DE1568755C - - Google Patents

Description

40

That for the synthesis of d - (+ ^ pantothenic acid and d - (-) - a-hydroxy- ■ / Jj / S-dimethyl-y-butyrolactone, d - (-) - pantolactone for short, required by d - (+) - panthenol called, can in different ways by splitting the racemic lactone into the optical antipodes be won.

The method of separating the optical antipodes that has so far been used most frequently for the technical production of d - (-) - pantolactone consists in converting the racemic lactone into the diastereomeric α, γ- dihydroxy- β, β- dimethyl-butyric acid salts of quinine transferred, separates these diastereomeric salts from one another by fractional crystallization and converts the quinine salt of the desired optical antipode back into the lactone.

Quinine is now a comparatively expensive substance which, moreover, is insufficient at certain times Quantities is available. A process for the resolution of racemic α-hydroxy - /?, /? - dimethyl -} '- butyrolactone using quinine is thus, from an economic point of view, largely subject to fluctuations in the Dependent on the market situation.

Another method analogous to the separation by means of quinine is, for example, that as Cleavage agent l- (+) - 1 - (p-nitrophenyl) -2-aminopropanediol- (l, 3) used, but this has the disadvantage that this substance is involved in the production of chloramphenicol, in which it occurs as a physiologically less effective form, is bound and thus, just like quinine, is not always available in sufficient quantities.

Furthermore, there are previously used cleavage methods such. B. in the fact that the racemic pantolactone by means of d - (-) - galactamine converted into the diastereomereh dulcitylpantamides, these from one another separates and then hydrolyzed or esterified by means of diacyltartaric acid, the esters obtained by means of Pyridine is converted into the corresponding pyridine salts, these are separated from one another and then hydrolyzed. However, these processes have the serious disadvantage that the reactions mentioned, d. H. amide formation and hydrolysis, or ester formation and hydrolysis, organic-chemical reactions represent, which in general do not proceed quantitatively and thus considerable losses of substance have as a consequence.

The invention aims to address the disadvantages outlined above, which with the use of the cleavage agents mentioned there, and to develop a process which a cheaper and, above all, always available in sufficient quantities is used.

It was found that substituted in the 1-position by the amino group or the aminomethyl group 1,4a-Dimethyl-7-isopropyl-octa-, -dodeca- and - tetradecahydro - phenanthrene - derivatives, which from Colophony, a by-product of turpentine oil production, can be easily produced, for the cleavage of d, l-pantolactone (racemic a-hydroxy- / 9, /? - dimethyl-y-butyrolactone) very well suited.

The process according to the invention for the cleavage of racemic α-hydroxy- β, β- dimethyl-γ-butyrolactone into its optical antipodes by separating salts of the α, γ-dihydroxy - / ?, | 3-dimethylbutyric acid derived from this lactone is thus characterized in that the cleavage is carried out with a 1-amino- or 1-aminomethyl-1,4a-dimethyl-7-isopropyl-octa-, -dodeca- or -tetradecahydro-phenanthrene or one of its acid addition salts as the cleavage reagent. ·

The phenanthrene derivatives used by the process according to the invention can be obtained by the following Formulas are represented:

CH ₃ R.

CH (CH ₃ ) ₂

(I)

(II)

H ₁ C

CH (CH ₃ J ₂

CH, R

(III)

CH (CH ₃ ),

The compound of the formula II contains a single double bond in one of the rings B, C the layers indicated by lines and is therefore a dodecahydrophenanthrene derivative.

The symbol R in the above formulas I, II and III means the amino group or the aminomethyl group.

The substituent R is the aminomethyl group

-CH ₂ NH ₂

preferred. Compounds of this type can be selected from the corresponding carboxyl compounds according to the the following reaction scheme can be obtained:

—COOH
> -CONH ₂

-C = N
-CH ₂ NH ₂

The 1-carboxyl compounds of the formulas used here as starting materials

CH, COOH

H, C

CH, COOH

CH (CH ₃ ),

(Ia)

(Ha)

H, C

CH, COOH

-CH (CH ₃ ),

The abietic acid of the formula

CH, COOH

(IV)

CH (CH ₃ ),

is obtained by isomerizing rosin with acid or alkali. The connections Ia, II a and IHa are due to thermal disproportionation available from abietic acid (IV). Furthermore, the compounds of the formulas Ha and III a can by partial or complete hydrogenation of abietic acid can be obtained.

