Nucleic Acids in Chemistry and Biology

146 Chapter 4

synthesis with either dichloroacetic acid or trichloroacetic acid in non-aqueous solvent, conditions that
prevent other side reactions, such as depurination. During deprotection, the bright orange-red DMT cation
is liberated and is used as a measure of the yield of coupling of that nucleoside unit (Section 4.1.4).

4.1.2.3 Introduction of Phosphate. In the original chemistry developed by Khorana and co-workers

(phosphodiester, Section 4.1.3), deoxynucleoside 5
-phosphates were used as building blocks. In other
chemistries developed more recently 5
-O-dimethoxytrityl-(N-acylated)-2
-deoxynucleosides are phosphor-
ylated or phosphitylated at the 3
-hydroxyl group (Figure 4.5). In these cases the products of synthesis after
assembly of the oligonucleotide are phosphate triesters, where the internucleoside phosphate carries a pro-
tecting group. In phosphotriesterchemistry [P(V)] the best protecting groups are aryl (usually mono- or
di-chlorophenyl derivatives). This is because an aryl phosphodiester is a much more reactive deoxynucleo-
side building block than an alkyl phosphodiester in a coupling reaction. For example, 5
-O-dimethoxytrityl-
N^6 -benzoyl-2
-deoxyadenosine gives the corresponding 3
-O-(2-chlorophenyl) phosphodiester by reaction

OMe

MeO

Figure 4.4 The 4,4
-dimethoxyphenylmethyl (dimethoxytrityl, DMT) group

N

N

N

N NHBz

O

HO

HO

BzCl

BzCl

TMSCl

NaOH

NH 4 OH

N

N

N

N NBz 2

O

BzO

BzO

Route A

Per-acylation

Route B

Transient protection

N

N

N

N NH 2

O

HO

HO

N

N

N

N NH 2

O

TMSO

TMSO N

N

N

N NBz 2

O

TMSO

TMSO

Figure 4.3 Routes to N^6 -benzoyl-2
-deoxyadenosine

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