Bwiti (PVC-Analog Taste-Tester)
03-05-03 10:28
No 413998
      MPTP Solubility..  Bookmark   

  Alright, lets say one has a solution of freebase 1,3-dimethyl-4-phenyl-4-propionoxypiperidine and neurotoxic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in benzene or diethyl ether.. How can these two be separated without the use of vacuum distillation? Can their solubilities be taken advantage of? Does MPTP form a water-soluble hydrochloride salt? 

Love my country, fear my government.
 
 
 
 
    Bwiti
(PVC-Analog Taste-Tester)
03-05-03 10:49
No 414002
      what the merck says..  Bookmark   

  Just looked it up in the 13th edition Merck..

Monograph Number:  6319
Title:  MPTP
CAS Registry Number:  28289-54-5
CAS Name:  1,2,3,6-Tetrahydro-1-methyl-4-phenylpyridine
Additional Names:  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Molecular Formula:  C12H15N
Molecular Weight:  173.25. 
Percent Composition:  C 83.19%, H 8.73%, N 8.08%
Literature References:  Piperidine derivative which causes irreversible symptoms of parkinsonism in humans, monkeys.  Prepn as hydrochloride by Grignard reaction:  A. Ziering et al., J. Org. Chem. 12, 894 (1947).  Alternative prepn:  C. J. Schmidle, R. C. Mansfield, J. Am. Chem. Soc. 78, 425 (1956).  Identification as impurity in "synthetic heroin" and effect on drug users:  J. W. Langston et al., Science 219, 979 (1983).  Selective destruction of dopaminergic neurons in primates:  R. S. Burns et al., Proc. Nat. Acad. Sci. USA 80, 4546 (1983).  In vitro metabolism by rat brain monoamine oxidase to 1-methyl-4-phenylpyridinium ion (MPP+):  K. Chiba et al., Biochem. Biophys. Res. Commun. 120, 574 (1984). Studies on mechanism of neurotoxicity:  J. W. Langston et al., Science 225, 1480 (1984); S. P. Markey et al., Nature 311, 464 (1984).  Binding studies in rat brain:  C. M. Wieczorek et al., Eur. J. Pharmacol. 98, 453 (1984); B. Parsons, T. C. Rainbow, ibid. 102, 375 (1984); in rat, human brain:  J. A. Javitch et al., Proc. Nat. Acad. Sci. USA 81, 4591 (1984).  Comparison of idiopathic and MPTP-induced parkinsonism in humans:  R. S. Burns et al., N. Engl. J. Med. 312, 1418 (1985).  Review:  T. P. Singer et al., Trends Biochem. Sci. 12, 266-270 (1987); L. M. Sayre, Toxicol. Lett. 48, 121-149 (1989).
Properties:  Crystals from heptane, mp 40-42.  bp0.8 85-90.
Melting point:  mp 40-42
Boiling point:  bp0.8 85-90
-------------------------------------------

  Freebase MPTP isn't soluble in heptane? Or, are they talking about recrystallization?

Love my country, fear my government.
 
 
 
 
    Sunlight
(Pioneer Researcher)
03-05-03 13:00
No 414029
      Recrystallization  Bookmark   

Yes, they say that the crystals formed in heptane as solvent had that mp.
 
 
 
 
    M3Psych
03-06-03 03:42
      MPTP isn't neurotoxic, MPP+ is.
(Rated as: misinforming)
 Bookmark   
 
 
 
    Rhodium
(Chief Bee)
03-06-03 04:01
No 414168
      That is NOT enough!  Bookmark   

Taking deprenyl will inhibit a large number of MAO-B enzymes, and therefore lower the MAO-B activity throughout the body, but you will never ever completely shut it down, and as long as it is still the least functional, MPTP will be toxic.
 
 
 
 
    Megatherium
(Hive Bee)
03-06-03 15:44
No 414298
      The main question is: which procedure do you...  Bookmark   

The main question is: which procedure do you intend to use to make MPPP?

