title: Chemoenzymatic synthesis of Amaryllidaceae constituents and biological evaluation of their C-1 analogues. The next generation synthesis of 7-deoxypancratistatin and trans-dihydrolycoricidine.
abstract: An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; and oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds.
authors.affiliation: Chemistry Department and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Collins
authors.forename: Uwe
authors.initials: U
authors.lastname: Rinner
authors.forename: Michael
authors.initials: M
authors.lastname: Moser
authors.forename: Tomas
authors.initials: T
authors.lastname: Hudlicky
authors.forename: Ion
authors.initials: I
authors.lastname: Ghiviriga
authors.forename: Anntherese E
authors.initials: AE
authors.lastname: Romero
authors.forename: Alexander
authors.initials: A
authors.lastname: Kornienko
authors.forename: Dennis
authors.initials: D
authors.lastname: Ma
authors.forename: Carly
authors.initials: C
authors.lastname: Griffin
authors.forename: Siyaram
authors.initials: S
authors.lastname: Pandey
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001388:Aziridines / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C418326:7-deoxypancratistatin; D000447:Aldehydes; D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D001388:Aziridines; D004852:Epoxy Compounds; D007546:Isoquinolines; D010616:Phenanthrenes; C551128:trans-dihydrolycoricidine; C031181:phenanthrene; C033132:aziridine