Studies in the acid catalysed glycosylation of α-tocopherol

Article abstract of DOI:10.1515/znb-2002-0515

Condensation of α-tocopherol and 2,2,5,7,8-pentamethyl-6-hydroxychroman (the model compound) with peracetylated glucose, mannose and galactose was carried out. The influence of various acidic catalysts on the chemical yield and the stereochemical outcome

Full text of DOI:10.1515/znb-2002-0515

Studies in the Acid Catalysed Glycosylation of α-Tocopherol
S.Witkowski and P. Wałejko
Institute of Chemistry, University of Białystok, Piłsudskiego 11/4 Białystok, Poland
Reprint requests to Dr. S. Witkowski. E-mail: wit@uwb.edu.pl
Z. Naturforsch. 57b, 571Ð578(2002); received October 26, 2001
α-Tocopherol, Glycosylation, Acidic Catalysis
Condensation of α-tocopherol and 2,2,5,7,8-pentamethyl-6-hydroxychroman (the model
compound) with peracetylated glucose, mannose and galactose was carried out. The influence
of various acidic catalysts on the chemical yield and the stereochemical outcome of the
glycosylation was investigated.
The water insolubility of α-tocopherol is very pressure (40 mm Hg) yielded the mixture of α-
likely the predominant factor responsible for its and ꢀ-glycosides [6]. The composition of products
much-diminished absorption following oral ad- depended mostly on the catalyst used for the reac-
ministration. Therefore, several attempts have tion.
been made to increase the bioavailability of vita-
The formation of a glycosidic carbon-oxygen
min E. One of the most promising ways is to con- bond employing activated sugar derivatives and
vert α-tocopherol into an amphiphilic glycoconju- phenols has been explored extensively [7, 8]. The
gate. The synthesis of some tocopheryl mono- and stereoselective formation of anomeric centers is a
disaccharides has already been reported [1Ð4]. major problem in the synthesis of glycosides.
The preparations were mostly based on the Helfe- Many combinations of leaving group, promoter,
rich method and usually yielded trans-1,2-glyco- and protecting group have been devised to achieve
sides [5].The described methods revealed some this. The synthesis of aryl glycosides, in general, is
shortcomings: low yields [1], a large excess (6-fold) more difficult because of lower nucleophilicity of
of tocopherol was needed [2] or long protection- phenolic hydroxy groups in comparison with that
deprotection procedure was used [3]. We have re- of alcohols. Glycosylation of α-tocopherol en-
cently reported that heating of a neat perace- counters some additional problems due to the
tylated sugar with α-tocopherol in the presence of steric hindrance around the phenolic group from
ZnCl2, FeCl3 or SnCl4 at 140 ∞C under diminished two flanking 5,7-dimethyl groups as well as due to
some specific stereoelectronic effects occurring in
the 6-hydroxychromanyl system.
In continuation of our project we decided to
study the influence of an acidic catalyst on the
chemical yield and stereochemical outcome of the
glycosylation of α-tocopherol.
Results and Discussion
In preliminary experiments, α-tocopherol (1) or
its model compound 2, and 1.5 equiv. of a perace-
tylated sugar (3, 4, 13, 18 or 19) were heated with
catalytic amounts of ZnCl2 for 4 h at 130Ð140 ∞C
with continuous removal of acetic acid (vacuum
30Ð40 mm Hg). After aqueous work-up, the gly-
cosidic fractions were purified by column chroma-
1
Scheme 1.
tography and analysed by H and 13C NMR.
0932Ð0776/2002/0500Ð0571 $06.00 ” 2002 Verlag der Zeitschrift für Naturforschung, Tübingen · www.znaturforsch.com
D
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

572
S. WitkowskiÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
decoupling [10] or by comparison of the proton
5Љ-H signal intensity [9]). In all cases the 1,2-trans-
glycosides (ꢀ-glucoside, ꢀ-galactoside or α-manno-
side) were the prevailing products. According to
the commonly accepted mechanism, the trans con-
figuration results from the involvement of the
neighbouring 2-Ac group with formation of a
cyclic oxycarbonium intermediate [11, 12]. The
1,2-cis-glycosides are less abundant.
Scheme 3.
There are controversial opinions on the mecha-
nism of formation of α-glucosides in the reaction
of peracetylated glucose with phenols. Some au-
thors considered that a prolonged heating of per-
acetylated ꢀ-glucose with phenol initially leads to
an anomerization [13]. Nevertheless, it is known
that aryl glycosides are stable under acidic condi-
tions of anomerization (opposite to the alkyl gly-
cosides) [14, 15]. The α-isomer can also be created
by trans-glucosylation with an excess of a phenol
[16] or by removal of the ꢀ-isomer from the reac-
tion mixture by a selective cleavage [17, 18].
Scheme 2.
The (+)-α-tocopheryl 2,3,4,6-tetra-O-acetyl-ꢀ-
The yields and composition of the reaction pro- D-glucopyranoside (5) was subjected to the heat-
ducts (α- and ꢀ-glycosides) are summarised in ing with freshly molten ZnCl2 at 120Ð130 ∞C. The
Table 1.
progress of the reaction was monitored by 1H
The anomeric pairs of glycosides were unsepara- NMR spectroscopy (Table 1). A partial isomeriza-
ble by column chromatography. The composition tion of ꢀ-glucoside (5) to the α-isomer was ob-
of the mixtures was determined by integration of served. The maximum of conversion was achieved
the anomeric carbon signals (recorded with gated after ca. 4 h (see Fig. 1). The α/ꢀ ratio was approxi-
Table 1. Chemical yields
Catalyst
and α/ꢀ ratio of the gly-
Sugar
Aglycon
ZnCl2
BF3 ·Et2O
FeCl3
cosylation products of 1
and 2.
yield [%]b ratioc (α/ꢀ) yield [%]b yield [%]a,b yield [%]b
(α + ꢀ)
a In the presence of
molecular sieves; b Iso-
lated yields by dry-flash
chromatography; c deter-
mined by 13C NMR for
C-1Љ and 1H NMR for
HЈЈ [9].
