How about modifying this:

Method for producing L-3,4-dihydroxyphenylalanine - European Patent (EP 0636695-A1)

(http://l2.espacenet.com/espacenet/viewer?PN=EP0636695&CY=ep&LG=en&DB=EPD). There's lots of stuff similar to that.

1: Instead of aiming for DOPA one could aim for alpha-methyl-DOPA by using catechol with alpha-methyl-serine. Possibly may not work but surely worth investigating.

People have discussed the conversion of alpha-methyl-DOPA to MDA via decarboxylation followed by methylenation but Rhodium told me that it wouldn't work. I can't see why not. But I suppose it's academic without any alpha-methyl-DOPA.

2nd point. Why not try the above Euro patent with hydroquinone and serine rather than catechol and serine? - to, possibly, get 2,5-dihydroxy-phenyl-alanine - which is just a decarboxylation and a methylation (I daren't go further) away from something interesting.

Apologies is this post interrupts the thread and is thought to be off-topic.

As acetaldehyde is very useful in the biosynthesis of l-PAC I want to point interested bees here:

Post 502712

(Organikum: "Rhodium wrote: Re: If you do not remove the...", Stimulants)

ferrous/ferric sulfate + hydrogen peroxide + ethylalcohol
=
acetaldehyde + acetic acid

ORG

Free for this week, Encyclopedia of Bioprocess Technology - Fermentation, Biocatalysis, and Bioseparation, Volumes 1-5:

http://www.knovel.com/knovel2/Toc.jsp?BookID=678

You can make pyruvic acid with the dry distillation of tartaric acid which is OTC and cheap

Or you can search froogle for "calcium pyruvate"

But pyruvic acid may be useful in another way.
- pyruvic acid and diluted H2SO4 gives acetaldehyde.

Well, if this is true, since the patent I was just reading claims that potassium bitartrate and H2SO4 mixed in equimolar ratios, yields 90% pyruvic acid when heated at 170C to 270C for one hour, can't one just use an excess of H2SO4, thereby turning this reaction into an acetaldehyde generator?

This sounds too easy and too OTC to be true?
Anyone going to try this before I get a chance?

I cannot answer your question on the tartrate to acetaldehyde borolithium, sorry, but I must tell that FeSO4 + H2O2 + EtOH = acetaldehyde maybe theoretically nice but is practically a pain in the ass as the reaction tends to runaways.

Except one wants to go for real large amounts of product - kilos - I would suggest to skip the acetaldehyde, to concentrate on the production of benzaldehyde instead and to get a bigger bucket for the fermentation  
Also I suggest to use diethylether for the extraction of the fermentation broth as the reductive amination/alkylation can be done directly onto the raw extract in ether  - say: extract with ether, reduce the volume and do the Al/Hg in ether instead of alcohol.

It is not that hard to get you know. Where I am from, the grocery store will suffice. Granted, they are tiny bottles, but can't one just send a bunch of people out for the day?

IMITATION ALMOND EXTRACT

Also, bitter almond oil is not hard to get abroad. There are a thousand ways to smuggle it in, as I doubt there are any dogs that are trained to smell it. Shampoo Bottle?

That being said, it is my understanding that the presence of acetaldehyde is critical to the yield of L-PAC. Valuable benzaldehyde will be converted to benzyl alcohol in the absense of the acetaldehyde, and since acetaldehyde cannot be readily purchased, a simple and cost effective system of generating it is needed.

There are several patents detailing the use of acetylene, passed through a mercury or heavy metal catalyst at moderate temperatures.

Acetylene is available to all of us without raising any suspicion, but the mercury salts may be an issue.

Tartrates are OTC and would provide simple means of generating acetyldahyde without working with hard to obtain and dangerous ingredients, such as mercury salts.

There are lots of ways to oxidise ethanol, for example pass ethanol/air over hot copper in a tube. Simple and cost-effective.

http://86.1911encyclopedia.org/P/PY/PYRUVIC_ACID.htm

 When heated with hydrochloric acid to 10o C. it yields carbon dioxide and pyrotartaric acid C5H804, and when warmed with dilute sulphuric acid to 150 C it gives carbon dioxide and acetaldehyde.

This sounds waaaaaaaaaaaaaaaaaaayyyyyyyyyyyy easier than bulding some high temp, silver coated mesh catalyst burning tube, injecting ethanol and air streams in perfect proportions, and hopefully not having a big ass blow back or explosion. State of the art 19th century technology.

So, to simplify things:

Potassium Bitartrate + conc. H2SO4 in equimolar amounts, heated to 170C to 270C for 1 hour = 90% pyruvic acid

AND

Pyruvic Acid + dilute H2S04 heated to 150C = CO2 + acetaldehyde = essential ingredient for high yielding L-PAC

I would run the evolving gas through a cooling tube at 40C to condense any moisture, while allowing the acetaldehyde to mostly pass through. The gas can be bubbled into an aqueous solution, with conc. estimated by weight or volume. This solution can be later introduced into the bioreactor with the benzaldehyde to maximize the L-PAC yield.

Any objections?

---

Any objections?

---

No.  

Of course you will need some routine to get the very good yields told in literature (as always   ), but it will work exactly like this. A powerful condensor for the acetaldehyde or bubbling it into ice-cold water is recommended.

