[Enantioselective biotransformation of a new theophylline derivative].
Reductive amination of 4 with (RS)-2 is an improved method to obtain 7-((RS)2-((RS)-1-Methyl-2-phenyl-ethylamino)propyl)-theophylline (3) (ratio of diastereomers 1:1) compared with SN-displacement of proxyphyllintosylate with (RS)-2 (ratio of diastereomers 9:1). Due to steric hindrance 3 is no noteworthy prodrug for the intermediate formation of (RS)-2 in rats. The enantioselectivity of 2 after a single oral dose of 3 is determined in 24-h urine by HPLC on a Cyclobond-column using the isoindole derivatives, formed from o-phthalaldehyde, thioglycolic acid, and 2. The R(-)-amphetamine isomer is formed to a lesser amount (34.8%, range 32-37%) than the S(+)-isomer (65.2%, range 63-68%).
Harsche
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Institut für Pharmazeutische Chemie, Johann Wolfgang Goethe-Universität, Frankfurt am Main.
Oelschläger
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Engel
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D000818:Animals; D001711:Biotransformation; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013806:Theophylline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C073108:7-(2-(1-methyl-2-phenyl-ethylamino)propyl)theophylline; D013806:Theophylline
Enantioselektivität der Biotransformation eines neuen Theophyllinderivats.