An efficient method to prepare N-acylpyridinium ions like (III) is reported. Treatment of the latter with organometallic reagents leads to α-substituted N-acyldihydropyridines and N-acyldihydropyridones. The degree of stereoselectivity depends on the pyridine and organometallic reagent used. The auxiliary can smoothly be removed under basic conditions. -(HOESL, C. E.; MAURUS, M.; PABEL, J.; POLBORN, K.; WANNER*, K. T.; Tetrahedron 58 (2002) 33, 6757-6770; Inst. Pharm.,
Azetidine Derivatives as Novel γ-Aminobutyric Acid Uptake Inhibitors: Synthesis, Biological Evaluation, and Structure-Activity Relationship. -Azetidines, e.g. (I)-(III), are synthesized as structural analogues of four known GABA-uptake inhibitors. Their activities strongly depend on both the position of the carboxylic acid moiety and the nature of the lipophilic groups. The highest affinity at GAT-1 is observed for azetidinylacetic acid derivative (I) with a selectivity of 48:1 for GAT-1 over GAT-3. Azetidinecarboxylic acid derivative (II) is the most potent inhibitor of GAT-3 with IC50 of 15.3 μM and a selectivity greater than 7:1 for GAT-3 over GAT-1. Derivative (III) reveals moderate potency at and subtype selectivity for GAT-3. -(FAUST, M. R.; HOEFNER, G.; PABEL, J.; WANNER*, K. T.; Eur.
Amino acids
Amino acids U 0400Asymmetric Synthesis with 6-tert-Butyl-5-methoxy-6-methyl-3,6-dihydro-2H-1,4-oxazin-2-one as a New Chiral Glycine Equivalent: Preparation of Enantiomerically Pure α-Tertiary and α-Quaternary α-Amino Acids. -The synthetic utility of oxazinone (V) as key intermediate in the synthesis of enantiomerically pure α-amino acids is studied. Oxazinone is prepared from α-hydroxy acid (I), itself obtained in excellent optical purity by optical resolution using (R)-phenylalaninol. Monoalkylation, dialkylation and cyclopropanation reactions of oxazinone (V) proceed with excellent yields and diastereoselectivities. The cyclopropanation reaction with epichlorohydrin enantiomers (XII), however, does not proceed with the expected stereoselectivity and cannot be used to achieve all four possible diastereomers. Further functionalization of the cyclopropane side chain is studied. Hydrolysis conditions for the release of the corresponding α-amino acids from the oxazinones are optimized for each substrate. In contrast to a previously described oxazinone (XXIII), no side reactions due to additional functional groups are possible. -(KOCH, C.-J.; SIMONYIOVA, S.; PABEL, J.; KAERTNER, A.; POLBORN, K.; WANNER*, K. T.; Eur.
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