Compounds of the formulas I, II and III in which R represents an amino group can be selected from the corresponding 1-carboxyl compounds can be obtained, for example, according to the following reaction scheme:

—COOH

► -CONH ₂

> -N = C = O

> -NH ₂

The preferred cleavage reagents include the l ^ a-Dimethyl-l-aminomethyl-V-isopropyl-octa-, -dodeca- and -tetradecahydro-phenanthrene and the l ^ a-dimethyl-l-amino-V-isopropyl-octa-hydro-phenanthrene or their acid addition salts.

As examples of cleavage reagents, acid addition salts of the following can be used from rosin available phenanthrene derivatives are:

CH ₇ NH

H, C

H, C

NH

CH (CH ₃

(Ma)

- J— CH (CH ₃ ),

can be obtained from rosin via abietic acid.

H, C

CH (CH ₃ ) ₂

CH ₇ NH,

H, C

H ₁ C

CH ₂ NH ₂
H ₃ C j

\! H

(VIII)

H, C

These compounds are l / ?, 4a / S-dimethyl-1 a-aminomethyl-7-isopropyl-1,2,3,4, 4a, 9,10,10aa - octahydro - phenanthrene (V), referred to as dehydroabietylamine for short, lß, 4a /} - dimethyl

phenanthrene (VI), referred to as dehydroabietan-1-amine for short, 1 j3,4aß-dimethyl-1 a-aminomethy 1- 7a-isopropyl - l, 2,3,4,4a, 4ba, 5,6,7 ^, 9,10,10aa - dodecahydrophenanthrene (VII), briefly referred to as dihydroabietylamine, and lß, 4aß - dimethyl - Ια - aminomethyl- Ίβ - isopropyl - 1,2,3,4,43 ^ α, 5,6,7α, 8 ^, 9,10,103α-tetradecahydrophenanthrene (VIII), referred to as tetrahydroabietylamine for short.

The dehydroabietylamine of the formula V and the dehydroabietan-1-amine are particularly preferred Formula VI.

The cleavage of the racemic pantolactone takes place via the diastereomeric cy-dihydroxy- ^ / J-dimethylbutyric acid salts the phenanthrene derivatives used as cleavage reagents.

The procedure here is expediently such that the racemic α-hydroxy- / 3, / 3-dimethyly-butyrolactone (D, L-pantolactone) is converted into a salt of the racemic α, γ-ΏΊ by treatment with an alkali metal hydroxide, in particular with sodium hydroxide - Hydroxy - ß, ß - dimethyl - butyric acid is converted by converting the salt thus formed in a molar ratio of about 1: 0.5 to 1: 0.6, preferably in a molar ratio of 1: 0.55 to 1: 0.57, with an acid addition salt of the phenanthrene derivative in question, that the reaction mixture is subjected to an exchange reaction and that the alkali metal salt of d- (+) -a, y-dihydroxy - / ?, ß-dimethyl-butyric acid which is formed and which remains in solution is precipitated from the Phenanthrene derivative salt which separates L - (-) - α, γ - dihydroxy- ^ -dimethylbutyric acid and converts it into d- (-) - pantolactone in a known manner.

This process is explained in more detail below, with the symbol PD denoting a phenanthrene derivative one of the formulas I, II and III, in particular a phenanthrene derivative of one of the formulas V, VI, VII and VIII, is designated:

When 1 mole of D, L-pantolactone is reacted with sodium hydroxide, 1 mole of the sodium salt is formed of D ^ -a ^ -dihydroxy-zS ^ S-dimethyl-butyric acid. When adding half a mole of the hydrochloride of PD, the following salts are formed:

(VII) 0.25 mol PD salt of D- {+) - α, γ- dihydroxy-

(3, / 3-dimethyl-butyric acid,
0.25 mol PD - salt of 'L - (-) - α, γ - dihydroxy-

/ 3, /? - dimethyl butyric acid,
0.25 mol Na salt of D - (+) - <*, y-dihydroxy-

/?, / 5-dimethyl-butyric acid,
0.25 mol Na salt of L- (-) -a, y-dihydroxy-

(S, (3-dimethyl-butyric acid and
0.5 moles of NaCl.

The aqueous reaction mixture containing these salts is then subjected to an exchange reaction, a mixture of the following salts is obtained:

0.5 mol PD - salt of L - (-) - α, γ - dihydroxy-β, β-dimethyl-butyric acid (precipitates in solid form),

0.5 mol Na salt of D - (+) - α, γ - dihydroxy- | 3, j3-dimethyl-butyric acid (remains in solution) and

0.5 moles of NaCl.

