DE1963992B - Process for obtaining the pure optical antipodes D- and L-3,4-dihydroxyphenylalanine by crystallization of the quinchonine salt - Google Patents

Description

It is already known (H ari ng to η and R an- the N-benzoyl group in a manner known per se dall, The Biochem. J. 25, 1931, p. 1028), which splits off Di-40.

acetyl derivative of rac. N-Benzoyl-3,4-dihydroxy-phe- The resolution of the racemate by the method

nylalanine via the corresponding brucine salt in the invention using the 3,4-dihydroxyoptic to split pure antipodes. This connection method has the advantage that on the known however, it is unfavorable, since the crystallization only takes a very long time to dispense with the subsequent ether cleavage required takes place and can still be switched off after a fortnight.

is not completed. Surprisingly, it has been shown that in

According to one of Y a m a d a et al., In Chem. In contrast to the cinchonine salt of the corresponding Pharm. Bull. (Tokyo) 10, 1962, pp. 680 to 688, be 3-melhoxy compound, the cinchonine salt of the 3,4-letters Procedure, the resolution of the racemic hydroxy compound was not made by crystallization also already done by adding rac. 50 pure acetone can be separated as both anti-N-acetyl-S ^ -methylenedioxy-phenylalanine of the formula poden are largely soluble in pure acetone.

While in the known separation of the 3-methoxy-4-hydroxyderivats through crystallization

O, CH ₂ -CH-COOH acetone crystallizes out the i.-salt, the opti-

55 see antipodes in solution or do not form isolating

_ Bare, syrupy, precipitation, if one

- ~ ^{υ NH} CO-CH ₃ drive to the corresponding 3,4-dihydroxy derivative

applies.

converted into the cinchonine salt and this by one can, however, with an excellent yield

Crystallization from alcohol into the optical antipodes 60 can achieve a smooth separation of the racemate if one uses the separated. In this procedure, the corresponding cinchonine salt of N-benzoyl-3,4-dihydroxy-phenyI-L compound obtained as a solution in alcohol, selected alanine from a homogeneous mixture of one kidney the D-compound crystallizes out. their aliphatic ketone, alcohol or ether or

Another known process (HeIv. Chim. Several such compounds and water, esp. Acta 35, 1952, p. J 776) shows that by using 65 special a mixture of acetone and water, crystalline otherwise substituted starting product that leaves lisicren.

Solubility behavior of the salts is completely changed. The one present in the solvent mixture

According to this method, the optical anti-water amount should be so high that at least 1 mol

Water per mole of the N-benzoyl-dopa used before the salt is split. It arises in the aqueous

located. However, an excess of water has no in-phase soluble cinohonine hydrochloride and the o-N-

favorable influence on the racematic spectrum. Benzoyl-DOPA, which from the hydrochloric aqueous

For the purposes of the invention are particularly suitable layer is extracted with ethyl acetate, after removal Mixtures of aliphatic ketones, alcohols and / S of the solvent and recrystallization of the Rückoder Ethers with 2 to 6 carbon atoms and water. υ-N-Benzoyl-DOPA is obtained as a stand from water

The colorless liquid for crystallization phase used crystalline substance of mp. 17O ⁰ C and a

must be homogeneous. Therefore, if an alcohol, ether specific rotation of [*] V = + 3O ⁰ (c = 1; Me-

or ketone with too little water-manageability (ethanol).

a sufficient amount of an io is used. The following are found in the IR spectrum of this substance

Compound of the characteristic bands mentioned, which are readily miscible with water: Classes too.

