cases.
As the anomeric hydroxy group should be pseudoaxially ori-
ented,9e in order to determine the absolute configuration at the
newly created stereogenic centre C-2, suitable crystals of 9 were
grown and subjected to a single crystal X-ray analysis. As shown
OIn
O
O
CH3
H3C
O
OEt
O
O
H
O
InL2
O
O
O
OEt
in Figure 1, the most stable
a-configuration was confirmed and
an (R)-configuration at the C-2 position was established.
1
A plausible mechanism for this reaction, which is also sup-
ported by computational calculations, involves an attack by the
thermodynamically most stable Z organoindium enolate on the
less hindered re-face of the lactone (Fig. 2). This would result in
the formation of a chair-like transition state, leading to the (R)-
configuration for the C-2 position of the resulting adducts. Finally,
the resulting b-configured intermediate 14 would undergo rapid
O
O
O
CH3
CO2Et
CH3
CO2Et
O
O
O
anomerization
OH
OH
O
O
O
O
anomerization to the thermodynamically more stable
(Scheme 2).
a-anomer
9
14
The strong coordination between the THF and the active species
suggests that this mechanism is more probable than the alterna-
Scheme 2.
tive involving a chelated transition state from which the
would result directly.
a-anomer
Although products 10, 11 and 12 did not afford suitable crystals
for X-ray analysis, the absolute configuration of 11 was determined
by comparison with the previously reported data for this com-
pound. In addition, combined computational and NMR studies al-
lowed us to confirm the (R)-configuration expected for the C-2
position in 10 and 12. Thus, a computer-assisted conformational
search predicted that, in their lowest energy conformations, the
hydrogen at C-2 in these compounds should be quite close to
one of the methyl groups of the isopropylidene-protecting group.
The NOESY experiments showed a strong NOE effect between H-
2 and one of the methyl groups, thus confirming the predicted con-
figuration for both 10 and 12 (Fig. 3).
An additional aspect of the stereochemical outcome of this reac-
tion is the strong preference for the a-anomer as shown by the ulo-
sonic acid esters 9–13. These gave a single anomer while the
disubstituted analogue 8 afforded an anomeric mixture. This dif-
ferent behaviour can be explained in terms of the higher energy
barrier required for the
a?b anomeric interconversion in 9–13
than in 8, as established by computational calculations.
In order to gain an insight into the scope of this indium-medi-
ated Reformatsky reaction of sugar lactones, the reactions of 2-bro-
mo-lactones and the mannose-derived lactone 1 were studied.
When lactone 1 was reacted with 2-bromo-lactones 15–17 and in-
dium powder in THF under sonication, condensation products 18–
20 were obtained (Scheme 3, Table 2).
The configuration at C-2 of compound 18 was determined by
comparison with the previously reported data for this derivative.9e
The (S)-configuration at the new stereogenic C-2 centre is opposite
to that in previous similar compounds resulting from the reaction
with ethyl 2-bromo-alkanoates. This stereochemical difference can
be easily explained on the basis of the enolate being blocked in the
E-configuration. The attack of the organoindium enolate again oc-
curs at the less hindered re-face of the lactone (Fig. 4) to form a
chair-like transition state, leading to the (S)-configuration for the
C-2 position of the resulting b-configured adduct, which undergoes
rapid anomerization to the thermodynamically more stable
mer (Scheme 4).
a-ano-
According to this mechanism, the stereochemistry of the stere-
ogenic centre C-2 in 19 and 20 would also be (S), although exper-
imental evidence for this proposed configuration could not be
obtained.
Taking into account the results achieved in the Reformatsky
reaction of sugar lactones described here, we decided to further
Figure 1.

R. G. Soengas / Tetrahedron: Asymmetry 21 (2010) 2249–2253
2251
Figure 3.
R2
O
O
O
OIn
H
O
O
O
O
O
O
InL2
O
O
R1
O
O
O
O
O
O
R2
O
R1
O
In
+
O
O
O
OH
O
THF
O
O
O
Br
1
1
15-17
18-20
Scheme 3.