1
2
1
2
1
2
4836:64
44
47 (
28:72
38:62
21:79
13:87
82:18
ꢀ)
49 (ꢀ)
45 (ꢀ)
39 (ꢀ)
47 (α)
47 (α)
65 (ꢀ)
66 (ꢀ)
66 (ꢀ)
69 (ꢀ)
64 (α)
67 (α)
45 (ꢀ)
47 (ꢀ)
35 (ꢀ)
41 (ꢀ)
51 (α)
53 (α)
3
35
13
45
45
18 + 19 (1:1)
40
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

S. WitkowskiÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
573
mately the same as that obtained during glycosyla- with inversion of configuration at the anomeric
tion by melting of α-tocopherol with peracetylated centre [19].
sugar 3 (Table 1). Similarly, (+)-α-tocopheryl
Glucosylation of (+)-α-tocopherol by perace-
2,3,4,6-tetra-O-acetyl-ꢀ-D-galactoside (15) at tylated ꢀ-D-glucose (3) in the presence of other
130 ∞C isomerised to the mixture of both anomers acidic catalysts was also carried out (Table 2).
with the same α/ꢀ ratio as that obtained by melting Melting and heating of the reagents (see Experi-
of α-tocopherol with 13 (α/ꢀ 38:62). The pro- mental, procedure B) yielded mixtures of pro-
longed time of heating or increasing of temper- ducts, which after aqueous work-up were analyzed
1
ature above 140 ∞C led only to decomposition of by H and 13C NMR spectroscopy. The chemical
the mixture with liberation of free α-tocopherol. yields ranged from 10 to 50% and depended on
Under the same conditions, the attempts of iso- the catalyst used. The highest contents of the α-
merization of peracetylated ꢀ-glucose (3) and phe- anomer were obtained (43%) when SnCl4 was
nyl 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucoside in the used; however, a higher chemical yield of the glu-
presence of ZnCl2 under atmospheric pressure led cosides was obtained in case of ZnCl2 or FeCl3..
to carbonisation with liberation of acetic acid. The latter seems to be the most effective catalyst.
Thus, one can conclude that isomerization of ꢀ- It gave not only the best chemical yield (50%), but
to α-glycosides is possible only when a substrate also a relatively high content of the α-glucoside
undergoes melting with ZnCl2 below the temper- (30%). When peracetylated α-glucose was used in-
ature of carbonisation.
stead of the ꢀ-isomer, the reaction gave a poor
The similar anomerization was not possible for yield of α- and ꢀ-glucosides (15%) with the same
deacetylated glycosides, which usually have higher ratio as that for peracetylated ꢀ-D-glucose. The
melting points. For instance, the (+)-α-tocopheryl elimination of α-acetoxy group followed by crea-
ꢀ-D-glucoside (7) (m.p. 159Ð160 ∞C) did not un- tion of cyclic oxonium intermediate is impossible
dergo any reaction during heating with ZnCl2 at due to steric requirements. Therefore, the isomer-
130Ð160 ∞C. Above 165 ∞C only decomposition ization of α- to ꢀ-peracetyl glucose must have oc-
products were observed. Some similar observa- curred, and this step influences the overall yield.
tions were reported for the glycosylation of cou- In the course of the reaction, the initially formed
marins [17].
ꢀ-glucoside probably undergoes an anomerization
The formation of less abundant 1,2-cis-manno- to the α-isomer. The prolonged time of the reac-
sides seems to be unclear. The attempts of isomer- tion (up to 8h) led to an increase of yield (up to
ization of the model compounds methyl 2,3,4,6- 40%) with retention of the α/ꢀ ratio (Table 2).
tetra-O-acetyl-α-D-glucopyranoside, phenyl 2,3,4,6-
Glycosylation of α-tocopherol according to Lah-
tetra-O-acetyl-α-D-mannopyranoside, and 2,2,5,7,8- mann and Thiem [2] gave 1,2-trans-glycosides with
pentamethyl-6-chromanyl 2,3,4,6-tetra-O-acetyl-α- high yields (up to 67%) on the condition, that a
D-mannoside (22) to the respective 1,2-trans de- six-fold excess of tocopherol was applied. When
rivatives by prolonged heating with anhydrous equimolar amounts of the substrates are used, the
ZnCl2 failed. The minor 1,2-cis-mannosides are
probably formed according to the SN2 mechanism
Table 2. Glucosylation of 1 in the presence of various
acidic catalysts.
Sugar
Catalysta
Yield [%]b
(α + ꢀ)
Ratio [%]c
(α/ꢀ)
3
3
3
3
4
ZnCl2
FeCl3
SnCl4
PPA
4836/64
50
30/70
43/57
100 ꢀ
37/63
35/65
35
10
15 (4 h)
40 (8h)
ZnCl2
a 50 mg of a catalyst per 1 equiv. of 1 and 1.2 equiv. of
Fig 1. The progress of isomerization of 5 in the presence sugar; b yield of isolated fraction of glucosides; c by 13C
1
of ZnCl2 at 120Ð130 ∞C.
NMR [10] or H NMR [9].
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

574
S. WitkowskiÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
Melting points were measured in a Boetius appa-
ratus and are uncorrected. The course of the reac-
tions and the purity of products were checked by
TLC (DC Fertigplatten 60 F 254 Merck). Prepara-
tive thin layer chromatography (PTLC) was per-
formed on DC Fertigplatten 60 F 254 Merck
(thickness 0.5 mm). Column chromatography was
performed on Merck silica gel (70Ð230 mesh).
yield drops to ca. 40%. Therefore, the synthesis
using the relatively expensive natural (+)-α-toco-
pherol by this method seems not economically
profitable. We improved the synthesis by addition
˚
of activated molecular sieves (4 A) to the reaction
mixture. The mannosylation and galactosylation of
tocopherol was also carried out more efficiently
(Table 1).