A method for carrying out the ^{process according} to the invention 34O ° ^{cm- 1 m8 cm} " ¹

The most preferred medium is water-containing ^{1725 cm} ~ ^{X 1078 cm} ~ ^X

^{Acetone, water 15 1632 cm} * ^{960 cm. r} . also lead to good results

containing n-butanol, hydrous methyl ^{ethyl ketone, J 600 cm} " ^{x 9} fj> cm j

to which a small amount of isopropanol has been added, a * ⁵ ' ^{0 cm 88} ° ^cm "

water-containing mixture of isopropyl ether and iso- ■ '• 533 cm ^J 870 cm ^l

propanol, hydrous isopropanol and water- ^{1511 cm} ~ ^{l 80} ^ ^ ¹ " ¹

pure ethanol. _ao 1318 cm- ¹ 790 cm- ¹

For the practical implementation of the process of ^{1282 cm x 695 cm} _ ^:

First invention is the cinchonine salt of ^{1233 cm} ~ ^{3 574 cm 3}

Di.-N-Benzoyl-3,4-dihydroxyphenylalanine (DL-N-Ben- H ^{82 cm -1}

zoyl-Dopa). For this purpose one can saponify one D-N-Benzoyl-DOPA by boiling

Both salt-forming components in a suitable mixture with acids, especially hydrochloric acid, are obtained

th solvent, such as methanol, D-3,4-dihydroxyphenylalanine, which is pure with one another, melting point = 274.degree

put and the salt by evaporation of the solution (dec.); [x] f - + 11.3 °.

isolate by means of. This salt is then dissolved in the water-containing solvent, if necessary by concentrating the mother liquor of the D salt with heating - the cinchonine salt of the LN-benzoyl-DOPA mixture is kept. 30 which, after recrystallization from ethyl acetate, gives a particularly advantageous embodiment of the Er melting point of 154 to 155 ° C and a specific invention is that equimolar amounts of rotation of [oi \ f = + 135 ° (c = 1; methanol) Cinchonine and DL-N-Benzoyl-Dopa immediately show in that.

Water-containing used for crystallization In the IR spectrum of the substance, the following mixture occurs heated until a clearly visible characteristic band appears: Conversion of the crystal structure, the end of the reaction is indicated. In general, this is achieved ³³⁸ - * ^cm ~ ¹ 1382 ^cm-1 by heating the reactants in the ^"2 ^ cm" ¹ 1276 · cm- ¹ solvent-water mixture under reflux. ^{1585 cm} _ ^{1108 cm} _ * By allowing the solution to ^{stand, crystals 40 156} ° ^cm _ [ ^{918 cm} _ * of the cinchonine salt of DN-benzoyl-diopa are obtained, which are filtered off from 1502 cm ^ 795 cm ^ of the solution. I ^{474 cm} ~ ¹ 768 cm- ¹

The corresponding salt of the L-compound is ^{1435 clTrl 708 cm}

by evaporating the solvent mixture or splitting the cinchonine salt of the L-N-benzoyl-

obtained by precipitation with a nonsolvent. 45 DOPA, as described for the D salt, is obtained in this way

The separated and isolated salts after the work-up of the organic phase

the D- and the L-compound can in the usual way L-N-Benzoyl-DOPA as a colorless crystalline sub-

by treating with acids or bases in d- or punching point with a melting point of 172 ° C and a specific one

LN-Benzoyl-DOPA are transferred. Acid rotation [x] f - - 30 ° (c = 1; methanol).

Saponification of the N-benzoyl compound results in DOPA. The following occurs in the IR spectrum of this substance

won. characteristic bands on:

According to the invention from the solvent-water _ _χ _ _χ

ser mixture crystallized cinchonine salt of ^{3340 cm} _ H ^{85 cm} _

D-N-Benzoyl-DOPA contains 1 mol of crystal water, 1695 cm ^ 1150 cm

shows a specific rotation of [λ]? = + 85 ° ₅₅ ¹⁶² J ^cm ~ ^{1140 cm}

(c = 1; methanol) and melts at melting point 168 ° C. ^1588cm _ * ^1105cm _ ₃

The following 15 °? cm 959 cm

characteristic bands: 1530 cm ^-1 932 cm ^-1

1505 cm- ¹ 922 cm- ¹

3380 cm- ¹ 1390 cm- ¹ 1478 cm- ¹ 890 cm- ¹

1632 cm- ¹ 1260 cm- ¹ 1425 cm- ¹ 798 cm- ¹

1589 cm- ¹ 1102 cm- ¹ 1355 cm- ¹ 711cm- ¹

1580 cm- ¹ 770 cm- ¹ 1340 cm- ¹ 682 cm- ¹

1560 cm- ¹ 718 cm- ¹ 1272 cm- ¹ 578 cm- ¹

1496 cm- ¹ 635 cm- ¹ ₆ 1210 cm- ¹

1468 cm ^-1 572 cm " ¹ LN-Benzoyl-DOPA is saponified by boiling with it

If this cinchonine salt is treated with aqueous hydrochloric acid, pure L-3,4-dihydroxy-phe-

