Synthesis of C-2- and C-3-Sulfonatomethyl O- and S-Glycosides by Horner–Wadsworth–Emmons Olefination

Article abstract of DOI:10.1002/ejoc.201600526

The applicability of the Horner–Wadsworth–Emmons olefination to the introduction of the sulfonatomethyl moiety at the 2- and 3-positions of orthogonally protected O- and S-glycosides has been studied. The conformational preferences and relative energies of the exo- and endocyclic alkenesulfonic acids obtained were analysed by high-temperature molecular dynamics and DFT calculations. Thioglycosides bearing a sulfonatomethyl moiety at the secondary position have been prepared for the first time. Finally, the attempted synthesis of 2-sulfonatomethyl glucoside by nucleophilic substitution reaction is also described.

Full text of DOI:10.1002/ejoc.201600526

DOI: 10.1002/ejoc.201600526
Full Paper
Carbohydrate Sulfonic Acids
Synthesis of C-2- and C-3-Sulfonatomethyl O- and S-Glycosides
by Horner–Wadsworth–Emmons Olefination
Dániel Eszenyi,[a] Attila Mándi,[b] Mihály Herczeg,[a] Attila Bényei,[a] István Komáromi,[c] and
Anikó Borbás*[a]
Abstract: The applicability of the Horner–Wadsworth–Emmons dynamics and DFT calculations. Thioglycosides bearing a sulf-
olefination to the introduction of the sulfonatomethyl moiety
at the 2- and 3-positions of orthogonally protected O- and S-
glycosides has been studied. The conformational preferences
and relative energies of the exo- and endocyclic alkenesulfonic
acids obtained were analysed by high-temperature molecular
onatomethyl moiety at the secondary position have been pre-
pared for the first time. Finally, the attempted synthesis of 2-
sulfonatomethyl glucoside by nucleophilic substitution reaction
is also described.
Introduction
tomethyl moiety at the 2- or 3-position. Unfortunately, the ma-
jority of the methods published for the synthesis of carbohy-
drate sulfonic acids are incompatible with thioglycosides, which
are susceptible to oxidation, and a modified new synthetic ap-
proach is necessary to circumvent this problem.
Horner–Wadsworth–Emmons (HWE) olefination is a powerful
and reliable reaction providing access to a variety of alkenic
compounds bearing various functional groups including sulf-
ides.[23,24] Previous investigations have demonstrated that dif-
ferent sulfonate-stabilized phosphonates are efficient olefinat-
ing agents allowing the preparation of α,ꢀ-unsaturated sulf-
onates from both aldehydes and ketones.[25,26] Surprisingly, this
method has scarcely been applied to the synthesis of carbohy-
drate sulfonic acids, with only three examples reported in the
literature.[4,7,19] Therefore, we decided to study the HWE-based
route to glycosyl donor and acceptor building blocks bearing
the sulfonatomethyl group at secondary positions.
Sulfated carbohydrates play essential roles in many diverse bio-
logical processes including blood clotting, inflammation, the in-
hibition and promotion of tumour growth as well as host–path-
ogen interactions.[1] The isosteric sulfonic acid analogues of
carbohydrate sulfates are enzymatically stable compounds that
can be used as tools to better understand these biological func-
tions or to develop leads for new anticoagulant, antitumour
and antimicrobial agents. Accordingly, various approaches have
been developed for producing sulfonic acid analogues of the
sulfated Lewis X trisaccharide,[2] glucose 6-sulfate,[3] sulfated
glycolipids[4,5] and heparin.[6] Moreover, carbohydrate sulfon-
ates are of interest as bioisosters of phosphates and carboxyl-
ates such as nucleotides,[7–9] mannose-6-phosphate[10,11] and si-
alic acid derivatives.[12–15]
Some years ago we initiated a research project to prepare
isosteric sulfonic acid analogues of the antithrombin binding
pentasaccharide domain of heparin to access new anticoagu-
lants.[6,16–22] Recently, we demonstrated that the blood clotting
inhibitory activity of the parent highly sulfated pentasaccharide
could be improved by the replacement of the primary sulfate
esters with a sodium sulfonatomethyl group.[19] Continuing on
from this, we targeted the synthesis of further pentasaccharide
analogues bearing the sulfonic acid moiety at secondary posi-
tions by using thioglycoside building blocks bearing a sulfona-
As it has been reported that a 2-C-methyl-
could be obtained in good yield from the corresponding 2-O-
triflyl-α-
-mannopyranoside upon treatment with MeLi,[27] we
D-gluco derivative
D
considered nucleophilic substitution of mannose-2-O-triflate
derivatives with lithiated methanesulfonate ester to be a feasi-
ble approach to 2-sulfonatomethyl-containing glucosides.
Results and Discussion
[a] Department of Pharmaceutical Chemistry, University of Debrecen,
Egyetem tér 1, 4032 Debrecen, Hungary
The synthesis started from compounds 1–3, all of which are
easily available from the corresponding α-D-manno- and ꢀ-D-
E-mail: borbas.aniko@pharm.unideb.hu
glucopyranosides in two steps, namely acetalation and regiose-
lective etherification (Figure 1). We planned to prepare the cor-
responding 2-sulfonatomethyl glucoside from the mannoside
derivative 1 both by nucleophilic displacement and HWE olefin-
ation, whereas glucosides 2 and 3 could give access to 2- and
3-sulfonatomethyl derivatives through the HWE reaction. Owing
to the orthogonal protection pattern of 1–3, the planned
http://pharmchem.unideb.hu/borbas_a.htm
[b] Department of Organic Chemistry, University of Debrecen,
Egyetem tér 1, 4032 Debrecen, Hungary
[c] Division of Clinical Laboratory Science, Department of Laboratory
Medicine, University of Debrecen,
Nagyerdei krt 1, 4032 Debrecen, Hungary
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600526.
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sulfonatomethyl derivatives could be useful building blocks in
the synthesis of oligosaccharide sulfonic acids.
Table 1. HWE olefination of 6 in different solvents.
Entry Solvent
T [°C]
Reaction time
[h]
Yield[a] [%]
7a
7b
8
1
2
3
4
5
6
THF
THF
THF
Et2O
Bu2O
tBuOMe
–78 to –15
–78 to r.t.
–78 to +10
–78 to r.t.
–78 to r.t.
–78 to r.t.
4 h
16 h
6 h
6 h
6 h
6 h
15
7
17
6
3
16
52
46
61
10
11
23
–
25
–
2
4
6
[a] Isolated yields after silica gel column chromatography.
Figure 1. Starting compounds 1–3.
First we applied the nucleophilic approach to transform 1[28]
into a C-2-sulfonatomethyl glucoside. Compound 1 was treated
with triflic anhydride in the presence of pyridine to afford 4,[27]
which was treated with lithiated ethyl methanesulfonate in THF.
It is known that SN2 reactions of 2-sulfonylated α-D-manno-
pyranosides occur with difficulty.[29] Indeed, a very sluggish re-
action was observed and consumption of 4 was incomplete
even after 5 d. As a result, instead of the expected nucleophilic
substitution reaction only ꢀ-elimination took place to provide
the unsaturated 5[30] in 21 % yield (Scheme 1).
Scheme 2. Oxidation and subsequent HWE olefination of 1. Reagents and
conditions: a) DMSO, (COCl)2, DIPEA, –78 °C, 82 %; b) (EtO)2POCH2SO3Et,
nBuLi; see Table 1 for the details.
Scheme 1. Attempted nucleophilic substitution route to 2-C-sulfonatomethyl
glucoside. Reagents and conditions: a) Tf2O, abs. CH2Cl2, abs. pyridine, –10 °C;
b) nBuLi, CH3SO3Et, THF, –78 °C to r.t., 5 d, 21 % over two steps.
Next, compound 1 was oxidized by the Swern method and
the resulting 2-ulose 6 was subjected to HWE olefination with
the lithiated ethylsulfonylphosphonate reagent in THF. The re-
action after 4 h furnished a mixture of 7a and 7b. However, the
conversion of ketone 6 was incomplete and separation of the
products and remaining starting compound was difficult. Sur-
prisingly, after an overnight reaction, enopyranoside 8 was also
formed, decreasing the yield of the expected derivatives 7a and
7b (Table 1, entry 2). The isomerization of exocyclic alkenes
into the endocyclic isomers upon Wittig reaction or Horner–
Wadsworth–Emmons olefination of cyclic ketones has been re-
ported previously in the literature.[31] We were pleased to find
that almost complete conversion of 6 without the formation of
8 was observed after 6 h and that the global yield of 7a,b
reached 78 %. Our attempts to further increase the yields of
the desired sulfonatomethylene derivatives by changing THF to
different ether-type solvents were unsuccessful (Table 1, en-
tries 4–6, Scheme 2).
Figure 2. Diagnostic part of the ROESY spectrum of 7b.
H to 5.35 ppm and the smaller 3-H/4-H coupling constant (J3,4
=
6.3 Hz), the E isomer 7a prefers a boat-like conformation, proba-
bly due to allylic strain between the sulfonate and 2-O-benzyl
moieties.
To gain an insight into the conformational preferences and
relative energies of compounds 7a, 7b and 8, high-temperature
molecular dynamics and DFT calculations were performed.[32]
B3LYP/6-31G(d) re-optimization of the clustered high-tempera-
ture dynamics structures by neglecting the rotation of the Ph,
SO3Et and OMe groups resulted in global minima, in agreement
ROESY experiments were performed for configurational as-
signment of the two geometric sulfonate isomers. A strong ef-
fect between 3-H and the methylene proton in the ROESY spec-
trum demonstrates the Z configuration of 7b (Figure 2).
