Alkyne probes and natural products

Thesis

This thesis is split into two projects, both of which involve efforts to synthesise compounds containing alkynes. The first project is related to the synthesis of probes to label plant CYP450s, a key superfamily of enzymes involved in plant metabolism. The second project details efforts undertaken towards the synthesis of natural products isolated from the Laurencia genus of red algae.

Chapters 1 and 3 provide introductions to the respective projects. CYP450 enzymes and activity-based protein profiling (ABPP) are introduced in chapter 1. Chapter 3 provides some background to the Laurencia natural products; the biosynthetic postulates proposed for the formation of the diverse skeletons seen in the chemical structures are presented and a selection of interesting total syntheses carried out by numerous groups are also set forth.

Chapter 2 details the synthesis of CYP450 probes of a number of generations (termed G1 through G4) and outlines some of the challenges faced not only in the synthesis of these probes, but also with respect to observing labelling of the CYP450 enzymes in planta.

Chapters 4 and 5 concern the synthetic endeavours undertaken towards the total synthesis of ent-laurepinnacin, a natural product from the Laurencia genus, using a key silver(I)-mediated skeletal rearrangement involving complex oxonium ions as key intermediates. Chapter 6 concludes the thesis by detailing the development of an alternative protocol for the skeletal rearrangement, allowing access to alternative natural products ent-(E)-notoryne and laurendecumenyne B.

Authors: Brown, D

• DOI: 10.5287/ora-kzgpy4onj
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: organic chemistry; synthesis