Synthesis of novel migrastatin and dorrigocin A analogues from D-glucal

Anquetin, G; Rawe, SL; Mcmahon, K; Murphy, EP; Murphy, PV

HERO ID

4943269

Reference Type

Journal Article

Year

2008

Language

English

PMID

18038383

HERO ID 4943269
In Press No
Year 2008
Title Synthesis of novel migrastatin and dorrigocin A analogues from D-glucal
Authors Anquetin, G; Rawe, SL; Mcmahon, K; Murphy, EP; Murphy, PV
Journal Chemistry: A European Journal
Volume 14
Issue 5
Page Numbers 1592-1600
Abstract 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.
Doi 10.1002/chem.200701033
Pmid 18038383
Wosid WOS:000253326200023
Is Certified Translation No
Dupe Override No
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Language Text English