La Fee Review from Bangkok

Sepulchritude Forum: The Absinthe Forum Archives Thru July 2001: Topics Archived Thru Oct 2000:La Fee Review from Bangkok
By Don_walsh on Monday, November 06, 2000 - 04:42 am: Edit

Here's the thujone.flc animation and the required aawin.exe player in a .zip file attachment. For anyone who wants it.

Pls note that you should set the animation speed to 4 fps if you want to read the text tags easily, and 8-12 fps if you faster action. The default is 51 fps which is nuts.

Enjoy!

application/x-zip-compressedthujone anim
aawin.zip (298 k)

By Don_walsh on Sunday, November 05, 2000 - 05:55 am: Edit

Dear Marc

Maybe they should start using that image as a Rorshach test?

Anyway if that's how you perceive it, you really ought to get off on the animation.

By Marc on Sunday, November 05, 2000 - 02:15 am: Edit

there's something strangely erotic about the thujone molecule. A vaginal, triangular opening from whence emits a bead of blood, the head of a cock or a renegade clit.

By Marc on Sunday, November 05, 2000 - 02:09 am: Edit

Don,

you the man! I'm using the thujone molecule
illustration as wallpaper on my desktop.

By Don_walsh on Sunday, November 05, 2000 - 01:06 am: Edit

I have pretty much completed the analysis and animation of the isomerization of a-thujone and b-thujome via their tautomeric enol or enolate intermediate. Sounds like a mouthful but the animation is very cute, I TOLD you molecules do dance. Imagine thujone doing the macarena!

I don't know how to post an animation file, so I won't try. If anyone wants this I will email it to them on request. You will need a .flc file player, AAWIN.EXE is available for free and is a pretty small (<1 Mb) program. If anyone wants to see the animation and doesn't have the player I will give the URL where it can be downloaded.

I started with 2D models of both thujones in ISISDraw, conveted to 3D in AccuModel, and exported as MDL .mol files for Babel conversion to MOPAC input files. The number crunching was done in MOPAC 6, a large Fortran scientific package ported to Win 95. The output was converted to multistep .xyz format with BabelWin, and then edited in Re_View and converted to .pov format and processed into high quality ray tracings in POV-Ray. Those files were them assembled into a .flc file by DTA.

Whew! I hope someone wants to see this thing because it was a pain in the neck...

By Don_walsh on Tuesday, October 31, 2000 - 08:56 pm: Edit

Here are the corrected pair of models in gif format; pls ignore the earlier post with mistake in connectivity in one; I will ask Admin to delete that one.

Here's a-thujone:

athujone2

and b-thujone:

b-thujone

And here's a simple sketch of both from the old JACS article.

abthuj

And the 'enol' form of both which is intermediate in the isomerization at high temperatures -- higher than wormwood or absinthe ever sees.

thujenol

Note that the Me group at the 4-carbon goes coplanar in the enol, thus losing its chirality (stereochemical nature) and so when it reverts to ketone, thujone, the Me can go either up or down, axial or equatorial. And does. And that's how the isomerization proceeds, folks.

By Don_walsh on Tuesday, October 31, 2000 - 08:13 pm: Edit

Whoops, one of those drawings I loaded is wrong.

I will get that taken care of.

Thanks to Anatomist1 and Mr.Wormwood for their help in obtaining a JACS article and one from Tetr.Lett. It is now clear that the isomerization of a-thujone and b-thujone, while it does proceed via the enol intermediate I suspected, does NOT take place at room temperature, at least not at any significant rate and probably not at all. a-Thujone at 120 C for 100 hours didn't isomerize at all; b-thujone did but not very much (<8%). As the 120 C temp is quite relevant to distillation of an absinthe steep at standard pressure, this is interesting. It means all a-thujone that is present will remain while a small amount of any b-thujone present will likely isomerize to a-thujone. Thus, distillation does not denature a-thujone, and in instance of a mixture of the two isomers being present in steep, a-thujone may be slightly increased by distillation conditions.

Absintheur's friend's 'Stovetop Stuffing' suggestion, as to whether cooking conditions might denature a-thujone in sage, and other culinary spices, is apparently contradicted by this article, so I will be happy to send it to Absintheur for his examination and comment. Cooking conditions may well be well in excess of 120 C and if anywhere near 280 C then a-thujone will also undergo isomerization, but more slowly than b-thujone. This is due to the 4-carbon hydrogen being axial in b-thujone and equatorial in a-thujone. b-Thujone will undergo bisulfite addition (a standard ketone test), a-thujone will not, for same reason.

