Stereocontrolled Total Synthesis of 13C Labelled 9-cis Retinals

Abstract

This thesis reports research towards a stereoselective synthesis of 9-cis retinal from commercially available beta-ionone, with the ability to enrich it with 13C in different positions indicated in figure 4 (C8, C9, C10, C11, C14, C15, C19). A synthesis of 9-cis retinal 13C enriched in positions 14 and 15 was explored, and the work is described in the results and discussion section of this thesis. Some suggested routes to enable 13C enrichment at different positions in 9-cis retinal are also given. There is a lot of interest in studying retinal’s role inside a biological environment such as in the retina, or an isolated protein. Studying retinals inside a biological environment such as retina can be a difficult task due to intervening signals from that environment. Therefore, introducing a retinal isotopically labelled to such an environment can allow for researchers to get structural information by using a modern technology and techniques. NMR structural studies of retinal proteins will be carried out by our collaborators in Germany. In this thesis we report a total synthesis of 9-cis-retinal that is suitable to introduce C-13 labels in some positions of interest to allow the NMR structural studies to be carried out. The route described in this thesis to synthesise 13C14,15 9-cis-retinal was established by adaptation of published routes to 9-cis-retinoic acid and it is analogue retinal by both Bennani1 and Molloy et al.2 . Key steps include the olefination of synthesised 9-cis aldehyde in stereoselective manner and synthesised Weinreb amide phosphonate followed by a reduction via DIBAL-H to give the corresponding 9-cis retinal.