Reduction of structural complexity while retaining biological potency has proven to be a powerful method in natural product-based drug development. We envisioned adapting this approach to develop simplified analogues of a marine macrolide Spirastrellolide A. Due to its novel antimitotic potency (IC<sub>50</sub> = 100 ng/mL) and selective inhibition of protein phosphatase 2A (IC<sub>50</sub> = 1 nM), Spirastrellolide A is potentially a lead compound for anti-cancer therapeutics. A convergent synthesis of southern hemisphere of spirastrellolide A was designed featuring two gold catalyzed cyclization methods developed in our group, namely 1) Gold-catalyzed dehydrative cyclization of monoallylic diols for the synthesis of tetrahydropyran, and 2) Regioselective gold-catalyzed spiroketalization for the efficient generation of [6,6]-spiroketal. Progress towards the synthesis of Spirastrellolide A analogues will be presented.

Synthesis and biological evaluation of spirastrellolide A analogues

2019 Spring National Meeting

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