Nucleic Acids in Chemistry and Biology

This reaction has all the hallmarks of an SN1 ionization process, as shown both by the intramolecular
transfer of a sugar residue from N-7 to N-9 of 6-chloro-1-deazapurine and by the anomerisation of
- into
-nucleosides. Transglycosylation is also a useful method for the preparation of -anomers of nucleosides
from their natural isomers. The mixture of - and
-species that is usually formed can be separated by
chromatography. However, the thermodynamically favoured regioselectivity of these processes is not eas-
ily predictable.

3.1.1.6 Enzymatic Methods. Hóly, Hutchinson and others have made good use of biotransforma-

tions of readily available nucleosides into novel derivatives by enzyme-catalysed transglycosylation.33,34
Uridine phosphorylase and thymidine phosphorylase degrade uridine, 1-
-D-arabinofuranosyluracil (ara-U)
and thymidine into the corresponding pentose-1--phosphates. These may be converted into the corres-
ponding nucleosides containing purines, modified purines or substituted imidazoles in situin the presence
of the new nucleobase and the enzyme purine nucleoside phosphorylase(PNP). The method also works
for some 3-deazapurines.^35 Some examples are shown in Figure 3.10.
A number of other enzymes have also been used, such as PNP from Enterobacter aerogenes that can trans-
form inosine into virazole in the presence of 1,2,4-triazole-3-carboxamide^36 and the enzyme nucleoside
2 -deoxyribosyltransferase from Lactobacillus leichmanniithat has been used for the large scale transfor-
mation of thymidine or 2-deoxycytidine into corresponding purine nucleosides,^37 as well as into a number of
1-deazapurine nucleosides.^38 The transfer of the sugars 2,3-dideoxy-D-ribofuranose and D-arabinofuranose
are also practicable propositions. In general, enzymatic transglycosylations are relatively efficient and highly
stereospecific as only
-glycosides are formed, and they can often be employed on a gram scale.

3.1.1.7 Control of Anomeric Stereochemistry. Condensation of sugars having a 2-acyloxy substituent

with a base invariably gives N-glycoside products that have the 1,2-trans-configuration. This control of
anomeric stereochemistry led Baker to suggest that neighbouring group participation by the acyloxy moiety
at the 2-position is responsible.^39 In the case of ribonucleosides, ionization of the leaving group at C-1 of
the sugar generates a carbocation that is then captured by the carbonyl group of the adjacent acyl group
to form an acyloxonium ion on the lower face of the sugar (Figure 3.3). This is independent of the initial con-
figuration of the sugar halide and is followed by nucleophilic displacement of the base from the opposite

84 Chapter 3

AcO O

N 3

N

NH

O

O

H 3 C

HO O

N 3

N

N

N

N

NH 2

N

NH

O

O O

HO

HO NHCOCF 3

(iii), (ii)

N

NH

N

N

O

NH 2

HO O

HO NH 2

(i),(ii)

N

N N

N

TMSNCOC 7 H 15

TMS

+ 27% 9-35% 9-αβ

+ 60%

AcO O

N 3

N

NH

O

O

H 3 C

HO O

N 3

N

NH

N

N

O

(i),(ii)

N

N N

N

OTMS

TMS

+ 14% 9-28% 9-αβ

13% 7-α β,

N

TMS

COC 15 H 31

NH 2

N

N N

N

OTMS

TMS

N

TMS

COC 15 H 31

Figure 3.9 Transglycosylation synthesis of nucleosides. Reagents: (i) TMSOTf in CH 3 CN, reflux; (ii) NH 3 , MeOH;
and (iii) TMSOTf, BSA in CH 3 CN, reflux

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