Acids or bases, e.g. B. aqueous hydrochloric acid, then nylalanine, melting point 290 ° C (dec.); [«]" = -11.3 °.

5 '6

Example χ water, 30.10 g of pure D-DOPA (= 9I ⁰ I ₀

") Production of the Cinchonln-Saize of pN-Benzoyl- ^{der Theone) from m.p. 27} ^ f ^ ⁰ V _ft ",, DOPA specific rotation Wf - 11.3 ° ± 0.5 ° (c «1;

159.5 g of rac are dissolved in an Erlenmeyer flask. 5

N-benzoyl-DOPA monohydrate (0.5 mol) and 147 g of "_. , ". . . _c ". "" _Λη . _{MR (% n} cinchonine (0.5 mol) in approx. 750 ml of methanol and ^d > recovery of the cinchonine salt from tN-benfiltrated the solution into a 4-1 round bottom flask and decoyi-uui λ
removes the solvent while heating in water. Vaporize the under 1, a) after suction and jet vacuum. The remaining, syrupy salt dissolves io washing of the D-salt crystals obtained mother liquor in the one with vigorous shaking or stirring in a water jet vacuum to dryness and washes the boiling mixture of 2.5 I acetone and 250 ml water. The crude residue is obtained with ethyl acetate. Immediately thereafter, the cinchonine salt of the cinchonine salt of LN-Benzoyl-DOPA begins to crystallize out in an Aus-DN-Benzoyl-DOPA. To complete 95 to 99% of theory. For further understanding of the crystallization, the mixture is left as processing to LN-Benzoyl-DOPA or L-DOPA, the compound is pure enough overnight at room temperature or in the refrigerator.

stand. The crystals are sucked off and with good For the analytical investigations a part was

cool, aqueous acetone (about 10 ^u / ₀ water) the substance recrystallized from ethyl acetate. The following

to wash. Yield: 150.25 g (= 98% of theory). Values were obtained:

For further processing to DN-Benzoyl-DOPA ao ρ _ 154 his 1 ^ 5 ⁰ C ^-

is the substance pure enough and therefore does not need r ^ __ ^l ₄ _ 1350 ", _ γ> (c = 1 · methanol)

to be further cleaned. L 'Jo - - t ^ - ■

For the analytical investigations a "," "".

Part of the substance from the acetone-water mixture ^e ) Production of LN-Benzoyl-DOPA

recrystallized. It then shows the following values: 25 150 g of the cin-

M.p. = 168 ^° C; LN-Benzoyl-DOPA chonine salt with 100 ml

ui »_ 1 oco, -, Oz ₁ . _M .L η of half-concentrated hydrochloric acid and 400 ml of ethyl acetate and

shake the mixture until the solution has entered

,. _u . ,, _{XI D} ι t ^ rxriA is. The ethyl acetate layer is separated off, the aqueous one

b) Production of υ-N- _{Benzoyl-DOPA 3o layer} ^ «^ _{five times} , _{each consisting of 2} ^δ _{00 ffll ethyl acetate} .

Shake mixed to isolate D-N-Benzoyl-DOPA. The combined ethyl acetate extracts are

man 150 g of the under 1, a) washed out of the solvent with water, _{dried with Na 2} SO ₄ and im

mixture of crystallized cinchonine salt concentrated in a water jet vacuum. Received as residue

D-N-ßenzoyl-DOPA with 100 ml of half-concentrated one L-N-Benzoyl-DOPA, which is used for the additional HCl and 400 ml of ethyl acetate and shake the mixture to make L-DOPA pure enough.

until the solution is found. The organic yield- 12 c ( -96 ° / of theory)

Layer is separated, the aqueous layer is yield. 72 g (-% / "of the ineone).

extracted five more times with 200 ml of ethyl acetate each time. Part of the substance was recrystallized from water

The combined ethyl acetate layers are lized with to determine the analytical data.

