Design, Synthesis and Conformational Studies of Peptidomimetics Containing β-Prolines and Application of Titanium(3) Induced Radical Cyclization of Epoxyolefins in Natural Product Synthesis

Abstract

The thesis entitled “Design, Synthesis and Conformational Studies of Peptidomimetics Containing β-Prolines and Application of Titanium(3) Induced Radical Cyclization of Epoxyolefins in Natural Product Synthesis” consists of three chapters: Chapter I: Deals with synthesis of substituted β2,3-proline (β2,3-pro) and β3-homoproline (β3- Hpro) and conformational study of their homodimers. This chapter consists two parts: Part A: Describes design and synthesis of substituted β2,3-pro and β3-Hpro. Part B: Describes synthesis and conformational studies of the homodimers derived from β2,3-pro and β3-Hpro. Chapter II: Deals with synthesis and conformational studies of oligomers of β2,3-pro and β3- Hpro and glycopeptides derived from β3- Hpro. Chapter III: Deals with application of Titanium(3) induced radical cyclization of epoxyolefins in natural product synthesis. Chapter I Part A: Design and synthesis of substituted β2,3-proline and β3-homoproline. Unnatural foldamers had drawn enormous attraction of scientific community because it became clear that short oligomers constructed from subunits other than α-amino acids or nucleotides can adopt discrete secondary structures. The ability to control molecular shape has allowed creation of unnatural foldamers with desired functions. β-Peptides are most extensively studied unnatural foldamers because all three types of regular secondary structures, i.e. helix, sheet and reverse turn, observed in protein are found to be present in β-peptides. Hydrogen bonding plays a significant role in the secondary structure acquired by them. Non-hydrogen bonded secondary structures also occur occasionally. There has been ongoing project in our group on development of new designer molecules based on multifunctional amino acid. At this point we focused on studying secondary structure of oligomers based on cyclic β-amino acid which are devoid of Abstract ii hydrogen bonds, like β-prolines. While β2-proline and β3-homoproline have already been studied by other groups, we focused our attention on substituted β2-proline 1 and β3-homoproline 2 that have side-chains suitable for functional group attachments and attachment of probes, besides influencing the 3D structures of the peptides derived from them. The beauty of these substituted β-prolines lies on the fact that both of them can be derived from a common orthogonally protected pyrrolidine precursor 3 ( Scheme 1).