Chatterjee and Nuhn [20] described a stereosel-
ective α-glycosylation of alcohols in the presence
of anhydrous FeCl3. The glycosylation of α-toco-
pherol in the presence of anhydrous FeCl3 accord-
ing to the procedure A (see Experimental Section)
gave the proper glycosides with good yields (45Ð
50%) (Table 1). The final success strictly depended
on the anhydrous conditions of the reaction. In the
solution containing a trace of water, α-tocopherol
is partially oxidised by the system Fe+3/Fe+2 to
α-tocopherylquinone and the yield of glycosyla-
General method for glycosylation of phenols
with ꢀ-peracetylated sugars in the presence of
acidic catalyst (for details see Table 1)
To the stirred mixture of a phenol (1 mmol) and
sugar (1.2 mmol) in 5 ml CH2Cl2 was added 3
equiv. of BF3 ·Et2O or 0.25 equiv. of anhydrous
FeCl3. The stirred mixture was kept in the dark
under nitrogen atmosphere for 12 h. The reaction
mixture was diluted with ethyl acetate (50 ml) and
washed with water (3 ¥ 30 ml). The organic layer
was dried over MgSO4 and evaporated to dryness.
tion is lowered even in the presence of molecular The crude reaction mixture was purified by col-
umn chromatography (hexaneÐethyl acetate 15:1,
v/v). The yields of corresponding glycosides are
summarized in Table 1.
sieves.
The glycosylation of α-tocopherol in the pres-
ence of anhydrous FeCl3 yielded selectively only
1,2-trans-glycosides (Table 1). The α-stereoselec-
tivity described for alkyl glycosides [20] was not
observed when aryl aglycones were used.
(+)-α-Tocopheryl 2,3,4,6-tetra-O-acetyl-ꢀ-D-glu-
copyranoside (5): M.p. 81Ð2 ∞C, [α]2D0 = Ð10.4∞
(CHCl3, c = 1). Ð IR (CHCl3): ν = 2980, 2930, 1745
(C=O), 1455, 1370, 1060, 1030 cmÐ1. The 1H and 13
C
NMR spectra were identical with those described
earlier [2].
Experimental Section
The numbering of the carbon atoms and the no-
(+)-α-Tocopheryl 2,3,4,6-tetra-O-acetyl-ꢀ-D-galac-
menclature proposed by the IUPAC in tocopherol topyranoside (14): Oil, [α]2D0 = +5.4∞ (CH2Cl2,
(1) and its model compound 2 have been used [21, c = 1). Ð IR (CHCl3): ν = 2980, 1745 (C=O), 1455,
22] (Scheme 1). In the sugar parts of the toco- 1370, 1060, 1030, 900 cmÐ1. Ð 1H NMR (200.13
3
pheryl glycosides the numbering with double MHz, CDCl3): δ = 1.85 (t, J = 6.5 Hz, 2H, 3-H),
primes (1Љ, 2Љ, 3Љ etc.) was used, and for the respec- 2.00Ð2.20 (7¥s, 21H, 5a-, 7a-, 8b-H and all OAc),
3
tive chromanyl glycosides the numbering with 2.55 (t, J = 6.5 Hz, 2H, 4-H), 3.77Ð3.74 (m, 1H,
2
3
primes (1Ј, 2Ј, 3Ј etc.) was used. Natural (+)-α- 5Љ-H), 4.07 and 4.11 (ddd, J = 8.7, J5Љ,6Љ = 6.3 and
3
tocopherol (1) was purchased from Aldrich. 3J5Љ,6Љ = 6.8Hz, 2H, 6 Љ-H2), 4.68(d, J1Љ,2Љ = 7.9 Hz,
2,2,5,7,8-Pentamethyl-6-chromanol (2) was syn- 1H, 1Љ-H), 5.05Ð5.12 (m, 1H, 2Љ-H), 5.54Ð5.38(m,
thesised according to Smith et al. [23]. Perace- 2H, 3Љ and 4Љ-H). Ð 13C{1H} NMR (50.32 MHz,
tylated sugars (3, 4, 13, and a mixture of 18 and CDCl3): δ = 11.8(5a), 12.8(8b), 13.4 (7a), 19.7, 19.6
19) were obtained by acetylation of commercially (4Јa, 8Јa), 20.5 (4), 20.6, 20.7, 20.6 (all OAc), 21.0
available glucose, galactose and mannose by acetic (2Ј), 22.5, 22.6 (12Јa and 13Ј), 23.8(2a), 24.3 (6 Ј),
1
1
anhydride in pyridine. H, 13C, H decoupling and 24.9 (10Ј), 27.8(12 Ј), 31.1 (3), 32.6, 32.7 (4Ј and 8Ј),
1HÐ13C HETCOR NMR spectra were obtained 37.2, 37.4 (3Ј, 5Ј, 7Ј and 9Ј), 39.3, 39.5 (11Ј and 1Ј),
using a Bruker AC 200F spectrometer (200.13 61.7 (6Љ), 68.0 (4Љ), 69.4 (5Љ), 70.4 (2Љ), 71.0 (3Љ), 74.8
MHz). Chemical shifts (δ) are reported in ppm (2), 102.6 (1Љ), 117.7 (4a), 122.8(5), 126.9 (7), 128.2
downfield from TMS. Spectra were taken for (8), 145.3 (6), 148.5 (8a). Ð MS (LSIMS, NBA, 8
CDCl3 or CD3OD solutions. IR spectra were re- kV): m/z (%) = 761 (10) [M+H]+, with NaOAc 783
corded on Nicolette Magna 550 FTIR spectrome- (16) [M+Na]+.