Washed water, _{dried with Na 2} SO ₄ and in the 40 _F _ 1790p.
Water jet vacuum concentrated. The residue obtained is * ~~

Concentrated water jet vacuum. As a residue, Nl

^[äJd ~ ~ ^{3Ü ± 2}

gg
one DN-Benzoyl-DOPA, which is pure enough for further processing into ü-DOPA.

^b f) Production of L-DOPA

Yield: 71 g (96.50% of theory).

45 50 g of L-N-Benzoyl-DOPA are made for 2 hours

For the analytical investigations, a with about 225 ml of 20% hydrochloric acid was used under nitrogen

Part of the substance recrystallized from water. Then heated to boiling as a protective gas. During the subsequent

the following values were maintained. Cooling crystallizes part of the released

Pp_ _] 70 ° C; Benzoic acid and is removed by filtration.

r _a jg) _ _ | _30o '^ _ 2 ° (c = 1; methanol). ⁵ ° The remainder is extracted from the solution with ether. the

aqueous solution is under protective gas (nitrogen) to

. ,,, "_> ..,. ... evaporated dry. The L-3,4-dihydroxyphenyl

c) Preparation of D-Dihydroxy-phenylalamn alanine hydrochloride is taken up in water, the

50 g of D-N-benzoyl-DOPA are obtained for 2 hours with a base, z. B. triethylamine,

adjusted to the isoelectric point as 55 with about 255 ml of 20% hydrochloric acid under nitrogen. After length

Protective gas heated to the boil. When you then stand (preferably overnight) in the refrigerator

Cooling crystallizes part of the released 31 g of l-DOPA (= 92% of theory).

Benzoic acid and is filtered off. The remainder is made after recrystallization from SO ₂ -containing water

extracted from the solution with ether. The aqueous solution gives 30.0 g of L-DOPA (= 89% of theory) from is brought to dryness under protective gas (nitrogen)

ρ, a "rvi λ ι ii · ι a .1 ■ ·> [«]? = -11.3 ° ± 0.5 ° (c = 1; InHCl).
The DS ^ -dihydroxyphenylalanine hydrochloride

is taken up in water, the resulting solution B eisdie 1 2
with a base, e.g. B. triethylamine, adjusted to the isoelectric point. After standing for a long time, on 65 a) Production of the cinchonine salt of DN-benzoyl-

best overnight, DOPA crystallize in the refrigerator

31.5 g of D-DOPA (= 96% of theory). 159.5 g of rac.

After recrystallization from SO ₂ -containing N-benzoyl-DOPA-monobydrate (0.5 mol), 147 g of Cm-

chonine (0.5 mol), 2.5 l acetone and 250 ml water and heated to the boil until the initially has converted a coarsely crystalline mixture into a uniform, finely crystalline crystal mass. That is the case after about 2 hours. To complete the crystallization, the mixture is left at room temperature overnight or in the refrigerator.

The crystals are then suctioned off and washed with well-cooled aqueous acetone (about 10% Water).

Yield: 148 g (= 96.5% of theory).

After recrystallizing part of the substance from an acetone-water mixture, one obtains the following values:

M.p. = 167.5 ° C;

[ _K ] f = + 85 ° ± 2 ° (c = 1; methanol).

If you proceed as described under 1, b) and 1, c), you get D-N-benzoyl-DOPA or D-DOPA with the properties and yields listed there.

b) Obtaining the cinchonine salt of LN-Benzoyl-DOPA _a .

The crystals obtained in Example 2, a) after suctioning off and washing the D-salt crystals are vaporized Mother liquor to dryness in a water jet vacuum and the residue was washed with cold ethyl acetate, this is how the crude cinchonine salt of L-N-benzoyl-DOPA is obtained.

