Synthesis of Enantiomerically Pure Tetrahydro-2-methylharman

✍ Scribed by Shiqi, Peng ;Min, Guo ;Winterfeldt, Ekkehard

• Book ID: 102365403
• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 357 KB
• Volume: 1993
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199319930125

✦ Synopsis

Abstract

L‐Tryptophan methyl ester reacts with acetaldehyde in a Pictet‐Spengler condensation to give a 2.5:1 mixture of the stereoisomers (1__S__,3__S__)‐2 and (1__R__,3__S__)‐2. These were converted by ammonolysis into the corresponding amides (1__S__,3__S__)‐3 or (1__R__,3__S__)‐3. On methylation of (1__S__,3__S__)‐3 or (1__R__,3__S__)‐3 the corresponding 2‐methylcarbolineamide (1__S__,3__S__)‐4 or (1__R__,3__S__)‐4 were obtained. Dehydration of (1__S__,3__S__)‐4 or (1__R__,3__S__)‐4 affords 2‐methylcarbolinenitrile (1__S__,3__S__)‐5 or (1__R__,3__S__)‐5. After reduction with NaBH~4~ (1__S__,3__S__)‐5 or (1__R__,3__S__)‐5 was decyanated and the title compound (1__S__)‐6 or (1__R__)‐6 was obtained. With NOE experiments their stereochemistry were determined and their optical purities were confirmed by measurements using a chiral shift reagent.