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Table 2
Cleavage conditions to cleave adenosine from solid phase adenosine scaffold
Type
Condition
Yielda (%)
(%) Of adenosine7b
Acidic
Acidic
Acidic
TFA 80%, 15 min, RTc
91
67
24
11
14
41
2
88
80
90
78
77
93
99
99
—
TFA 80%, 30 min, RTc
TFA 5%, 30 min, RTc
Oxidation
Oxidation
Oxidation
Catalyst
Catalyst
Catalyst
Catalyst
Catalyst
Catalyst
Catalyst
Catalyst
Acidic
DDQ 1.5 equiv, 3 h, RTc
DDQ 3 equiv, 3 h, RTc
DDQ 3 equiv, 24 h, RT
8 mol % In(OTf)3, 6 min, 100 °C (MW assisted)c
8 mol % In(OTf)3, 30 min, 100 °C (MW assisted)c
8 mol % In(OTf)3, 30 min, 130 °C (MW assisted)c
6
NAd
NAd
15
6
c
8 mol % In(OTf)3, 30 min, 150 °C (MW assisted)
40 mol% In(OTf)3, 30 min, 100 °C (MW assisted)c
8 mol% In(OTf)3, 1 h, 50 °C (MW assisted)c
8 mol% In(OTf)3, 24 h, RTc
—
91
99
99
98
82
99
5
40 mol% In(OTf)3, 24 h, RTc
22
88
89
Acetic acid/TBAF (1:1), DMSO/water, rt, 2 he
Acetic acid 10% v/v, 2 h, RTe
Acidic
a
b
c
% Yield was determined by NMR using alanine as an internal standard.
% Of adenosine is the ratio between adenosine and adenine (decomposed product from adenosine).
R = OH.
NA: adenosine was not observed.
R = TBDMS.
d
e
shown in Table 2. TFA is commonly used as a reagent to cleave the
ribose acetal linker, and was found to efficiently cleave the nucle-
oside in 15 min with 80% TFA. Extending the reaction time resulted
in cleavage of the glycosidic bond and formation of free adenine
and ribose moieties. Mild acidic conditions (5% TFA, 24 h) were
tested in hopes of improving adenosine cleavage while maintain-
ing the glycosidic bond. These conditions reduced product yield
and did not prevent adenosine decomposition. Oxidative cleavage
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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Acknowledgement
This work was supported by the National Institutes of Health
(GM087638 to K.S.C.).