ORG

A bioreactor seems to be the best way to maximize yields in a minimal amount of space. Constant aeration, agitation, and the slow introduction of the benzaldehyde and acetaldehyde are reported to provide the highest yield in the smallest amount of space.

Now if one was trying to purchase a bioreactor, there is only a handful of companies manufacturing these units, and they would likely ask what it was being used for, as these units are often customized. Can anyone think of a good, plausible industrial reason for wanting a bioreactor?

You want to do some carefully controlled beer brewing experiments.

Thanks Foxy. I suppose that's too obvious. Mind you, I can't imagine any company getting too suspicious about a bioreactor.

Now here is a question for you foxy. as I remember a post you had put up eons ago regarding the strain candidus utilis. The majority of research papers I have come across using bioreactors use a strain of Sacharamyces Cerevesiae (I'm spelling this from memory so forgive me), a common yeast for white wine, for the conversion of benzaldehyde to L-PAC.

Is the candidus utilis (tarula yeast) superior in it's L-PAC/Benzyl Alcohol production ratio, and would it function much the same in a bioreactor as a substituted yeast strain?

An interesting Brewing Chemistry article for you L-PACer's.

http://www.brewingtechniques.com/library/backissues/issue1.2/fix.html

You can buy different yeast strains from a brewing yeast company that has high and low diacetyl strains.  A high diacetyl strain might bump up yeilds nicely?

pyruvic acid synthesis from K bitartrate and Sulfuric acid

Post 384565 (missing)

(cthulhujr: "Pyruvic Acid Synthesis and 24%", Stimulants)

The pyruvic acid route to acetaldehyde sounds much more practical than from EtOH at high temperatures.

It's preparing an effective yeast that I have my doubts about.
The yeasts in industry are specially selected from colonies prepared. They are more resilient to B-aldehyde induced death. The hard-working ones are then extracted for the next experiment.


What about isolating yeast that survive certain treatments, and very small test-runs, then culturing those?


There's a method at Rhodium's using yeast from moldy apricots, and the yield from 264gm of B-Aldehyde was 24gm of L-PAC.

Not encouraging considering the level of skill in the art, that the experimenter probably has, and the equipment available.
Although no acetaldehyde was incorporated, or EtOH.

Here's that write-up:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/ppa.l-pac.raney-ni.html

How many liters of B-aldehyde is your average joe-bee going to go through before being comfortable with his procedure? For personal use I mean. (toluene will disappear.)

What B-aldehyde contaminents and by-products from it's preparation absolute no-no's for yeast, and which, if any, are acceptable?

How should air bee sterilized before introduction in to the bioreactor?

How should air bee sterilized before introduction in to the bioreactor?

Depending on the sensitivity of the reaction, usually using two in-line .2micron air sterilizing filters would work on the intake line.  Or even placing an activated charcoal in- line filter upstream from the air sterilizing filters.  If humidity would have to be introduced it can be done downstream from the .2 micron filters using water for injection as a source of humidity introduction.  You can pick up the .2 micron air sterilizing filters for ~1.00 a piece USD for a pack of 100.

m_e

Adv Microb Physiol. 1999;41:1-45.   


Factors affecting the production of L-phenylacetylcarbinol by yeast: a case study.

Oliver AL, Anderson BN, Roddick FA.

Department of Chemical and Metallurgical Engineering, RMIT University, Melbourne, Victoria, Australia.

L-Phenylacetylcarbinol (L-PAC) is the precursor for L-ephedrine and D-pseudoephedrine, alkaloids possessing alpha- and beta-adrenergic activity. The most commonly used method for production of L-PAC is a biological method whereby the enzyme pyruvate decarboxylase (PDC) decarboxylates pyruvate and then condenses the product with added benzaldehyde. The process may be undertaken by either whole cells or purified PDC. If whole cells are used, the biomass may be grown and allowed to synthesize endogenous pyruvate, or the cells may be used as a catalyst only, with both pyruvate and benzaldehyde being added. Several yeast species have been investigated with regard to L-PAC-producing potential; the most commonly used organisms are strains of Saccharomyces cerevisiae and Candida utilis. It was found that initial high production rates did not necessarily result in the highest final yields. Researchers then examined ways of improving the productivity of the process. The substrate, benzaldehyde, and the product, L-PAC, as well as the by-products, were found to be toxic to the biomass. Methods examined to reduce toxicity include modification of benzaldehyde dosing regimes, immobilization of biomass or purified enzymes, modification of benzaldehyde solubility and the use of two-phase reaction systems. Various means of modifying metabolism to enhance enzyme activity, relevant metabolic pathways and yield have been examined. Methods investigated include the use of respiratory quotient to influence pyruvate production and induce fermentative activity, reduced aeration to increase PDC activity, and carbohydrate feeding to modify glycolytic enzyme activity. The effect of temperature on L-PAC yield has been examined to identify conditions which provide the optimal balance between L-PAC and benzyl alcohol production, and L-PAC inactivation. However, relatively little work has been undertaken on the effect of medium composition on L-PAC yield.

Publication Types:
Review
Review, Academic

PMID: 10500843 [PubMed - indexed for MEDLINE]

Yes, everyone who UTFSE for it will be able to access it here:

Post 505265

(Organikum: "Benzaldehyde -> L-PAC -> Ephedrine", Stimulants)

This article is also excellent:

Post 507915

(Rhodium: "Benzaldehyde -> L-PAC -> PPA", Stimulants)