# Design and synthesis of nonpeptide peptidomimetic enzyme inhibitors, and synthesis and characterization of C(60)O, the first buckminsterfullerene epoxide

#### Abstract

This dissertation is divided into two parts. The first chapter describes the design and synthesis of three novel nonpeptide peptidomimetic renin inhibitors*. The selection of sidechains, N- and C-termini, and transition state mimetics were based largely on the prior art. Thus for the model renin inhibitors R-Phe-His-TS, we selected the Abbott erythro-glycol transition state mimetic and the Kissei morpholine amide as the N-terminal R group. The P$\sb2$ side chains contained either a novel cyclopentene ring, or iBu side chain. Synthesis and assay of the renin inhibitors provided vital information to the hydrogen bonding and steric interactions between the inhibitors and the enzyme. It was determined that the pyrrolinone ring functions as an effective amino-acid isostere, and greatly contributes to the $\beta$-strand conformation found in bound inhibitor-enzyme complex. The second chapter describes the synthesis, isolation, and characterization of the first epoxide of buckminsterfullerene, C$\sb{60}$O. Both photochemical and chemical means were explored to prepare C$\sb{60}$O, and novel isolation and characterization protocols were developed. By analysis of spectral data and arguments of symmetry, the structure of C$\sb{60}$O was assigned as the closed epoxide structure, as opposed to the isomeric open oxidoannulene structure. ftn*Please see dissertation for diagrams.

#### Subject Area

Organic chemistry

#### Recommended Citation

Jones, David Robert, "Design and synthesis of nonpeptide peptidomimetic enzyme inhibitors, and synthesis and characterization of C(60)O, the first buckminsterfullerene epoxide" (1993). Dissertations available from ProQuest. AAI9413856.
https://repository.upenn.edu/dissertations/AAI9413856

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