After filtration, the Na salt contained in the filtrate becomes D - (+) - a, y-dihydroxy-jS, / S-dimethyl-butyric acid in a known manner by acidification, for example with sulfuric acid, into the desired d - (-) - pantolactone transferred, which is extracted with an organic solvent, for example with ether can be.

The precipitate containing the PD salt of L- (-) - a, y-dihydroxy- (S, ^ - dimethyl-butyric acid) can be removed by means of an alkali metal hydroxide, for example sodium hydroxide, with the formation of the free PD base and the Na salt of l - (-) - a, y-Dihydroxy-ß, | 9-dimethyl-butyric acid. The PD base, after being converted into an acid addition salt, can be used again as a cleavage reagent, and the Na salt of the L- (- ) -a, y-dihydroxy- / S, j3-dirnethylbutyric acid can be converted into the l - (+) - pantolactone by means of a mineral acid, the latter can be racemized in a known manner to give D, L-pantolactone, and the D, L- Pantolactone can again be subjected to cleavage.
In this way, optically pure d - (-) - pantolactone is obtained in high yield (85 to 90%), and it is possible to repeatedly (25 times and more) the cleavage reagent, which can be recovered in practically 100% yield. to use.

The above exchange reaction can be carried out by heating the reaction mixture (e.g. to 85 ° C for about 75 minutes).

In a simpler and therefore preferred way, the exchange reaction can take place at room temperature be achieved by adding a water-miscible organic to the aqueous reaction solution Solvents, especially a lower aliphatic alcohol; like ethanol, or a ketone, such as acetone, a nitrile such as acetonitrile, an acid amide such as dimethylformamide, or a sulfoxide such as dimethyl sulfoxide, clogs. The exchange reaction is complete within a few minutes.

The acid addition salt of the phenanthrene derivative is preferably a salt of a lower aliphatic

Carboxylic acid, especially acetic acid, or a salt of a mineral acid, for example the hydrochloride or the hydrobromide is used. When reacting these salts with an alkali metal salt the a, y-dihydroxy - /?, /? - dimethyl butyric acid obtained diastereomeric salts can have the general formula

CH,

-ι θ

HOCH ₂ -C-CHOh-COO ®HPD (K)

CH ₃

can be attributed.

example 1

In a 1.5-1 four-necked flask equipped with a stirrer, reflux condenser, thermometer and 500 ml dropping funnel, 78.0 g (0.6 mol) of racemic α-hydroxy-β, β- dimethyl- γ- butyrolactone ( d, l - pantolactone, pure recrystallized from isopropyl ether, mp 86 to 88 ° C) with 315 ml (0.03 mol) of 2 N sodium hydroxide solution * was added, and the solution is heated 20 minutes 70 to 8O ⁰ C... The pH of the solution is then adjusted to 8.5 by adding 3η hydrochloric acid. The solution then becomes a solution of 114.0 g (0.33 mol) 1 / S, 4a ^ -Dimethylihl with stirring

Hydro-phenanthrene acetate (dehydroabietylamine acetate) (melting point 135 to 137 ° C.) in 500 ml of distilled water was added over the course of 10 minutes. The reaction mixture is then heated ³ / _A hours with stirring to 85 ° C and then cooled with an ice bath to 5 ° C. A white crystal pulp, consisting of the dehydroabietylamine salt of l- (-) -a, γ-dihydroxy - ß, ß - dimethylbutyric acid, precipitates out, which is suction filtered and washed three times with 80 ml of water each time.

The combined filtrates are concentrated to 250 ml in a rotating evaporator, and the precipitate formed is filtered off, about 100 mg of the dehydroabietylamine salt of L - (-) - α, γ - dihydroxy - β, β - dimethylbutyric acid still being obtained, which be added to the previously separated main amount of the precipitate.

The filtrate is mixed with 20 ml of concentrated sulfuric acid acidified (pH = 1), after standing for 1 hour at room temperature with about 25 g of sodium chloride saturated and in the in »Z. physiol. Chem. «, 39 (1903), pp. 473 to 476, described extraction apparatus extracted with about 300 ml of ether for 15 hours. The d - (-) - a-hydroxy- / 3, / 3-dimethyl-y-butyrolactone Extract containing (d - (-) - pantolactone) is dried over 20 g of sodium sulfate, filtered and concentrated and evaporated twice with 50 ml of toluene on a rotating evaporator to remove acetic acid. 38.3 g of the D - (-) - pantoactone are obtained; [«)« = -42.0 ° (1% in water). Used for cleaning this crude lactone recrystallized from 50 ml of isopropyl ether, 30.9 g (88%) of pure D - (-) - pantolactone obtained; M.p. 91 to 93 ° C; [α] ?, ' = -52.0 ° (1% in water).

The precipitate obtained in this way, consisting of the dehydroabietylamine salt of L- (-) -a, y-dihydroxy- / j, /? - dimethylbutyric acid, is suspended in 200 ml of water in a separating funnel, and the suspension obtained is covered with a layer of 200 ml of ether. The dehydroabietylamine base is then released from the salt by adding about 35 ml of 40% strength sodium hydroxide solution (up to the phenolphthalein-alkaline reaction). After vigorous shaking, the organic and aqueous phases are separated from one another. The aqueous phase is brought to a pH of 1 with about 10 ml of concentrated sulfuric acid and left to stand at room temperature for 1 hour. After saturation with sodium chloride and extraction in the above-mentioned extraction apparatus, 39.4 g (92%) of the L- (+) -pantolactone are obtained; [_a] ² o ³ = +45.7 ⁰ C (1% in water). This (+) - lactone can be racemized in a known manner, whereupon the racemate can be returned to the process.

The dehydroabietylamine acetate used as the separation agent in the above example is a known one Substance that can be obtained from rosin.

In the following the physical data of the two diastereomeric salts of dehydroabietylamine with α, γ - dihydroxy - β, β - dimethyl - butyric acid are given:
Dehydroabietylamine salt of the D - (+) - a, v-dihydroxy

^ -dimethylbutyric acid: melting point 157 to 158 ⁰ C (not corrected, after crystallization from water), 154 to 156 ° C (not corrected, after crystallization from ethanol); [a] ² _D ⁴ = + 38.6 ° (5% in CH ₃ OH); Solubility: 1.5 g in I IH ₂ O at 25 ⁰ C.

Dehydroabietylamine salt of L- (-) -a, - / - dihydroxy- / M-dimethyl-butyric acid; Melting point 185 to 186 ° C (not corrected, after crystallization from water), 185 to 187 ° C (not corrected, after crystallization from ethanol); [α]? = + 17.2 ° (1% in CH ₃ OH); Solubility: 1.4 g in 10 1 H ₂ O at 25 ° C.

B ice pie I 2

In a 1.5-1 four-necked flask equipped with a stirrer, reflux condenser, thermometer and 500 ml dropping funnel, 78.0 g (0.60 mol) of racemic a-hydroxy- / S, /? - dimethyl-y- butyrolactone (D, L-pantolactone) are mixed with 310ml of 2η sodium hydroxide solution, whereupon the solution is heated to 70 to 80 ° C. for 20 minutes. The pH of the solution is then adjusted to 8.5 by adding 1η hydrochloric acid and, after adding 100 ml of water, it is cooled to room temperature. A solution of 118.16 g of dehydroabietylamine acetate (0.342 mol) in 400 ml of ethyl alcohol is then allowed to run into this solution while stirring. (181 a, y-dihydroxy-jS ^ -dimethyl-butyric acid, mp 183 ⁰ C Dehydroabietylaminsalz the L- (-) -.), In that the exchange reaction is complete after 15 minutes, the melting point shows the precipitated crystal slurry. The precipitate is filtered off with suction and washed three times with 80 ml of water each time.

The combined filtrates are concentrated to 250 ml in a rotating evaporator, and the precipitate formed (dehydroabietylamine salt of L - (-) - α.γ - dihydroxy - β, β - dimethyl - butyric acid) is filtered off and added to the bulk of the precipitate. The filtrate is acidified with 20 ml of concentrated sulfuric acid and, after standing for 1 hour at room temperature, extracted with 300 ml of ether in the extractor mentioned in Example 1.

The extract containing the d- (-) -pantolactone is dried over sodium sulfate, filtered and concentrated and evaporated twice with 50 ml of toluene on a rotating evaporator to remove acetic acid.

209512/374

32.9 g of the crude d- (-) -pantolactone are obtained: [a] I ⁴ = -47 ° (1% in H ₂ O). For purification, this crude lactone is recrystallized from 50 ml of isopropyl ether, 29.4 g (87.7%) of pure d - (-) - pantolactone being obtained, [α] % = -51.7 ° (3% in H ₂ O ).

