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Figure 3.3 Energy-minimized model of 163a with potential hydrogen bonds labeled in green.
MeO 2C
O
O
NH
O
N
H
NH
Bn
O
N
Ph
163a
O
2.287 Å
2.140 Å
energy-minimized model of 163a; the two phenyl groups were
replaced with a methyl group for clarity purposes
Consequently, the focus shifted to designing a library of these polycyclic scaffolds using the
synthetic routes that were developed. As outlined in Scheme 3.32, this synthetic pathway offers
at least five points of diversity to be introduced gradually as the complexity of the scaffold
increases. The imino-oxazolidinone moiety was envisioned as a crucial part of the triene
precursor 166 because in enables a highly stereo- and chemoselective Diels-Alder reaction with a
number of maleimides. Furthermore, this moiety is used as a key diversity element, because the
transformation of 167 to 168 results in the conversion of a molecule rich in hydrogen-bond
acceptors to one that contains two hydrogen-bond donor groups. This transformation is expected
to bring about significant differences in the physico-chemical properties and potentially the
biological activity of the compounds. Since both classes of compounds were envisioned as
library members, a broad range of diversity was therefore accessed via a relatively simple set of
transformations. The library synthesis was put into practice by the staff at the University of
Pittsburgh Center for Chemical Methodologies and Library Development (UPCMLD,
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