1
The significant differences observed in the H NMR spectro- with the experimental findings. Compound 7b adopts a 4C1-like
scopic data of 7a and 7b suggest that they adopt different sugar ring with ωO5–C1–C2–C3 = 47.3° and ωC3–C4–C5–O5 = –61.4°
conformations. The 1-H signal at δ = 6.38 ppm and the large (ꢀ: 286.570°, θ: 10.193°, Q: 0.546), whereas 7a has
vicinal 3-H/4-H coupling J3,4 = 9.8 Hz demonstrate that 7b has ωO5–C1–C2–C3 = –44.1° and ωC3–C4–C5–O5 = –58.9° value (ꢀ:
a chair-like conformation. Based on both the upfield shift of 1- 304.753°, θ: 84.808°, Q: 0.751) corresponding to a B2,5 conforma-
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tion.[33] These data are also in agreement with the results of
single-crystal X-ray diffraction studies performed on the 3-de-
oxy-3-C-sulfonatomethylene derivative 19a (see below). In the
case of 8, the ωO5–C1–C2–C3 and ωC3–C4–C5–O5 values are 7.6 and
–57.1°, respectively (ꢀ: 311.702°, θ: 51.588°, Q: 0.518), that is,
halfway between the E5 and OH5 conformation in the lowest-
energy conformer (Figure 3).[34]
Table 2. Reaction leading to the saturation of compound 7.
Entry Starting compound Reagents Conditions
Ratio[a]/yield[b]
[%] of products
9
10
1
2
3
4
5
7b (Z isomer)
7a (E isomer)
7b (Z isomer)
7 (E,Z mixture)
7 (E,Z mixture)
H2, Pd0/C CH2Cl2, r.t., 2 h
H2, Pd0/C CH2Cl2, r.t., 2 h
95
89
87
49
66
5
11
13
4
NaBH4
H2, Pd0/C CH2Cl2, r.t., 2 h
NaBH4 MeOH, r.t., 2 h
MeOH, r.t., 3 h
10
[a] Entries 1–3, determined by 1H NMR analysis of the product mixture. [b]
Entries 4 and 5, isolated yield of products after silica gel column chromatog-
raphy.
assignment (Figure 4). The singlet 1-H signal and the small 2-
1
H/3-H coupling (J2,3 = 5.7 Hz) in the H NMR spectrum demon-
strate the α- -manno configuration of 10. Although compound
D
9 can be used in the synthesis of heparinoid derivatives (e.g.,
sulfonic acid containing anticoagulants), the manno derivative
10 might also be a valuable building block for bioactive mann-
ose-containing oligosaccharide mimics. Among others, the po-
tent antiangiogenic, antitumour and antimetastatic agent PI-88
Figure 3. Computed DFT-optimized global minima of 7a, 7b and 8 (top) along
with their sugar ring conformations and first non-hydrogen atoms (bottom;
hydrogen atoms are not displayed).
Compound 7a has a substantially higher energy than 7b. At bearing a highly sulfated 3,6-branched oligomannoside struc-
the B3LYP/6-31G(d) gas-phase level of theory the energy differ- ture is a potential synthetic target.[35,36]
ence between the global minima is 21.8 kJ/mol. Although the
solvent may compensate somewhat the difference or rotation
of the neglected groups may have an impact on the relative
energies, the results show a clear preference for the Z isomer
over the E isomer. Interestingly, the global energy minimum of
8 has an even lower energy than that of 7b. The energy differ-
ence is 31.9 kJ/mol at the applied level of theory, that is, accord-
ing to in vacuo calculations the yields of the three emerging
products are expected to be 8 >> 7b >> 7a.
Continuing the planned synthetic route towards the targeted
sulfonatomethyl derivative, saturation of the double bond was
studied. Catalytic hydrogenation of either the E or Z isomer,
respectively, showed high stereoselectivity in favour of the
gluco-configured product 9 (Scheme 3). Double-bond reduction
of 7b with sodium borohydride also took place with good ster-
eoselectivity to afford a mixture of the gluco and manno deriva-
tives in an 87:13 ratio. On the preparative scale, sodium boro-
hydride turned out to be more efficient, providing compound
9 in 66 % yield from the E,Z mixture with the manno-configured
derivative 10 also isolated in 10 % yield (Table 2).
Figure 4. ORTEP view of 9 with partial numbering scheme. Ellipsoids are
drawn at the 50 % probability level. Selected bond lengthd [Å] and torsion
angles [°]: C1–C2 1.562(16), C2–C3 1.478(16), C3–O3 1.425(12), C3–C4
1.517(14), C4–C5 1.514(15), C1–O5 1.429(12); O5–C1–C2–C3 48.0, C3–C4–C5–
O5 –56.0.
Hence, we focused our attention on the HWE olefination of
thioglycosides. First, the oxidation of compound 2[37] with
Dess–Martin periodinane afforded ketone 11, which was
treated with the sulfonyl-stabilized phosphonate anion. Apply-
ing the optimized conditions, the Horner–Wadsworth–Emmons
reaction resulted in a 7:1 mixture of the E- and Z-configured
exo-methylene derivatives 12a,b in 73 % global yield
(Scheme 4). The E configuration of the major isomer 12a was
ascertained by contact between 1-H and the methylene proton
in the ROESY spectrum.
Scheme 3. Saturation of compound 7 by catalytic hydrogenation or sodium
borohydride reduction.
Reduction of the 2,3-unsaturated compound 8 by catalytic
hydrogenation failed, probably due to steric hindrance of the
endocyclic double bond.
Reduction of the major product with sodium borohydride
afforded a mixture of the saturated product 13 and the endo-
cyclic 14 in a ratio of 1:1 (Scheme 5). The configuration at C-2
The configuration at C-3 of 9 and 10 was determined by the of compound 13 was deduced from the singlet 1-H and 2-H
1
vicinal coupling constants. The α-
main product 9 was deduced from the J1,2 = 3.5 Hz and J2,3
8.8 Hz coupling constants, and the X-ray data corroborate this alkene into the more stable endocyclic isomer, which takes
D
-gluco configuration of the signals in its H NMR spectrum. The unexpected formation of
=
14 can be explained by the isomerization of the exocyclic
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ylsulfonylphosphonate reagent under the optimized conditions
to produce the 3-C-sulfonatomethylene derivatives 19a and
19b in 68 % global yield (Scheme 6). The E and Z isomers were
formed in an approximately 2:1 ratio, and the configuration of
the crystalline major product 19a was determined from the X-
ray structure (Figure 5).
Scheme 4. HWE olefination of 11. Reagents and conditions: a) Dess–Martin
periodinane, CH2Cl2, r.t.; b) (EtO)2POCH2SO3Et, nBuLi, abs. THF, –78 to 0 °C,
6 h, 73 % global yield over two steps (E/Z ≈ 7:1).
place competitively with the reduction. As sodium borohydride
can only reduce an activated double bond, compound 14 re-
mained intact during the reduction reaction as it has a non-
activated double bond. Catalytic hydrogenation has previously
been applied successfully to the saturation of a 6-C-sulfonato-
methylene heptosyl thioglycoside derivative.[19] However, cata-
lytic hydrogenation of 12a led to the isomerization of the dou-
ble bond and desulfurization instead of the desired saturation
reaction to provide the 2-substituted glycal 15. Using Pd/C un-
der 10 bar H2, compound 12a was sluggishly transformed into
15, whereas in the presence Raney-Ni, this transformation took
place readily. (Although thee desulfurization of S-alkyl and -aryl
compounds with Raney nickel is a well-known reaction, it gen-
erally requires a very large excess of Ra-Ni and elevated temper-
atures.)[38] Catalytic transfer hydrogenation with Pd/C and tri-
ethylsilane[39] was also carried out resulting in a ca. 2:1:1 mix-
ture of the unsaturated derivatives 15, 16 and 17. It is worth
mentioning that the hemiacetal derivatives 16 and 17 were
formed from an unstable product of higher chromatographic
mobility during the work-up procedure.
Scheme 6. Synthesis and HWE olefination of ulose 18. Reagents and condi-
tions: a) DMSO, (COCl)2, DIPEA, –78 °C, 87 %; b) (EtO)2POCH2SO3Et, nBuLi, abs.
THF, –78 to 0 °C, 6 h, 44 % of 19a, 24 % of 19b.
Figure 5. ORTEP view of 19a with partial numbering scheme. Ellipsoids are
drawn at the 50 % probability level. Only one of two positions of the disor-
dered benzyl group is shown. Selected bond lengths [Å] and torsion angles
[°]: C1–S1 1.760(17), C2–C3 1.54(2), C3–C30 1.32(2), C30–S20 1.769(16), C5–
O5 1.456(19), C1–O5 1.42(2); O5–C1–C2–C3 51.3, C3–C4–C5–O5 –58.8.
Sodium borohydride reduction of 19a,b took place with high
efficacy to provide the saturated products 20 and 21 in 69 %
overall yield (Scheme 7). The ratio was 4:1 in favour of the allo
isomer, according to the integration of the benzylidene proton
(δ = 5.55 ppm for the allo isomer and δ = 5.61 ppm for the
gluco isomer). The catalytic hydrogenation of 19a,b in the pres-
ence of Pd/C led to negligible conversion after 3 days, whereas
the Raney-Ni-mediated reduction led to desulfurization without
affecting the carbon–carbon double bond to provide 22 in
32 % yield.