Example 3

In a 300-ml four-necked flask equipped with stirrer, reflux condenser and dropping funnel, 13.0 g of D, L-pantolactone to be (0.10 mol) with 52 ml of 2N-sodium hydroxide solution and the solution 20 minutes 65 to 70 ⁰ C heated. The excess of alkali is then back-titrated to pH 8.5 with 1 η-hydrochloric acid, and then 17.5 g (0.057 mol)
methyl-la-ammo-7-isopropyl-1,2,3,4 ^, 10,
hydro - phenanthrene hydrochloride (dehydroabietan-1-amine hydrochloride) [mp. 280 to 285 ° C, [α] ?? = + 48 ° (3% in CH ₃ OH)] was added as a suspension in 20 ml of ethanol and 70 ml of water. The reaction mixture is stirred at room temperature for 10 minutes and then the dehydroabietan-1-amine salt of L - (-) - a, y-dihydroxy - /?, / 5-dimethylbutyric acid (melting point 157 to 159 ° C.) is suction filtered and carefully washed with water.

The combined filtrates are concentrated to 50 ml in a rotary evaporator and the precipitate formed is filtered off and added to the main precipitate. The filtrate is acidified with 3.5 ml of concentrated sulfuric acid (pH 1) and, after standing for 1 hour at room temperature, extracted with ether overnight in the extraction apparatus mentioned in Example 1. The ether solution is then dried over sodium sulfate, filtered and concentrated on the steam bath. Residue: 7.3 g of crude D - (-) - pantolactone, [α] ² ₀ ² = about -35 ° (1% in H ₂ O; exact value was difficult to determine because of turbidity). The crude lactone is recrystallized twice from isopropyl ether and gives 5.0 g (87%) of pure lactone, [a] ² _D ⁴ = -52 ° (3% in H ₂ O).

The dehydroabietan-1-amine hydrochloride used as a cleavage reagent can be obtained from the known dehydroabietan-1-amine by treatment with hydrochloric acid. The dehydroabietan-1-amine can be obtained in a known manner from dehydroabietic acid.

The following gives the physical data of the two diastereomeric salts of dehydroabietan-1-amine with a, y-dihydroxy- (3, j9-dimethyl-butyric acid: Dehydroabietan-1-amine salt of the D - (+) - a, γ - dihydroxy -β, β- dimethyl - butyric acid: sublimes at 22O ⁰ C; [Vp ₀ ⁵ = + 51 ° (3% in CH ₃ OH); solubility in water: 1 g in 230 ml H ₂ O at 20 ° C. dehydroabietane -1-amine salt of L - (-) - a, y-dihydroxy-jS, ß-dimethyl-butyric acid: melting point 157 to 159 ° C; [α]! "= + 25 ° (3% in CH ₃ OH ); Solubility: 1 g in 500 ml H ₂ O at 20 ° C.

Example 4

In a 200 ml four-necked flask equipped with a stirrer, reflux condenser and dropping funnel, 10 ml of 2N sodium hydroxide solution and 10 ml of water are added to 2.61 g of D, L-pantolactone (0.020 mol) and the mixture is ^{heated to 70 °} C. for 20 minutes . At 75 ° C., a slurry of 3.76 g (0.011 mol) of l ^, 4a / i-dimethyl-l «-aminomethyl-7u-isopropyl-l, 2,3,4,4a, 4b«, is added to the sodium salt formed 5,6,7 ^, 9,10,10aa - dodecahydrophenanthrene hydrochloride [dihydroabietylamine hydrochloride; M.p. 261 to 264 ° C; [α] !? = -29 ° (1% in CH ₃ OH)] in 65 ml of water and rinsed with 15 ml of water. The reaction mixture is heated to 85 ° C. (internal temperature) for 60 minutes using an oil bath and then cooled to room temperature using a water bath. The white crystal slurry, consisting of the Dihydroabietylaminsalz the L - (-) -. A, y-dihydroxy- (3, (S-dimethyl-butyric acid (m.p. 152-153 ⁰ C), filtered off under suction and washed thoroughly with water.