ter. Mass spectra were performed on an MS
(+)-α-Tocopheryl 2,3,4,6-tetra-O-acetyl-α-D-man-
AMD-604 spectrometer. Specific rotation was nopyranoside (20): Oil, [α]2D0 = +27.67∞ (CH2Cl2,
measured on a Perkin-Elmer 141 polarimeter. c = 1). Ð IR (CHCl3): ν = 2980, 1747 (C=O), 1461,
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

S. WitkowskiÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
575
1
1372, 1246, 1133, 1083, 1052, 1012, 981 cmÐ1. Ð H
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl
NMR (200.13 MHz, CDCl3): δ = 1.83 (t, 3J = 6.7 Hz, 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
(22):
2H, 3-H), 2.05Ð2.22 (7¥s, 21H, 5a-, 7a-, 8b-H and all M.p. 115- 17 ∞C, [α]2D0 = Ð21.2∞ (CHCl3, c = 0.5). Ð
3
OAc), 2.57 (t, J = 6.7 Hz, 2H, 4-H), 4.39 and 4.13 IR (CHCl3): ν = 3465, 2968, 1743 (C=O), 1455, 1369,
(ddd, 2J6Љ,6Љ = 12.1, 3J5Љ,6Љ = 2.4 and 3J5Љ,6Љ = 5.4 Hz, 2H, 1252, 1227, 1130, 1086, 1058 cmÐ1. Ð 1H NMR
6Љ-H2), 4.48Ð4.55 (m, 1H, 5Љ-H), 4.91 (~s, 1H, 1Љ-H), (200.13 MHz, CDCl3): δ = 1.29 (s, 6H, 2a and
5.44Ð5.39 (m, 1H, 3Љ-H), 5.68Ð5.60 (m, 2H, 3Љ and 2Љ- 2b-H), 1.78(t, 3J = 7.8Hz, 2H, 4-H), 2.04 Ð2.21 (7¥s,
H). Ð 13C{1H} NMR (50.32 MHz, CDCl3): δ = 11.9 21H, 5a-, 7a-, 8b-H and all OAc), 2.59 (t, J = 7.8
3
2
(5a), 12.8(8b), 13.7 (7a), 19.7, 19.6 (4 Јa, 8Јa), 20.5 (4), Hz, 2H, 4-H), 4.38and 4.12 (ddd, J6Ј,6Ј = 12.1,
20.6, 20.7, 20.8(all OAc), 21.0 (2 Ј), 22.6, 22.7 (12Јa 3J5Ј,6Ј = 2.4 and J5Ј,6Ј = 4.3 Hz, 2H, 6Ј-H2), 4.47Ð
3
and 13Ј), 23.8(2a), 24.4 (6 Ј), 24.7 (10Ј), 27.9 (12Ј), 31.2 4.55 (m, 1H, 5Ј-H), 4.91 (s, 1H, 1Ј-H), 5.34Ð5.44 (m,
(3), 32.6, 32.7 (4Ј and 8Ј), 37.2- 37.5 (3Ј, 5Ј, 7Ј and 9Ј), 1H, 3Ј-H), 5.60Ð5.68(m, 2H, 2 Ј- and 3Ј-H). Ð
39.3 (11Ј), 39.8(1 Ј), 62.7 (6Љ), 66.1 (4Љ), 69.0 (2Љ), 69.9 13C{1H} NMR (50.32 MHz, CDCl3): δ = 11.9 (5a),
(3Љ), 70.0 (5Љ), 74.8(2), 101.5 (1 Љ), 117.6 (4a), 123.2 (5), 12.8(8b), 13.7 (7a), 20.7 Ð20.8(all OAc), 21.1 (4),
125.5 (7), 127.4 (8), 148.0 (6), 148.4 (8a). Ð MS 26.7 (2a and 2b), 32.8(3), 62.7 (6 Ј), 66.1 (4Ј), 69.0
(LSIMS, NBA, 8kV): m/z (%) = 761 (8) [M+H]+, (2Ј), 69.9 (3Ј), 70.0 (5Ј), 72.8(2), 101.5 (1 Ј), 117.4
with NaOAc 783 (12) [M+Na]+.
(4a), 123.1 (5), 125.5 (7), 127.5 (8), 148.1 (6), 148.5
(8a). Ð MS (LSIMS, NBA, 8kV): m/z (%) = 551
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl
2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranoside (9): M.p. (11) [M+H]+, with NaOAc 573 (17) [M+Na]+.
141Ð3 ∞C, [α]2D0 = Ð7.06∞ (CHCl3, c = 1). Ð IR
(CHCl3): ν = 2943, 1754 (C=O), 1457, 1369, 1231,
1168, 1064, 1040 cmÐ1. Ð 1H NMR (200.13 MHz,
General method for glycosylation of
(+)-α-tocopherol and ꢀ-peracetylated sugars in the
presence of a Lewis acid (for details see Table 2)
3
CDCl3): δ = 1.3 (s, 6H, 2a- and 2b-H), 1.79 (t, J =
6.9 Hz, 2H, 4-H), 2.03Ð2.33 (7¥s, 21H, 5a-, 7a-,
(+)-α-Tocopherol (430 mg, 1 mmol), sugar
(1.5 mmol) and 0.25 equiv. of a Lewis acid (see
Table 2) was heated on an oil bath at 130 ∞C under
diminished pressure (40 Torr) for 4 h. The reaction
mixture was diluted with ethyl acetate (50 ml) and
washed with water (3 ¥ 30 ml). The organic layer
was dried over MgSO4 and evaporated to dryness.
The crude reaction mixture was purified by col-
umn chromatography (hexaneÐethyl acetate 15:1,
v/v). The unseparable by column mixture of α- and
ꢀ-glycosides was obtained. The composition of
anomers in the mixture was identified by compari-
son of the intensity of 1Љ-H or 5Љ-H NMR signals
or C-1Љ signals in the 13C NMR spectrum of the
sugar residue.
3
8b-H and all OAc), 2.58 (t, J = 6.9 Hz, 2H, 4-H),
3.51Ð3.56 (m, 1H, 5Ј-H), 4.06 and 4.12 (ddd, 2J6Ј,6Ј
=
3
3
12.2, J5Ј,6Ј = 2.7 and J5Ј,6ЈR = 4.5 Hz, 2H, 6Ј-H2),
3
4.72 (d, J1Ј,2Ј = 7.6 Hz, 1H, 1Ј-H), 5.27Ð5.35 (m,
1H, 2Ј , 3Ј and 4Ј-H). Ð 13C{1H} NMR (50.32 MHz,
CDCl3): δ = 11.8(5a), 12.6 (8b), 13.3 (7a), 20.9 (4),
20.5 Ð20.7 (all OAc), 26.6, 26.8(2a and 2b), 32.7
(3), 61.7 (6Ј), 68.5 (4Ј), 71.4 (5Ј), 71.8(2 Ј), 72.8(2),
73.0 (3Ј), 101.9 (1Ј), 117.2 (4a), 122.8(5), 126.8(7),
128.2 (8), 145.2 (6), 148.6 (8a). Ð MS (LSIMS, NBA,
8kV): m/z (%) = 551 (13) [M+H]+, with NaOAc
573 (14) [M+Na]+.
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl
2,3,4,6-tetra-O-acetyl-ꢀ-D-galactopyranoside
(16):
M.p. 71Ð3 ∞C, [α]D20 = Ð2.4∞ (CHCl3, c = 0.5). Ð IR
(CHCl3): ν = 2931, 2863, 1748 (C=O), 1459, 1370,
General method for deacetylation of
phenyl glycosides.