O
O
O
O
O
O
O
O
anomerization
O
O
Table 2
OH
OH
Indium-mediated Reformatsky reaction of lactone 1 with 2-bromo-lactones
O
O
O
O
Lactone
R1
R2
Product
Yield (%)
a/b
21
15
16
17
–H
–CH3
–H
–H
–H
–CH3
18
19
20
53
85
51
100:0
58:42
100:0
17
Scheme 4.
O
O
O
O
In
O
O
O
O
In
+
Br
OH
O
THF
O
O
O
O
O
O
O
O
1
22
23
O
O
Scheme 5.
on the basis of the mechanistic hypothesis discussed. The resulting
novel branched chain sugars constitute a new family of ulosonic
acids.
Figure 4.
Moreover, the indium-mediated allylation of sugar lactones was
also developed. The resulting sugar derivatives have proven to be
useful intermediates for the synthesis of spirosugar derivatives.10
Work is currently in progress aimed at transforming the ad-
ducts reported here into branched chain imino sugars of biological
interest and into novel biopolymers based on branched chain het-
erocyclic amino acids.
explore the applications of the addition of indium organometallic
reagents to sugar lactones. Accordingly, the indium-mediated ally-
lation of sugar lactone 1 with allyl bromide 22 was attempted
(Scheme 5). The corresponding addition adduct 23 was obtained
in good yield as a mixture of anomers (a/b 82:12).
3. Conclusion
4. Experimental
In conclusion, we have reported a full description of our initial
results on a new method for the homologation of sugar lactones
involving an indium-mediated Reformatsky reaction of aldonolac-
tones with ethyl 2-bromo-alkanoates and 2-bromo-lactones. The
corresponding condensation products were obtained with remark-
ably high levels of stereoselectivity, which can be easily explained
Melting points were determined using a Kofler Thermogerate
apparatus and are uncorrected. Specific rotations were recorded
on a JASCO DIP-370 optical polarimeter. Nuclear magnetic reso-
nance spectra were recorded on a Varian DPX-200 or a Bruker

2252
R. G. Soengas / Tetrahedron: Asymmetry 21 (2010) 2249–2253
300 apparatus. Mass spectra were obtained on a Hewlett Packard
5988A mass spectrometer. Thin layer chromatography (TLC) was
performed using Merck GF-254 type 60 silica gel and ethyl ace-
tate/hexane mixtures as eluants; the TLC spots were visualized
with the Hanessian mixture. Column chromatography was carried
out using Merck type 9385 silica gel.
ppm): 14.1, 24.5, 25.6, 26.1, 27.0 (5 ꢀ CH3), 53.1 (C-2), 61.5, 67.0
(C-7, –OCH2CH3), 73.4, 79.5, 80.2, 84.2 (C-4, C-5, C-6, C-7), 106.5
(C-3), 109.3, 112.7 (2 ꢀ –C(CH3)2), 127.9, 128.3, 130.0 (5 ꢀ ArCH),
133.5 (ArC), 173.6 (C@O). LRMS (ESI, m/z,%): 445.18 (100,
[M+Na]+). HRMS for C22H30O8Na ([M+Na]+) calculated 445.1832.
Found: 445.1843.
4.1. General experimental procedure for the reaction of 2,3:5,6-
4.5. (2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropylidene-2-bromo-
a-
di-O-isopropylidene-
D
-mannonolactone 1 and ethyl 2-bromo-
D-manno-3,6-furanoso-3-octulosonate 11
alkanoates 2–7
Purification of the crude material by flash column chromatogra-
To a suspension of indium powder (0.5 mmol) and the corre-
sponding ethyl 2-bromo-alkanoate (0.75 mmol) in THF (1 mL)
was added lactone 1 (0.5 mmol) and the mixture was sonicated
for 6 h. The reaction was quenched with saturated aqueous sodium
hydrogen carbonate (10 mL) and the reaction mixture was ex-
tracted with ether (3 ꢀ 25 mL). The combined organic layers were
dried over magnesium sulphate, filtered and evaporated in vacuo.
