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A highly selective nonpeptidic δ opioid receptor agonist TAN-67, (4aS*, 12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1,2,3,4,4a,5,12,12a-octahydropyrido[3,4-b]acridine was designed on the basis of the message-address concept and the accessory site theory. (−)-TAN-67 is a potent and selective δ1 opioid receptor agonist and shows strong antinociceptive, cardioprotective, and antiarrhythmic effects. By contrast, (+)-TAN-67 induced hyperalgesia, the opposite effect of antinociception. An important intermediate ketone for the TAN-67 synthesis, (4aS*, 8aR*)-4a-(3-methoxyphenyl)-2-methyl-6-oxodecahydroisoquinoline, has two structural features: a trans-fused bicyclic heterocycle and a quaternary carbon stereocenter at the bridgehead position. Syntheses of the intermediate ketone reported by some research groups are described. The synthesis of chiral TNA-67 is also shown. [ABSTRACT FROM AUTHOR]