Nucleic Acids in Chemistry and Biology

terminal alkynes to 5-iodo- or 5-triflate esters of 2-deoxyuridine (Figure 3.27). Coupling with allylamine
or propargylamine (Figure 3.27c) allows the functionalization of 2-deoxyuridine or its 5-triphosphate with
nucleophilic amino groups that allow further elaboration of the nucleoside through reaction with N-hydrox-
ysuccinimidyl esters. Examples include coupling with carboxylic acids of compounds such as imidazole for
use in SELEX64,65(Section 5.7.3), or in the preparation of 2,3-dideoxy-UTP analogues labelled with, for exam-
ple, biotin or fluorescein,2,66,67the latter finding application in dideoxy DNA sequencing (Section 5.1).
In a number of cases, a minor, fluorescent bicyclic furanopyrimidine has been isolated during Sonogashira
coupling reactions involving 5-iodo-2-deoxyuridine, which takes place in the presence of CuI. This latter

94 Chapter 3

HO O

HO

N

NH

O

O

CF 3 SO 2 O

HO O

HO

N

NH

O

O

H

HO O

HO

N

NH

O

O

R

RH

HO O

HO

N

NH

O

O

I

HO O

HO

N

NH

O

O

X

HX HO O

HO

N

N

O

O

X

HO O

HO

N

NH

O

O

I

H

NHCOCF 3

HO O

HO

N

NH

O

O

CF 3 CONH

HO O

HO

N

NH

O

O

I

HO O

HO

N

N

O

O

(CH 2 ) 9 OR

HOR(CH 2 ) 9

HO O

HO

N

NH

O

O

(CH 2 ) 9

RO

HO O

HO

N

N

O

O

CF 3 CONH

O

HO

N

NH

O

O

H 2 N

O 9 P 3 O

b

(i) (i), (ii)

R = HOMe 2 C, Ph, 4-MeOC 6 H 4 -,

4-CF 3 C 6 H 4 , 4-F-C 6 H 5

R = TMS

(i)

X = H, Me,

Br or Cl

(i)

(iv) (v)

R = C 4 H 9 , C 5 H 11 , (CH 2 ) 4 Cl

minor

minor

4

(iii)

a

c

d

+

+ +

major

+

+

+

Figure 3.27 Palladium-catalysed coupling reactions as routes to C-5-substituted pyrimidine nucleosides. Reagents:
(i) Pd(PPh 3 ) 4 , CuI, Et 3 N, DMF; (ii) TBAF, MeOH; (iii) synthesis of triphosphate then NH 4 OH;
(iv) Pd(PPh 3 ) 4 , CuI, i-Pr 2 EtN, DMF; and (v) CuI, Et 3 N, MeOH, heat

http://www.ebook3000.com