Acetogenic isoquinoline alkaloids. L: The synthesis of all possible isomeric 6,8-dioxygenated 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline methyl ethers : useful chiral building blocks for naphthylisoquinoline alkaloids

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.