Nucleic Acids in Chemistry and Biology

Reduction of ribonucleosides directly to 2
-deoxyribonucleosides can be accomplished by one of the
several Barton procedures involving tributyltin hydride (cf. Figure 3.11). A nice example is the synthesis
of a mixture of 2
- and 3
-deoxyadenosines, which are easily separable.^4 This type of reduction has been
widely employed to transform various extensively modified ribonucleosides and their nucleotide ana-
logues into the corresponding deoxyribonucleosides.
2
,3
-Dideoxyribonucleosidesare valuable for use in DNA sequence analysis and also showed promise
for AIDS therapy, both features being related to their chain-terminator activity (Sections 3.7.2 and 5.1). One
synthesis involves hydrogenation of 2
,3
-unsaturated nucleosides or an appropriate precursor (Figure 8.2).

8.3 Oxidation of Nucleosides, Nucleotides and Nucleic Acids

In general, strong oxidizing agents such as potassium permanganate destroy nucleoside bases. Hydrogen
peroxide and organic peracids can be used to convert adenosine into its N-1-oxide^5 and cytidine into its
N-3-oxidewhile the 5,6-double bond of thymidine is a target for oxidation by osmium tetroxide, forming
a cyclic osmate ester of the cis-5,6-dihydro-5,6-glycol.^6 This reaction is sensitive to steric hindrance and
so has been employed to study some details of cruciform structure in DNA (Section 2.3.3). This thymine
glycolis also formed as a result of ionising radiation (Section 8.9.2).
Recent studies on the oxidation of DNA with hypochlorite and similar oxidants have identified the for-
mation of 8-hydroxyguanine residues as an important mutagenic event (Sections 8.8.3 and 8.9.3).^7
The pentoses are sensitive to free radicals produced by the interaction of hydrogen peroxide with Fe(III)
or by photochemical means, and this causes strand scission (Section 8.9.1). Peter Dervan has made this
process sequence-specific in vitro by linking radical-generating catalysts to a groove-binding agent
(Section 8.8.2) and has also employed it as a ‘footprinting’device by linking an Fe–EDTA complex to an
intercalating agent such as methidium (Section 5.8).^8 Other useful oxidative reactions of the pentose moi-
eties are typical of the chemical reactions of primary alcohols and cis-glycols. In particular, periodate
cleavageof the ribose 2
,3
-diol gives dialdehydes.^9 These can be stabilized by reduction to give a ring-
opened diol or condensed either with an amine or with nitromethane to give ring-expanded products

Covalent Interactions of Nucleic Acids with Small Molecules and Their Repair 297

O

O

N

N

N

N

NH 2

R

O

H

O

O R

O

H O

O R

O

OH

Figure 8.1 Mild acidic hydrolysis of purine glycosides in DNA (RH) and RNA (ROH)

O B

HO OH

HO O B

OH

O

O O

O

Br

HO O B HO O B

i ii, iii iv

Figure 8.2 Synthesis of 2
,3
-dideoxynucleosides by reduction. Reagents: (i) Me 2 C(OAc)COBr; (ii) Cr^2 , (CH 2 NH 2 ) 2 ,
75°C; (iii) KOH; and (iv) H 2 /PdC