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. 2008 Jul 14;64(29):6997-7007.
doi: 10.1016/j.tet.2008.02.033.

Skeletal and Appendage Diversity as Design Elements in the Synthesis of a Discovery Library of Nonaromatic Polycyclic 5-Iminooxazolidin-2-ones, Hydantoins, and Acylureas

S Werner  1 , D M Turner  1 , P G Chambers  1 , K M Brummond  1
Affiliations

Skeletal and Appendage Diversity as Design Elements in the Synthesis of a Discovery Library of Nonaromatic Polycyclic 5-Iminooxazolidin-2-ones, Hydantoins, and Acylureas

S Werner et al. Tetrahedron. .

Abstract

Amino acid-derived cross-conjugated trienes were used as a starting point for the synthesis of a discovery library of over 200 polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas. The main feature of this library synthesis is a triple branching strategy which provides efficient access to five skeletally diverse scaffolds. In addition, four sets of building blocks were applied in both a front end and a back end diversification strategy. Multiple fused rings were obtained by cyclization of diamides with phosgene and stereoselective Diels-Alder reactions with maleimides. The 5-iminooxazolidin-2-one scaffold was rearranged into the isomeric hydantoin scaffold through a sequence of ring opening and ring closing reactions.

Keywords: Appendage Diversity; Diels Alder Reaction; Library Design; Polycycles; Skeletal Diversity.

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Figures

Figure 1
Figure 1
δ-Lactams A as key intermediates for a structurally diverse discovery library.
Figure 2
Figure 2
Building Blocks 1{1–2} used as starting points in the library synthesis.
Figure 3
Figure 3
Building Blocks 2{1–6} used in the library synthesis.
Figure 4
Figure 4
Building Blocks 3{1–5} used in the library synthesis.
Figure 5
Figure 5
Building Blocks 4{1–6} used in the library synthesis.
Figure 6
Figure 6
X-Ray structures of 11{1,1,4}, 12{2,1,4} and 13{1,1,4}.
Scheme 1
Scheme 1
Synthesis of polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas.
See this image and copyright information in PMC

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