Chemistry Reference
In-Depth Information
Fig. 8.1
Silicon-containing
amino acids and peptides
Fig. 8.2
Examples of
replacement of tetrasubsti-
tuted carbon by silicon
[
23
] and Si-heteroatom bonds are easily hydrolyzed. Taken together, these prin-
ciples seemingly identify quaternary carbons as the only carbons that can be readily
replaced by silicon in the design of bioactive organosilanes.
The application of these principles to a Si/C swap are exemplified in Fig.
8.2
. For
the seven unique carbons in known barbiturate
6
, [
24
] only the quaternary carbons
(arrows) are suitable for replacement by silicon. Replacement of the neopentyl car-
bon with silicon leads to
7
(arrow a), which is notably faster acting and has a longer
effect than the non-silane
6
[
25
]. Replacement of the quaternary carbon between the
carbonyl groups in
6
(arrow b), has not been reported and structures with silicon
between two amide carbonyls are unknown. Silicon close to carbonyl groups tend
to have limited stability [
26
].
Replacement of carbon with silicon is not, however, restricted solely to quater-
nary carbons. Haloperidol is a dopamine receptor antagonist incorporating a tertiary
alcohol. Replacement of the tertiary alcohol carbon with silicon yields sila-halo-
peridol
8
[
27
,
28
]. Once again, the only site in haloperidol that is suitable for sub-
stitution of silicon for carbon is at the position shown. Sila-haloperidol
8
has very
interesting pharmaceutical properties [
27
]. Metabolism studies of
8
have provided
much insight into comparative metabolic fates for silanes relative to their carbon
analogs [
29
].
