Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use of ring-closing olefin metathesis

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Abstract
A divergent strategy is described for synthesis of the novel phosphatidylinositols 1–3. The synthetic approach commences from benzyl-protected methyl 6-iodo-6-deoxy-α-D-glucopyranoside, which undergoes zinc-mediated reductive fragmentation followed by vinyl Grignard addition and ring-closing metathesis to afford the key conduritol B intermediate 7. This can trifurcate to form three different benzyl-protected myo-inositol headgroups 4–6, which after phosphorylation and attachment of the glycerolipid part give phosphatidylinositols 1–3. Preliminary biological testing against human colon adenocarcinoma cells reveals that analogues 1–3 are significant anti-tumour agents.