1
1067, 1125, 1076 cmÐ1. Ð H NMR (200.13 MHz,
CDCl3): δ = 1.05 (2¥s, 6H, 2a- and 2b-H), 1.79 (t,
3J = 6.8, 2H, H-4), 1.95Ð2.21 (7¥s, 21H, 5a-, 7a-,
The glycosides were deacetylated according to
Herzig et al. (MeOH, KCN, RT) [24]. After evapo-
ration to dryness, the solid residue was extracted
3
8b-H and all OAc), 2.58 (t, J = 6.8Hz, 2H, 4-H),
3.74Ð3.77 (m, 1H, 5Ј-H), 4.06 and 4.09 (ddd, 2J6Ј,6Ј
=
3
3
8.8, J5Ј,6Ј = 6.8and J5Ј,6Ј = 7.3 Hz, 2H, 6Ј-H2), 4.68 with ethyl acetate (4 ¥ 30 ml). The combined ex-
3
(d, J = 8.0 Hz, 1H, 1Ј-H), 5.04Ð5.11 (m, 1H, 2Ј-H), tracts were concentrated and purified by “dry-
5.37Ð5.56 (m, 2H, 3Ј- and 4Ј-H). Ð 13C{1H} NMR flash” chromatography. The yield of deprotection
(50.32 MHz, CDCl3): δ = 11.8(5a), 12.7 (8b), 13.4
(7a), 20.4Ð20.8(all OAc), 21.0 (4), 26.8and 26.6 (2a
ranged from 95 to 98%. After preliminary purifi-
cation, the chromatographic separation was pos-
and 2b), 32.7 (3), 60.7 (6Ј), 66.9 (4Ј), 69.4 (2Ј), 70.4 sible only for the α- and ꢀ-tocopheryl or 6-hy-
(3Ј), 71.0 (5Ј), 72.8(2), 102.5 (1 Ј), 117.2 (4a), 122.8 droxychromanyl glucosides. For mixtures α and ꢀ
(5), 126.8 (7), 128.3 (8), 145.3 (6), 148.6 (8a). Ð MS galactosides or mannosides the separation failed.
(LSIMS, NBA, 8kV): m/z (%) = 551 (10) [M+H]+,
(+)-α-Tocopheryl ꢀ-D-glucopyranoside (7): M.p.
with NaOAc 573 (16) [M+Na]+.
159Ð60 ∞C, [α]2D0 = +7.26∞ (MeOH, c = 1). Ð IR
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

576
S. WitkowskiÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl ꢀ-D-
(KBr): ν = 3390, 2927, 2868, 1461, 1378, 1254, 1072,
1035, 1012 cmÐ1. The 1H and 13C NMR spectra were glucopyranoside (11): M.p. 145Ð6 ∞C, [α]D20 = Ð5.8∞
identical with those described earlier [2].
(MeOH, c = 1). Ð IR (KBr): ν = 3050Ð3600, 2972,
(+)-α-Tocopheryl
α-D-glucopyranoside
(8): 2925, 1643, 1412, 1381, 1272, 1225, 1168, 1077, 1039,
[α]2D0 = +17.4∞ (MeOH, c = 1). Ð IR (KBr): ν = 3386, 926 cmÐ1. Ð H NMR (200.13 MHz, MeOH): δ =
1
3
2952, 2868, 1462, 1411, 1378, 1248, 1110, 1076, 1051, 1.26 (s, 6H, 2a- and 2b-H), 1.77 (t, J= 6.8Hz, 2H,
1017 cmÐ1. Ð H NMR (200.13 MHz, MeOH): δ = 3-H), 2.02, 2.18, 2.21 (3¥s, 9H, 5a-, 7a- and 8b-H),
1
3
1.71 (m, 2H, 3-H), 1.97, 2.17, 2.18(3 ¥s, 9H, 5a-, 2.59 (t, J = 6.8Hz, 2H, 4-H), 3.08 Ð3.15 (m, 1H,
7a- and 8b-H), 2.50 (m, 2H, 4-H), 3.20Ð3.67 (m, 5H, 5Ј-H), 3.29Ð3.55 (m, 3H, 2Ј-, 3Ј-, 4Ј-H), 3.78Ð3.58
2Љ-, 3Љ-, 4Љ-, 6Љ-H), 3.80Ð3.88 (m, 1H, 5Љ-H), 4.93 (d, (ddd, J = 11.7, 3J5Ј,6Ј = 2.6 and 3J5Ј,6Ј = 5.16 Hz, 2H,
2
3J = 4.2 Hz, 1H, 1Љ-H). Ð 13C{1H} NMR (50.32 MHz, 6Ј-H2), 4.55 (d, J = 7.40 Hz, 1H, 1Ј-H). Ð 13C{1H}
3
MeOH): δ = 11.7 (5a), 13.0 (8b), 14.0 (7a), 19.5, 19.6 NMR (50.32 MHz, MeOH): δ = 11.6 (5a), 12.8(8b),
(4Јa, 8Јa), 20.2 (4), 20.3 (2Ј), 22.4, 22.5 (12Јa and 13.7 (7a), 22.6 (4), 26.6 (2a and 2b), 33.6 (3), 62.5
13Ј), 23.4 (2a), 24.7 (6Ј), 24.1 (10Ј), 27.4 (12Ј), 31.0 (6Ј), 71.6 (4Ј), 73.4 (2), 75.5 (2Ј), 77.4 (5Ј), 77.6 (3Ј),
(3), 31.9, 32.1 (4Ј and 8Ј), 36.6, 36.7, 36,8(3 Ј, 5Ј, 7Ј 105.6 (1Ј), 117.9 (4a), 123.0 (5), 127.6 (7), 129.3 (8),
and 9Ј), 38.8, 38.9 (11Ј and 1Ј), 60.8(6 Љ), 69.9 (4Љ), 146.9 (6), 149.0 (8a). Ð MS (LSIMS, NBA, 8kV):
72.3 (5Љ), 72.6 (2Љ), 74.6 (3Љ), 74.2 (2), 102.5 (1Љ), m/z (%) = 383 (8) [M+H]+, with NaOAc 405 (13)
117.1 (4a), 121.5 (5), 125.6 (7), 127.4 (8), 146.9 (6), [M+Na]+.
