Lauryl and stearyl thioglycosides: Preparation and reactivity of the glycosyl donor

Article abstract of DOI:10.1246/cl.2000.326

Lauryl and stearyl thioglycosides were prepared by the Lewis acid catalyzed reaction of 1-O-acetylated sugars with non-volatile and almost odorless 1-dodecanethiol and 1-octadecanethiol, respectively. These thioglycosides were activated by N-iodosuccinimi

Full text of DOI:10.1246/cl.2000.326

326
Chemistry Letters 2000
Lauryl and Stearyl Thioglycosides: Preparation and Reactivity of the Glycosyl Donor
Hideaki Matsui, Jun-ichi Furukawa, Takuro Awano, Norio Nishi, and Nobuo Sakairi*
Division of Bioscience, Graduate School of Environmental Earth Science,
Hokkaido University, Kita-ku, Sapporo 060-0810
(Received December 9, 1999; CL-991041)
Lauryl and stearyl thioglycosides were prepared by the
Lewis acid catalyzed reaction of 1-O-acetylated sugars with
non-volatile and almost odorless 1-dodecanethiol and 1-octade-
canethiol, respectively. These thioglycosides were activated by
N-iodosuccinimide-TfOH to glycosyl donors producing disac-
charides in good yields.
Thioglycosides are quite versatile intermediates in
oligosaccharide synthesis due to their ease of preparation and
activation by a potent thiophilic reagent that affords highly
reactive glycosylating reagents.1 Furthermore, a distinct advan-
tage of the thioglycosides is that the hemithioacetal function
can serve as a temporary protecting group stable under various
conditions for chemical transformations of their hydroxyl
groups.2 Although the phenyl and ethyl thioglycosides are the
most commonly used glycosyl donors, it is not easy to perform
comfortably the preparation of these compounds using standard
procedures even in a closed system or a well-organized draft
chamber because of the pervasive stench of the volatile thiols.
In this communication, we describe the preparation of the thio-
glycosides of almost non-volatile mercaptans and applicability
to the glycoside synthesis.
In a similar way as described for the preparation of ethyl
and phenyl thioglycosides,3 pentaacetyl-β-D-glucopyranose 1
and its 3-O-benzyl derivative4 2 were treated with 2 molar
equivalents of 1-dodecanethiol (bp = 266 °C) and 1-octade-
canethiol (mp = 18-20 °C) in the presence of BF3⋅OEt2 (1
equiv) in 1,2-dichloroethane. The reactions completed at room
temperature for 30 min to give the corresponding thioglyco-
sides5 (3a, 3b, 4a) in almost quantitative yields. This reaction
was applicable to such disaccharides as fully acylated lactose
and laminaribiose without cleavage of their glycosidic bonds.
After Zemplèn deacetylation of 3a and 3b, the resulting tetraols
were treated with benzoyl chloride or pivaloyl chloride in pyri-
dine, thus giving the fully acylated thioglycosides5 (5a, 5b, 6b)
in more than 90% overall yields. However, conventional ben-
zylation of the thioglycosides in DMF was unsuccessful, since
aggregation of the starting material occurred during the reac-
tion. This problem was overcome by carrying out the reaction
under less polar conditions. Thus, benzylation of the lauryl
thioglucoside with benzyl bromide-NaH in DMF-THF (2:1)
and phase-transfer benzylation6 of the stearyl thioglucoside in
CH2Cl2-aq NaOH afforded the corresponding perbenzylated
derivatives5 (7a, 7b) in 64% and 77% yield, respectively.
Next, applicability to various chemical modifications was
examined, employing the lauryl thioglucoside 4a as the model
compound. Saponification of 4a in aq KOH gave a lipophilic
triol, which was isolated by usual extractive work-up in chloro-
form. The resulting triol was treated with α,α-dimethoxy-
toluene (DMT) in DMF in the presence of camphorsulfonic
acid (CSA) to give the 4,6-O-benzylidene derivative 8, of
