produces the 2-monoalkylated nucleoside together with the 2,3-bis alkylated by-product. Subsequent
hydrolysis provides a simple and efficient route to 2-O-methylguanosine (Figure 3.38).^82
2 ,3-Dideoxynucleosideswere first prepared in the groups of Todd and Robins in the 1950s. More
recently, many such nucleoside derivatives have been discovered to have important anti-viral properties,
particularly effective against HIV (Section 3.4), and they have been used widely in DNA sequencing using
the Sanger method (Section 5.1). While glycosylation routes to these analogues are known, they generally
give anomeric mixtures of - and -nucleosides. A general route to these compounds via the correspond-
ing 2 ,3-didehydro-2,3-dideoxynucleosidesis shown in Figure 3.39.^83
Nucleosides and Nucleotides 99
PxO OPxOOHNNN
NNHPx
HO OHO NH 2NNHN
NONH 2
HO OHO NHCOCF 3NNHOOHO OHO FNNN
NNH 2
HO OHO NH 2NNN
NNH 2(iii), (iv)
(i), (ii) (v), (iv)Figure 3.35 Preparation of various 2-modified purine nucleosides. Reagents: (i) DAST, DMF, CH 3 CN (px pixyl/
9-phenylxanthyl); (ii) H; (iii) N^2 -palmitoyl guanine, bistrimethylsilyl acetamide, reflux; (iv) NH 3 /MeOH;
and (v) N^6 -octanoyl adenine, bistrimethylsilyl acetamide, reflux
4-MeOC 6 H 4 COO O NN
OO
Me
HO ON 3NNHOOMe4-MeOC 6 H 4 COO OHONNHOOMe(i) (iii),(iv)Figure 3.36 Synthesis of AZT via O^2 ,3-cyclonucleoside. Reagents: (i) i-PrO 2 CN^ NCO 2 i-Pr, Ph 3 P, DMF; (ii) LiN 3 ,
DMF; and (iii) NaOMe in MeOH
HO OHO OMeNNHOOHO OHO OMeNNNH 2Oi-PrOi-Pr
i-PrOOHNNHOOOOSiSii-PrNNOONO 2OOMeOOSiSii-Pr
i-PrOi-Pr
i-Pr(iii),(iv)(i),(ii)
(v), (iv)Figure 3.37 Syntheses of 2-OMe modified pyrimidine nucleosides. Reagents: (i) MeSO 2 Cl,DMAP then 2-nitrophenol;
(ii) MeI,Ag 2 O in acetone; (iii) 4-O 2 NC 6 H 4 CH^ NO.(Me 2 N) 2 C NH 2 then H 2 O/dioxan; (iv) TBAF in
THF; and (v) NH 3 in THF