Once again, analogies from THC models (to thujone) appear to be dangerous.

By Don_walsh on Tuesday, October 31, 2000 - 12:50 am: Edit

Okay, here's a pair of simplified ball and stick models courtesy of RasWin 2.6's export facility -- I can now output to gif.

a-thujone:

athujone

amd b-thujone

bthujone

Note that these are mirror images of each other, and that the 4-methyl group (the single ball hanging off the 5-ring next to the red oxygen) is on same side as the 3-balls in Y shape opposite it, in a-thujone, and on other side in b-thujone. THAT is the only difference.

Hope this helps everyone understand. I removed the hydrogens from images because they make the view of model too 'busy'.

By Anatomist1 on Monday, October 30, 2000 - 07:45 am: Edit

Don,

I may be able to get that at one of the UW libraries while I'm "at work" today.

K.

By Gman on Monday, October 30, 2000 - 06:57 am: Edit

Don, my first, and most likely last, experience w/durian was in Bangkok. "I brazenly get drunk even on bad smells" -Arthur Cravan

By Don_walsh on Monday, October 30, 2000 - 12:05 am: Edit

PS Anyone have ready access to a decent college library? If so, I'd love to have scans (or xeroxes) of:

Eastman, Winn, Journal of the ACS, Vol 82, p.5908 (1960)

Hoch et al, Tetrahedron Letters, p.3175, (1970)

which may very well contain the wisdom of how a- and b- thujones interconvert.

By Don_walsh on Monday, October 30, 2000 - 12:00 am: Edit

After a few hours of playing with both thujones on 3D modelers and animators and a molecular-orbital program called MOPAC, I think I was wrong. Thujones are not conformers, they are true stereoisomers. They can't interchange without bonds breaking/reforming. But they DO interchange. Therefore, bonds ARE breaking and reforming. Very likely, the intermediate structure is what we call an 'enol' or 'enolate' which is short lived -- if I am right it could probably be observed by NMR at low temperatures. Anyway, both a- and b-thujone convert to the intermediate structure, and the intermediate then goes back to thujone, and the thermodynamics favor the b-form. At this point, this explanation is just an educated guess. From the 'user' poitn of view, the mechanism of interchange doesn't matter. That these isomers do equilibrate (in favor of the b-form by 2 to 1) is a fact.

By Don_walsh on Sunday, October 29, 2000 - 06:46 pm: Edit

Anyone who wants to have a professional 2D drawing system and viewer for chemical structures can go to MDL's site:

http://www.mdli.co.uk/downloads/isisdraw.html

and download version 2.3 of ISIDraw, free, for personal use. This is not crippleware, this is the real thing. I just produced two drawings, one of a-thujone and one of b-thujone. Unfortunately, I can't export them to .jpg or .gif, or to any format that I know how to convert to either.

The download is 4.9 Mb for the executable and 3.3 for the help file. They have versions for 95/98/NT4, and for the Mac.

I also have an older (version 1.2) edition that fits on a floppy disk, and does most of what 2.3 will do. That version is small enough to email. Anyone who wants it, I'll be happy to send.

This software won't produce the 3D models, those applications tend to cost $$. The one I have (Accumodel) was $800 but now seems to be out of business. It works very well, though.

I have a bunch of software that can be used to produce animations of 3D chemical structure models, I haven't looked at them for a long time but I am sure I could (with some sweat) make an animation of a-thujone/b-thujone interconverting. It would be neat. Molecules DO dance, they never stop (above absolute zero anyway.) They dance like disco bunnies on Ecstasy. But, aren't as cute.

By Don_walsh on Sunday, October 29, 2000 - 06:28 pm: Edit

It's important to remember that conformers (short for conformational isomers) are not typical of stereoisomers. Conformers can interchange without bonds being broken. Most stereoisomers can't do that. If we set out in the lab to make a product that contains a chiral center at the reaction site we usually get an equal mixture of two isomeric products, because the reaction can go either way and does. A lot of effort goes into figuring out how to make chiral products stereospecifically (getting one stereoisomer rather than the equal mixture which is called a racemic mixture.) Even partial stereoselectivity is always of great interest to synthetic chemists, esp those who work at making natural compounds. Nature is often far more stereospecific than we know how to be.