Scheme 5. Reductive transformations of compound 12a. Reagents and condi-
tions: a) NaBH4, MeOH, r.t., 3 h, 38 % of 13, 37 % of 14; b) Ra-Ni, H2, overnight,
78 %; c) Pd0/C, 10 bar H2, 60 h 35 % (45 % of 12a was recovered); d) Pd0/C,
10 equiv. Et3SiH, 1 h, 24 % of 15, 10 % of 16, 12 % of 17.
Finally, compound 3[40] was oxidized by the Swern method
and the 3-ulose 18 obtained was treated with the lithiated eth-
Scheme 7. Reduction of compound 19. Reagents and conditions: a) NaBH4,
MeOH, r.t., 3 h, 69 % of a mixture of 20 and 21; b) Ra-Ni, H2, 32 %.
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tometer at 293 K with Cu-Kα radiation (λ = 1.54184 Å), respectively.
All non-hydrogen atoms were refined anisotropically.
Conclusions
Horner–Wadsworth–Emmons (HWE) olefination proved to be an
efficient method for the introduction of the sulfonatomethylene
moiety at secondary positions of the O- and S-glycosides. For
saturation of the double bond, sodium borohydride reduction
was applied successfully in all cases. Catalytic hydrogenation
was also a useful method for the transformation of the O-glyc-
oside 7 into the saturated product. However, in the case of
thioglycosides, catalytic hydrogenation led to desulfurization or
CCDC 1483395 (for 9) and 1483396 (for 19a) contain the supple-
mentary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre.
Computational Section: The molecular dynamics simulations
(500 ns, 1200 K constant temperature, 1 fs time step) and the pre-
liminary geometry optimizations using the suitably developed
GAFF empirical force field on the equidistantly saved 500000 trajec-
allylic isomerization of the double bond instead of saturation, tory snapshot geometries were carried out by means of the Amber
molecular dynamics simulation package.[32,41] Distance-based clus-
independently of the nature of the catalyst.
tering of both the GAFF and the DFT-optimized structures was per-
We have found that the anomeric configuration has a great
formed for the heavy atoms of the sugar ring, the dioxane ring, the
influence on the stereochemical outcome of both the olefin-
double bond and the first connecting heavy atoms by applying a
ation and the reduction reactions. Upon the HWE reaction, the
formation of the Z isomer was preferred from α-glycoside 6,
0.5 Å cut-off with an in-house code (written by A. Mándi). B3LYP/6-
31G(d) density functional calculations were carried out by using
whereas the E configuration was preferred in the case of ꢀ-
glycoside 11. Saturation of the double bond showed high gluco
selectivity for α-glycoside 7 and exclusive manno selectivity for
ꢀ-glycoside 12. These results suggest that 2-C-sulfonatomethyl
glucopyranosides may be available from the corresponding 2-
ulosyl α-thioglycosides.
The undesired formation of the endoglycal derivatives upon
prolonged olefination (8) and saturation (14 or 15) can be ex-
plained by the higher thermodynamic stability of the endocy-
clic derivatives over the exocyclic congeners. The results of
high-temperature molecular dynamics and DFT calculations
corroborated these results.
Utilisation of the gluco-configured sulfonatomethyl deriva-
tives for the synthesis of heparinoid pentasaccharide sulfonic
acids as potential anticoagulants is under way in our laboratory.
The orthogonally protected manno-configured sulfonic acid de-
rivative may also be a useful building block in the synthesis of
sulfonic acid analogues of sulfated oligomannosides such as
the antitumour and antimetastatic agent PI-88.
the Gaussian 09 package.[42] Ball-and-stick representations of the
conformers were generated by using the VMD software.[43]
Puckering values were generated based on the model proposed by
Cremer and Pople using the Cremer–Pople Parameter Calculator.[33]
Methyl 3-O-Benzyl-4,6-O-benzylidene-2-O-trifluoromethylsulf-
onyl-α-
benzyl-4,6-O-benzylidene-α-
D
-mannopyranoside (4):[27] A solution of methyl 3-O-
D
-mannopyranoside (1;[28] 370 mg,
1.00 mmol) in dry CH2Cl2 (1.5 mL) and dry pyridine (0.2 mL) was
cooled to –10 °C and trifluoromethanesulfonic anhydride (0.16 mL)
in dry CH2Cl2 (0.5 mL) was added dropwise. After stirring for 1 h
the reaction mixture was diluted with CH2Cl2, extracted with water,
1
N HCl solution and a saturated aqueous NaHCO3 solution, dried
and concentrated. The crude product (241 mg) was used in the next
1
step without purification. Rf = 0.78 (1:1 n-hexane/ethyl acetate). H
NMR (360 MHz, CDCl3): δ = 7.55–7.19 (m, 10 H, arom.), 5.58 (s, 1 H,
CH benzylidene), 5.07 (s, 1 H, 1-H), 4.86–4.70 (m, 3 H, CH2Ph, 2-H),
4.29–4.18 (m, 1 H, 3-H), 4.06–3.96 (m, 2 H), 3.86–3.74 (m, 2 H), 3.34
(s, 3 H, OCH3) ppm. 13C NMR (91 MHz, CDCl3): δ = 137.3, 137.1 (2
C, 2 Cq arom.), 128.9–126.0 (10 C, arom.), 120.2 (CF3), 101.6 (CH
benzylidene), 98.7 (C-1), 83.2, 78.0, 72.2, 63.6 (C-2, C-3, C-4, C-5),
73.0 (CH2Ph), 68.3 (C-6), 55.2 (OCH3) ppm.
Methyl
3-O-Benzyl-4,6-O-benzylidene-2-deoxy-α-D-erythro-
Experimental Section
hex-2-enopyranoside (5):[30] Ethyl methanesulfonate (0.43 mL,
0.955 mmol) was dissolved in abs. THF (2 mL) and the stirred mix-
General Methods: Optical rotations were measured at room tem-
perature with a Perkin–Elmer 241 automatic polarimeter. TLC analy-
sis was performed on Kieselgel 60 F254 (Merck) silica gel plates with
visualization by immersion in a sulfuric acid solution (5 % in EtOH)
followed by heating. Column chromatography was performed on
silica gel 60 (Merck 0.063–0.200 mm) and flash column chromatog-
raphy was performed on silica gel 60 (Merck 0.04–0.063 mm). Or-
ganic solutions were dried with MgSO4 and concentrated under
vacuum. 1H (360 and 400 MHz) and 13C NMR (90.54 and
100.28 MHz) spectra were recorded with Bruker DRX-360 and DRX-
400 spectrometers. 2D COSY, 1H-13C HSQC and 2D ROESY experi-
ments were performed to assist NMR assignments. Chemical shifts
are referenced to SiMe4 (δ = 0.00 ppm for 1H nuclei) and to the
residual solvent signal (CDCl3: δ = 77.00 ppm for 13C nuclei). MS
(MALDI-TOF) analysis was carried out in positive reflectron mode
with a BIFLEX III mass spectrometer (Bruker, Germany) with delayed-
ion extraction. The matrix solution was a saturated solution of 2,4,6-
trihydroxyacetophenone (THAP) in MeCN. Elemental analysis (C, H,
S) was performed with an Elementar Vario MicroCube instrument.
X-ray diffraction data for compounds 9 and 19a were collected with
a Bruker Nonius MACH3 diffractometer at 293 K with Mo-Kα radia-
ture was cooled to –78 °C under argon before 2.5
M n-butyllithium
(0.166 mL, 0.955 mmol) was added dropwise. After 30 min at this
temperature a solution of 4 (241 mg, 0.477 mmol) in THF (4 mL)
was added and the mixture was warmed to room temperature.
After stirring for 5 d the reaction mixture was diluted with ethyl
acetate, extracted with saturated aqueous ammonium chloride and
water, dried and concentrated. The crude product was purified by
column chromatography to yield 5 (35 mg, 21 % over two steps) as
a colourless syrup. lit:[30] [α]D24 = –59 (c = 0.6, CHCl3); Rf = 0.40 (65:35
C6H14/ethyl acetate). 1H NMR (360 MHz, CDCl3): δ = 7.57–7.20 (m,
10 H, arom.), 5.56 (s, 1 H, CH benzylidene), 5.00 (d, J1,2 = 2.61 Hz, 1
H, 1-H), 4.90 (d, Jgem = 12.07 Hz, 1 H, CH2a benzyl), 4.77 (d, Jgem
=
12.10 Hz, 1 H, CH2b benzyl), 4.74–4.70 (m, 1 H, 2-H), 4.33–4.21 (m,
2 H, 4-H, 6-Ha), 4.10 (dt, J5,6a = 9.65, J5,6b = 9.65 Hz, J4,5 = 4.57 Hz,
1 H, 5-H), 3.82 (t, Jgem = 10.23, J5,6 = 10.23 Hz, 1 H, 6-Hb), 3.40 (s, 3
H, OCH3) ppm. 13C NMR (91 MHz, CDCl3): δ = 154.4 (C-3), 137.2,
136.0 (2 C, 2 Cq arom.), 128.9–126.3 (10 C, arom.), 102.1 (CH benzyl-
idene), 97.2, 95.8, 74.9, 69.4, 69.0, 63.6 (C-1, C-2, C-4, C-5. C-6, CH2
benzyl), 55.4 (OCH3) ppm.
