Enzymatic resolution and evaluation of enantiomers of cis-5'-hydroxythalidomide.
The straightforward synthesis of both enantiomers of cis-5'-hydroxythalidomide, a major metabolite of thalidomide, has been accomplished by enzymatic kinetic resolution of a racemic substrate catalyzed by Pseudomonas stutzeri lipase TL. cis-5'-Hydroxythalidomide shows resistance to racemization (and epimerization) at physiological pH. A tube formation assay to assess the ability to inhibit angiogenesis revealed that cis-5'-hydroxythalidomides are inactive.
Yamamoto
Takeshi
T
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan.
Shibata
Norio
N
Takashima
Masayuki
M
Nakamura
Shuichi
S
Toru
Takeshi
T
Matsunaga
Nozomu
N
Hara
Hideaki
H
D002384:Catalysis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D008968:Molecular Conformation; D044223:Pseudomonas stutzeri / Q000201:enzymology; D013237:Stereoisomerism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
C452282:5'-hydroxythalidomide; D013792:Thalidomide; D008049:Lipase