which the 2-hydroxyl group was benzoylated in a one-pot man-
ner to give the fully protected derivative5 9 in 74% overall yield
from 4a. By reductive ring opening of the benzylidene group
7
with BH3⋅NHMe2-BF3⋅OEt2 in CH2Cl2, 9 was converted into
the 3,4-di-O-benzyl derivative5 10. These results suggested
that most of the conventional methods for the protection of the
hydroxyl groups of the monosaccharides were applicable to
these amphiphilic thioglycosides.
Next, our interest focused on the behavior of these lauryl
and stearyl thioglycosides during the glycosylation reaction.
Upon activation with N-iodosuccinimide (NIS)-TfOH8 in
CH2Cl2 in the presence of molecular sieves 4A (MS 4A) at –20
°C for 20 min, the thioglycosides (3ab, 5ab, 6b, 7ab) were
reacted with methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside 11
to give the disaccharides5 12. These results are summarized in
Table 1. As expected, the acyl protecting donors predominant-
ly afforded the β-linked disaccharides, i.e., cellobiose deriva-
tives. Among several thioglycosides, the best results were
obtained when we used the fully benzoylated lauryl thiogluco-
side 5a. It produced the disaccharide 12 (R2 = Bz) in greater
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
327
with brine, dried over anhydrous MgSO4, and evaporated.
Column chromatography on silica gel using hexane-EtOAc
(10:1) gave a β-linked disaccharide (301 mg, 94%).
Further studies of the synthetic application using the lauryl
thioglycosides are now in progress.
This work was financially supported by a grant-in aid for
scientific research of priority area (No. 09240101) from the
Ministry of Education, Science, Sports, and Culture of Japan.
References and Notes
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All new compounds gave satisfactory spectral data and ele-
1
mental analyses. Selected physical data. 3a: H NMR
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0.12, CHCl3); 3b: δΗ 4.48 (d, 1H, J = 10.0 Hz, H-1), [α]D
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+12.4° (c 1.70); 5b: δΗ 4.85 (d, 1H, J = 9.9 Hz, H-1), [α]D
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[α]D –22.6° (c 0.87); 7a: δΗ 4.44 (d, 1H, J = 9.7 Hz, H-1),
[α]D +5.8° (c 0.58); 7b: δΗ 4.43 (d, 1H, J = 9.7 Hz, H-1),
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than 94% yield.9 In contrast to this, the reactions with the
stearyl thioglycosides (5b and 6b) formed highly viscous sus-
pension, which prevented the smooth reaction. The acetates
3ab were rapidly consumed during the reaction and TLC
showed several decomposed products, one of which was identi-
fied as O-acetylated acceptor.10 Furthermore, similar reaction
of the O-benzylated donors 7ab in CH2Cl2 gave an anomeric
mixture of disaccharides with an α/β ratio of 63:37. Although
poor yields of the reaction in MeCN and Et2O were probably
due to production large amount of insoluble materials, the sol-
vent effects on the α/β ratio shown in Table 1 were quite inter-
esting.
A typical procedure is as follows. To a suspension of lau-
ryl 2,3,4,6-tetra-O-benzoyl-1-thio-β-D-glucopyranoside 5a (241
mg, 0.31 mmol), 11 (184 mg, 0.40 mmol), NIS (72 mg, 0.32
mmol), and MS 4A (ca. 300 mg) in CH2Cl2 (10 mL) with stir-
ring at –20 °C was added TfOH (3 µL). After stirring at the
same temperature for 20 min, pyridine (2 mL) and aq Na2S2O3
were successively added to quench the reaction. The mixture
was filtered though a Celite pad, and the filtrate was washed
6
7
8
9
Reaction of the corresponding phenyl thioglycoside under
the same conditions gave 12 (R2 = Bz) in 77% yield.
10 K. Fukase, A. Hasuoka, I. Kinoshita, and S. Kusumoto,
Tetrahedron Lett., 33, 7165 (1992).