Yield: 93 to 99% of theory.

Recrystallization of the crude product from ethyl acetate gives a substance with the following values: Mp = 153-155 ° C;

[<x] g> = + 135 ° ± 2 ° (c = 1; methanol).

If one proceeds as described in Examples 1, e) and 1, f), L-N-benzoyl-DOPA or L-DOPA with the properties listed there.

Example 3

a) Production of the cinchonine salt of DN-Benzoyl-DOPA ^s

In an Erlenmeyer flask, as described in Example 1, a) , 159.5 g of rac are dissolved. N-benzoyl-DOPA monohydrate (0.5 mol) and 147 g of cinchonine (0.5 mol) in about 750 ml of methanol, the solution is filtered into a 4-1 round bottom flask and the solvent is removed while warming in a water-jet vacuum. The remaining syrupy salt is dissolved with vigorous shaking or stirring in a boiling mixture of 2 liters of isopropanol, 1 liter of diisopropyl ether and 250 ml of water. Soon afterwards the cinchonine salt of DN-Benzoyl-DOPA begins to crystallize out. To complete the crystallization, the mixture is left to stand overnight at room temperature or in the refrigerator. The crystals are filtered off with suction and washed with well-cooled aqueous acetone or with diisopropyl ether.

The product obtained in this way is sufficiently pure for further processing.

Yield: 149 g (= 97.27% of theory). ^6s

Recrystallization from a mixture of acetone-water, as in Example 1, a), or from a mixture of isopropanol-diisopropyl ether-water gives a substance with the following values:

M.p. = 167 to 168 ° C;

[«]? = 85 ° ± 2 ° (c = 1; methanol).

If one proceeds as described under 1, b) and 1, c), one obtains D-N-benzoyl-DOPA or D-DOPA with the properties and yields listed there.

b) Obtaining the cinchonine salt of L-N-Benzoyl-DOPA

The obtained according to Example 3, a) after suctioning off and washing the D-salt crystals is vaporized Mother liquor to dryness in vacuo and the residue was washed with cold ethyl acetate or di-isopropyl ether, this is how the crude cinchonine salt of L-benzoyl-DOPA is obtained.

Yield: 93 to 99% of theory.

Recrystallization from ethyl acetate results in a substance with the following values:

Mp = 154-155 ° C;

[oi] f = + 135 ° ± 2 ° (c = 1; methanol).

Example 4

a) Preparation of the cinchonine salt of D-N-benzoyl-

DOPA

159.5 g of rac are dissolved in an Erlenmeyer flask. N-Benzoyl-DOPA and 147 g cinchonine with heating in 2 1 isopropanol, the solution clarifies with activated charcoal and filtered it into a 4-1 round bottom flask. Man heated to boiling and mixed the boiling solution with 11 di-isopropyl ether and 250 ml of water, the boils Dissolve the solution again briefly and then let it cool down. Soon after, the cinchonine salt of D-N-Benzoyl-DOPA begins to crystallize. After standing overnight at room temperature or in the refrigerator, the Crystallization ended. The crystals are filtered off with suction and washed with well-cooled acetone or with diisopropyl ether. The product obtained is sufficiently pure for further processing.

Yield: 145 g (= 94.75% of theory).

Recrystallization from an acetone-water mixture, as in Example 1, a), or from a Gemisct isopropanol-di-isopropyl ether-water gives a substance with the following values:

M.p. = 167 to 168 ° C;

[a] p = + 85 ° ± 2 ° (c == 1; methanol).

b) Obtaining the cinchonine salt of L-N-benzoyl

DOPA

The procedure is as described in Example 3, b) receives a substance with the properties described there.

Example 5

a) Preparation of the cinchonine salt of D-N-Benzoy DOPA

In an Erlenmeyer flask, as described in Be game 1, a), 159.5 g of rac. N-Benzoyl-DOP / monohydrate (0.5 mol) and 147 g of cinchonine (0.5 Mo in about 750 ml of methanol, the solution obtained is filtered in a 4-1 round bottom flask and removed the solvent while heating in a water jet vacuum. Tuesday

209 529 ":

9 10

remaining salt is dissolved with vigorous shiit- one obtains the crude cinchonine salt of L-N-benzoyl-

pour or stir in a boiling mixture of DOPA.

