Chemistry Reference
In-Depth Information
incorporation of each synthon always involves the same series of steps, namely
coupling of a suitably protected building block and removal of a temporary protect-
ing group to liberate the functional group to which the next unit has to be attached.
The elongation of oligonucleotide chains in automatic synthesizers utilizes the phos-
phite triester approach,
61
which is the most effective methodology, even though it
involves the largest number of steps. Nevertheless, the H-phosphonate method
62,63
has also provided satisfactory results for the preparation of some oligonucleotide
analogues. It can be used in automatic synthesizers, provided that the standard syn-
thesis cycles are suitably modifi ed.
The preparation of platinated oligonucleotides from platinated nucleoside
monomers was fi rst described in 1996 by two separate groups.
64,65
Both aimed at
introducing platinum at an internal position of the oligonucleotide chain, and used
the platinated H-phosphonate nucleoside derivatives depicted in Figure 9.6A, which
shows the differences in the nucleobase involved, as well as in the nature of the
ligands and the stereochemistry of the complexes.
Cech and coworkers
64
argued that H-phosphonates were more robust
than phosphoramidites, and that phosphitylation had to precede platination.
H
3
N
NH
3
Cl
O
A
Cl
Pt
O
Pt
H
3
N
N
N
NH
NH
3
DMT
O
N
O
DMT
O
N
N
NH
2
O
O
O
P
O
O
P
O
HO
HO
Cl
H
3
N
Pt
B
O
NH
3
N
HN
Bhoc
N
NH
O
O
Fmoc
N
NH
OH
DMT = 4,4'-dimethoxytrityl
Bhoc = benzhydryloxycarbonyl
Fmoc = 9-fluorenylmethoxycarbonyl
Figure 9.6
Structures of the 2
-deoxyguanosine H-phosphonate
monomers used to assemble platinated oligonucleotides by stepwise solid-phase synthesis
(A), and of the platinated PNA monomer used to obtain platinated PNAs (B)
′
-deoxythymidine- and 2
′
