The pectenotoxins (PTXs) are a group of cyclic poly-ether macrolide toxins first isolated in Japan in 1985 from the digestive glands of scallops (Patinopecten yessoensis). To date, there have been more than 20 PTXs identified, with the main differences in structure being the oxidation state at C43, and the stereochemistry at the spiroacetal stereocentre at C7. These molecules have exhibited selective cytotoxicity in tumour cells, and their complex structures have been the subject of considerable research efforts. To date, only two total syntheses of the PTX molecules have been achieved: PTX-4 (1) by Evans in 2002, and PTX-2 (2) by Fujiwara in 2014. Large fragments of PTX-4 (1) have already been synthesised within the Donohoe group, with the completion of the ABC ring system (3) and more recently the coupling of the E ring to the F ring (4). The final ring system to be synthesised is the D ring, which we aim to disconnect acetal 5 to reveal triol 6, which should be accessible by the asymmetric dihydroxylation of 7. Homoallylic alcohol 7 can be accessed via a rhodium-catalysed 1,4-addition of boronate 9 to enone 8. Model studies have been completed to test the feasibility of these disconnections before applying it to the real system.

Synthetic studies towards the D ring of pectenotoxin-4

253rd National Meeting (2017)

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