Methyl 3-O-Benzyl-4,6-O-benzylidene-2-deoxy-2-C-(E)-(ethyl-
tion (λ = 0.71073 Å) or with an Oxford Diffraction SuperNova diffrac- sulfonatomethylene)-α-D-arabino-hexopyranoside (7a), Methyl
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3-O-Benzyl-4,6-O-benzylidene-2-deoxy-2-C-(Z)-(ethylsulfonato- for 3 h the mixture was concentrated. Methanol was added and the
methylene)-α-
D
-arabino-hexopyranoside (7b) and Methyl 3-O-
mixture was concentrated again. This step was repeated two more
Benzyl-4,6-O-benzylidene-2-deoxy-2-C-(ethylsulfonatomethyl)-
times. The residue was dissolved in CH2Cl2 and extracted with satu-
α-D-erythro-hex-2-enopiranoside (8): Ethyl diethylphosphoryl- rated aqueous ammonium chloride and water, dried and concen-
methanesulfonate[19,25] was dissolved in the current solvent (see
Table 1) and the stirred mixture was cooled to –78 °C under argon
trated. The crude product was purified by column chromatography
to yield 9 (66 mg, 66 %) and 10 (10 mg, 10 %) as a white crystalline
solid.
before 2.5
M n-butyllithium was added dropwise. After 30 min at
this temperature a solution of 6 in the current solvent and THF
(1.5 mL) was added and the mixture was warmed to room tempera-
ture. After 6 h the mixture was diluted with CH2Cl2, extracted with
saturated aqueous ammonium chloride and water, dried and con-
centrated. The crude product was purified by column chromatogra-
phy (65:15:20 C6H14/ethyl acetate/toluene) to give 7a, 7b and 8.
Method B: Palladium on activated charcoal (30 mg, 10 m/m%) and
Et3N (30 μL) were added to a solution of 7a and 7b (300 mg) in
methanol (10 mL) and CH2Cl2 (5 mL). When the reaction was com-
pleted, the mixture was diluted with CH2Cl2, filtered through Celite
and concentrated. The crude product was purified by column chro-
matography to give 9 (144 mg, 49 %) and 10 (12 mg, 4 %).
7b: Colourless syrup, [α]D = –20.54 (c = 0.50, CHCl3); Rf = 0.65 (6:4
C6H14/ethyl acetate). 1H NMR (400 MHz, CDCl3): δ = 7.74–7.45 (m,
10 H, arom.), 6.84 (d, J = 1.7 Hz, 1 H, CHSO3Et), 6.38 (s, 1 H, 1-H),
5.79 (s, 1 H, CH benzylidene), 5.12 (d, Jgem = 11.6 Hz, 1 H, CH2a
9: White crystals, m.p. 113–120 °C. [α]D = +79.46 (c = 0.41, CHCl3);
Rf = 0.48 (65:20:15 C6H14/ethyl acetate/toluene). H NMR (360 MHz,
CDCl3): δ = 7.52–7.24 (m, 10 H, arom.), 5.61 (s, 1 H, CH benzylidene),
5.06 (d, J1,2 = 3.47 Hz, 1 H, 1-H), 4.97 (d, Jgem = 11.43 Hz, 1 H, CH2a
1
benzyl), 4.92 (d, Jgem = 11.6 Hz, 1 H, CH2b benzyl), 4.79 (d, J3,4
=
benzyl), 4.57 (d, Jgem = 11.44 Hz, 1 H, CH2b benzyl), 4.28 (dd, Jgem
=
9.8 Hz, 1 H, 3-H), 4.51 (dd, J3,4 = 10.3, J4,5 = 4.8 Hz, 1 H, 4-H), 4.38
9.51, J5,6a = 4.00 Hz, 1 H, 6-Ha), 4.21–4.11 (m, 2 H, SO3CH2CH3), 3.88–
3.71 (m, 3 H, 6-Hb, 5-H, 4-H), 3.64 (dd, J = 10.45, J = 8.79 Hz, 1 H, 3-
H), 3.42 (dd, Jgem = 14.54, J2,CH2a = 1.93 Hz, 1 H, CH2aSO3Et), 3.37 (s,
3 H, OCH3), 3.23 (dd, Jgem = 14.52, J2,CH2b = 10.82 Hz, 1 H,
3
(q, JH,H = 7.1 Hz, 2 H, SO3CH2CH3), 4.23 (dt, J5,6 = 9.9, J4,5 = 4.8 Hz,
1 H, 5-H), 3.98 (t, Jgem = 10.4, J5,6 = 10.4 Hz, 1 H, 6-Ha), 3.92 (t, Jgem
9.7, J5,6 = 6.7 Hz, 1 H, 6-Hb), 3.66 (s, 3 H, OCH3), 1.58 (t, JH,H
=
=
3
7.1 Hz, 3 H, SO3CH2CH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 150.0
(C-2), 137.5, 137.2 (Cq), 129.2, 128.6, 128.3, 128.1, 128.0, 126.1 (10 C,
arom.), 121.4 (CHSO3Et), 101.5 (CH benzylidene), 95.2 (C-1), 84.1 (C-
4), 76.0 (C-3), 74.6 (CH2 benzyl), 68.8 (C-6), 67.3 (SO3CH2CH3), 63.1
(C-5), 55.6 (OCH3), 14.9 (SO3CH2CH3) ppm. C24H28O8S (476.54): calcd.
C 60.49, H 5.92, S 6.73; found C 60.24, H 6.09, S 6.82.
3
CH2bSO3Et), 2.48–2.37 (m, 1 H, 2-H), 1.31 (t, JH,H = 7.10 Hz, 3 H,
SO3CH2CH3) ppm. 13C NMR (91 MHz, CDCl3): δ = 137.8, 137.3 (2 C,
2 Cq arom.), 128.9–125.9 (10 C, arom.), 101.3 (CH benzylidene), 98.5
(C-1), 83.9 (C-4), 74.6 (CH2 benzyl), 74.5 (C-3), 68.9 (C-6), 66.5
(SO3CH2CH3), 62.3 (C-5), 55.2 (OCH3), 47.1 (CH2,SO3Et), 42.0 (C-2),
14.8 (SO3CH2CH3) ppm. C24H30O8S (478.56): calcd. C 60.23, H 6.32,
S 6.70; found C 61.01, H 6.56, S 6.61.
7a: Colourless syrup; Rf = 0.52 (6:4 C6H14/ethyl acetate). 1H NMR
(400 MHz, CDCl3): δ = 7.72–7.41 (m, 10 H, arom.), 6.88 (d, J = 1.1 Hz,
1 H, CHSO3Et), 5.74 (s, 1 H, CH benzylidene), 5.35 (s, 1 H, 1-H), 5.30
(d, J3,4 = 6.3 Hz, 1 H, 3-H), 5.08 (d, Jgem = 11.0 Hz, 1 H, CH2a benzyl),
4.98 (d, Jgem = 10.95 Hz, 1 H, CH2b benzyl), 4.54 (d, J5,6 = 5.37 Hz, 1
10: White syrup, [α]D = +3.6 (c = 0.14, CHCl3); Rf = 0.42 (65:20:15
C6H14/ethyl acetate/toluene). 1H NMR (360 MHz, CDCl3): δ = 7.53–
7.22 (m, 10 H, arom.), 5.57 (s, 1 H, CH benzylidene), 5.01 (s, 1 H, 1-H),
4.75 (d, Jgem = 11.80 Hz, 1 H, CH2a benzyl), 4.69 (d, Jgem = 11.80 Hz,
1 H, CH2b benzyl), 4.29–4.20 (m, 3 H, 6-Ha, SO3CH2CH3), 4.16 (dd,
J3,4 = 10.1, J2,3 = 5.7 Hz, 1 H, 3-H), 3.88–3.69 (m, 3 H, 5-H, 6-Hb,
CH2aSO3Et), 3.53 (t, J3,4 = 9.50, J4,5 = 9.50 Hz, 1 H, 4-H), 3.37 (s, 4 H,
OCH3, CH2aSO3Et), 3.16 (dd, Jgem = 14.57, J2,CH2b = 10.58 Hz, 1 H,
CH2bSO3Et), 2.93 (dd, J2,CH2b = 10.56, J2,3 = 5.61 Hz, 1 H, 2-H), 1.35
(t, 3JH,H = 7.11 Hz, 3 H, SO3CH2CH3) ppm. 13C NMR (91 MHz, CDCl3):
δ = 137.8, 137.3 (2 C, 2 Cq arom.), 129.0–126.0 (10 C, arom.), 101.6
(CH benzylidene), 100.4 (C-1), 79.7 (C-4), 73.0 (C-3), 72.6 (CH2
benzyl), 68.9 (C-6), 66.7 (SO3CH2CH3), 62.9 (C-5), 55.2 (OCH3), 45.8
(CH2SO3Et), 40.0 (C-2), 14.9 (SO3CH2CH3) ppm. C24H30O8S (478.56):
calcd. C 60.23, H 6.32, S 6.70; found C 59.73, H 6.21, S 6.54.
H, 6-Ha), 4.45–4.38 (m, 2 H, SO3CH2CH3), 4.16–4.10 (m, 1 H, 4-H),
3
4.02–3.89 (m, 2 H, 5-H, 6-Hb), 3.63 (s, 3 H, OCH3), 1.52 (t, JH,H
=
7.13 Hz, 3 H, SO3CH2CH3) ppm. 13C NMR (101 MHz, CDCl3): δ =
147.8 (C-2), 137.5, 136.8 (2 C, 2 Cq arom.), 128.8, 128.1, 128.0, 127.4,
125.9 (11 C arom., CHSO3Et), 101.2 (CH benzylidene), 99.2 (C-1), 83.0
(C-4), 74.5 (C-3), 73.5 (CH2 benzyl), 68.9 (C-6), 66.7 (SO3CH2CH3), 63.7
(C-5), 55.2 (OCH3), 14.7 (SO3CH2CH3) ppm. C24H28O8S (476.54): calcd.
C 60.49, H 5.92, S 6.73; found C 60.66, H 5.81, S 6.92.
8: [α]D = –16.75 (c = 1.34, CHCl3); Rf = 0.63 (6:4 C6H14/ethyl acetate).