3 1 methyl ethyl ketone, 100 ml isopropanol and 200 ml Yield: 93 to 99% of theory

Water. Soon after, the cinchonine salt begins

Crystallize D-N-Benzoyl-DOPA. 5 After recrystallization, the substance shows the following

If the crystallization continues, the mixture is left with the following values:

stand overnight. The crystals are sucked off and p _p _ - ^ 4 ^ ₈ 155 ⁰ C-

with well-cooled aqueous acetone or di-iso- [«]» = + 135 ° ± 2 ° (c = 1; methanol).

propyl ether washed.

Yield: 145 g (94.75% of theory). ¹⁰ B eis ρ ie 1 7

After recrystallization, the substance shows fol- ^a ) Production of the cinchonine salt of DN-benzoyl-

The following values: DOPA

F = 166 to 168 ° C - 159.5 rac. N-Ben-

rJi "* rL 4- 85 ° -I 2 ° Cc - 1 · methanol) ^{15 z} oyl-DOPA monohydrate, 147 g cinchonine, 31 iso-

l * J. - + "J_ L (c_l, methanol). _PrO panol and 300 ml of water and heated the Mi

_prO panol and 300 ml of water and heats the mini

If you proceed as described under 1, b) and 1, c), bring to the boil until solution has occurred.

so one obtains D-N-Benzoyl-DOPA or D-DOPA with After cooling to room temperature the begins

the properties and yields listed there. Crystallization, which is completed after standing overnight

, ^ ,, ".,.", -VT v> 1 ^{ao sen} ist- The crystals are sucked off and washed with them

b) recovery of the cinchonine salt of LN-benzoyl _{well Ekue} g hltem aqueous acetone or diisopropyl

DOPA |

If you steam the according to Example 5 a) according to the yield: 144 g (= 94 »/ 0 of theory),

sucking and washing the D-salt crystals obtained ' ^u '

Mother liquor to dryness in a vacuum and washes 25 After recrystallization, the substance shows the following

the residue with cold ethyl acetate or diisopro- gende values:

pylether, the crude cinchonine salt of p _o _ 155 ° £ is obtained.

L-benzoyl-DOPA. _{ ^ _{f = + 85} ° _{± 2} ° (c = 1; methanol).

Yield: 95 to 99% of theory.

Recrystallization gives a substance with the following ^ ^b ) Production of the cinchonine salt of LN-Benzoyl-

Values: ^DWA

Fd = 154 b's 155 ⁰ C ^- ^ ^ ^{at ve nrt w 'e' m} Example 3 described b) and

Γ \ 1 ^Μ ~ == + 135 ° 4- o ° (c = 1 · methanol) contains a substance with the properties described there

L · Jo -r ± - *. ι J- _{35 scna} ften.

Example 8

a) Preparation of the cinchonine salt of D-N-benzoyl-

a) Preparation of the cinchonine salt of D-N-benzoyl-DOPA

DOPA

40 159.5 g of rac are dissolved in an Erlenmeyer flask.

159.5 g of rac. N-Benzoyl-DOPA and 147 g cinchonine under heating

N-benzoyl-DOPA monohydrate (0.5 mol), 147 g cinmen in 2 liters of ethanol, clears the solution with activated charcoal

chonine (0.5 mol) and about 3 liters of water-saturated n-Bu- and filtered off. It is heated to the boil and added

tanol and heated to the boil until the boiling solution with 11 water solution, boils again

entry. After cooling, the crystallization begins briefly and is then allowed to cool. Soon afterwards

tion, which is practically over after standing overnight. the cinchonine salt of D-N-Benzoyl-DOPA begins to grow

The crystals are suctioned off and washed with well crystallized. After standing overnight at room temperature

chilled acetone or diisopropyl ether. temperature or in the refrigerator is the crystallization

