title: Improved Synthesis of MDL 73811 - a Potent AdoMetDC Inhibitor and Anti-Trypanosomal Compound.
abstract: An improved synthesis of MDL 73811 - a potent AdoMetDC (S-adenosylmethionine decarboxylease) inhibitor and anti-trypanosomal compound with in vivo activity has been completed in four steps from commercially available 2',3'-O-isopropylideneadenosine. Utilization of Mitsunobu chemistry was crucial for the reliable and scalable introduction of the 5'-methylamine moiety, which was problematic using traditional activation/displacement chemistry as previously reported. All reactions in this synthesis were run on gram-scale resulting in a five-fold increase in yield over the original synthesis.
authors.affiliation: Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brockway
authors.affiliation: Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Cosner
authors.affiliation: Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas,6001 Forest Park Road, Dallas, Texas 75390-9041, United States.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Volkov
authors.affiliation: Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas,6001 Forest Park Road, Dallas, Texas 75390-9041, United States.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Phillips
authors.affiliation: Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
authors.forename: Jef K
authors.initials: JK
authors.lastname: De Brabander
keywords: drug discovery; nucleosides