Biomedical Engineering Reference
In-Depth Information
SCHEME 7.3
Synthesis of four different benzopyran core skeletons.
7.2.1.1.2 Nitrogen Heterocycles
Diverse pharmaceutically interesting nitroge-
nous heterocyclic compounds were synthesized using selenium resin [12]. Polymer-
supported pyrrolidine
25
was prepared by a three-step reaction sequence (Scheme
7.5). This key precursor was subjected to different reaction conditions to yield 2,5-
dihydro-1
H
-pyrroles
26
, 1,3-dioxo-2,3,5,7a-tetrahydro-1
H
-pyrrolo[1,2-
c
]imidazoles
28
, and 1,4-dioxo-1,2,3,4,6,8a-hexahydropyrrolo[1,2-
a
]pyrazines
30
, respectively.
First, polymer-supported pyrrolidine
25
was acylated with acyl chlorides to yield
the corresponding amide, which was cleaved from the resin with 30% H
2
O
2
to
afford final 2,5-dihydro-1
H
-pyrroles
26
. Alternatively, treatment of the precursor
25
with isocyanates afforded polymer-supported urea derivatives
27
. Subsequently,
the fused five-membered ring was closed under basic conditions and the final prod-
uct
28
was released from the resin under the same cleavage conditions. The last
nitrogen-containing heterocycle reported was obtained by reaction of pyrrolidine
25
with
o
-chloroacetyl chloride to yield chloromethylamide
29
chlorine was substi-
tuted with amines to afford, after cleavage from resin, final 1,4-dioxo-1,2,3,4,6,8a-
hexahydropyrrolo[1,2-
a
]pyrazines
30
.
The next example illustrates the synthesis of spirocompounds, spirohydantoins,
and spiro-2,5-diketopiperazines, which are pharmacologically important molecules
[13].
Spirohydantoins
were
shown
to
have
antiepileptic
[14],
antidepressant,
