4DQSAR
Bluelighter
- Joined
- Feb 3, 2025
- Messages
- 6,192
Has anyone else notice the structure of cabergoline? I was just thinking back and in 2002 when cabergoline was quite a new medication, a post graduate friend just mentioned it in passing but numb-nuts here totally forgot about it.
Now, unsaturating that 9-10 bond from alkane to alkene i.e. oxidizing it from an N-allylpiperidine to an N-allyltetrahydropyridine is a novel route to 8-allyl-norlysergic acid. I freely admit I haven't bothered to find the most likely hydrolysis to split that amide to get the intermediate cabergolinic acid but it appears facile.
I've never sampled AL-LAD but a trusted friend described it as 'LSD with training wheels' i.e. it was far less likely to result in a 'bad trip'.
I do apologize if this has been gone over again and again but it always struck me as a bit odd that someone would lose over half of their lysergic acid to produce a less potent product and wondered if maybe cabergoline was the explaination.
I can't speak for anyone else but I've always considered that N-demethylation gives you options for simple, moderate yields that use some very nasty reagents right (left, up, down, sideways, in a circle and have a lie down) to somewhat more benign reagents with not to great yields. In the last couple of decades there have been some really nice examples of non-classicial Polonovski reactions but of course one has to go via the N-oxide. I suppose if the two oxidations could somehow be combined, that would be quite elegant. Probably impossible, but it would be elegant (and efficient).
I suppose one is also free to either acquire or synthesize (S,S)-2,4-dimethylazetidine. It seems new technolgies/methodologies have made it a more practical target as compared to 2002. The paternò–büchi reaction sounds intriguing.
That said, I'm not even sure if the (S,S)-2,4-dimethylazetine is still regarded as exotic or preferable. I seem to recall Nick Sands made LSB for ages and nobody seemed to notice.
If one is forced to 'protect' that indole nitrogen, there may be options other than amidation.
Now, unsaturating that 9-10 bond from alkane to alkene i.e. oxidizing it from an N-allylpiperidine to an N-allyltetrahydropyridine is a novel route to 8-allyl-norlysergic acid. I freely admit I haven't bothered to find the most likely hydrolysis to split that amide to get the intermediate cabergolinic acid but it appears facile.
I've never sampled AL-LAD but a trusted friend described it as 'LSD with training wheels' i.e. it was far less likely to result in a 'bad trip'.
I do apologize if this has been gone over again and again but it always struck me as a bit odd that someone would lose over half of their lysergic acid to produce a less potent product and wondered if maybe cabergoline was the explaination.
I can't speak for anyone else but I've always considered that N-demethylation gives you options for simple, moderate yields that use some very nasty reagents right (left, up, down, sideways, in a circle and have a lie down) to somewhat more benign reagents with not to great yields. In the last couple of decades there have been some really nice examples of non-classicial Polonovski reactions but of course one has to go via the N-oxide. I suppose if the two oxidations could somehow be combined, that would be quite elegant. Probably impossible, but it would be elegant (and efficient).
I suppose one is also free to either acquire or synthesize (S,S)-2,4-dimethylazetidine. It seems new technolgies/methodologies have made it a more practical target as compared to 2002. The paternò–büchi reaction sounds intriguing.
That said, I'm not even sure if the (S,S)-2,4-dimethylazetine is still regarded as exotic or preferable. I seem to recall Nick Sands made LSB for ages and nobody seemed to notice.
If one is forced to 'protect' that indole nitrogen, there may be options other than amidation.
