title: Total synthesis of bistramide A and its 36(Z) isomers: differential effect on cell division, differentiation, and apoptosis.
abstract: The total synthesis of bistramide A and its 36(Z),39(S) and 36(Z),39(R) isomers shows that these compounds have different effects on cell division and apoptosis. The synthesis relies on a novel enol ether-forming reaction for the spiroketal fragment, a kinetic oxa-Michael cyclization reaction for the tetrahydropyran fragment, and an asymmetric crotonylation reaction for the amino acid fragment. Preliminary biological studies show a distinct pattern of influence of each of the three compounds on cell division, differentiation, and apoptosis in HL-60 cells, thus suggesting that these effects are independent activities of the natural product.
authors.affiliation: Université de Lyon, ICBMS-UMR CNRS 5246, LCO2-Glycochimie, Université Claude Bernard Lyon 1, Bat. 308 CPE Lyon, 43, bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Tomas
authors.forename: Gustav
authors.initials: G
authors.lastname: Boije af Gennäs
authors.forename: Marie Aude
authors.initials: MA
authors.lastname: Hiebel
authors.forename: Peter
authors.initials: P
authors.lastname: Hampson
authors.forename: David
authors.initials: D
authors.lastname: Gueyrard
authors.forename: Béatrice
authors.initials: B
authors.lastname: Pelotier
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.forename: Olivier
authors.initials: O
authors.lastname: Piva
authors.forename: Janet M
authors.initials: JM
authors.lastname: Lord
authors.forename: Peter G
authors.initials: PG
authors.lastname: Goekjian
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003500:Cyclization; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000081:Acetamides; D011714:Pyrans; D013141:Spiro Compounds; C059975:bistratene A