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Synthesis of the Macrolactone of Migrastatin and Analogues with Potent Cell‐Migration Inhibitory Activity
Author(s) -
Dias Luiz C.,
Finelli Fernanda G.,
Conegero Leila S.,
Krogh Renata,
Andricopulo Adriano D.
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201001097
Subject(s) - chemistry , stereocenter , dihydroxylation , cell migration , stereochemistry , inhibitory postsynaptic potential , tunicate , metathesis , human breast , cell , oligopeptide , cancer cell , biochemistry , cancer , peptide , organic chemistry , biology , polymer , neuroscience , polymerization , enantioselective synthesis , catalysis , ecology , genetics
The synthesis of the macrolactone core of migrastatin 2 , its potent anti‐metastasis analogue 34 , and ester derivatives 35 and 38 are reported. The approach involves the use of a dihydroxylation reaction to establish the desired C‐8 stereocenter followed by a metathesis cyclization reaction. The effects of the compounds on the migration and invasion of human breast cancer cells were evaluated by using the wound‐healing and the Boyden‐chamber cell‐migration and cell‐invasion assays. The results revealed a high potency of the macrolactones 2 and 34 and the ester analogues 35 and 38 , which suggests they have potential as antimetastatic agents.