Biomedical Engineering Reference
In-Depth Information
FIGURE 5.2
Bicyclobutane and allylbromide building blocks.
was completed in a parallel format from reductive aminations of the corresponding
pyrrolidine substrates (Scheme 5.29 and Table 5.18). High-throughput biological
assay screening of this library identified a series of inhibitors of the malaria parasite,
Plasmodium falciparum
[33].
Frutos and Curran expanded previously reported studies of a radical cascade pro-
cess en route to the synthesis of the camptothecin class of antitumor agents and
generated a structurally related mappicine and mappicine ketone library of 112 com-
pounds using established parallel synthesis techniques (Scheme 5.30) [34]. This
study highlighted a late-stage cascade radical annulation approach for the assembly
of the polycyclic core, using readily available building blocks in a relatively short
reaction sequence (six or seven steps) (Scheme 5.30). As a second point of diver-
sification,
N
-alkylation of lactams
78
with the desired propargyl bromides (
79
, four
variants) afforded the cyclization precursors
80
. lodopyridones
80
underwent the rad-
ical cascade annulation when combined with phenyl isonitriles
81
(four variants) and
