hxxp://pubs.acs.org/doi/abs/10.1021/jo01156a007
Product looks a bit like pethidine, huh? Use phenethylamine HCl instead, perhaps...
hxxp://pubs.acs.org/doi/abs/10.1021/jo00406a025
As seen above, the Baeyer Villiger rxn could be used to create a phenolic ester to cleave and decarboxylate... then all that's left to do is acylate that alcohol and you've got a powerful pethidine analog. In fact, you don't even have to acylate it...
hxxp://www.scribd.com/doc/43445467/Some-N-Phenethyl-4-Heteroaryl-4-Piperidinols-and-Related-Compounds-Beckett-AH-Casy-AF-Phillips-PM-J-Med-Chem-2-3-245-261-1960-J-Med-Che
(view page 252)
...but why not?
Hopefully the elimination product isn't anywhere near as neurotoxic as MPTP.
What would potentially be very exciting is if this ester didn't even need to be cleaved.
hxxp://www.scribd.com/doc/37631284/Synthetic-analgesics-F-Bergel-and-A-L-Morrison-Q-Rev-Chem-Soc-1948-2-349-382-DOI-10-1039-QR9480200349
(go to page 366)
This suggests it *MAY* not interfere with binding to our favorite receptor. If this is the case, tedious and potentially messy/low yielding decarboxylation could be avoided - simply acylate, hit with MeOH under transesterification conditions and... walah. Perhaps even the phenolic ester would be active, or even the PhCO compound, though steric factors probably preclude this from occurring. Alternatively, perhaps a mixture of acetone and acetophenone could be used, as the 3-methyl compound is active, so the 3-ethyl should be as well, and 3-ethyl is only a Zn/HCl away when you've got the keto compound (which, again, may actually be active). Yields would never reach 50%, but sloppy bastards would love it.
The skeleton of a mu agonist from acetophenone, formaldehyde, and phenethylamine - not bad at all.
Product looks a bit like pethidine, huh? Use phenethylamine HCl instead, perhaps...
hxxp://pubs.acs.org/doi/abs/10.1021/jo00406a025
As seen above, the Baeyer Villiger rxn could be used to create a phenolic ester to cleave and decarboxylate... then all that's left to do is acylate that alcohol and you've got a powerful pethidine analog. In fact, you don't even have to acylate it...
hxxp://www.scribd.com/doc/43445467/Some-N-Phenethyl-4-Heteroaryl-4-Piperidinols-and-Related-Compounds-Beckett-AH-Casy-AF-Phillips-PM-J-Med-Chem-2-3-245-261-1960-J-Med-Che
(view page 252)
...but why not?
Hopefully the elimination product isn't anywhere near as neurotoxic as MPTP.What would potentially be very exciting is if this ester didn't even need to be cleaved.
hxxp://www.scribd.com/doc/37631284/Synthetic-analgesics-F-Bergel-and-A-L-Morrison-Q-Rev-Chem-Soc-1948-2-349-382-DOI-10-1039-QR9480200349
(go to page 366)
This suggests it *MAY* not interfere with binding to our favorite receptor. If this is the case, tedious and potentially messy/low yielding decarboxylation could be avoided - simply acylate, hit with MeOH under transesterification conditions and... walah. Perhaps even the phenolic ester would be active, or even the PhCO compound, though steric factors probably preclude this from occurring. Alternatively, perhaps a mixture of acetone and acetophenone could be used, as the 3-methyl compound is active, so the 3-ethyl should be as well, and 3-ethyl is only a Zn/HCl away when you've got the keto compound (which, again, may actually be active). Yields would never reach 50%, but sloppy bastards would love it.
The skeleton of a mu agonist from acetophenone, formaldehyde, and phenethylamine - not bad at all.
:
Kinetics of the Baeyer-Villiger reaction of acetophenones with permonophosphoric acid.pdf
These types of compounds were first brought up on the Hive by Epikur and related articles were/are hosted on Rhodium's page: