Studies Towards the Synthesis of DKP Analogues. Investigations of Bis-lactim Ether Reactivity with Aldehydes and Ketones

Abstract

A group of molecules with the name diketopiperazines (DKP) are called so, because of their diketopiperazine ring as the core structural unit. Mainly there are 3 types of diketopiperazies which only differ in in the position of the keto group, one type has the keto groups in 2,3- position; another in 2,5-; and the third in 2,6- position. The 2,5- isomer has attracted great interest, because of compounds that have the same core structure unit occur in nature. One good example of such compounds that have been studied lately is Barettin. Since DKPs have some similarities to peptides and are biologically active natural products, like Barettin, studies in synthesis of DKP analogues have been performed to use DKP analogues to improve the metabolic properties of peptides.

In this thesis, studies towards the synthesis of DKP analogues from the 2,5- isomer are described. The preparation of 2,5-diketopiperazine itself is described by two different methods. The first one is the more general approach and the second method is microwave assisted synthesis. Exploration of the use of Schöllkopf bis-lactime ethers in the synthesis of functionalized DKPs. The Schöllkopf ether was studied in a range of transformations through aldol condensation with aldehydes and ketones with various bases followed by dehydration.

Both 2,5-DKP syntheses and alkylation were found to be successful whereas the aldol condensation step turned out to be a little bit problematic. Through the course of the project a range of compounds were synthesized for analogue library.