title: Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
abstract: The first asymmetric synthesis of (S)- and (R)-5-hydroxythalidomides, one of thalidomide's major metabolites, was achieved using HMDS/ZnBr(2)-induced imidation as a key reaction. 5-Hydroxythalidomide was found to be configurationally more stable than thalidomide at physiological pH. Stereochemical biological effects of thalidomide and 5-hydroxythalidomide on anti-angiogenesis and antitumor activities were also investigated using racemic and pure enantiomers.
authors.affiliation: Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Shibata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sukeguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takashima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toru
authors.forename: Nozomu
authors.initials: N
authors.lastname: Matsunaga
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tanaka
authors.forename: Tohru
authors.initials: T
authors.lastname: Obata
authors.forename: Takuma
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013237:Stereoisomerism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C544471:5-hydroxythalidomide; D013792:Thalidomide