147.7 (8a). Ð MS (LSIMS, NBA, 8kV): m/z (%) =
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl α-D-
761 (12) [M+H]+, with NaOAc 783 (18) [M+Na]+.
glucopyranoside (12): M.p. = 159Ð60 ∞C, [α]D20
=
(+)-α-Tocopheryl ꢀ-D-galactopyranoside (15): +7.26∞ (MeOH, c = 0.5). Ð IR (KBr): ν = 3424, 2972,
M.p. 174Ð77 ∞C, IR (KBr): ν = 3409, 2953, 2869, 2930, 1459, 1405, 1367, 1261, 1223, 1170, 1080, 1013,
1464, 1377, 1252, 1088, 1044 cmÐ1. Ð 1H NMR 926 cmÐ1. Ð H NMR (200.13 MHz, MeOH): δ =
1
3
3
(200.13 MHz, MeOH): δ = 1.76 (t, J = 6.4 Hz, 2H, 1.27 (s, 6H, 2a- and 2b-H), 1,79 (t, J = 6.8Hz, 2H,
3-H), 1.97, 2.12, 2.14 (3¥s, 9H, 5a-, 7a-, and 8b-H), 3-H), 2.09, 2.23, 2.26 (3¥s, 9H, 5a-, 7a- and 8b-H),
3
2.50 (t, J = 6.5 Hz, 2H, 4-H), 3.17Ð3.60 (m, 6H, 2.60 (t, 3J = 6.8Hz, 2H, 4-H), 3.40 Ð3.92 (m, 5H, 2Ј-,
3
2Љ-, 3Љ-, 4Љ-, 5Љ- and 6Љ-H), 4.30 (d, J = 7.6 Hz, 1H, 3Ј-, 4Ј-, 6Ј-H), 4.03Ð4.11 (m, 1H, 5Ј-H), 5.18(d, 3J =
1Љ-H). Ð 13C{1H} NMR (50.32 MHz, MeOH): δ = 4.4 Hz, 1H, 1Ј-H). Ð 13C{1H} NMR (50.32 MHz,
11.6 (5a), 12.6 (8b), 13.6 (7a), 19.5, 19.6 (4Јa, 8Јa), MeOH): δ = 11.6 (5a), 13.3 (8b), 14.3 (7a), 21.7 (4),
20.3 (4), 20.4 (2Ј), 20.5, 20.4 (12Јa and 13Ј), 23.4 (2a), 26.6 (2a and 2b), 33.7 (3), 62.2 (6Ј), 71.1 (4Ј), 73.4
23.7 (6Ј), 24.1 (10Ј), 27.3 (12Ј), 31.9 (3), 31.9, 32.0 (2), 73.6 (2Ј), 74.1 (5Ј), 75.1 (3Ј), 103.2 (1Ј), 117.9
(4Ј and 8Ј), 36.5, 36.6, 36.7 (3Ј, 5Ј, 7Ј and 9Ј), 40.3, (4a), 123.4 (5), 126.5 (7), 128.3 (8), 148.5 (6), 148.6
40.7 (11Ј and 1Ј), 60.0 (6Љ), 67.7 (4Љ), 71.1 (2Љ), 74.3 (8a). Ð MS (LSIMS, NBA, 8kV): m/z (%) = 551
(3Љ), 74.9 (5Љ), 73.2 (2), 105.4 (1Љ), 116.9 (4a), 121.2 (9) [M+H]+, with NaOAc 573 (16) [M+Na]+.
(5), 126.6 (7), 128.3 (8), 145.9 (6), 147.3 (8a). Ð MS
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl ꢀ-D-
(LSIMS, NBA, 8kV): m/z (%) = 593 (11) [M+H]+, galactopyranoside (17): M.p. 125Ð6 ∞C, [α]2D0
=
with NaOAc 615 (14) [M+Na]+.
Ð5.13∞ (MeOH, c = 0.5). Ð IR (KBr): ν = 3449,
(+)-α-Tocopheryl α-D-mannopyranoside (21): 2971, 2928, 1462, 1381, 1263, 1082, 926 cmÐ1 Ð H
1
M.p. 117Ð19 ∞C, [α]2D0 = +50.3∞ (MeOH, c = 1). Ð NMR (200.13 MHz, MeOH): δ = 1.26 (s, 6H, 2a and
3
IR (KBr): ν = 3492, 2972, 2919, 1454, 1421, 1386, 2b-H), 1.76 (t, J= 6.7 Hz, 2H, 3-H), 2.02, 2.18, 2.21
1
3
1364, 1263, 1221, 1160, 1010, 958cm Ð1. Ð H NMR (3¥s, 9H, 5a-, 7a- and 8b-H), 2.58 (t, J = 6.7 Hz,
3
(200.13 MHz, MeOH): δ = 1.83 (t, J = 5.0 Hz, 2H, 2H, 4-H), 3.02Ð3.30 (m, 1H, 5Ј-H), 3.51Ð3.87 (m,
3
3-H), 2.04, 2.14, 2.17 (3¥s, 9H, 5a-, 7a- and 8b-H), 5H, 2Ј-, 3Ј-, 4Ј-, 6Ј-H), 4.46 (d, J = 7.6 Hz, 1H, 1Ј-
2.55 (t, 3J = 5.0 Hz, 2H, 4-H), 3.99Ð3.76 (m, 5H, 2Љ-, H). Ð 13C{1H} NMR (50.32 MHz, MeOH): δ = 11.6
3Љ-, 4Љ- and 6Љ-H), 4.20Ð4.23 (m, 1H, 5Љ-H), 4.83 (d, (5a), 12.8(8b), 13.8(7a), 21.5 (4), 26.5, 26.6 (2a and
3J = 6.5 Hz, 1H, 1Љ-H). Ð 13C{1H} NMR (50.32 MHz, 2b), 33.6 (3), 61.7 (6Ј), 69.7 (4Ј), 73.3 (2), 72.8(2 Ј),
MeOH): δ = 11.7 (5a), 12.8(8b), 13.7 (7a), 19.5, 19.6
74.4 (3Ј), 75.8(5 Ј), 106.2 (1Ј), 117.9 (4a), 122.9 (5),
(4Јa, 8Јa), 20.1 (4), 20.4 (2Ј), 20.5, 20.6 (12Јa and 127.6 (7), 129.4 (8), 147.0 (6), 148.9 (8a). Ð MS
13Ј), 22.5 (2a), 23.6 (6Ј), 24.1 (10Ј), 27.3 (12Ј), 31.9 (LSIMS, NBA, 8kV): m/z (%) = 383 (11) [M+H]+,
(3), 32.0 (4Ј and 8Ј), 36.6, 36.7 (3Ј, 5Ј, 7Ј and 9Ј), with NaOAc 405 (15) [M+Na]+.
