Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
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.
Yamamoto
Takeshi
T
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya , Japan.
Shibata
Norio
N
Sukeguchi
Daisuke
D
Takashima
Masayuki
M
Nakamura
Shuichi
S
Toru
Takeshi
T
Matsunaga
Nozomu
N
Hara
Hideaki
H
Tanaka
Motohiro
M
Obata
Tohru
T
Sasaki
Takuma
T
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
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C544471:5-hydroxythalidomide; D013792:Thalidomide