1H NMR (360 MHz, CDCl3): δ = 7.51–7.26 (m, 10 H, arom.), 5.58 (s, 1
H, CH benzylidene), 5.29 (s, 1 H, 1-H), 5.17 (d, Jgem = 10.68 Hz, 1 H,
CH2a benzyl), 4.95 (d, Jgem = 10.68 Hz, 1 H, CH2b benzyl), 4.46–4.37
(m, 2 H, CH2SO3Et), 4.31 (dd, Jgem = 10.26, J5,6a = 4.56 Hz, 1 H, 6-Ha),
Phenyl 6-O-tert-Butyldiphenylsilyl-3,4-O-(2′,3′-dimethoxybut-
ane-2′3′-diyl)-1-thio-ꢀ-D-arabino-hexopyranoside-2-ulose (11):
3
3
4.19 (q, JH,H = 7.01 Hz, 1 H, SO3CH2aCH3), 4.18 (q, JH,H = 7.00 Hz,
1 H, SO3CH2bCH3), 4.06 (td, J = 10.02, J = 9.84 Hz, J5,6a = 4.54 Hz, 1
H, 5-H), 3.85 (t, Jgem = 10.34, J5,6b = 10.34 Hz, 1 H, 6-Hb), 3.60 (d,
Dess–Martin periodinane (687 mg, 1.62 mmol) was added to a solu-
tion of 2[37] (675 mg, 1.08 mmol) in dry CH2Cl2. After stirring for 1 h
at room temperature, the mixture was diluted with diethyl ether
and NaOH (432 mg, 10.8 mmol) in H2O (8.3 mL) was added and the
mixture stirred vigorously for 10 min. The organic layer was sepa-
rated and washed with water three times, dried and concentrated.
The crude product was used in the next step without purification.
Rf = 0.40 (7:3 C6H14/ethyl acetate). 1H NMR (360 MHz, CDCl3): δ =
7.79–7.14 (m, 15 H, arom.), 5.40 (s, 1 H, 1-H), 4.62 (d, J3,4 = 10.5 Hz,
1 H, 3-H), 4.19 (t, J3,4 = 10.0, J4,5 = 10.0 Hz, 1 H, 4-H), 4.03–3.91 (m,
3 H, 5-H, 6-Ha, 6-Hb), 3.25 (s, 3 H, OCH3 butanedione), 3.17 (s, 3 H,
OCH3 butanedione), 1.39 (s, 3 H, CH3 butanedione), 1.28 (s, 3 H, CH3
butanedione), 1.06 (s, 9 H, tBu) ppm. 13C NMR (91 MHz, CDCl3):
δ = 194.0 (C-2), 135.8–127.5 (18 C, arom.), 100.7, 99.6 (2 C, 2 Cq
butanedione), 89.2 (C-1), 78.9, 75.2, 68.3 (3 C, C-3, C-4, C-5), 62.1 (C-
6), 48.5, 48.2 (2 C, 2 OCH3 butanedione), 26.8 (3 C, 3 CH3, tBu), 19.3
J
4,5 = 14.14 Hz, 1 H, 4-H), 3.45 (s, 3 H, OCH3), 1.32 (t, 3JH,H = 7.09 Hz,
3 H, SO3CH2CH3) ppm. 13C NMR (91 MHz, CDCl3): δ = 154.2 (C-2),
136.8, 136.4 (2 C, 2 Cq arom.), 129.1, 128.4, 128.2, 126.1 (10 C, arom.),
106.9 (C-3), 101.8 (CH benzylidene), 97.4 (C-1), 74.2 (C-4), 72.7 (CH2
benzyl), 69.1 (C-6), 66.7 (SO3CH2CH3), 63.7 (C-5), 56.2 (OCH3), 46.9
(CH2SO3Et), 15.0 (SO3CH2CH3) ppm. C24H28O8S (476.54): calcd. C
60.49, H 5.92, S 6.73; found C 59.99, H 5.81, S 6.69.
Methyl 3-O-Benzyl-4,6-O-benzylidene-2-deoxy-2-C-(ethylsulf-
onatomethyl)-α-D-glucopyranoside (9) and Methyl 3-O-Benzyl-
4,6-O-benzylidene-2-deoxy-2-C-(ethylsulfonatomethyl)-α-D-
mannopyranoside (10)
Method A: Sodium borohydride was added to a solution of 7a and
7b (100 mg) in methanol (10 mL) and CH2Cl2 (5 mL). After stirring
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(Cq, tBu), 17.6, 17.5 (2 C, 2 CH3 butanedione) ppm. C34H42O7SSi
(622.24): calcd. C 65.57, H 6.80, S 5.15; found C 63.11, H 6.51, S 4.98.
dried and concentrated. The crude product was purified by column
chromatography (85:15 C6H14/ethyl acetate) to give the products
13 (46 mg, 38 %) and 14 (44 mg, 37 %).
Phenyl 6-O-tert-Butyldiphenylsilyl-2-deoxy-2-C-(E)-(ethylsulf-
onatomethylene)-3,4-O-(2′,3′-dimethoxybutane-2′3′-diyl)-1-
13: White crystals, m.p. 152–159 °C. [α]D = –9.11 (c = 0.21, CHCl3);
Rf = 0.63 (7:3 C6H14/ethyl acetate). 1H NMR (360 MHz, CDCl3): δ =
7.77–7.12 (m, 15 H, arom.), 4.97 (s, 1 H, 1-H), 4.36 (dd, J = 6.9, 2.7 Hz,
1 H), 4.02–3.32 (m, 1 H, skeleton protons, CH2SO3Et), 3.27 (s, 3 H,
OCH3 butanedione), 3.20 (s, 3 H, OCH3 butanedione), 2.94 (s, 1 H,
thio-ꢀ-
Butyldiphenylsilyl-2-deoxy-2-C-(Z)-(ethylsulfonatomethylene)-
3,4-O-(2′,3′-dimethoxybutane-2′3′-diyl)-1-thio-ꢀ- -arabino-
D-arabino-hexopyranoside (12a) and Phenyl 6-O-tert-
D
hexopyranoside (12b): Ethyl diethylphosphorylmethanesulfonate
(141 mg, 0.540 mmol) was dissolved in abs. THF and the stirred
3
2-H), 1.43 (t, JH,H = 6.9 Hz, 3 H, SO3CH2CH3), 1.29 (s, 3 H, CH3
mixture was cooled to –78 °C under argon before 2.5
M n-butyllith-
butanedione), 1.26 (s, 3 H, CH3 butanedione), 1.06 (s, 9 H, tBu) ppm.
13C NMR (91 MHz, CDCl3): δ = 136.0, 135.6, 131.0, 129.8, 129.0, 127.8,
127.3, 134.5 (15 C, arom.), 133.7, 133.0 (3 C, 3 Cq arom.), 100.5, 100.0
(2 C, 2 Cq butanedione), 85.9 (C-1), 79.3, 70.6, 63.1 (3 C, C-3, C-4, C-
5), 67.2 (SO3CH2CH3), 61.9 (C-6), 48.2 (2 C, 2 OCH3 butanedione),
45.4 (CH2SO3Et), 40.3 (C-2), 27.0 (3 C, 3 CH3, tBu), 19.4 (Cq, tBu), 17.8,
17.7 (2 C, 2 CH3 butanedione), 15.1 (SO3CH2CH3) ppm. C37H50O9S2Si
(730.27): calcd. C 60.79, H 6.89, S 8.77; found C 59.78, H 6.41, S 8.57;
ium (234 μL, 0.585 mmol) was added dropwise. After 30 min at this
temperature 11 (281 mg, 0.452 mmol) dissolved in abs. THF was
added dropwise and the mixture was warmed to 0 °C. When com-
plete conversion of the starting material was observed (by TLC), a
saturated ammonium chloride solution was added. The mixture was
diluted with dichloromethane and the organic layer was washed
with water three times, dried, filtered and concentrated. The crude
product was purified by silica gel chromatography to give 12a
(212 mg, 64 %) and 12b (26 mg, 9 %).
14: Yellow syrup, [α]D = +74.80 (c = 0.28, CHCl3); Rf = 0.76 (7:3
C6H14/ethyl acetate). 1H NMR (400 MHz, acetone): δ = 7.65–7.17 (m,
15 H, arom.), 4.75 (d, J3,4 = 9.2 Hz, 1 H, 3-H), 4.42 (dd, Jgem = 14.2,
12a: Yellow syrup, [α]D = +24.21 (c = 0.04, CHCl3); Rf = 0.67 (7:3
C6H14/ethyl acetate). 1H NMR (400 MHz, acetone): δ = 7.80–7.28 (m,
15 H, arom.), 6.83 (dd, J3,CH = 2.4, J1,CH = 1.3 Hz, 1 H, CHSO3Et), 5.82
(d, J1,CH = 1.0 Hz, 1 H, 1-H), 4.81 (dd, J3,4 = 9.7, J3,CH = 2.4 Hz, 1 H,
3
J = 0.6 Hz, 1 H, CH2aSO3Et), 4.34 (dq, JH,H = 7.1, J = 1.5 Hz, 2 H,
SO3CH2CH3), 4.31–4.25 (m, 1 H, 5-H), 4.26 (d, Jgem = 14.2 Hz, 1 H,
CH2b,SO3Et), 4.09 (dd, J4,5 = 10.5, J3,4 = 9.2 Hz, 1 H, 4-H), 3.99 (dd,
3
3-H), 4.19 (q, JH,H = 7.1 Hz, 2 H, SO3CH2CH3), 4.02–3.96 (m, 3 H, 4-
Jgem = 11.8, J5,6a = 3.2 Hz, 1 H, 6-Ha), 3.91 (dd, Jgem = 11.7, J5,6b
=
H, 6-Ha, 6-Hb), 3.92 (dt, J = 9.9, 3.1 Hz, 1 H, 5-H), 3.31 (s, 3 H, OCH3
butanedione), 3.21 (s, 3 H, OCH3 butanedione), 1.37 (t, 3JH,H = 7.1 Hz,
3 H, SO3CH2CH3), 1.33 (s, 3 H, CH3 butanedione), 1.25 (s, 3 H, CH3
butanedione), 1.07 (s, 9 H, tBu) ppm. 13C NMR (101 MHz, acetone):
δ = 149.0 (C-2), 136.8, 136.5, 135.8, 134.5, 134.0, 131.7, 130.8, 130.3,
128.8, 128.7, 128.5 (18 C, arom.), 125.8 (CHSO3Et), 101.4, 100.5 (2 C,
2 Cq butanedione), 86.3 (C-1), 79.7 (C-5), 71.8 (C-3), 68.1 (C-4), 67.4
(SO3CH2CH3), 63.5 (C-6), 49.0, 48.6 (2 C, 2 OCH3 butanedione), 27.5
(3 C, 3 CH3, tBu), 20.0 (Cq, tBu), 18.1, 17.6 (2 C, 2 CH3 butanedione),
15.3 (SO3CH2CH3) ppm. C37H48O9S2Si (728.25): calcd. C 60.96, H 6.64,
S 8.80; found C 62.11, H 6.82, S 8.85.
