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Methylenedioxy ring

Canis aureus

Canis aureus

Bluelighter
Joined
Nov 25, 2005
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930
Well,

I'm not a chemist, but I'm interested in that ring.... Who isn't?


But could that ring be found in some natural products, or medicines?

What is the primary reason for it (that ring)? The essential effect(s) etc...?
 
The MDO ring is found in many places in nature, eg myristicin (nutmeg oil isolate) and protopine (California Poppy). The simplistic use for modern psychopharmacologists is to reduce the polarity of molecules like 3,4-dihydroxyamphetamine (alpha-methyl-DA) so that they cross over the blood brain barried more easily and bind uniquely once they get there (MDA).
 
Another interesting occurance in nature can be found in Noscapine, one of the lesser-known constituents of Opium (picture below). In fact, I see an entire MMDA molecule embedded in it! Well, actually N-methyl-Lophophine to be more accurate.

Noscapinem.png
 
Interesting....could "brain movies" have a connection with "opium dreams"?
 
Maybe, but I doubt the methylenedioxy ring on Noscapine has anything to do with it.

As far as I know, Noscapine's action is just a mild antitusive...
 
Quite right, lycorine though does, or at least it's less controversial but it still needs hydrogenation to be strictly correct.

c12715114-image.gif


See the attached link and judge for yourself. Im not using it as a source for commerce, rather one of education.
 
What I'm wondering (and what I think the OP was asking about) is why the MDO-Phenyl/Benzyl ring is found in naturally occurring plant alkaloids. What is their function in plants?

Cell signalling molecules? (ala resemblance to catecholamine neurotransmitters in mammals) ?

Pharmacological agents to deter preditor consumption of the plant?

Or simply just metabolic biproduct/intermediate?

Edit: Looks like lycorine is a toxin, which can be lethal to animals, but is also utilized as an anti-tumorgenic compound in chemotherapy (specifically, skin cancer?). Is this just an accidental benefit from a compound designed to kill animals which might eat the plant? Or again, is there some other role these MDO compounds play in plants which synthesize them.
 
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The methylenedioxybenzene ring system is found in many natural products (such safrole, used by the Cherokee as a treatment for syphilis) and medicines (such as the antibiotic Ciproflaxin) because of chemical stability (aromaticity) and easy of biosynthesis (from the common amino acid tyrosine). It is used recreationally to get high in MDMA because of its resemblence to DA and its interaction with DA's, which it physically resembles, receptors.

Huckel's rule of aromaticity (unusually large stability) of an organic chemical compound is defined as a compound that is flat, planar, circular (for n>0) and one that has H(n)=4n +2 pi electrons. If n=0, then H(0)=2 and we have the unusually stable/hard to separate case of the lone pair of electrons. If n=1, then H(1)=4(1)+2=6 and we have examples such as thiophene, pyrrole, furan, and benzene. If n=2, then H(2)=4(2) + 2=10 and we have azulene and 1,3-benzodioxole (the IUPAC word for 3,4-methylenedioxybenzene).

The biggest catch here is that the two H's of the methylene unit are basically at 45 degree angles to the plane of the molecule at large (one up and one down; this is of minor importance) and that the C of the methylene unit is not a conductor of electrons but rather an insulator of electricity. Still, this addition of a CH2 to a catechol (a vicinal di-hydroxy aromatic chemical functionality) makes the two O's more in the plane and allows one each of their two per O lone pairs of electrons to better geometrically and electronically line up with the circuit of the parent benzene ring. Also, being connected as two rings within a larger ring allows for better vibrational communication leading to, in some cases, greater resonance energy advantages.

From a biological/biochemical/evolutionary perspective, dopamine is synthesized from tyrosine and tyrosine is one of the naturally occurring, ubitquitous 20 amiino acids found after the break down of any protein, such as meat. The methylene unit added to the dopamine derived from tyrosine (each with its generally somewhere to be found -CH2CH2NH2 side chain harking back to its days as a subunit of a protein) also makes the 1,3BNZDXL compound less polar and therefore better able to cross lipid filled membranes such as that of spirochetes or of the mammalian blood brain barrier, helping both sarole, Ciproflaxin and MDMA do their jobs better.

The 1,3-BZDXL/3,4MDOB bicyclic ring system is everywhere because it is both stable/easily formed AND useful.
 
Was thinking its significance in plants and effects to humans or animals. Supposed hallucinogenic nature...
 
Canis aureus said:
Was thinking its significance in plants and effects to humans or animals. Supposed hallucinogenic nature...
Click to expand...

It's similar to dopamine, except much less polar, so can pass the BBB, but what's interested me most about MDMA (not the MD), is the oxytocin/vasopressin release, which seems to be lacking extremely in MDEA and partially in MDA (in my own experience, though if there is a study which shows levels of vasopressin/oxytocin release of MDA, MDMA and MDEA i'd be very happy to see it).
 
fastandbulbous said:
And that's probably the thing that makes people talk about 'smacky' pills
Click to expand...

Because of an inability to piss? I generally thought MDEA was considered smacky because of the mongy-ness of it, not MDMA being considered smacky because of water retention, or is that what you were suggesting? (where's the link with vasopressin)
 
The effects of oxytocin are not that dissimilasr to endorphins in some ways - it's role in some things like after childbirth is to form a strong bond between mother & baby. Both produce a sense of inner contentment, only with oxytocin it also has a strong empathy component to it
 
Coolio said:
Haha what the hell is "mongy" ?
Click to expand...

It might be a UK-only term, if one is "monged out" then it generally means, drowsy, lacking in cognitive abilities, just a general head-fuck really.

fastandbulbous said:
The effects of oxytocin are not that dissimilasr to endorphins in some ways - it's role in some things like after childbirth is to form a strong bond between mother & baby. Both produce a sense of inner contentment, only with oxytocin it also has a strong empathy component to it
Click to expand...

Ok, I guess somebody who has taken opiates before would think that, but to most of the average joes i know: drowsy pills = smacky pills, either way its false.
 
The good doctor wrote a whole book containing hundreds of compounds with the ring in it (the simple plant isoquinolines). Lots of benzazepines also contain the ring. I spent a summer synthesizing some of the natural product analogues. I was not able to test any for CNS activity though :( (well, besides the ones of known activity :))
If you are searching pubmed or anything similar, it is important to keep in mind that lots of non-drug related researchers refer to the ring as the benzodioxole structure. Using methylene- when refering to a saturated carbon, while completely kosher, can be somewhat confusing.

On another topic related to oxytocin, is that what causes the post-orgasm drowsiness in males (and to a lesser extent [unless your KA, of course], females)? Or is it enkephalins?
 
Endorphins are polypeptides (strings of amide linked amino acids) associated with pain relief. Morphine stimulates (agonizes, in this case) the same receptors as endorphins.

Oxytocin is released after orgasm. MDMA resembles orgasm.

MDMA leads to urinary hesitancy to its anti-diuretic hormone (ADH) agonist activity.
 
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