The residues were purified by flash column chromatography in
mixtures of ethyl acetate/hexane to give the compounds shown
in Table 1.
phy (ethyl acetate/hexane 1:4?1:3) afforded 11 (55.1 mg, 26%) as
a clear oil together with some ethyl 2-deoxy-4,5:7,8-di-O-isopro-
pyliden-a-D-manno-3,6-furanoso-3-octulosonate (46.5 mg, 24%).
½
a 2D2
ꢁ
¼ þ43:8 (c 0.7, CHCl3). 1H NMR (CDCl3, ppm): 1.27–1.47 (m,
0
15H, 5 ꢀ –CH3), 3.91 (dd, 1H, J8,8 = 5.8 Hz, J7,8 = 3.0 Hz, H-8), 3.91
(dd, 1H, J = 5.8 Hz, J7,8 = 4.1 Hz, H-80), 4.13 (dd, 1H, J = 5.1 Hz,
J = 9.8 Hz, H-6), 4.20–4.28 (m, 2H, –OCH2CH3), 4.59 (d, 1H,
J4,5 = 3.9 Hz, H-4), 4.74 (s, 1H, H-2), 4.82 (dd, 1H, J4,5 = 2.5 Hz,
J5,6 = 3.9 Hz, H-5). 13C NMR (CDCl3, ppm): 14.0, 24.5, 25.6, 26.0,
27.0 (6 ꢀ CH3), 41.2 (C-2), 62.8, 66.8 (C-8, –OCH2CH3), 73.1, 80.1,
81.0, 84.7 (C-4, C-5, C-6, C-7), 105.2 (C-3), 109.5, 113.3 (2 ꢀ
–C(CH3)2), 170.2 (C@O). LRMS (ESI, m/z,%): 447.06, 449.06 (38,
[M+Na]+). HRMS for C18H25O8NaBr ([M+Na]+) calculated 447.0625.
Found: 447.0616.
4.2. Ethyl 2-deoxy-4,5:7,8-di-O-isopropylidene-2,2-dimethyl-
a,b-D-manno-3,6-furanoso-3-octulosonate 8
Purification of the crude material by flash column chromatogra-
phy (ethyl acetate/hexane 1:5) afforded a 80:20 mixture of the
anomers
and b 8 (0.16 g, 87%) as a clear oil. 1H NMR (CDCl3,
4.6. (2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropylidene-2-propyl-
D-manno-3,6-furanoso-3-octulosonate 12
a-
a
ppm): 1.15–1.44 (m, 42H, 12 ꢀ –CH3, 2 ꢀ –OCH2CH3), 3.40–3.51
(m, 4H, 2 ꢀ H-8, 2 ꢀ H-80), 4.01–4.13, 4.27–4.40 (2 ꢀ m, 6H,
2 ꢀ H-4, 2 ꢀ H-5, 2 ꢀ –OCH2CH3), 4.53–4.60 (m, 2H, 2 ꢀ H-5),
4.81 (dd, 1H, J = 5.0 Hz, J = 7.5 Hz, H-6), 4.88 (dd, 1H, J = 5.0 Hz,
J = 7.5 Hz, H-6). 13C NMR (CDCl3, ppm): 14.13, 15.42, 19.50,
21.24, 22.14, 23.95, 24.53, 25.40, 25.47, 25.67 (14 ꢀ CH3), 48.28,
50.11 (2 ꢀ C-2), 60.98, 61.29 (2 ꢀ –OCH2CH3), 66.38, 61.29
(2 ꢀ C-7), 73.64, 73.82 (2 ꢀ C-6), 78.71, 79.85, 79.98, 86.64
(2 ꢀ C-4, 2 ꢀ C-5), 105.33, 106.54, 109.10, 109.48, 112.82, 113.72
(2 ꢀ C-3, 4 ꢀ –C(CH3)2), 176.00, 178.34 (C@O). LRMS (ESI, m/z,%):