2.1 Hz, 1 H, 6-Hb), 3.34 (s, 3 H, OCH3 butanedione), 3.23 (s, 3 H,
OCH3 butanedione), 1.35 (s, 3 H, CH3 butanedione), 1.33–1.26 (m, 3
H, SO3CH2CH3), 1.30 (s, 3 H, CH3 butanedione), 0.97 (s, 9 H,
tBu) ppm. 13C NMR (101 MHz, acetone): δ = 136.5, 136.2, 130.6,
130.5, 130.0, 128.6, 128.6, 127.9 (15 C, arom.), 134.1, 133.7, 133.4 (3
C, 3 Cq arom.), 107.5, 101.5, 101.1, 79.8 (C-5), 68.1 (SO3CH2CH3), 67.1
(C-3), 65.4 (C-4), 62.1 (C-6), 49.2 (CH2SO3Et), 48.8, 48.6 (2 C, 2 OCH3
butanedione), 27.4 (3 C, 3 CH3, tBu), 19.8 (Cq, tBu), 18.3, 18.2 (2 C,
2 CH3 butanedione), 15.5 (SO3CH2CH3) ppm. C37H48O9S2Si (728.25):
calcd. C 60.96, H 6.64, S 8.80; found C 62.91, H 6.65, S 8.86.
1,5-Anhydro-6-O-tert-butyldiphenylsilyl-2-deoxy-2-C-(ethyl-
12b: Yellowish syrup, [α]D = –51.22 (c = 0.04, CHCl3); Rf = 0.65 (7:3,
C6H14/ethyl acetate). 1H NMR (360 MHz, CDCl3): δ = 7.72–7.21 (m,
sulfonatomethyl)-3,4-O-(2′,3′-dimethoxybutane-2′3′-diyl)-
D-ar-
abino-hex-1-enitol (15)
15 H, arom.), 6.87 (d, J1,CH = 1.9 Hz, 1 H, CHSO3Et), 6.43 (dd, J1,3
=
Method A: Pd0/C (10 wt.-%, 16 mg) was added to a solution of 12a
(157 mg, 0.215 mmol) in CH2Cl2 (2 mL) and stirred under H2 (10 bar).
After 3 d the mixture was diluted with CH2Cl2, filtered through Cel-
ite and concentrated. The crude product was purified by column
chromatography (85:15 C6H14/ethyl acetate) to give 15 (47 mg,
35 %).
Method B: Raney-Ni slurry (220 mg) was added to a solution of
12a (321 mg, 0.440 mmol) in methanol (10 mL) and CH2Cl2 (2 mL)
and stirred under H2 overnight. When the reaction was completed,
the mixture was filtered through Celite and concentrated. The crude
product was purified by column chromatography (85:15 C6H14/ethyl
acetate) to give 15 (212 mg, 78 %).
2.6, J1,CH = 2.1 Hz, 1 H, 1-H), 4.52 (dd, J3,4 = 10.5, J1,3 = 2.6 Hz, 1 H,
3-H), 4.37–4.28 (m, 2 H), 4.21–4.08 (m, 2 H), 4.03–3.92 (m, 2 H, 4-H,
5-H, 6-Ha, 6-Hb, SO3CH2CH3), 3.29 (s, 3 H, OCH3 butanedione), 3.10
(s, 3 H, OCH3 butanedione), 1.39 (t, 3JH,H = 7.1 Hz, 3 H, SO3CH2CH3),
1.37 (s, 3 H, CH3 butanedione), 1.27 (s, 3 H, CH3 butanedione), 1.03
(s, 9 H, tBu) ppm. 13C NMR (91 MHz, CDCl3): δ = 151.4 (C-2), 135.8,
135.7, 134.5, 133.6, 130.9, 129.7, 129.7, 129.4, 129.2, 127.8, 127.7 (18
C, arom.), 118.2 (CHSO3Et), 100.3, 99.0 (2 C, 2 Cq butanedione), 81.5
(C-1), 79.2, 66.9, 65.4 (C-3, C-4, C-5), 67.5 (SO3CH2CH3), 66.2 (C-6),
48.5, 48.3 (2 C, 2 OCH3 butanedione), 26.9 (3 C, 3 CH3, tBu), 19.4 (Cq,
tBu), 17.8, 17.7 (2 C, 2 CH3 butanedione), 15.2 (SO3CH2CH3) ppm.
C37H48O9S2Si (728.25): calcd. C 60.96, H 6.64, S 8.80; found C 63.28,
H 6.79, S 8.92.
15: Colourless syrup. [α]D = +37.10 (c = 0.06, CHCl3); Rf = 0.24 (85:15
Phenyl 6-O-tert-Butyldiphenylsilyl-2-deoxy-2-C-(ethylsulfonato- C6H14/ethyl acetate). 1H NMR (400 MHz, CDCl3): δ = 7.71–7.33 (m,
methyl)-3,4-O-(2′,3′-dimethoxybutane-2′3′-diyl)-1-thio-ꢀ-
mannopyranoside (13) and Phenyl 6-O-tert-Butyldiphenylsilyl- H), 4.31 (q, JH,H = 7.1 Hz, 2 H, SO3CH2CH3), 4.17–4.11 (m, 4 H, 4-H,
2-deoxy-2-C-(ethylsulfonatomethyl)-3,4-O-(2′,3′-dimethoxy- 5-H, CH2aSO3Et), 4.02 (d, Jgem = 11.8 Hz, 1 H, 6-Ha), 3.94 (d, Jgem
butane-2′3′-diyl)-1-thio- -arabino-hex-1-enopyranoside (14):
D
-
10 H, arom.), 6.44 (d, J1,3 = 1.8 Hz, 1 H, 1-H), 4.72–4.68 (m, 1 H, 3-
3
=
D
11.4 Hz, 1 H, 6-Hb), 3.56 (d, Jgem = 14.5 Hz, 1 H, CH2bSO3Et), 3.35 (s,
3 H, OCH3 butanedione), 3.26 (s, 3 H, OCH3 butanedione), 1.40 (t,
3JH,H = 7.1 Hz, 3 H, SO3CH2CH3), 1.37 (s, 3 H, CH3 butanedione), 1.34
(s, 3 H, CH3 butanedione), 1.04 (s, 9 H, tBu) ppm. 13C NMR (101 MHz,
Sodium borohydride (15.5 mg, 0.410 mmol) was added to a solution
of 12a (113 mg, 0.164 mmol) in methanol (10 mL) and CH2Cl2
(5 mL). After stirring for 3 h the mixture was concentrated. Methanol
was added and the mixture was concentrated again. This step was CDCl3): δ = 147.0 (C-1), 136.0, 135.6, 133.8, 133.1, 129.8, 129.8, 127.8,
repeated two more times. The residue was dissolved in CH2Cl2 and
extracted with saturated aqueous ammonium chloride and water,
127.7 (12 C, arom.), 100.6, 100.5, 100.0 (3 C, C-2, 2 Cq butanedione,),
77.8, 65.1, 64.9 (3 C, C-3, C-4, C-5), 66.8 (SO3CH2CH3), 61.4 (C-6),
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48.6, 48.5 (2 C, 2 OCH3 butanedione), 47.9 (CH2SO3Et), 27.0 (3 C, 3
CH3, tBu), 19.5 (Cq, tBu), 18.0, 17.9 (2 C, 2 CH3 butanedione), 15.4
(SO3CH2CH3) ppm. C31H44O9SSi (620.25): calcd. C 59.97, H 7.14, S
5.16; found C 56.73, H 6.97, S 5.08.
