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R
2
OH
R
2
OAc
R
1
Lawesson's reagent
Dry Dioxane, 110
o
C
O
O
R
3
R
3
HO
OH
AcO
SH
R
1
R
1
=R
3
=OH,R
2
=H,61% / 1:9
Glucose
Galactose R
1
=R
2
=OH,R
3
=H,48%
α
β
anomer
Mannose R
1
=OH, R
2
=H,R
3
= OH, 58%
α
α
/
β
1:8
SCHEME 2.5
Davis synthesis of glycosyl thiols from unprotected sugars with Lawesson's
reagent [26].
S
-thiodisaccharides
via
TEC and TMEA are also discussed in Chapter 1 and for that
reason are not included in this chapter.
2.4 SYNTHESIS OF GLYCOSYL THIOLS
As mentioned before, sugar thiols are essential substrates for thio-click reactions
in carbohydrate chemistry. The reactivity of glycosyl thiols is sufficient enough for
practical application in many TEC or TYC coupling. These key building blocks for
construction of many thiodisaccharides, thiooligosaccharides and
S
-glycoconjugates
are also quite stable and their anomeric configuration can be effectively preserved dur-
ing the thioglycosylation reactions. Notably, the anomeric thiols of 1-thiopyranoses
anomerize much more slowly than the corresponding oxygen analogs, particularly
under basic conditions or when heated. This particular character can be exploited
for the synthesis of thioglycosides including thiodisaccharides and oligothiosaccha-
rides. The high nucleophilicity of the thiol group under basic conditions enables
base-promoted
S
-glycosylation. This great practical utility and potential is mainly
attributable to glycosyl thiols with the thiol group in the equatorial position. The
glycosyl thiols with the opposite anomeric configuration (with the thiol group in the
axial position) were essentially unknown until recently [25-33].
Davis and coworkers [26] (Scheme 2.5) reported an important strategy of direct
formation of glycosyl thiols using Lawesson's reagent in the reaction with protected
or unprotected anomeric lactols/reducing sugars. However, in this procedure configu-
rationally impure glycosyl thiols as anomeric mixture were often obtained. Therefore,
the development of a direct and highly stereoselective methodology for the synthesis
of
-glucosyl thiols seems to be of utmost importance.
The Zhou group [27, 28] (Scheme 2.6) developed an excellent approach to
-
glucosyl thiols starting from 1,6-anhydro sugar templates with different protecting
group patterns and wide structural diversity. The series of
-glucosyl thiols were syn-
thesized and most importantly no trace of
-anomers was produced in all the reactions.
This ring-opening protocol is a significant milestone development because of the
overall yield of the final products, and its exclusive
-anomeric purity. The choice of
an excellent sulfur nucleophile, bis(trimethylsilyl) sulfide (BTMSS) in combination
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