Synthesis of Novel Migrastatin and Dorrigocin A Analogues from D ‐Glucal

The synthesis of a range of analogues of the migrastatin macrolide core has been achieved from tri‐ O ‐acetyl‐ D ‐glucal in order to facilitate structure–activity studies. Efficient macrolactone formation was achieved in the presence of a reactive olefin, by increasing steric hindrance in the olefin environment. Acyclic analogues of migrastatin, structurally related to dorrigocin A, have also been prepared from D ‐glucal. The dorrigocin A analogues were prepared using the combination of the cross metathesis of ethyl 6‐heptenoate with a glycal derivative and a subsequent allylic rearrangement–alkene isomerisation reaction (Perlin reaction). A synthetic route is thus provided that will enable dorrigocin A analogues to be prepared in parallel to migrastatin analogues in the search for novel anti‐cancer and anti‐arthritic therapeutics. Biological evaluation of one migrastatin and one dorrigocin A sugar derived analogue show that they inhibit proliferation and serum‐induced migration of tumour and synovial cells at higher concentrations than evodiamine. Dorrigocin A analogues displayed similar potency to analogues of the migrastatin core.