397.18 (60, [M+Na]+). HRMS for C18H30O8Na ([M+Na]+) calculated
397.1832. Found: 397.1846.
Purification of the crude material by flash column chromatogra-
phy (ethyl acetate/hexane 1:5) afforded 12 (98 mg, 51%) ½a D26
¼
ꢁ
ꢂ8:5 (c 0.5, CHCl3). 1H NMR (CDCl3, ppm): 0.90 (t, 3H, J = 4.8 Hz,
–OCH2CH3), 1.23–1.43 (m, 15H, 5 ꢀ –CH3), 1.58–1.82 (m, 4H),
2.84 (q, 1H, J = 3.3 Hz, H-2), 4.00–4.18 (m, 5H), 4.29–4.32 (m, 1H,
H-7, H-8, H-80, –OCH2CH3), 4.25–4.33 (m, 1H, H-5), 4.45 (d, 1H,
J = 3.9 Hz, H-4), 4.78 (dd, 1H, J = 2.5 Hz, J = 3.9 Hz, H-6). 13C NMR
(CDCl3, ppm): 14.2, 14.3, 24.8, 25.6, 26.1, 27.1 (6 ꢀ CH3), 21.2,
29.2 (2 ꢀ CH2), 48.2 (C-2), 61.0, 67.1 (C-8, –OCH2CH3), 73.4, 80.0,
80.1, 87.1 (C-4, C-5, C-6, C-7), 105.5 (C-3), 109.4, 113.0 (2 ꢀ
–C(CH3)2), 176.1 (C@O). LRMS (ESI, m/z,%): 411.19 (53, [M+Na]+).
HRMS for C19H32O8Na ([M+Na]+) calculated 411.1898. Found:
411.2003.
4.3. (2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropylidene-2-methyl-
a-
D-manno-3,6-furanoso-3-octulosonate 9
4.7. Ethyl 2-deoxy-4,5:7,8-di-O-isopropyliden-2,2-difluoro-
-manno-3,6-furanoso-3-octulosonate 13
a,b-
Purification of the crude material by flash column chromatogra-
D
phy (ethyl acetate/hexane 1:5) afforded 9 (91.6 mg, 51%) as a white
solid. Mp 151–153 °C (Et2O/Hex); ½a D25
ꢁ
¼ þ1:3 (c 0.9, CHCl3). 1H
Purification of the crude material by flash column chromatogra-
NMR (CDCl3, ppm): 1.21–1.43 (m, 18H, 6 ꢀ –CH3), 2.87 (q, 1H,
J = 4.8 Hz, H-2), 3.89–4.07 (m, 2H, H-8, H-80), 4.11 (q, 2H,
J = 4.7 Hz, –OCH2CH3), 4.25–4.33 (m, 1H, H-7), 4.42 (d, 1H,
J = 3.9 Hz, H-5), 4.63 (s, 1H, H-4), 4.78 (dd, 1H, J = 2.5 Hz,
J = 3.9 Hz, H-6). 13C NMR (CDCl3, ppm): 13.9, 14.3, 24.6, 25.6,
26.0, 27.0 (6 ꢀ CH3), 42.4 (C-2), 61.1, 67.0 (C-8, –OCH2CH3), 73.3,
79.4, 80.2, 84.4 (C-4, C-5, C-6, C-7), 106.6 (C-3), 109.3, 112.9
(2 ꢀ –C(CH3)2), 176.6 (C@O). LRMS (ESI, m/z,%): 383.17 (10,
[M+Na]+). HRMS for C17H28O8Na ([M+Na]+) calculated 383.1676.
Found: 383.1690.
phy (ethyl acetate/hexane 1:4) afforded 13 (89 g, 49%) as a clear oil.
