Synthesis and stereochemistry of the terminal spiroketal domain of the phosphatase inhibitor dinophysistoxin-2

An expedient synthesis of both axially and equatorially C35 methyl substituted spiroketals representing the C28–C38 domain of the potent and selective protein serine/threonine phosphatase inhibitor dinophysistoxin-2 (DTX-2) was developed to enable comparative stereochemical analyses and a stereochemically correct total synthesis of DTX-2. Comparison of proton and carbon NMR data of the synthetic diastereomers with those published for DTX-2 indicates that DTX-2 possesses the (30S∗,34R∗,35S∗)-relative configuration with an axial C35 methyl substituent.

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