By Anatomist1 on Sunday, October 29, 2000 - 05:54 pm: Edit

I question whether the cannabinoids in raw hashish have already undergone the transformation. You see, I have this friend... he ate a fairly substantial lump of raw hash one time on a tour bus headed from Holland to Germany. He had a hard time staying awake, and felt pretty sick - for a about 2 days - but didn't get very high. He always attributed this to the mentioned difference between cannabinoids heated to a certain extent, and those that are.. uh.. undercooked. After all, hash is a product that is intended to be burned, not eaten. Even if the commercial stuff is often cooked during production, which I'm not sure about, it may not be brought up to a high enough temperature...

One thing I'm certain of, is that my.. friend.. is very sorry that he ate that hash, and will never eat uncooked hash again.

K.

By Don_walsh on Sunday, October 29, 2000 - 05:06 pm: Edit

Hey Gman, I agree about the durian, but Ted loves them. So does my wife.

By Don_walsh on Sunday, October 29, 2000 - 04:43 pm: Edit

I'd have to know a lot more about THC than I do, before I could comment. There's more than one sort of isomerism; that sort your friend is talking about may not be the simple equilibrium at a single chiral center that occurs in thujone. It may be irreversible, it may involve actual breaking of bonds, etc. I just don't know. THC's are much more complex molecules than thujone or any other monoterpene.

Stereochemistry gives most people, even most chemistry students, a blinding headache. I aced it, but what can I say? On the other hand I hated p-chem, too much math! These things all balance out. It has a language all its own, and I won't bore the forum with more jargon. Suffice it to say that the whole thing boils down to 'handedness' and superimposibility; one's right hand and your left are same in sense of connectivity, but are mirror images of each other and thus not superimposible. Carbon atoms because of their tetrahedral geometry, have same charateristic, if each of its 4 bonds are connected to a different thing. In large molecules this can occur multiple times and give rise to very complex mixtures that are difficult to seperate by normal means.

By Timk on Sunday, October 29, 2000 - 10:56 am: Edit

Don, thanks for the information, it is certainly interesting, btw unfortunately i dont have either program but you descriptions were very detailed and i can understand exactly what you mean as to the structure, thanks again
Tim

By Gman on Sunday, October 29, 2000 - 10:29 am: Edit

Ok, chemistry and cool graphics aside, I can think of no place more magical to ponder over an abs than Bangkok. Just keep upwind of the durian!

By Absintheur on Sunday, October 29, 2000 - 08:07 am: Edit

"external stimulus (heat) can drive this in one direction (to favor a-thujone) while removal of heat will return the mixture to the above proportions."

Ironically, this is the first time that I've seen this explanation.

When I came to the forum one of my first questions about thujone was one of interconversion between isomers, as an acquaintance (a researchers in the Purdue Psychopharmachology department) had hypothesized that the reason that absinthe was perceived to be psychoactive and, say, Stovetop was not, was due to conversion enduced by the heat of distillation.

His model for this was THC, which undergoes isomerization when smoked or cooked (at a temperature just below that where it would be destroyed), doubling or trippling the active content of the drug. Because bonds are broken in that process there is no return to equalibrium, which is why hashish, when unconcentrated and taken orally, will be dramatically stronger than leaf marijuana.

He presumed that thujone would be interconvertable only in the heat of distillation, and as such that the absinthe would have significantly more active thujone than leaf sage, or even prepared foods. It seems, though, that because no breaking of bonds are required to acheive this, that a return to equalibrium is inevitable.

By Don_walsh on Sunday, October 29, 2000 - 07:09 am: Edit

Just one more point:

Notice that bulky, rotating prop-like isopropyl group again. Molecules like to arrange themselves so that things hanging off them don't bump into each other (something called steric hindrance). So it is easy to see that conformations which minimize this will be thermodynamically favored.

Likewise, when molecules have to interact with enzymatic, protein-based receptor sites in the brain, they must do so rather precisely, in a geometric fit called the 'lock 'n key' hypothesis. So, even conformal isomers can (and almost always do!) have very different biochemical consequences, fortunately for us as a species, and in fact for all life on this particular planet. Amino acids, sugars etc are all chiral (stereochemically differentiated) molecules.

End of lecture, you can wake up now...