(c = 0.20, CHCl3); Rf 0.48 (75:25 C6H14/ethyl acetate). 1H NMR
(360 MHz, CDCl3): δ = 7.58–7.27 (m, 15 H, arom.), 5.51 (s, 1 H, CH
benzylidene), 4.92 (s, 1 H, CH2a benzyl), 4.89 (s, 1 H, CH2b benzyl),
4.57 (d, J = 11.0 Hz, 1 H, skeleton proton), 4.45 (dd, J = 10.5, 4.8 Hz,
1 H, 6-Ha), 4.21 (d, J = 9.9 Hz, 1 H, skeleton proton), 3.88 (d, J =
9.6 Hz, 1 H, skeleton proton), 3.85 (t, J = 10.2 Hz, 1 H, 6-Hb), 3.65
(dt, J = 9.8, 4.8 Hz, 1 H, 5-H) ppm. 13C NMR (91 MHz, CDCl3): δ =
197.3 (C-3), 136.9, 136.4, 133.7, 131.5, 129.5, 129.2, 128.7, 128.6,
128.6, 128.4, 128.3, 126.5 (15 C, arom.), 101.8 (CH benzylidene), 89.7
(C-1), 82.1, 81.1 (2 C, skeleton carbons), 73.9 (CH2 benzyl), 72.1 (skel-
eton carbon), 69.2 (C-6) ppm. C26H24O5S (448,13): calcd. C 69.62, H
5.39, S 7.15; found C 71.52, H 5.31, S 7.22.
6-O-tert-Butyldiphenylsilyl-2-deoxy-2-(E)-(ethylsulfonatometh-
ylene)-3,4-O-(2′,3′-dimethoxybutane-2′3′-diyl)-ꢀ-D-arabino-hex-
opyranose (16), 6-O-tert-Butyldiphenylsilyl-2-deoxy-2-(E)-(eth-
ylsulfonatomethylene)-3,4-O-(2′,3′-dimethoxybutane-2′3′-diyl)-
α-D-arabino-hexopyranose (17) and Compound 15: Et3SiH
(408 μL, 2.551 mmol) and Pd0/C (10 wt.-%, 19 mg) was added to a
solution of 12a (186 mg, 0.255 mmol) in CH2Cl2 (10 mL) and stirred
under H2. After 1 h, when the starting material had completely
disappeared, the mixture was filtered through a pad of Celite and
concentrated. The crude product was purified by column chroma-
tography (95:5 → 7:3 C6H14/ethyl acetate) to give 15 (38 mg, 24 %),
16 (17 mg, 10 %) and 17 (19 mg, 12 %).
Phenyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-3-C-(E)-(ethyl-
sulfonatomethylene)-1-thio-ꢀ-
Phenyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-3-C-(Z)-(ethyl-
sulfonatomethylene)-1-thio-ꢀ- -ribo-hexopyranoside (19b):
D-ribo-hexopyranoside (19a) and
D
Ethyl diethylphosphorylmethanesulfonate (857 mg, 3.293 mmol)
was dissolved in abs. THF and the stirred mixture was cooled to
16: Colourless syrup, [α]D = +84.82 (c = 0.13, CHCl3); Rf = 0.14 (8:2
C6H14/ethyl acetate). 1H NMR (400 MHz, CDCl3): δ = 7.73–7.67 (m, 4
H, arom.), 7.48–7.36 (m, 6 H, arom.), 6.37 (d, J3,CH = 2.5 Hz, 1 H,
CHSO3Et), 5.33 (s, 1 H, 1-H), 4.95 (dd, J3,4 = 9.9, J3,CH = 2.5 Hz, 1 H,
–78 °C under argon before 2.5
M n-butyllithium (1.427 mL,
3.568 mmol) was added dropwise. After 30 min at this temperature
18 (1.231 g, 2.744 mmol) dissolved in abs. THF was added dropwise
and the mixture was warmed up. When complete conversion of the
starting material was observed (by TLC), a saturated ammonium
chloride solution was added. The mixture was diluted with dichloro-
methane. The organic layer was washed with water three times,
dried, filtered and concentrated. The crude product was purified by
silica gel chromatography to give 19a (647 mg, 44 %) and 19b
(346 mg, 24 %).
3-H), 4.31–4.26 (m, 2 H, SO3CH2CH3), 4.17 (ddd, J4,5 = 10.1, J5,6a
=
3.9, J5,6b = 2.2 Hz, 1 H, 5-H), 3.99–3.85 (m, 3 H, 6-Ha, 6-Hb, 4-H), 3.37
(s, 3 H, OCH3 butanedione), 3.19 (s, 3 H, OCH3 butanedione), 1.43
3
(t, JH,H = 7.1 Hz, 3 H, SO3CH2CH3), 1.38 (s, 3 H, CH3 butanedione),
1.30 (s, 3 H, CH3 butanedione), 1.06 (s, 9 H, tBu) ppm. 13C NMR
(101 MHz, CDCl3): δ = 148.6 (C-2), 136.1, 136.0, 135.8, 135.7, 129.8,
127.9, 127.7, 127.7 (12 C, arom.), 124.0 (CHSO3Et), 95.7 (C-1), 71.6
(C-5), 68.2 (C-3), 68.0 (C-4), 66.5 (SO3CH2CH3), 62.5 (C-6), 48.9, 48.3
(2 C, 2 OCH3 butanedione), 27.0 (3 C, 3 CH3, tBu), 19.5 (Cq, tBu),
17.7, 17.2 (2 C, 2 CH3 butanedione), 15.0 (SO3CH2CH3) ppm. MS
(MALDI-TOF): m/z = 659.4 [M + Na]+. C31H44O10SSi (636.24): calcd. C
58.47, H 6.96, S 5.03; found C 59.46, H 7.02, S 4.98.
19b: Colourless syrup, Rf = 0.61 (75:25 C6H14/ethyl acetate). 1H NMR
(360 MHz, CDCl3): δ = 7.63–7.12 (m, 15 H, arom.), 6.58 (s, 1 H,
CHSO3Et), 5.49 (s, 1 H, CH benzylidene), 4.67 (d, J1,2 = 8.29 Hz, 1 H,
1-H), 4.59 (d, Jgem = 10.99 Hz, 1 H, CH2a benzyl), 4.45 (d, Jgem
=
10.98 Hz, 1 H, CH2b benzyl), 4.26 (dd, J = 10.06, 4.50 Hz, 1 H, 6-Ha),
4.22–4.16 (m, 1 H, 4-H), 3.99–3.90 (m, 2 H, SO3CH2CH3), 3.81–3.74
(m, 1 H, 2-H), 3.72–3.54 (m, 2 H, 6-Hb, 5-H), 1.08 (t, JH,H = 7.09 Hz,
17: Colourless syrup, [α]D = +70.23 (c = 0.19, CHCl3); Rf = 0.25 (8:2
C6H14/ethyl acetate). 1H NMR (400 MHz, CDCl3): δ = 7.70–7.65 (m, 4
3
H, arom.), 7.44–7.33 (m, 6 H, arom.), 6.61 (s, 1 H, 1-H), 6.43 (d, J3,CH
=
3 H, SO3CH2CH3) ppm. 13C NMR (91 MHz, CDCl3): δ = 148.1 (C-3),
136.3, 136.2 (2 C, 2 Cq arom.), 132.3, 128.9, 128.4, 128.2, 128.0, 127.8,
126.4 (10 C, arom.), 122.0 (CHSO3Et), 102.0 (CH benzylidene), 89.5
(C-1), 78.3 (C-2), 76.9 (C-4), 73.9 (CH2 benzyl), 71.7 (C-5), 68.9 (C-6),
66.1 (SO3CH2CH3), 14.6 (SO3CH2CH3) ppm. C29H30O7S2 (554.14):
calcd. C 62.80, H 5.45, S 11.56; found C 64.91, H 5.62, S 11.72.
2.3 Hz, 1 H, CHSO3Et), 4.82 (dd, J3,4 = 10.0, J3,CH = 2.3 Hz, 1 H, 3-H),
4.26–4.17 (m, 2 H, SO3CH2CH3), 4.14–4.09 (m, 1 H, 5-H), 3.98 (dd,
Jgem = 11.5, J5,6a = 3.5 Hz, 1 H, 6-Ha), 3.89 (t, J3,4 = 10.0, J4,5 = 10.0 Hz,
1 H, 4-H), 3.85 (dd, Jgem = 11.5, J5,6b = 1.9 Hz, 1 H, 6-Hb), 3.26 (s, 3
H, OCH3 butanedione), 3.23 (s, 3 H, OCH3 butanedione), 1.39–1.35
(m, 6 H, SO3CH2CH3, CH3 butanedione), 1.32 (s, 3 H, CH3 butanedi-
one), 1.02 (s, 9 H, tBu) ppm. 13C NMR (101 MHz, CDCl3): δ = 150.2
19a: Colourless syrup, [α]D = –62.88 (c = 0.26, CHCl3); Rf = 0.50
(C-2), 136.1, 135.7, 133.2, 129.8, 129.7 127.7, 127.7 (12 C, arom.), (75:25 C6H14/ethyl acetate). 1H NMR (360 MHz, CDCl3): δ = 7.52–
117.4 (CHSO3Et), 100.7, 99.9 (2 C, 2 Cq butanedione), 87.9 (C-1), 70.9
(C-5), 69.0 (C-4), 67.6 (C-3), 67.3 (SO3CH2CH3), 61.9 (C-6), 48.5 (2 C,
2 OCH3 butanedione), 27.0 (3 C, 3 CH3, tBu), 19.5 (Cq, tBu), 17.8 (2
C, 2 CH3 butanedione), 15.0 (SO3CH2CH3) ppm. MS (MALDI-TOF):
7.22 (m, 15 H, arom.), 6.67 (dd, J = 2.05, 1.14 Hz, 1 H, CHSO3Et), 5.61
(s, 1 H, CH benzylidene), 5.46 (d, J1,2 = 3.11 Hz, 1 H, 1-H), 5.25–5.22
(m, 1 H, 2-H), 4.94–4.88 (m, 1 H, 4-H), 4.77 (d, Jgem = 10.63 Hz, 1 H,
CH2a benzyl), 4.71 (d, Jgem = 10.64 Hz, 1 H, CH2b benzyl), 4.38 (dd,
m/z = 659.3 [M + Na]+. C31H44O10SSi (636.24): calcd. C 58.47, H 6.96, Jgem = 10.52, J5,6a = 4.96 Hz, 1 H, 6-Ha), 4.23–4.12 (m, 3 H, 5-H,
S 5.03; found C 58.31, H 7.13, S 5.12.