1H NMR (CDCl3, ppm): 1.21–1.44 (m, 15H, 5 ꢀ –CH3), 3.41–3.53
(m, 2H, H-8, H-80), 4.03–4.57 (m, 3H, H-4, H-5, –OCH2CH3), 4.76–
4.82 (m, 1H, H-6). 13C NMR (CDCl3, ppm): 14.1, 24.7, 25.4, 26.0,
27.2 (5 ꢀ CH3), 63.5, 67.3 (C-8, –OCH2CH3), 73.2, 79.0, 80.0, 84.4
(C-4, C-5, C-6, C-7), 109.3, 112.9 (2 ꢀ –C(CH3)2), 113.3 (C-3),
162.2 (C@O). LRMS (ESI, m/z,%): 405.13 (100, [M+Na]+), 383.15
(30, [M+H]+). HRMS for C16H25O8F2 ([M+H]+) calculated 383.1521.
Found: 383.1512.
4.8. General experimental procedure for the reaction of 2,3:5,6-
4.4. (2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropylidene-2-phenyl-
di-O-isopropylidene-D-mannonolactone 1- and 2-bromo-
a-
D-manno-3,6-furanoso-3-octulosonate 10
lactones 15–17
Purification of the crude material by flash column chromatogra-
To a suspension of indium powder (0.5 mmol) and the corre-
sponding 2-bromo-lactone (0.75 mmol) in THF (1 mL) was added
lactone 1 (0.5 mmol) and the mixture was sonicated for 6 h. The
reaction was quenched with saturated aqueous sodium hydrogen
carbonate (10 mL) and the reaction mixture was extracted with
phy (ethyl acetate/hexane 1:7) afforded 10 (115 mg, 52%) as a
yellow oil. ½a 2D5
ꢁ
¼ þ23:5 (c 0.4, CHCl3). 1H NMR (CDCl3, ppm):
1.19–1.56 (m, 15H, 5 ꢀ –CH3), 3.99–4.12 (m, 8H), 4.75 (dd, 1H,
J = 3.9 Hz, J = 5.8 Hz, H-6), 5.06 (s, 1H, –OH). 13C NMR (CDCl3,

R. G. Soengas / Tetrahedron: Asymmetry 21 (2010) 2249–2253
2253
ether (3 ꢀ 25 mL). The combined organic layers were dried over
magnesium sulfate, filtered and evaporated in vacuo. The residue
was purified by flash column chromatography in mixtures of ethyl
acetate/hexane to obtain the compounds shown in Table 2.
(2 ꢀ C@O). LRMS (ESI, m/z,%): 381.15 (61, [M+Na]+), 359.17 (8,
[M+H]+). HRMS for C17H27O8 ([M+H]+) calculated 359.1700. Found:
359.1711.
4.12. Trideoxy-5,6:8,9-di-O-isopropylidene-a,b-D-manno-non-1-
eno-4-ulofuranose 23
4.9. (2S)-2-Deoxy-2-(20-hydroxyethyl)-4,5:7,8-di-O-
isopropylidene-
lactone 18
a-D
-manno-3,6-furanoso-3-octulosonate-1,20-
Purification of the crude material by flash column chromatogra-
phy (ethyl acetate/hexane 1:4) afforded 23 (102 mg, 68%) as a
white solid. 1H NMR (CDCl3, ppm): 1.32–1.49 (m, 24H, 8 ꢀ –CH3),
2.52–2.64 (m, 4H, 2 ꢀ H-3, 2 ꢀ H-30), 3.97, 3.40 (m, 4H, 2 ꢀ H-7,
2 ꢀ H-9), 4.01–4.13, 4.37–4. (m, 4H, 2 ꢀ H-8, 2 ꢀ H-90), 4.53–4.60
(m, 2H, 2 ꢀ H-5), 4.84 (m, 2H, 2 ꢀ H-6), 5.23–5.59 (m, 4H, 2 ꢀ H-
1, 2 ꢀ H-10), 5.75–5.93 (m, 2H, 2 ꢀ H-2). 13C NMR (CDCl3, ppm):
13.9, 14.3, 24.6, 25.6, 26.0, 27.0 (6 ꢀ CH3), 39.6 (C-3), 66.3 (C-9),
73.3, 79.4, 80.2, 84.4 (C-5, C-6, C-7, C-8), 106.3, 108.9 (2 ꢀ
–C(CH3)2), 112.2 (C-4), 119.0 (C-1), 125.0 (C-2). LRMS (ESI, m/z,%):
323.20 (60, [M+Na]+).