39.3 (11Ј), 39.8(1 Ј), 61.3 (6Љ), 66.6 (4Љ), 70.5 (2Љ),
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl α-D-
70.9 (3Љ), 75.9 (5Љ), 74.2 (2), 105.0 (1Љ), 117.3 (4a), mannopyranoside (23): M.p. 167Ð70 ∞C, [α]D20
=
121.6 (5), 125.5 (7), 127.2 (8), 147.2 (6), 147.9 (8a). Ð +66.26∞ (MeOH, c = 0.5). Ð IR (KBr): ν = 3396,
MS (LSIMS, NBA, 8kV): m/z (%) = 593 (15) 2973, 2932, 1459, 1411, 1382, 1367, 1262, 1225, 1168,
[M+H]+, with NaOAc 615 (18) [M+Na]+.
1125, 1064, 1004, 978cm Ð1. Ð NMR (200.13 MHz,
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

S. WitkowskiÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
577
3
MeOH): δ = 1.23 (s, 6H, 2a- and 2b-H), 1.73 (t, J = 6Љ-H2), 4.57Ð4.49 (m, 1H, 5Љ-H), 5.30Ð5.06 (m, 3H,
3
7.0 Hz, 2H, 3-H), 1.99, 2.02, 2.10 (3¥s, 9H, 5a-, 7a- 1Љ-, 2Љ- and 4Љ-H), 5.86 and 5.80 (dd, J = 9.4 Hz,
3
and 8b-H), 2.49 (t, J = 7.0 Hz, 2H, 4-H), 3.40Ð3.72 1H, 3Љ-H). Ð 13C{1H} NMR (50.32 MHz, CDCl3).
(m, 5H, 2Ј-, 3Ј-, 4Ј-, 6Ј-H), 4.01 (m, 1H, 5Ј-H), 4.83 δ = 13.0 (5a), 13.3 (8b), 13.9 (7a), 19.7, 19.6 (4Јa
3
(d, J = 1.6 Hz, 1H, 1Ј-H). Ð 13C{1H} NMR (50.32 and 8Јa), 20.6 (4), 20.8, 20.5 (OCOCH3), 21.0 (2Ј),
MHz, MeOH): δ = 11.8(5a), 12.8(8b), 13.7 (7a),
22.7, 22.6 (12Јa and 13Ј), 23.6 (2a), 24.8(10 Ј), 24.4
20.5 (4), 26.4, 26.5 (2a and 2b), 32.3 (3), 61.3 (6Ј), (6Ј), 27.9 (12Ј), 31.3 (3), 32.8and 32.7 (4 Ј and 8Ј),
66.6 (4Ј), 72.5 (2), 70.5 (2Ј), 70.9 (3Ј), 72.5 (2), 75.9 37.4, 37.2 (3Ј, 5Ј, 7Ј and 9Ј), 39.3 (11Ј), 40.2 (1Ј),
(5Ј), 105.9 (1Ј), 117.1 (4a), 121.6 (5), 125.6 (7), 127.2 62.0 (6Љ), 69.0 (4Љ), 70.0 (5Љ), 71.0 (2Љ), 74.8(3 Љ),
(8), 147.4 (6), 147.9 (8a). Ð MS (LSIMS, NBA, 74.9 (2), 98.7 (1Љ), 117.7 (4a), 123.3 (5), 124.8(7),
8kV): m/z (%) = 383 (12) [M+H]+, with NaOAc 126.8 (8), 147.6 (6), 148.0 (8a), 169.5, 169.6, 169.9,
405 (17) [M+Na]+.
170.2 (OCOCH3). Ð MS (LSIMS, NBA, 8kV):
m/z (%) = 761 (12) [M+H]+, with NaOAc 783
(15) [M+Na]+.
2,2,5,7,8-Pentamethyl-6-hydroxychromanyl
Acetylation of α-tocopheryl α-D-glucoside (8)
and 2,2,5,7,8-pentamethyl-6-hydroxychromanyl
α-D-glucoside (12)
2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside
(10):
Oil, [α]2D0 = +23.2∞ (CH2Cl2, c = 0.5). Ð IR (CHCl3):
ν = 2987Ð2935, 1746, 1454, 1378, 1060, 1030, 923
To the glucoside 8 or 12 (0.25 mmol) dissolved cmÐ1. Ð H NMR (200.13 MHz, CDCl3): δ = 1.27
in 5 ml of anhydrous pyridine, 1.5 mmol of acetic and 1.30 (2¥s, 6H, 2a- and 2b-CH3), 1,79 (t, 3J =
anhydride was added. The mixture was allowed to 6.9 Hz, 2H, 3-H), 2.30Ð2.00 (7¥s, 21H, 5a-, 7a-,
1
3
stand at room temp. for 12 h. After evaporation to 8b-H and all OAc), 2.58 (t, J = 6.9 Hz, 2H, 4-H),
2
3
dryness in vacuum, the resulted acetylated gluco- 4.32 and 4.15 (ddd, J6Ј,6Ј = 12.5, J5Ј3,6Ј = 2.3 and
sides were purified by PTLC. The yields for both 3J5Ј,6Ј = 4.5 Hz, 2H, 6Ј-H2), 4.53 (ddd, J = 10.3 Hz,
glycosides were 97%.
