Organic Letters
Letter
Scheme 6. Reduction of Acetyl Oxime Thiodisaccharides 12E
and 12Z
ACKNOWLEDGMENTS
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Financial support from Universidad de Buenos Aires
( 2 0 0 2 0 1 3 0 1 0 0 5 7 1 B A ) a n d C O N I C E T ( P I P
11220150100443CO, PUE 2292016010006800) is gratefully
acknowledged. V.E.M. and O.V. are research members and L.D.
is a fellow from CONICET.
REFERENCES
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the reducing end. The configuration at C-2 was established
according to the relatively small coupling constant values
observed for the H-2 signal (J1,2, J2,3eq < 1 Hz, J2,3ax = 4.5 Hz) of
1
15. In contrast, the H NMR spectrum of 16 showed J values
(J1,2 = 3.6 Hz, J2,3eq = 4.8 Hz, J2,3ax = 12.3 Hz) in accordance with
an axial disposition for H-2.
The protected thiodisaccharides 14−16 were O-deacetylated
with sodium methoxide in MeOH to give the corresponding free
target compounds 2, 17, and 18, respectively (Scheme 7).
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Scheme 7. O-Deacetylation of Thiodisaccharides 14−16
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The thiodisaccharides 2, 17, and 18 were evaluated as
inhibitors of the β-galactosidase from E. coli, an enzyme widely
used in the field of glycobiology.17 This enzyme is highly specific
for β-galactopyranosyl nonreducing residues bonded to a wide
variety of aglycons. In particular, thioglycosides9,18 and (1→4)-
thiodisaccharides5c,9b have shown inhibitory activity. Knowing
the key aspects of the inhibition process at the molecular level
for 1,11 one of the most potent inhibitors, we have designed and
synthesized the analogue 2. The 2-acetamido-2,3-dideoxy
thiodisaccharides 17 and 18 formed by two hexopyranose
units have also been prepared. All these compounds inhibited
the enzyme (Figure S1), with 17 being the weaker inhibitor. The
kinetics of the inhibition showed that 2 (Ki = 70 μM) and 18 (Ki
= 0.10 mM) were, respectively, competitive and mixed inhibitors
the same order as that of 1, and both were much stronger
inhibitors than methyl 4-thiolactoside5c and other 4-thiolacto-
sides.9b
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ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge on the
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Additional tables, experimental details, characterization
data, inhibition plots and NMR spectra (PDF)
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
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Org. Lett. XXXX, XXX, XXX−XXX