Die absolute Konfiguration von (+)‐Glutethimid

Abstract

Knabe und ReischigArch. Pharm. 3a: vgl. Tab. 1, NMR (CDCI3, 6 (ppm), TMS) = 4.29 (d.J 6.5, H-4); 3.57 (m, H-3);4.05 (d.J 4a: vgL Tab. 1, NMR (CDC13, 6 (ppm), TMS) = 4.63 (d.J 8, H-4); 3.92 (m, H-3); 4.28 (d.J 8, 6.5, H-3); 4.19 (4, J 7,4 H); 1.24 (4, J 7, 3H); 1.23 (q, J 7, 3H); 7.22 (s.NH). H-2); 3.77 (dq, 2 H); 0.83 (t, J 7, 3 H); 4.23 (q, J 7, 2 H); 1.27 (t, J 7, 3 H); 7.25 (s.NH). 3. 1.8-H-trans-6-Acetamino-2-athoxycarbonyl-I phenyl-pyrrolizidin-3,5,7-trion (5a) aus 3a 160 mg (3.3 mmol NaH, 50 7% Suspension in 01) werden analog 1. mit 0.48 g (3.3 mmol) NaAcetylglyinester und 500 mg (1.65 mmol) 3a umgesetzt und aufgearbeitet. Man erhalt 260 mg (45 % d. Th.) 5a.In klassischen Arbeiten berichteten Branchini und Mitarb. ') und unabhiingig dawn Keberle, Riess und Hoffmann') uber die Gewinnung der Enantiomere von Glutethimid. Sie fanden, daB beide Enantiomere unterschiedlich metabolisiert werden und dal3 das (+)-Enantiomer 2-3 mal starker sedativ wirksam ist als das (-FEnantiomer. Offen blieb die Frage nach der absoluten Konfiguration der Enantiomere. Wir haben uns deshalb der Klarung dieser Frage zugewandt. Durch Kettenverlangerung der (+)-3-Cyano-3-phenyl-pentansaure [(t) 11, die S-Konfiguration besitzt3), nach Arndt-Eistert4) uber die Zwischenstufen (t) 2 und (-) * H e m Prof. Dr. Felix Zymlkowski zum 65. Geburtstag gewidmet.

2,6‐Piperidinediones, I. Synthesis of the Racemates and the Enantiomers of 3,3‐Disubstituted 2,6‐Piperidinediones

“…75" C.NMR (CDCI,): 6 (ppm) = 9,3 (s; lH, OH), 7,4 (m; 5H aromat. ), 2,8-2,0 (m; 4H, CH,CH,-), 1,7 (s;3H,CH,). IR (KBr): 3000 (OH), 2240 (CN), 1720 (CO), 760 cm-' (phenyl).…”

“…"): 100-104" C. NMR (CDCl,): 6 (ppm) = 9,[2][3][4][5][6][7][8]7 (broad;lH,NH),7,3 (m;5H aromat. ), 2,8-2,0 (m; 4H, -CHz-CH2-), 1,6 (s;3H,CH,). IR (KBr): 3120 (NH), 1720 and 1740 (O=C-N-C=O), 870 (aromat.).…”

“…o, l 55-56' C. NMR (CDCl,): 6 (ppm) = 5,8 (t; lH, olefin. ), 3,2 (4; lH, CH), 2,6-1,5 (m; 8H, CH,),1,4 (d; 3H, CH,). IR (NaCl): 2940-2960 (CH), 2220 and 2240 cm-' (CN).2-(I ' -Cy clohexeny I) -2-ethy l-acetonitrile (le) Yield 83,8 %, b.p.…”

Circular dichroism spectra and molecular geometry of six-membered ring anhydrides and imides

“…This study deals with the six-membered ring anhydrides and imides which present a greater variety of structures than the former compounds and they may serve as a basis for testing sector rules. '** Several model compounds (1)- (21) have been synthesized and their spectra examined. Molecular Geometries.-Since knowledge of preferred conformations is a decisive factor in the interpretation of chiroptical spectra molecular mechanics (MM), calculations have been performed for model compounds.…”

“…' However, in all cases the distortion of the chromophores rarely exceeds 10" in terms of the C-0-C=O or C-N-C=O torsion angles. Different types of geometries are presented by bridgehead bicyclic compounds (16)- (21) for which the sizeable twisting of the chromophores is almost impossible; e.g. anhydride moieties in 3-oxabicyclo[3.2.1]octane-2,4-dione (19) and its 6,6-dimethyl derivative (Ma) were calculated to be almost planar.…”