The synthesis of carbon-linked bisbenzylisoquinolines via ruthenium-mediated olefin-metathesis

Synthesis of 2′-aminoalkyl-1-benzylisoquinoline derivatives and medium sized ring analogues with mu opiod receptor binding activities

“…The structures of known CNS active compounds. [8][9][10][11][12] In our continuing project concerned with the discovery of new bioactive benzylisoquinoline derivatives, [13][14][15] the 2'-aminoalkyl-1-benzylisoquinoline compound 7 and the medium side ring analogues 8 were of interest. We report here our attempts to synthesise these compounds and the biological activities of four of these analogues on 48 different CNS receptors.…”

“…With the aim of preparing 2'-aminoethyl-1-benzylisoquinoline derivatives, we first examined the method reported by Seijas et al towards the preparation of phenylethylamines derivatives by addition of primary and secondary lithium amides to styrene. 16 The racemic 2'-vinyllaudanosine derivative 10 was prepared from the known N-TFA derivative 9 14,15 in 75% overall yield. Morpholine was treated with nbutyl lithium and the resulting solution of lithium morpholinamide in THF was added to compound 10 at 0 o C. The mixture was left at 0 o C for 18 h. 1 H NMR analysis only showed unreacted starting material 10 and no morpholine ethylene signals were observed.…”

“…and 12, [14][15] respectively, using the 2 step sequence of dihydroxylation, followed by oxidative cleavage. 17,18 N TFA The aldehydes 15 and 16 were subjected to reductive amination reactions with several amines to give the corresponding aminated products in moderate to good yields (Scheme 3, Table 1).…”