Enantioselective synthesis of diketopiperazines and triketopiperazines

Cabanillas Navarro, Alejandro (2015). Enantioselective synthesis of diketopiperazines and triketopiperazines. University of Birmingham. Ph.D.

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Abstract

The diketopiperazine scaffold can be found in a large number of natural products and commercialised drugs. Conversely, the triketopiperazine one is far less common in Nature and scarce research has been conducted to determine its utility. The project goal was to develop enantioselective organocatalysis on these two frameworks. Chapter 1 gives an introduction on their presence in Nature and the pharmaceutical industry, the most relevant synthetic advances as well as an overview of the organocatalysis tools previously reported.
Although diketopiperazines have been the subject of intense research, no asymmetric methods have been previously reported despite the myriad of available methodologies. Chapter 2 discusses the particular organocatalytic precedents that motivated this project and the initial efforts devoted to develop such methodology. Unfortunately, diketopiperazines showed complete lack of reactivity under a wide range of conditions.
Our interest in developing this enantioselective method in heterocycles related to diketopiperazines made us turn our attention to the triketopiperazine scaffold. The successful application of a cinchona alkaloid derived catalysed Michael addition on this scaffold is described in Chapter 3. Progresses made in the manipulation of the chiral products are also included.
An extension of the previously developed methodology, where selected Michael acceptors afford bicycle[2.2.2]diazaoctane derived products via a tandem Michael–ring-closure process, is discussed in Chapter 4.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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