1H, 5Ј-H), 5.09Ð5.26 (m, 3H, 1Ј-, 2Ј- and 4Ј-H), 5.81
3
(+)-α-Tocopheryl 2,3,4,6-tetra-O-acetyl-α-D-glu- (dd, J = 9.4 Hz, 1H, 3Ј-H). Ð 13C{1H} NMR (50.32
copyranoside (6): Oil, [α]2D0 = +33.2∞ (CH2Cl2, c = MHz, CDCl3): δ = 20.6 (4), 20.8, 20.5 (OCOCH3),
0.5). Ð IR (CHCl3): ν = 2980Ð2930, 1745, 1455, 21.0 (2Ј), 23.6 (2a and 2b), 31.3 (3), 62.0 (6Ј), 69.0
1370, 1060, 1030, 900 cmÐ1. Ð H NMR (200.13 (4Ј), 70.0 (5Ј), 71.0 (2Ј), 74.8(3 Ј), 74.9 (2), 98.7 (1Ј),
1
MHz, CDCl3): δ = 1.78(t, 3J = 6.5 Hz, 2H, 3-H), 117.7 (4a), 123.3 (5), 124.8(7), 126.8(8), 147.6 (6),
2.30Ð2.00 (7¥s, 21H, 5a-, 7a-, 8b-H and all OAc), 148.0 (8a), 169.5, 169.6, 169.9, 170.2 (OCOCH3). Ð
3
2.55 (t, J = 6.5 Hz, 2H, 4-H), 4.33 and 4.15 (ddd, MS (LSIMS, NBA, 8kV): m/z (%) = 551 (19)
3
3
2J6Љ,6Љ = 12.3, J5Љ,6Љ = 2.2 and J5Љ,6Љ = 4.5 Hz, 2H, [M+H]+, with NaOAc 573 (22) [M+Na]+.
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM

578S. Witkowski
ÐP. Wałejko · Studies in the Acid Catalysed Glycosylation of α-Tocopherol
[1] a) Jpn. Kokai Tokkyo Koho JP 60 56,994. Chem. [11] T. K. Lindhorst, Essentials of Carbohydrate Chem-
Abstr. 104, 34290a (1986); b) T. Satoh, Y. Miyataka,
istry and Biochemistry, p. 81, Wiley-VCH, Wein-
heim (2000).
T. Masumoto, K. Asai, K. Hasegawa, H. Kakegawa,
Eur. Pat. Appl. EP 169 716, Chem. Abstr. 104, [12] G. J. Boons, B. Heskamp, in G. J. Goons (ed.): Car-
213266u (1986); c) Y, Katsuragi, N. Matsuda,
Y. Saiga, Y. Kobayashi, S. Nakamura, T. Sato, Jpn
bohydrate Chemistry, p. 100, Blacki Academic &
Professional, London (1998).
Kokai Tokkyo Koho JP 61,130,229, Chem. Abstr. [13] T. D. Audichya, T. R. Ingle, J. L. Bose, Indian J.
105, 178449c (1986); d) Y, Sano, H, Takagaki, Jpn.
Kokai Tokkyo Koho Jp 02,144,151, Chem. Abstr. [14] R. U. Lemieux, W. P. Shyluk, Can. J. Chem. 31, 529
113, 152926e (1990); e) T. Shoi, K. Tani, N. Iku- (1953).
shima, Jpn. Kokai Tokkyo Koho JP 04 05,299, [15] F. Shafizadeh, M. H. Meshreki, R. A. Susott, J. Org.
Chem. Abstr. 116, 255969d (1992); f) T. Shoi, N. I- Chem. 38, 1190 (1973).
kushima, Jpn. Kokai Tokkyo Koho JP 04 05,298, [16] K. J. Jensen, M. Meldal, K. Bock, J. Chem. Soc. Per-
Chem. Abstr. 116, 255970x (1992); g) T. Shoi, kin Trans. 1, 2119 (1993).
K. Mizuraya, Jpn. Kokai Tokkyo Koho JP 04 09,395, [17] M. Ch. Courtin-Duchateau, A. Veyrieres, Carbo-
Chem. Abstr. 116, 255971y (1992). hydr. Res. 65, 23 (1978).
[2] M. Lahmann, J. Thiem, Carbohydr. Res. 299, 23 [18] K. Honma, K. Nakakazma, T. Uematsu, A. Ha-
(1997). mada, Chem. Pharm. Bull. 24, 394 (1976).
[3] R. K. Uhrig, M. A. Picard, K. Beyreuther, M. Wiess- [19] M. Blanc-Musser, J. Defaye, H. Driguez, Tetra-
ler, Carbohydr. Res. 325, 72 (2000). hedron Lett. 4307 (1976).
[4] T. Satoh, H. Miyataka, K. Yamamoto, T. Hirano, [20] S. K. Chatterjee, P. Nuhn, Chem. Commun. 1279
Chem. Pharm. Bull. 49, 948(2001). (1998).
Chem. 11, 705 (1973).
[5] B. Helferich, E. Schmitz-Hillebrecht, Chem. Ber. 66, [21] IUNS (International Union of Nutritional Science)
278(1933).
Committee on Nomenclature, Nutr. Abstr. Rev.
48A, 831 (1978).
[22] IUPAC-IUB Joint Commission of Biochemical No-
menclature of Tocopherol and Related Compounds:
Recommendations 1981, Eur. J. Biochem. 123, 473
(1982).
[6] S.Witkowski, P. Wałejko, Z. Naturforsch. 56b, 411
(2001).
[7] R. R. Schmidt, in B. M. Trost, J. Fleming (eds):
Comprehensive Organic Synthesis, Vol. VI, Perga-
mon Press, Oxford (1991).
[8] K. Toshima, K. Tatsuta, Chem. Rev. 93, 1503 (1993). [23] L. I. Smith, H. E. Ungnade, H. E. Hoehn, J. J. Waw-
[9] P. Wałejko, S. Witkowski, I. Wawer, T. Szczepanik,
Mol. Phys. Rep. 29, 192 (2000).
[10] V. M. Sokolov, E. P. Studentsov, G. A. Briukova,
M. A. Ivanov, V. I. Zakharov, E. G. Sotchilin, Zh.
Obsch. Khim. 50, 1401 (1979).
zonek, J. Org. Chem. 4, 311 (1939).
[24] J. Herzig, A. Nudelman, H. E. Gotlieb, J. Org.
Chem. 51, 727 (1986).
Brought to you by | American University of Beirut
Authenticated
Download Date | 6/12/19 3:22 AM