By Don_walsh on Sunday, October 29, 2000 - 06:59 am: Edit

Note that the molecule is very far from flat! It is also very far from still, as the bonds are each stretching and bending and vibrating in multiple modes. And the isopropyl group (at right in the 3D view) is rotating like a propeller around the single bond, while the 4-methyl group is spinning also, like a mixmaster. You can't see the bridge very well in the 3D view but it is there, fusing a 3-carbon and a 5-carbon ring together into a sort of mouse shape.

Now look at the 2D view. The Y-shaped isopropyl group is 'up' in both conformers, as is a hydrogen at the other bridge point (that H not shown here.) The 4-methyl group is 'down' in beta-thujone and 'up' in alpha-thujone, and that is the one and only difference. Due to the tetrahedral arrangement of carbon bonds, the flexing of the less rigid 5 membered ring can place the 4-methyl group 'up' or 'down' thus producing the two conformers -- only one of which is particularly active in the brain. Based on the LD50 data in Merck for subcutaneous inhection in mice, b-thujone is 80% less toxic to mice than the a-form. LD50 by the way means 'lethal dose for 50% of test subjects.' And the numbers for a-thujone were quite similar to the i.p.-injected LD50 values in the Berkeley study.

So, try not to inject yourselves with pure wormwood oil, pals.

By Don_walsh on Sunday, October 29, 2000 - 06:46 am: Edit

...and a somewhat l;ess 'busy' 2D sketch:

thujone2

By Don_walsh on Sunday, October 29, 2000 - 06:44 am: Edit

That's reasonable as a workaround, but I wish we had a more direct way to assay, that's all.

Meanwhile here's a 3D model...

thujone

By Tabreaux on Sunday, October 29, 2000 - 06:39 am: Edit

The standard I use contains both the a and b forms at equilibrium. Since the bp of both thse isomers is nearly identical, any concern that the a form would convert to the b form in the column shouldn't be a problem. Simply account for total thujone and assume that each will be at equilibrium at room temp.

By Don_walsh on Sunday, October 29, 2000 - 05:35 am: Edit

Dear TimK (and all)

OK, here's the technical stuff:

a- and b-thujones differ only in the orientation of the 4-methyl group. I.e, b-thujone, which is the thermodynamically and sterically favored, has the 4-methyl 'down' when the other substituents are all 'up'. What is happening is that the 6-membered main ring is going from a chair to a boat conformation. Think of thujone as a cyclohexanone derivative and it will be clear.

At equilibrium, the a-form is 33% and the b-form, 67%, obviously a 2 to 1 predominance. Note: at equilibrium. That means external stimulus (heat) can drive this in one direction (to favor a-thujone) while removal of heat will return the mixture to the above proportions. Therefore be very suspicious of '99% a-thujone from Fluka AG' as how does Fluka stabilize this ready, bidirectional interconversion?

Incidentally the a-form is levorotatory, and the b-form is dextrorotatory.

Pay attention, as I will be giving a pop quiz on this material shortly.

Monograph 9533, Merck Index 12th Edition

Eastman, Winn, Journal of the ACS, Vol 82, p.5908 (1960)

Hoch et al, Tetrahedron Letters, p.3175, (1970)

PS Anyone care to speculate on what happens when thujone is heated in a GC column? E.g., can an accurate measurement of the stereochemical mix be obtained by this method, which is far from ambient temperature? Or does the GC process not tweak the equilibrium significantly? THAT is a Schroedinger's Cat dilemna, folks. And it isn't even a quantum mechanical problem.

By Don_walsh on Sunday, October 29, 2000 - 04:49 am: Edit

TimK, I will have to look up the references but my recollection is that a-thujone is converted to b-thujone by heat. Yes, they are conformational stereoisomers. As you probably know it is usually the case that only one such isomer is (more) physiologically active.

Could such conversion occur in steam distillation of essential oils? Yes, it is certainly possible, but I'd have to either see it reliably in the lit. or else try it myself before I could say for sure.

My scanner is down so it will be hard for me to feed you any drawings, I wonder if you have any 3D (or 2D) chemical structure software? Like ChemDraw, or ISISDraw? If so I can send you stereochemical drawings of the two conformers without resorting to a scanner.

For that matter if I have to I can send you an older (smaller) version of ISISDraw by email, and you can then not only view the files but make your own.

