Synthetic approaches to thromboxane B2

Abstract

The first part of this thesis consists of a review concerning recent progress in the synthesis of thromboxane B2. Mention is also made of the synthesis of related compounds and precursors, i.e. the endoperoxides, prostacyclin and thromboxane A2 carbocyclic analogues. The biosynthesis and physiological properties of thromboxane B2 and these related compounds are also discussed. Key intermediates in a synthesis of thromboxane B2, 6, 8-dioxabycyclo [3.2.1] oct-2-ene(6) and the tricyclic lactone (5) were identified. The investigation of a synthesis leading to compound (6) in racemic form starting from the sodium salt of 3,4-dihydro-2H-pyran-2-carboxylic acid and the subsequent attempted elaboration of a γ-lactone ring on this compound by radical addition or dichloroketene addition to yield lactone (5) is described in Chapter 2. The isolation of a novel product of potassium tert-butoxide induced isomerisation is discussed. Work on a synthesis of compound (6) in optically active form starting from a sugar d-mannitol, by Grignard and Wittig reaction is also described. Chapter 2 concludes with a description of preliminary work done on two alternative approaches. Chapter 3 contains experimental details of the reactions performed.