(-)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane

[Riemann Zeta]

Here's a little drawing of tropane stimulant stereochemistry:

Changing the position of the two esters from cis (both exo in the active (-)-cocaine) to trans gives allocoaine, which is virtually inactive.

 

[haribo1]

^The last one surely WOULD be the most active. But how to make it without ending up with 2 isomers. I assume you dehydrate the trophine and add across the double-bond, but your going to get 4 isomers I assume (correct me if I'm wrong).
Of course, if you go through the dehydrated molecule, then you could add a methyl group where the COOCH3 is since I heartell it's very active...

 

[vecktor]

^The last one surely WOULD be the most active. But how to make it without ending up with 2 isomers. I assume you dehydrate the trophine and add across the double-bond, but your going to get 4 isomers I assume (correct me if I'm wrong).
Of course, if you go through the dehydrated molecule, then you could add a methyl group where the COOCH3 is since I heartell it's very active...

eh,
tropine pseudotropine are chiral, use a selective substitution reaction to swap the OH for a halogen or a sulphonate ester and a coupling to the aryl halide and Robert is your fathers brother... addition to tropinone can also be made enantioselectively
I have seen the last compound somewhere in the literature, probably in Singhs review of cocaine analogs.