Photochemistry of Mycolactone A/B, the Causative Toxin of Buruli Ulcer

Photochemistry of mycolactone A/B and related unsaturated
fatty
acid esters is reported. On exposure to visible light, mycolactone
A/B gave a mixture of four photomycolactones. Pentaenoates and tetraenoates,
representing the unsaturated fatty acid portion of mycolactone A/B,
were found to show the reactivity profile parallel with that of mycolactone
A/B. The structure of the four photomycolactones was elucidated via
(1) structure determination of the four photoproducts in the tetraenoate
series; (2) their transformation to the photoproducts in the pentaenoate
and then mycolactone series. Triplet quenchers did not affect the
photochemical transformation, thereby indicating an event at the singlet
state. A concerted, photochemically allowed [4πs + 2πa]
cycloaddition was suggested to account for the observed result. This
study provided the structurally defined and homogeneous material,
which allowed demonstration that photomycolactones exhibit significantly
reduced cytotoxicity, compared with mycolactone A/B.