The practicable synthesis of all imaginable isomeric heterocyclic moieties 8-11 and ent-8-ent-11 of the naphthylisoquinoline alkaloids is described. The stereoinformation at C-3 is induced by asymmetric reductive amination, using 1-phenylethylamines of either enantiomeric series as chiral auxiliaries. The key step of the stereocontrolled construction of the stereocenter at C-1 is the diastereoselective reduction of the corresponding dihydroisoquinolines, as obtained by Bischler-Napieralski synthesis, or the regio-and stereoselective Pictet-Spengler reaction of arylisopropylamines with acetaldehyde, respectively.
The “most unusuall of all the isoquinoline alkaloids,” the title compound 2, is characterized by a biphenyl system configurationally stable to above 200°C. The key step in the synthesis is intramolecular CC bond formation in the intermediate 1, in which the two molecular halves are joined by means of lactone formation.
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