Ever since I learned that paspalic acid could be isomerized into lysergic acid, I've been reexamining what I've thought about ergot chemistry. In particular, I've been thinking about hydergine and other 9,10-dihydrolysergic acid derivatives.
Hydrogenated lysergic acid derivatives are nowhere near as closely regulated as the non-hydrogenated ones. The reason for this is that 9,10-dihydrolysergamides are nowhere near as active or interesting.
But...
What if dehydrogenation really
is possible? Sure, H
2 isn't going to split off by itself spontaneously, but maybe under the right conditions there is a reaction, or a series of reactions, that would allow this to happen.
I know that DDQ has been used to dehydrogenate benzocyclohexane systems to afford a double bond that is conjugated with the benzene ring, but would it work here? This sort of reaction has been used rather extensively in recent terpenoid syntheses, but how will that pyrrole ring affect it?
Here's a general example of this reaction:
Molecule:
dehydrogenation1 ("[H][C@]24CC[C@]1(C)[C@@H]([R])CC[C@@]1([H])[C@]2([H])CCc3cc(O[R])ccc34>>[H][C@@]23CCc1cc(O[R])ccc1C2=CC[C@]4(C)[C@@H]([R])CC[C@@]34[H]")
Here are some articles related to this:
Tetrahedron Letters, (2002), 41(11), 1729-1731.
Comptes Rendus de lÏAcademie des Sciences, Serie IIc: Chimie, (2001), 4(3), 201-205.
J. Chem. Soc., Perkin Trans.1 (1955), (22), 2813-15
Steroids, (1995), 60(12), 809-11.
Recl. Trav. Chim. Pays-Bas, (1993), 112(12), 627-34.
Synlett, (1992), (10), 821-2.
Patent US4882319
Helv. Chim. Acta, (1989), 72(4), 725-30.
Another route might be to take it in two steps: allowing dihydrolysergamides to react with LDA and I
2 should add an iodide
beta to the carbonyl. If this were followed up with an E2 elimination reaction, you'd have successfully dehydrogenated your starting material.
I don't know. I'm throwing out guesses right now. Does anybody else have another approach to this problem?