title: Total synthesis of 2''',5'''-diepisilvestrol and its C1''' epimer: key structure activity relationships at C1''' and C2'''.
abstract: The first total synthesis of the low-abundance natural product 2''',5'''-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2''',5'''-diepisilvestrol (4) and its C1 epimer 1''',2''',5'''-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2''',5'''-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1''',2''',5'''-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1''' and C2''' has a large effect on the biological activity.
authors: School of Chemistry, The Bio21 Institute, The University of Melbourne, Victoria 3010, Australia.
authors: Jennifer M
authors: JM
authors: Chambers
authors: David C S
authors: DC
authors: Huang
authors: Lisa M
authors: LM
authors: Lindqvist
authors: G Paul
authors: GP
authors: Savage
authors: Jonathan M
authors: JM
authors: White
authors: Mark A
authors: MA
authors: Rizzacasa
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C554317:2''',5'''-diepisilvestrol; D001572:Benzofurans; D014315:Triterpenes; C489893:episilvestrol