Nucleic Acids in Chemistry and Biology

the most nucleophilic heteroatom on the base component. Such syntheses have, therefore, been widely
employed for the preparation of the imidazole nucleosides involved in the de novobiosynthesis of purine
nucleosides (Section 3.4.1), and of modified pyrimidine and purine nucleosides. A typical example of the
work of Gordon Shaw in this area is the synthesis of 2-thioribothymidine (Figure 3.18).^51
In a similar way, a cyanomethyl group at C-1 of D-ribose supports the syntheses of 9-deazainosine,
antibiotic oxazinomycin and pseudouridine (Figure 3.18).52,53

3.1.2.2 C-nucleosides. With the growing availability of chemical reactions having a high degree of

stereochemical selectivity, the synthesis of C-nucleosides by this route has moved away from sugars as
starting materials. Showdomycinis a product of Streptomyces showdowensisand has useful cytotoxic and
enzyme inhibitory properties. A route starting from a tricyclic precursor can branch to give either show-
domycin or psuedouridinein a stereospecific fashion (Figure 3.19).^54
The formal replacement of the 4-oxygen in the sugar by a methylene group gives a carbocyclic nucleoside.
Much of the activity in the synthesis of carbocyclic nucleosideshas been carried out in the search for poten-
tial anti-tumour and anti-viral agents, especially provoked by the search for agents effective against human
immunodeficiency virus (HIV) (Section 3.7.2). One of the particular values of carbocyclic nucleosides is

88 Chapter 3

HO O

HO OH

N

N

N

N

O

Me N Me

HO O

HO OH

N

N

CONH 2

NHMe

AcO O

AcO OAc

NCO

O

AcO

AcO OAc

O

HN

N

H

OMe

O

AcO

AcO

N

N

N

OMe

O

OAc

HO O

HO

N

N

N

NH 2

O

OH

(i) (ii) - (iv)

5-azacytidine

Wyosine

Figure 3.17 Building the Wye base and 5-azacytosine onto a C-1 isocyanate. Reagents: (i) three carbon fragment;
(ii) CNBr; (iii) NaOEt, EtOH; and (iv) BrCH 2 COCH 3

N

N

H 2 N

NH 2

SMe

O

BnO

HO OH

N

HN N

NH 2

SMe

O

HO

HO OH

N

N

N

N

NH 2

O

BnO

HO OH

N

HN N

NH 2

SMe

H 2 N

(i), (ii) (iii)

(iv), (v)

(vi)

Figure 3.16 Todd’s synthesis of adenosine. Reagents: (i) 5-O-benzyl-2,3,4-tri-O-acetyl-D-ribose; (ii) NH 3 (iii) dia-
zonium coupling or nitrosation followed by reduction; (iv) thiourea; (v) Raney nickel desulfurisation;
and (vi) H 2 /Pd-C debenzylation

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