title: Antineoplastic agents 320: synthesis of a practical pancratistatin prodrug.
abstract: Owing to its sparingly soluble properties, the potential anticancer drug pancratistatin (1) resisted conventional drug formulation procedures and the synthesis of a water-soluble prodrug became necessary. That important objective for further pre-clinical development was met by devising a route to a disodium phosphate derivative (5). The key step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3,4-tetraacetoxy-pancratistatin (2) with dibenzyloxy(N,N-diisopropylamido)-phosphine. Subsequent oxidation with m-chloroperbenzoic acid afforded phosphate 4a. Hydrogenolysis of the benzyl esters followed by base-catalysed hydrolysis of the acetate groups led to the water-soluble prodrug 5 in high yield.
authors.affiliation: Cancer Research Institute, Arizona State University, Tempe 85287-1604, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: S
authors.initials: S
authors.lastname: Freeman
authors.forename: M J
authors.initials: MJ
authors.lastname: Simpson
authors.forename: M A
authors.initials: MA
authors.lastname: Thompson
authors.forename: M R
authors.initials: MR
authors.lastname: Boyd
authors.forename: M D
authors.initials: MD
authors.lastname: Williams
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: D L
authors.initials: DL
authors.lastname: Doubek
mesh_terms: D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D007546:Isoquinolines / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D011355:Prodrugs / Q000138:chemical synthesis*; D013057:Spectrum Analysis
chemical_list: D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D007546:Isoquinolines; D011355:Prodrugs; C044997:pancratistatin