Author Topic: L-Tyrosine + Persulfate -> L-DOPA 3-O-sulfate  (Read 868 times)

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Rhodium

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L-Tyrosine + Persulfate -> L-DOPA 3-O-sulfate
« on: October 21, 2004, 04:55:00 PM »
Okay, the yields are a bit on the low side, but ammonium persulfate and ammonium hydroxide are very cheap reagents. There simply must be a way to make use of a reaction which is able to oxidize something with a 4-hydroxy-phenethylamine skeleton to the corresponding 3,4-dihydroxyphenethylamine...




L-DOPA-3-O-Sulfate by the Persulfate Oxidation of L-Tyrosine
E.J. Behrman & J.M. Bidinger

Org. Prep. Proced. Int. 21(3), 351-353 (1989)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/tyrosine2dopa.persulfate.pdf)

The Elbs persulfate oxidation of p-substituted phenols proceeds with poor yields of the catechol sulfates for unknown reasons;1 the oxidation of L-tyrosine is no exception. A dark, polymeric melanin-like material is the major product.2 Oxidation of the amino group does not appear to be responsible for the poor yields of the sulfate ester as this reaction is slow.3 We have studied various factors which might influence the yield of the sulfate ester.3 The best yields, as measured by the Folin-Denis phosphotungstic acid reagent,4 were around 25% with a persulfate-tyrosine ratio between two and three;3,5 the yield decreased with increasing concentration of alkali. Despite these relatively poor yields, we have carried out the isolation and characterization of the title compound because of considerable interest in the related dopamine sulfates6 and because persulfate oxidation yields the 3-O-sulfate without the ambiguity which might attend procedures involving sulfonation of a dihydric phenol. Syntheses of L-DOPA sulfates have not been previously reported. There are many unidentified metabolites of L-DOPA.7


Experimental

L-DOPA-3-O-sulfate

L-Tyrosine (9.05 g, 0.05 mol) was dissolved in a mixture of 100 ml of 28% aqueous NH4OH and 3.3 g of 85.5% KOH (0.05 mol). The solution was cooled to room temperature and then a solution of 22.8 g (0.1 mol) (NH4)2S2O8 in 100 ml water was added slowly with stirring during 5 hrs. After three days, analysis4 for L-DOPA following acid-catalyzed hydrolysis of the sulfate ester showed a yield of about 20%. The isolation was based on a procedure for tyrosine-O-sulfate.8 The solution was evaporated to dryness in vacuo at 40°C taken up in 50 ml of water, and filtered. The insoluble material was largely tyrosine. The filtrate was treated with 0.2 mol of barium hydroxide and barium sulfate removed by gravity filtration. The filtrate was again evaporated to dryness in vacuo, taken up in 20 ml of water, and the additional tyrosine which had precipitated after standing overnight was centrifuged. The supernatant material was brought to pH 2 by batchwise treatment with Dowex-50, H+ The resin was removed on a Buchner filter. Potassium hydroxide was carefully added to the filtrate to bring the pH to 5. The slow addition of ethanol and cooling gave crystals of the potassium salt of the sulfate ester as the monohydrate. Further crops of crystals may be obtained from the mother liquor if some of the colored material is removed by the following procedure. Both L-DOPA sulfate and the colored material are bound to DEAE cellulose, but L-DOPA sulfate is easily eluted with 2M NH4OH while most of the colored material remains bound. Further crops of crystalline material may be obtained from these fractions by the addition of ethanol. No detectable racemization occurred during this synthesis as expected9 as established by the rotation of the L-DOPA formed by acid hydrolysis of the sulfate ester: [?]D25 = -11.4±10, lit.10, -12.3°.



References

[1] E. J. Behrman, Org. React., 35, 421 (1988)
[2] H. Heinlein, Biochem. Z., 154, 24 (1924)
[3] J. M. Bidinger, M. S. Thesis, The Ohio State University, 1986.
[4] S. Scott and E. J. Behrman, Anal. Lett., 21, 183 (1988)
[5] K. B. Rao and N. V. S. Rao, J. Sci. Ind. Res., 14B, 130 (1955)
[6] For a recent review see: O. Kuchel and N. T. Buu, in "Norepinephrine", M. G. Ziegler and C. R. Lake, (Eds.), Williams & Wilkins, Baltimore, 1984, Chap. 17.
[7] M. Goodall and H. Alton, Biochem. Pharmacol., 21, 2401 (1972), especially Table 1.
[8] K. S. Dodgson, F. A. Rose and N. Tudball, Biochem. J., 71, 10 (1959)
[9] J. L. Bada, in "Chemistry & Biochemistry of Amino Acids", G. C. Barrett, Ed., Chapman & Hall, London, 1985, Chap. 13.
[10] H. Bretschneider, K. Hohenlohe-Oehringen, A. Kaiser and U. Wolcke, Helv. Chim. Acta, 56, 2857 (1973)


Saddam_Hussein

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Elbs persulfate reaction
« Reply #1 on: October 22, 2004, 04:56:00 AM »
There simply must be a way to make use of a reaction which is able to oxidize something with a 4-hydroxy-phenethylamine skeleton to the corresponding 3,4-dihydroxyphenethylamine...

The Elbs persulfate reaction is known to give low yields, but is sometimes favored because much of the unreacted precursor can be recovered (sometimes).

However, if you would end up with a 3,4-dihydroxyphenylethylamine, what are the chances you can methylenate this substance to the probably desired methylenedioxy analogue without ruining your product with "side reactions"? For instance, don't you think reacting the phenethylamine with DCM or DBM might alkylate the amine functional group as well? Possible alternatives: 4-hydroxybenzaldehyde, 1-(4-hydroxyphenyl)-2-nitropropane.


demorol

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Re: However, if you would end up with a ...
« Reply #2 on: October 22, 2004, 08:59:00 AM »

However, if you would end up with a 3,4-dihydroxyphenylethylamine, what are the chances you can methylenate this substance to the probably desired methylenedioxy analogue without ruining your product with "side reactions"?




Why would you want to methylenate the hydroxyls. AFAIK 3,4-methylenedioxy-PEA is not active in humans (read PiHKAL).


Captain_America

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....
« Reply #3 on: October 22, 2004, 11:10:00 AM »
there are some compounds with vague activity that could bee made by O-alkylating 3,4-dihydroxyphenethylamine. Leminger did some work on these compounds, one is

MEPEA

(http://www.erowid.org/library/books_online/pihkal/pihkal123.shtml)


Regarding the synthesis there was a simillar discussion bee-4 in this thread; 

Post 534515

(Captain_America: "problem w/ 4-Desmethylmescaline route", Novel Discourse)
. I don't get the usefulness of these routes. A bee has tried mitsunobu

Post 532595

(SpicyBrown: "A caveat regarding the Mitsunobu", Novel Discourse)
.

Even if it all went nice and in high yield, decarboxylation for 2-C cmpnds is OK, but to make active 3-C compounds it would require -COOH -> -CH3.


Saddam_Hussein

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PEA
« Reply #4 on: October 22, 2004, 11:39:00 PM »
Why would you want to methylenate the hydroxyls. AFAIK 3,4-methylenedioxy-PEA is not active in humans (read PiHKAL).

I meant a 3,4-methylenedioxyphenethylamine analogue, such as MDA or BDB.