Purification of the crude material by flash column chromatogra-
phy (ethyl acetate/hexane 1:5) afforded 18 (91 g, 53%) as a white
solid. Mp 125–128 °C; ½a D23
ꢁ
¼ þ15:8 (c 0.5, CHCl3). 1H NMR (CDCl3,
ppm): 1.31, 1.36, 1.43, 1.46 (4 ꢀ s, 12H, 4 ꢀ –CH3), 2.30–2.60 (m,
2H, H-20), 3.00–3.21 (m, 2H, H-2), 3.90–4.21 (m, 4H), 4.32–4.39,
(m, 2H), 4.59 (d, 1H, J = 5.9 Hz, H-6), 4.86 (dd, 1H, J = 3.9 Hz,
J = 5.9 Hz, H-5). 13C NMR (CDCl3, ppm): 23.8, 25.1, 26.9 (4 ꢀ CH3),
26.1 (C-10), 43.2 (C-2), 66.9, 67.4 (C-20, C-8), 73.0, 79.2, 79.7, 86.2
(C-4, C-5, C-6, C-7), 104.2 (C-3), 109.3, 112.9 (2 ꢀ –C(CH3)2),
178.8 (C@O). LRMS (ESI, m/z,%): 367.14 (56, [M+Na]+).
Acknowledgements
4.10. (2S)-2-Deoxy-2-(20-hydroxyethyl)-2-methyl-4,5:7,8-di-O-
isopropylidene-
a
-D
-manno-3,6-furanoso-3-octulosonate-1,20-
This work was supported by the Spanish Ministry of Science
and Innovation (CTQ2008-06493). R.G.S. thanks the Xunta de Gali-
cia for financial support (Isidro Parga Pondal program). I would like
to thank Professors Ramón J. Estévez and Juan C. Estévez for helpful
discussions.
lactone 19
Purification of the crude material by flash column chromatogra-
phy (ethyl acetate/hexane 1:4) afforded 19 (152 mg, 85%) as a yel-
low oil. 1H NMR (CDCl3, ppm): 1.31–1.56 (m, 30H, 10 ꢀ –CH3),
2.01–2.04 (m, 4H, 2 ꢀ H-20), 2.62–2.81 (m, 4H, 2 ꢀ H-2), 2.91 (bs,
1H, –OH), 4.02–4.16 (m, 6H), 4.25–4.40 (m, 5H), 4.56–4.59 (m,
2H), 4.82 (dd, 1H, J = 4.1 Hz, J = 6.0 Hz), 4.90 (dd, 1H, J = 3.9 Hz,
J = 5.9 Hz), 5.08 (d, 1H, J = 6.2 Hz). 13C NMR (CDCl3, ppm): 14.3,
18.7, 19.0, 23.6, 23.9, 24.4, 25.2, 25.3, 27.2, 27.3 (10 ꢀ CH3), 32.2,
32.3 (2 ꢀ C-10), 49.6, 50.6 (2 ꢀ C-2), 66.0, 66.2, 66.7, 66.8 (2 ꢀ C-
20, 2 ꢀ C-8), 73.2, 73.8, 79.3, 79.8, 80.1, 80.3, 86.8 (2 ꢀ C-4, 2 ꢀ C-
5, 2 ꢀ C-6, 2 ꢀ C-7), 104.9, 105.2 (2 ꢀ C-3), 109.3, 109.4, 112.9,
114.2 (4 ꢀ –C(CH3)2), 179.2, 180.3 (2 ꢀ C@O). LRMS (ESI, m/z,%):
381.15 (61, [M+Na]+). HRMS for C17H26O8Na ([M+Na]+) calculated
381.1519. Found: 381.1518.
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