Abstract
A new tandem one-pot acetalation-acetylation procedure
is reported which streamlines routine protecting-group manipulation
of carbohydrate molecules in production of differentially protected O- and thioglycosides. This new procedure
eliminates the use of highly toxic pyridine, and p-toluenesulfonic
acid is employed as catalyst for acetalation and acetylation. Synthetic
utility of the new procedure is demonstrated in the expeditious
preparation of differentially protected glycosides from a wide variety
of carbohydrate substrates including unprotected O-glycosides,
thioglycosides, and N-acetyl neuraminic
acid ester.
Key words
tandem - acetals - glycosides - oligosaccharides - protecting group
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General One-Pot
Benzylidenation-Acetylation Procedure
for the Preparation of 2 and 13-20
TsOH
(10-32 mol%, Table
[¹]
)
was added into a stirring mixture of carbohydrate substrate (1.0
equiv of methyl α-d-glucopyranoside, 3-8, 10, or 11) and
PhCH(OMe)2 (1.5 equiv) in MeCN under N2. Upon
complete conversion into benzylidene acetal intermediate as assessed
by TLC, Ac2O (1.5 equiv per OH, total OH equals to the
sum of OH of acetal intermediate plus MeOH released from acetalating reagent)
was added, and the reaction temperature was brought up to 40 or
50 ˚C (Table
[¹]
).
Specific reaction conditions are detailed in the supporting information.
Upon complete acetylation as assessed by TLC, excess EtOAc
(4 × volume
of MeCN used) was added to the mixture, which was then washed with
sat. NaHCO3, brine, dried over MgSO4, and
concentrated for purification by flash column chromatography over
SiO2. Elution with EtOAc-hexane mixture afforded
the compounds 2 and 13-20.
31
General One-Pot
Isopropylidenation-Αcetylation Procedure
for Preparation of 21-24
TsOH
(5-10 mol%, Table
[¹]
)
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equiv of 5, 6, 9, or NANA ester 12),
and Me2CH(OMe)2 (1.5 equiv) in acetone. The
mixture was stirred at r.t. or 40 ˚C under N2.
Upon complete conversion into glycosyl ketal intermediate as assessed
by TLC, Ac2O (1.5 equiv per OH, total OH equals to OH
from glycosyl acetal intermediate plus MeOH released from acetalating
reagent) was added, and the reaction temperature was brought up
to 35 or 40 ˚C (Table
[¹]
).
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detailed in the supporting information. Upon complete acetylation
as assessed by TLC, excess EtOAc (4 × volume of MeCN used)
was added to the mixture, which was then washed with sat. NaHCO3,
brine, dried over MgSO4, and concentrated for purification
by flash column chromatography over SiO2. Elution with
EtOAc-hexane mixture afforded compounds 21-24.
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prolonged reaction time would compromise the yield of reaction due
to the cleavage of the acetal function.
