N,N-dimethyl-lysergamide.

[Helios.]

No guarantees here but...

9,10-didehydro-6-(Me, Et, Pro, v Allyl)ergoline-8-(E v Z)-(R=C)-(NMe2 v NEt2)

&

1-(9,10-didehydro-6-[Me, Et, Pro v Allyl]ergolinyl-8,B)-1-(NMe2 v NEt2)-ethylene are two ideas.

^Here 'R' is a cyclic hydrocarbon (in this case, 8-ergolinyl) and 'v' stands for 'or.'
Formulating a hypothesis is a step of the scientific method.

 

[vecktor]

9,10-didehydro-6-(Me, Et, Pro, v Allyl)ergoline-8-(E v Z)-(R=C)-(NMe2 v NEt2)

&

1-(9,10-didehydro-6-[Me, Et, Pro v Allyl]ergolinyl-8,B)-1-(NMe2 v NEt2)-ethylene are two ideas.

^Here 'R' is a cyclic hydrocarbon (in this case, 8-ergolinyl) and 'v' stands for 'or.'
Formulating a hypothesis is a step of the scientific method.

quick question, why doesn't the enamine re arrange to the imino form and hydrolyse to the ketone and HNMe2 or HNEt2? do you expect this to be stable in aqueous solutions?

the carbonyl oxygen appears to take per in H bonding to the receptor, no carbonyl O and the pharmacology radically alters.

V

 

[swilow]

9,10-didehydro-6-(Me, Et, Pro, v Allyl)ergoline-8-(E v Z)-(R=C)-(NMe2 v NEt2)

&

1-(9,10-didehydro-6-[Me, Et, Pro v Allyl]ergolinyl-8,B)-1-(NMe2 v NEt2)-ethylene are two ideas.

^Here 'R' is a cyclic hydrocarbon (in this case, 8-ergolinyl) and 'v' stands for 'or.'
Formulating a hypothesis is a step of the scientific method.

??????????????

 

[Helios.]

weeping willow

vecktor, you're right. they both would, especially the second one.

then there's thia/mercapto-LSD-025 and thia/mercapto-DAM-57.

do R-(C=S)-NR'R'' functional groups happen?

 

[vecktor]

weeping willow

vecktor, you're right. they both would, especially the second one.

then there's thia/mercapto-LSD-025 and thia/mercapto-DAM-57.

do R-(C=S)-NR'R'' functional groups happen?

yes they're thioamides, think it will still have H bonding problems with the receptor.

I'm still waiting for the TR for DAM-57.......

I don't think this thread is going anywhere so I will bow out.

 

[fastandbulbous]

The carbonyl group is also imprtant in the formation of conjugated double bonds (keto-enol type tautomerism) to form the 'backbone' of LSD that makes it an almost planar molecule

On the molecule on the right, the darker bonds are all in the same plane due to conjugation with the aromatic rings (being planar seems to be a property essential to compounds with a high affinity to the 5HT2a receptor; another example being the bromo-dragonfly molecule)

 

[Helios.]

So the dideos I mentioned would or would not lyse?

 

[dtasrt_lk]

i would like to see more threads like this. The chemistry side of ergolines fascinate me

 

[Xorkoth]

You might get more in-depth responses from more people if you take it to ADD. I can move this thread there if you want, or we can leave it here. let me know.

 

[Xorkoth]

--> Moved to ADD

 

[Helios.]

I Am. I Am. I Am.

<tell 'em who THE FUCK I am.>

Will the dideos dissociate?>I think not.
Either way, it's worth a shot.

 

[vecktor]

keto enol Lysergide

the idea of keto enol tautomerism of lysergamides is interesting, I personally do not see the keto enol tautomerisation as being very important.

Whilst having a planar molecule over a proportion of the structure important for 5ht2a binding, egolines versus ergolenes. whether this is due to shape constraint or to presenting the aromatic electrons in a favourable flat alignment to enable pi electron, van der waals interactions with the receptor I know not. anyway back to the topic..

The reason I suspect the enol form is because the the enol form of isolysergic acid diethylamide 8 alpha is identical to that of the the 8b isomer LSD. if the enol form was important then the isoLSD would be active and as potent as LSD.
from this we can further infer that the conversion to the enol form of the sterocenter at the 8 position doesn't occur under physiological conditions. because that could lead to inversion at the centre, the migrated proton could reattach in the 8a or 8b position when the enol form reverted to the carbonyl form, producing LSD from iso LSD. this is energetically favourable, but doesn't occur, in vivo.

SAR of Ergolines is a bitch. Sandoz have most of the interesting data locked away: 8 disubstituted ergolenes, the aromatised d ring ergolines etc etc.

please point out if i have missed something,
V

 

[vecktor]

continuing with the theme, the electrons in the amide moety are going to be delocalised helped by the alkyl groups. has anyone seen data for the structure of Lysergide in aqueous solutions rather than X ray cystallographic data?

 

[vecktor]

continuing with the theme, the electrons in the amide moety are going to be delocalised helped by the alkyl groups. has anyone seen data for the structure of Lysergide in aqueous solutions rather than X ray cystallographic data?

sorry to answer own question I have found 1H NMR data for aq Lysergide.

 

[fastandbulbous]

The reason I suspect the enol form is because the the enol form of isolysergic acid diethylamide 8 alpha is identical to that of the the 8b isomer LSD. if the enol form was important then the isoLSD would be active and as potent as LSD.
from this we can further infer that the conversion to the enol form of the sterocenter at the 8 position doesn't occur under physiological conditions. because that could lead to inversion at the centre, the migrated proton could reattach in the 8a or 8b position when the enol form reverted to the carbonyl form, producing LSD from iso LSD. this is energetically favourable, but doesn't occur, in vivo.

Maybe it acts as a 'pre-requisite' for LSD being able to interact with the active site of the 5HT2a receptor protein - allows it the best 'lining up position'; then again, it (keto-enol tautomerism) does look like the mechanism by which LSD could rearrange into iso-LSD. It would also fit neatly into the temp. relation of LSD going off (when it's warmer, the tautomerism would occur more often and the N,N-diethylcarboxamide group would have the 'momentum' (bad modelling image I know, but I've not had enough coffee to have anything but the most rudinmentary vocabulary!) to go all the way and flip to the iso configuration when going from enol to keto tautomer.