Studies towards the synthesis of the core of Sarains A, B, & C

Sarains A-C are alkaloids isolated from the Mediterranean sponge Reniera sarai, whichpossess moderate antibacterial, insecticidal and antitumour properties. These alkaloidsare popular targets for total synthesis, thanks to their rather unusual and challengingstructure, which consists of a central diazatricyclic cage attached to two peripheralmacrocycles. Arguably the most challenging aspect of their synthesis is that of thetricyclic core, and our approach involves a novel rearrangement of a simpler bicyclicaminal system. This thesis describes various attempts to synthesise cis-fusedoctahydropyrrolo[2,3-b]pyrrole ring systems that bear an endo acetaldehyde-derivedsubstituent in the 3-position.The research into the synthesis of this ring system began with enantioselectiveapproaches, utilising asymmetric Diels-Alder reactions to establish the stereochemistryrequired for subsequent transformations into the bicyclic aminal. Progress from thesereactions was troublesome.In racemic approaches, the use of a Michael reaction was unsuccessful, but successfulinstallation of the required stereochemistry was achieved by use of a thio-Claisenrearrangement. Using this method, the aforementioned functionalised acetaldehyde wasproduced in good yield in ten steps from simple starting materials. This provided abranching point for the exploration of four different, but related routes to the sarain coreinvolving the generation of diazoketones, a bromoketone and hydroxy-aldehydes.Substrates to test our proposed rearrangement reaction were synthesised, buttransformations into the sarain core proved unfruitful. However, a different tricycliccompound has been produced from a hydroxy-aldehyde approach.In a separate investigation instigated by a result from previous research into synthesis ofthe sarain core, it was found that treatment of tertiary formamides with a silylateddiazoester in the presence of rhodium acetate leads to formation of 3-amino-2-silyloxyacrylates in good yields. The scope and limitations of this novel reaction wereinvestigated.