Nucleic Acids in Chemistry and Biology

good yields of the corresponding 2-deoxyribonucleoside with the natural
-configuration.^42 The useful
stereocontrol achieved in these reactions arises since the anomerisation of the chlorosugar in acetonitrile
is much slower than the nucleophilic displacement of chloride by the purinyl anion. The regioselectivity
of glycosylation (N-7/N-9) is variable, depending on the purine derivative, but such isomers can usually be
separated by chromatography. Some examples are shown in Figure 3.12. Treatment of the nucleosidic prod-
ucts with ammonia in methanol removes the sugar protecting groups, while heating with the same reagent
provides a useful route to amino-substituted purine nucleosides (Figure 3.13).
The nucleobase anion glycosylationprocedure has also been used to synthesise a wide variety of
2 -deoxyribonucleosides of deazapurines (Figure 3.14).42–44

3.1.1.9 C-nucleosides. A few C-nucleosides have been made by carbanion displacement reactions at

C-1 of a suitably protected sugar, although the high basicity of the carbanion can lead to an unwanted 1,2-
elimination. A classic example is Brown’s synthesis of pseudouridine,^46 a common component of tRNA
species, by the reaction of 2,4-bis-(t-butoxy)-5-lithiopyrimidine with 2,4;3,5-bis-O-benzylidene-D-ribose.
This gave more of the
-pseudouridine (18%) than the -anomer (8%) (Figure 3.15). Grignard reagents
have also been used in carbanion condensations at C-1 of 2-deoxyribose precursors; for example, in the
synthesis of fluorinated nucleobase analogues by Kool^47 (Figure 3.15). The use of palladium chemistry has
also been exploited.^48

86 Chapter 3

N

N N

N

X

M

Y

Z

p-TolO O

p-TolO

N

N

N

N

X

Y

Z

p-TolO O

p-TolO

Cl

O

p-TolO

p-TolO

N

N

N

N

Z

Y

X

XY

HH

HH

Cl H H

NH 2 H

Cl Cl Cl

Cl Cl H

Cl NH 2 H

Br Br H

(i) or (ii)

M=NaorK

N-9 isomer

N-7 isomer

Conditions ZN-9N-7

(i) 44 28

(i) 43 9

(i) 59 13

(i) 48 24

(ii) 56 -

(ii) 59 13

(ii) 57 -

(ii) 57 7

Yield (%)

OMe

SMe

OMe

Figure 3.12 Nucleobase anion route for synthesis of purine nucleosides. Reagents: (i) powdered KOH, TDA-1,
CH 3 CN; and (ii) NaH, CH 3 CN

N

N

Z

N

Cl

H

X

Y

N

N

Z

N

Cl

dR'

X

Y

N

N

Z

N

NH

dR'

X

Y

X

Cl H

HH

H

Cl I

Y

H

H

H

H

HHN

X

Cl H

HH

H

Cl I

Y

H

H

H

H

HHN

(i) (ii)

Z yield

(%)

60

71

66

71

32

Z yield

(%)

61

85

72

88

85

MeS MeS

Figure 3.13 Aminopurine nucleoside analogues prepared by the nucleobase anion route. Reagents: (i) NaH,
CH 3 CN then 3,5-di-O-p-toluoyl-b-D-ribofuranosyl chloride; and (ii) NH 3 /MeOH, heat

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