SO3CH2CH3), 3.73 (t, Jgem = 10.29, J5,6b = 10.29 Hz, 1 H, 6-Hb), 1.26
(t, J = 7.10 Hz, 3 H, SO3CH2CH3) ppm. 13C NMR (91 MHz, CDCl3): δ =
147.2 (C-3), 137.1, 136.6, 129.3, 129.2, 126.2 (10 C, arom.) 132.4 (2
C, 2 Cq arom.), 123.7 (CHSO3Et), 101.7 (CH benzylidene), 83.5 (C-1),
75.1 (C-4), 74.0 (C-2), 72.8 (CH2 benzyl), 69.9 (C-6), 67.2 (SO3CH2CH3),
66.6 (C-5), 14.7 (SO3CH2CH3) ppm. C29H30O7S2 (554.14): calcd. C
62.80, H 5.45, S 11.56; found C 63.41, H 5.39, S 11.68.
Phenyl 2-O-Benzyl-4,6-O-benzylidenethio-ꢀ-D-ribo-hexopyran-
oside-3-ulose (18): A solution of dry Me2SO (6.10 mL, 0.086 mmol)
in dry CH2Cl2 (70 mL) under argon was cooled to –78 °C and oxalyl
chloride (3.75 mL, 10.5 mmol) was added dropwise. After 15 min, a
solution of 3[40] (9.0 g, 5.24 mmol) in dry CH2Cl2 (70 mL) was added
slowly, keeping the temperature below –65 °C. After 30 min, N,N-
diisopropylethylamine (DIPEA; 37.00 mL, 212 mmol) was added and
the reaction mixture was allowed to warm to room temperature.
The reaction mixture was diluted with CH2Cl2 (300 mL) and the
Phenyl 2-O-Benzyl-4,6-O-benzylidene-3-deoxy-3-C-(ethylsulf-
onatomethyl)-1-thio-ꢀ-
Benzyl-4,6-O-benzylidene-3-deoxy-3-C-(ethylsulfonatomethyl)-
1-thio-ꢀ- -allopyranoside (21): Sodium borohydride (38 mg,
D-glucopyranoside (20) and Phenyl 2-O-
solution was washed with 1
M
aq. HCl (2 × 200 mL) and H2O
D
(200 mL). The organic layer was dried and concentrated. The crude
product was purified by silica gel chromatography in 98:2 CH2Cl2/
acetone to give 18 (7.80 g, 87 %) as white needles. [α]D = –15.89
0.99 mmol) was added to a solution of 19a (220 mg, 0.397 mmol)
in methanol (10 mL) and CH2Cl2 (5 mL). After stirring for 3 h the
mixture was concentrated. Methanol was added and the mixture
Eur. J. Org. Chem. 0000, 0–0
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[1]
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was concentrated again. This step was repeated two more times.
The residue was dissolved in CH2Cl2 and extracted with saturated
aqueous ammonium chloride and water, dried and concentrated.
The crude product was purified by column chromatography to yield
20 and 21 (153 mg, 69 %). Rf = 0.56 (7:3 C6H14/ethyl acetate).
[3]
[4]
[5]
1
21: H NMR (400 MHz, CDCl3): δ = 7.54–7.24 (m, 15 H, arom.), 5.56
L. Lázár, M. Csávás, A. Borbás, Gy. Gyémánt, A. Lipták, ARKIVOC (Gaines-
ville, FL, U.S.) 2004, 7, 196–207.
(s, 1 H, CH benzylidene), 4.91 (d, Jgem = 10.58 Hz, 1 H, CH2a benzyl),
4.61 (d, J1,2 = 9.88 Hz, 1 H, 1-H), 4.49 (d, Jgem = 10.58 Hz, 1 H, CH2b
benzyl), 4.35 (dd, J = 10.55, 4.99 Hz, 1 H, 6-Ha), 4.10–4.01 (m, 1 H,
SO3CH2aCH3), 3.99–3.89 (m, 1 H, SO3CH2bCH3), 3.80–3.69 (m, 2 H, 4-
H, 6-Hb), 3.62 (dd, J1,2 = 9.86, J2,3 = 5.13 Hz, 1 H, 2-H), 3.57–3.44 (m,
2 H, CH2SO3Et), 3.50–3.39 (m, 2 H, 5-H, 3-H), 0.97 (t, J = 7.05 Hz, 3
H, SO3CH2CH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 136.8, 132.8,
132.6, 129.2, 128.8, 128.3, 128.0, 126.2 (arom.), 101.7 (CH benzylid-
ene), 85.8 (C-1), 76.8 (C-4),75.0 (C-2), 72.5 (CH2 benzyl), 69.0 (C-6),
68.0 (C-5), 67.1 (SO3CH2CH3), 44.0 (CH2SO3Et), 36.5 (C-3), 14.5
(SO3CH2CH3) ppm. C29H32O7S2 (556.16): calcd. C 62.57, H 5.79, S
11.52; found C 63.82, H 5.59, S 11.67.
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[22]
1,5-Anhydro-2-O-benzyl-4,6-O-benzylidene-3-deoxy-3-C-(E)-
(ethylsulfonatomethylene)-1-thio-ꢀ-D-ribo-hex-1-enitol (22):
Raney-Ni (200 mg) in MeOH (10 mL) was added to a solution of 19
(133 mg, 0.240 mmol) in CH2Cl2 (2 mL). After stirring the suspension
overnight under H2, the Raney-Ni was removed by filtration and
the residue was concentrated under reduced pressure. The crude
product was purified by column chromatography to give 22 (34 mg,
32 %) as a colourless syrup. [α]D = –44.86 (c = 0.14, CHCl3); Rf 0.19
1
(8:2 C6H14/ethyl acetate). H NMR (400 MHz, CDCl3): δ = 7.71–7.28
(m, 10 H, arom.), 6.73 (t, JCH,2 = 1.7, JCH,4 = 1.7 Hz, 1 H, CHSO3Et),
5.59 (s, 1 H, CH benzylidene), 4.69 (d, Jgem = 11.9 Hz, 1 H, CH2a
benzyl), 4.61 (d, Jgem = 11.9 Hz, 1 H, CH2b benzyl), 4.36 (dd, Jgem
=
10.5, J5,6a = 4.9 Hz, 1 H, 6-Ha), 4.22 (dd, J4,5 = 9.1, JCH,4 = 1.8 Hz, 1
H, 4-H), 4.19–4.11 (m, 3 H, 1-Ha, SO3CH2CH3), 4.04 (ddd, J1b,2 = 9.7,
J1a,2 = 5.7, JCH,2 = 1.6 Hz, 1 H, 2-H), 3.71 (t, Jgem = 10.3, J5,6b
=
10.3 Hz, 1 H, 6-Hb), 3.56 (dt, J5,6b = 9.6, J4,5 = 9.6, J5,6a = 4.8 Hz, 1 H,
3
5-H), 3.36 (t, Jgem = 10.2, J1b,2 = 10.2 Hz, 1 H, 1-Hb), 1.27 (t, JH,H
=
7.1 Hz, 3 H, SO3CH2CH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 150.1
(C-3), 136.9, 136.6 (2 C, 2 Cq arom.), 129.1, 128.9, 128.6, 128.2, 127.9,
126.8 (10 C, arom.), 120.2 (CHSO3Et), 102.5 (CH benzylidene), 79.8
(C-4), 75.2 (C-2), 73.4 (C-5), 73.0 (CH2 benzylidene), 71.6 (C-1), 69.4
(C-6), 66.2 (SO3CH2CH3), 15.0 (SO3CH2CH3) ppm. C23H26O7S (446.14):
calcd. C 61.87, H 5.87, S 7.18; found C 60.73, H 5.96, S 7.20.
[23]
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Supporting Information (see footnote on the first page of this
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C
NMR spectra of all described compounds.
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Acknowledgments
The authors gratefully acknowledge the financial support of this
research by the Mizutani Foundation for Glycoscience (grant
number 150091). The work was also supported by the Richter
Gedeon Centenary Foundation and by the Baross Programme
of the National Research, Development and Innovation Office of
Hungary (REG_EA_09-1-2009-0028 (LCMS_TAN). B. A. and A. M.
thank the National Information Infrastructure Development In-
stitute (NIIFI 10038) for CPU time.
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Keywords: Carbohydrates · Glycosides · Configuration
determination · Conformational analysis · Allylic
compounds · Olefination
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Received: April 27, 2016
Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Na-
Published Online: ■
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Carbohydrate Sulfonic Acids
D. Eszenyi, A. Mándi, M. Herczeg,
A. Bényei, I. Komáromi,
A. Borbás* ......................................... 1–11
Synthesis of C-2- and C-3-Sulfonato-
methyl O- and S-Glycosides by
Horner–Wadsworth–Emmons Ole-
fination
The Horner–Wadsworth–Emmons ole- sis of biorelevant sulfated oligosac-
fination has been applied to the syn- charides. The configurations and con-
thesis of thioglycosides bearing a sec- formations of the products were inves-
ondary sulfonatomethyl moiety as po- tigated by NMR spectroscopy, X-ray
tential building blocks for the synthe- diffraction, and molecular dynamics.
DOI: 10.1002/ejoc.201600526
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