According to me, MPTP formation isn't going to be a problem if you use the procedure from US patent 2765315 since I think the MPTP producing side reaction is mechanistically impossible (see Post 410862 (Megatherium: "Very interesting. Then, in US patent 2765315 a", Methods Discourse) and the other posts in this thread).  I wouldn't recommend acylation of the piperidinol (after reaction of PhLi with the piperidone).

For safety reasons, I think it would be wise to do a flash chromatography of the product & check it out with TLC (whichever procedure you use).

So the best advice is probably not to fuck around with meperidine synths without the proper knowledge, chemicals, equipment and GCMS.
Yeah right, do you know how much a GC-MS apparatus costs?  Furthermore, the meperidine synth isn't a problem ... the reversed meperidine ester synthesis is !
 
 
 
 
    M3Psych
(Newbee)
03-06-03 17:42
No 414324
      Re: Taking deprenyl will inhibit a large ...  Bookmark   


Taking deprenyl will inhibit a large number of MAO-B enzymes, and therefore lower the MAO-B activity throughout the body, but you will never ever completely shut it down, and as long as it is still the least functional, MPTP will be toxic.




Dosages of Deprenyl 10mg/day inhibits CNS MAO-B about 90%, very litle MAO-B is found outside of the CNS. While what you have said is techinically true, studies using MPP+ and equivalent human normal Deprenyl dosgaes have failed to detect any evidence of neurotoxicity in animals. This is not to say that the same would hold true in humans, but given the rather extensive volume of research conducted with Deprenyl this would seem to be a very high probability.  Not that a person should gamble their dopaminergic neurons on something with a "very high probability"...

Furthermore, development of Parkinson's Disease in cigarette smokers, who have extremely diminished MAO-B activity compared to non-smokers is virtually non-existant. It is theorized that overactive MAO-B or TH is probably largely to blame for the development of PD in that excessive breakdown of DA produces hydroxyl and superoxide radicals which inflict the same type of neuronal cell damage as MPP+, albeit in a slower way.

Finally, I wasn't suggesting that a person actually attempt to use Deprenyl for neuroprotection aganist MPP+, it was more a tongue and cheek suggestion that messing with these types of compounds is best left to those with the knowledge, experience and equipment to safely deal with them. This is why I added my disclaimer regarding Deprenyl and meperidine, this combination is absolutely contraindicated.

 
 
 
 
    Bwiti
(PVC-Analog Taste-Tester)
03-06-03 21:51
No 414384
      Shit..  Bookmark   

  Guess I better learn flash chromatography quick. Or, would I rather risk neurotoxicity, because I'm too lazy to take a class on it? Fuck!smile Yes, US2765315 is what I had my eye on.....Would flash chromotography really remove the neurotoxin?

Love my country, fear my government.
 
 
 
 
    Megatherium
(Hive Bee)
03-06-03 23:25
No 414407
      To learn about flash chromatography, read: *...
(Rated as: excellent)
 Bookmark   

To learn about flash chromatography, read:
* Vogel, Textbook of practical organic synthesis, 5 th ed., p. 217 - 220
* J. Org. Chem. (1982) vol. 47 p. 1351
* J. Org. Chem. (1978) vol. 43 p. 2923

The last article happens to be on Rhodium's site, how convenient smile.
../rhodium/pdf /flash.chromatography.pdf

Yes, flash chromatography will seperate MPPP & MPTP efficiently if you find a good solvent (one which generates Rf values on TLC that are far apart).  Flash chromatography is a rather good technique to purify your product, but as I said, I don't think MPTP formation is going to be a problem with this procedure.  But, I wouldn't put my substantia nigra on risk - if I were you.  So, learn about flash chromatography & be patient (it is rather tedious).

 
 
 
 
    Bwiti
(PVC-Analog Taste-Tester)
03-08-03 09:43
No 414789
      Thanks..  Bookmark   

  Thanks for the advise! Sounds cheaper than buying vacuum distillation equipment. Peace!cool

Love my country, fear my government.
 
 
 
 
    Rhodium
(Chief Bee)
03-08-03 21:30
No 414863
      I have uploaded the other article too: TLC...  Bookmark   

I have uploaded the other article too: TLC Mesh Column Chromatography (../rhodium/pdf /tlc.mesh.column.chromatography.pdf)