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Paper | Regular issue | Vol 63, No. 12, 2004, pp. 2747 - 2767
Published online: 26th October, 2004
DOI: 10.3987/COM-04-10213
Stereoselective Synthesis of 1-Substituted 1,2,3,4-Tetrahydro-β-carbolines by Asymmetric Electrophilic α-Amidoalkylation Reactions

Ulrich Weber, Cornelia Hoesl, W. Ponikwar, M. Suter, Heinrich Nöth, and Klaus T. Wanner*

*Department of Pharmacy, Ludwig-Maximilians-University of Munich, Butenandtstr. 5-13 Haus C, D-81377 Munich, Germany

Abstract

An efficient procedure for the asymmetric synthesis of 1-substituted 1,2,3,4-tetrahydro-9-methyl-β-carbolines based on asymmetric electrophilic α-amidoalkylation reactions is described. Stereoselective addition of various organometallic reagents to a chiral N-acyl-β-carbolinium ion gave the corresponding 1-substituted 1,2-dihydro-β-carbolines in high yields and very good to excellent diastereomeric ratios. Catalytic hydrogenation followed by the removal of the chiral auxiliary via reductive cleavage of the amide bond proceeded with complete conservation of the absolute configuration at the newly created stereocenter leading to 1-substituted 1,2,3,4-tetrahydro-9-methyl-β-carboline derivatives in high yields. Their absolute stereochemistry was proven by X-Ray analysis. The 1-phenyl-substituted 1,2,3,4-tetrahydro-β-carbolines were evaluated for their affinity to the PCP binding site of the NMDA receptor.

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