Yield: 146 g (95% of theory). ^{One finishes clean} & ^{the crystals off and wash them}

. . ^{,, s} ° Yield: 148 g (= 96.5% of theory). Recrystallization gives a substance as follows

Values: Recrystallization gives a substance with the following

M.p. == 168 ^° C; ^Values:

[, *]?> = + 85 ° ± 2 ° (c = 1; methanol). M.p. = 166 to 168 ^° C;

55 [ _Λ ] §> = + 85 ± 2 ° (c = 1; methanol).

b) Extraction of the cinchonine salt of LN-Benzoy ¹ -

DOPA b) Production of the cinchonine salt of L-N-benzoyl- If the in Example 6, a) after the Ab-DOPA are inoculated

sucking and washing of the D-salt crystals obtained 60 The procedure is as described in Example 3, b) and

Mother liquor to dryness in a water jet vacuum a substance with the properties described there

Nrt washes the residue with cold ethyl acetate.

Claims (1)

τ. poden separated by removing the cinchonine salt from Claim: rac. N-ßenzoyl.3-methoxy-4-hydroxyphenylalanine pure acetone crystallized. The L-connection is Method for obtaining the pure optical bond obtained as a sparingly soluble salt.
Antipodes n- and L-3,4-dihydroxyphenylalanine 5 The processes mentioned, however, have the consequence, by crystallization of the cinchonine salt, that after the racemate separation, non-racemic 3,4-dihydroxyphenylalanine derivative is only cleaved and saponified and then converted of the i> N-benzoyl radical obtained, but also the cleavage of the and ^ derivatives in free υ- and 1,3,4-dihydroxy ether groups, which is a phenylalanine, thereby marked η et, io higher process costs conditional and the yield that one lowers the cinchonine salt of racemic. N-Benzoyl-3,4-dihydroxyphenylalanine by Kri- So, according to the known method, the removal of the ether groups from a homogeneous liquid phase, the cleavage of the ether groups in the case of the 3,4-methylene, a lower aliphatic ketone, a lower dioxy compound with hydriodic acid and red aliphatic Alcohol or ether with 2 to 8 carbo- 15 phosphorus in acetic anhydride,
lenstoffatornen or a mixture of such processes It has now been found that the racemate separation bonds and at least 1 mole of water per in a simple manner using N-Benzoyl-MoI of the N-benzoyl-3,4-dihydroxy-3,4-dihydroxyphenylalanine used via the corresponding phenylalanine, can be made into the cinchonine salt of n-cinchonine, which is a new compound and L-N-benzoyl-3,4-dihydroxyphenylalanine represents zer-20. lays out these salts by reacting with an acid. The invention therefore provides a process or base cleaves in the usual way and the to obtain the pure optical antipodes i> N-benzoyl group in a known manner from and i-3,4-dihydroxyphenylalanine by crystallization splits. of the cinchonine salt of a racemic 3,4-dihydroxy 25 phenylalanine derivative and subsequent conversion of the obtained i> - and L-derivative in free d- and L-3,4-dihydroxyphenylalanine, which is characterized in that the cinchonine salt of racemic N-Benzoyl-3,4-dihydroxyphenylalanine The invention relates to the recovery of pure crystallization from a homogeneous liquid phase, which optical antipodes D- and L-3,4-dihydroxyphenyl- a lower aliphatic ketone, a lower alialanine (D- and L-DOPA). phatic alcohol or ether with 2 to 8 carbon In this description and in the claims, atoms of matter or a mixture of such compounds all compounds from which dextrorotatory and at least 1 mole of water per mole of 3,4-dihydroxyphenylalanine are used (d-DOPA) contains 35 th N-benzoyl-3,4-dihydroxyphenylalanine, in den can, with d- and all of which levorotatory the cinchonine salt of d- and L-N-benzoyl-3,4-dihy-3,4-dihydroxyphenylalanine (l-DOPA), when broken down with droxyphenylalanine, these salts are formed by reaction L-labeled. with an acid or base in the usual way cleaves and