Synthesis of Polyene Natural Products

Abstract

A convergent approach was applied to the synthesis of a range of Xanthomonas pigments and a number of selected analogues, with a view to understanding more about their photoprotective properties, and utilising the group’s iterative Heck-Mizoroki/ iododeboronation cross-coupling methodology to access polyenyl intermediates. This involved the synthesis of a number of key arenyl building blocks. Three polyenyl building blocks were accessed via sequential Heck-Mizoroki and iododeboronation reactions, providing flexibility in the construction of the pigments and their analogues. Following some optimisation of final cross-coupling reactions, two truncated bacterial pigment analogues were successfully synthesised, with evidence of the synthesis of one of the natural product pigments also obtained. The key challenges in these syntheses lay in the considerable instability of many of the polyenyl intermediates (particularly the polyenyl iodides) and in the successful coupling onto the arenyl intermediates.
Extensive NMR analysis, along with UV-Vis analysis provided insight into the photochemical behaviour of the truncated model compounds, and also corroborated the initial characterisation obtained by Andrewes et al. when they isolated xanthomonadin in 1976.
Studies were also undertaken into novel methods of polyene synthesis, with vinyl iodide established as a potential Heck-Mizoroki coupling partner, providing access to a key dienyl boronate building block. This dienyl boronate was used to access a range of terminal dienes and trienes, providing a versatile route to such compounds. The group’s Heck-Mizoroki cross-coupling conditions were also re-optimised to operate at room temperature, at low catalyst loadings, and on much shorter timescales than had been utilised previously.