No pirating being done, MDL gives away even the much later version of same program for free, if you'd rather have the current version I can give you the URL and you can download it yourself.

Cheers

Don

By Tabreaux on Saturday, October 28, 2000 - 03:38 pm: Edit

I've done some testing, but we won't release any numbers until the testing is complete and the products are on the market.

The test results for the extract seem confusing because they are not accurate. Therefore, trying to make heads or tails out of them will only give you a headache.

By Timk on Saturday, October 28, 2000 - 02:57 pm: Edit

Don,
I know, i wasn't disagreeing with you at all, it's just that really we dont have a leg to stand on because of the way they phrase the labelling and due to the regulations to which they comply;
btw have you and ted tested your absinthe's alpha-thujone content?

also w.r.t the test results which were put on the forum,

Herb Pharm extract 10.72 mg/L 136.15 mg/L

why would this be so, as i understan it if this was a herbal extract then it should theoretically contain more alpha than beta because alpha is form mostly found in natural sources. Could this be a result of the processing?

Also i seem to remember you stating that no bonds need to be broken to convert between the two isomers of thujone - have you a diagram of a-thujone and b-thujone, are they just conformational isomers in 3 dimensions. Can the two forms undergo free interconversion? Or be interconverted by conditions experienced in the processing of products containing them?

Tim

By Don_walsh on Friday, October 27, 2000 - 06:43 pm: Edit

Dear TimK

The current EU regulations be damned! And I know the difference between 'ambiguity' and 'deception'. This language, coming from the perpetrators of Hill's, is deceptive IMHO. I stand by my remarks. The same is true of their 'authentic' flavor and 'authentic' colot. Little, if anything about this product is authentic, paid endorsement from DelaHaye notwithstanding.

La Fee is a nice drinkable modern absinthe in same class as MM Collectors Ed. and Deva and La Bleue. Thus it is in top 4 or so. It is about as 19th Century as Shultz or King. It is a good buy in UK for about $60 incl delivery.

BTW I think it needs no sugar, as bottled, and suspect they may have sweetened it a tad. Ted was right, this is about as good as one us going to see from any pastis maker.

BTW we don't give a damn about the UK/EU regs just in case I wasn't clear enough on that point. You ain't seen high thujone.

By Timk on Friday, October 27, 2000 - 11:06 am: Edit

Well don, high is totally ambiguous which is why they use the word, however it is high w.t.t. the current E.U. regulations

By Don_walsh on Friday, October 27, 2000 - 10:11 am: Edit

Well, my La Fee hand carry from UK came in this evening. I find this absinthe a pleasant and approachable drink rather reminiscent of both mari mayans 70% (but not as one dimensional) and of some La Bleues (but maybe not quite as full bodied.) It is most certainly a 'modern' interpretation, and not at all an 'authentic' 19th Century absinthe insofar as I am acquainted with those, and that is just the top end.

All that said, it's a good value for the $60 delivered in UK price -- forget the US price from resellers for twice that. You can spend more and do worse.

I won't bother comparing it to our own product, they really aren't in any wise comparable, and anyway you will all be able to see for yourselves soon and so won't have to decide whether to believe me or not. And I will leave the finer points of the flavor to Ted, I haven't his sophistication of nose.

No point in belaboring the artificial color, been there done that. The leaflet accompanying the bottle claims the stuff has a 'high thujone content' which flatly isn't true unless 'high' means 'low' -- no hedging such as 'healthy but legal' employed, they just say 'high', I just say 'lie'. Nothing that fits the required EU maximum (<10 mg/Kg) can be called 'high'.

In summary the flavor appears to have been concocted with very contemporary tastes in mind rather than 'authenticity'; the color as well, caters to contemporary misapprehensions of the old reality, and the marketing is sometimes fraudulent. But, I'd have to put it in the top 3-4 of present available absinthes. Unlike Sebor, this is a bottle I'll finish. The other czechs, I won't even start. La Fee is a giant step up for Green Bohemia/Utopia, who ought to just quit selling Hill's and focus on this one. No one ought to take them very seriously till they do.

Take all this if you wish with a grain of salt because as you all know we're the 'competition'. Ted was more impressed with this stuff than I am, but his taste buds are superior to mine own. I do like it, the 70 cl bottle won't last very long. But I just had a glass of Ted's Best to serve as a reality check, and, well, they can't stand up to that.

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