The combined filtrates are concentrated to 50 ml in a rotary evaporator and the precipitate formed is filtered off and added to the main precipitate. The filtrate is acidified to pH 1 with sulfuric acid and, after standing for 1 hour at room temperature, extracted with ether overnight in the extraction apparatus mentioned in Example 1. The ether solution is then dried over sodium sulfate, filtered and concentrated on the steam bath: residue 2 g, [α] ² / = -26 ° (3% in H ₂ O). Recrystallized from isopropyl ether, 1 g of d - (-) - pantolactone (85%), [α] ² / = -49.5 ° (3% in H ₃ O) is obtained.
The di- {/) used here as a cleavage reagent

hydroabietyl hydrochloride may result from the decision ^ speaking base by treatment with hydrochloric acid are obtained. The dihydroabietylamine itself is accessible from the known dihydroabietic acid via the acid chloride, the acid amide and the nitrile. The dihydroabietic acid, in turn, can be obtained by partial hydrogenation of abietic acid.

The physical data of the dihydroabietylamine salt of l - (-) - a, y-dihydroxy- / J, ß-dimethyl-butyric acid are as follows: melting point 152 to 153 ° C; [a] f = -24.5 ° (2% in C ₂ H ₅ OH); Solubility: 1 g in 16 1 H ₂ O at 20 ° C.

Example 5

In a 200 ml four-necked flask equipped with a stirrer, reflux condenser and dropping funnel, 3.25 g of D, L-pantolactone (0.025 mol) are mixed with 13 ml of 2N sodium hydroxide solution and die.Lösung at 65 to 70 ° C for 20 minutes warmed up. The excess of alkali is then titrated back to pH 8.5 with 1 η-hydrochloric acid and then 4.67 g (0.0142 mol) of ljS, 4ass-Dimethy 1 -1 α - aminomethyl - 7 β - isopropyl -1.2, 3,4,4 a, 4 ba, 5,6,7a, 8,8a / 3,9,10,10aa - tetradeca - phenanthrene hydrochloride (tetrahydroabietylamine hydrochloride) (melting point 265 to 270 ⁰ C, [a] f = + 13.8 ° [3% in H ₂ O]) was added as a suspension in 20 ml of water and 30 ml of alcohol. The reaction mixture is _{heated to 80 ° C. for 2} hours with stirring IV and then cooled to room temperature. The white crystal pulp, consisting of the tetrahydroabietylamine salt of L - (-) - α, γ - dihydroxy - β β - dimethyl butyric acid (melting point 186 to 188 ° C.), is suction filtered and carefully washed with water.

The combined filtrates are concentrated to 20 ml in a rotary evaporator and acidified with 1 ml of concentrated sulfuric acid (pH 1). After standing for 1 hour at room temperature, the extraction apparatus mentioned in Example 1 is used to extract with ether overnight. The ether solution is then dried over sodium sulfate, filtered and evaporated on the steam bath. Residue: 1.7 g, [α]! ⁴ = -37 ° (1% in H ₂ O). The crude product is made from iso-

propyl ether recrystallized. 1.0 g of D - (-) - pantolactorr (71.4%), [α] ² i = -50.6 ° (3% in H ₂ O) are obtained.

The tetrahydroabietylamine hydrochloride used here as a slicing reagent can be obtained from the corresponding base ... by treatment with hydrochloric acid. I ^ as Tetrahydroabietylamin itself is from the bekanEsvr = _n Tetrahydroabietic over

the acid chloride. aas acid amide and the nitrile

accessible. Turn ~ istrahydroabietinsäure can be obtained by _e vollstänsiäig hydrogenation of abietic acid.

The following are the physical data of the two diastereomeric salts of tetrahydroabietylamine indicated with a, y-dihydroxy- / S, / 3-dimethyl-butyric acid :

Tetrahydroabietylaminsalz of D - (+) - α, γ - dihydroxy-j3, ^ - dimethyl-butyric acid: mp 155 to 157 ⁰ C;. [ap _D ⁵ = + 25.0 ° (3% in CH ₃ OH); Solubility: Ig in 71 H ₂ O at 20 ⁰ C.

Tetrahydroabietylamine salt of L - (-) - α, γ - dihydroxy - β, β -dimethylbutyric acid: melting point 186 to 188 ° C; [α] S "= + 3 ° (0.5% in CH ₃ OH); solubility: Ig in 28 IH ₂ O at 20 ° C.

Claims (4)

Patent claims: 1. Process for the cleavage of racemic a- hydroxy- β, β- dimethyl- γ- butyrolactone (pantolactone) in its optical antipodes by separating salts from the! this derivative a ^ -dihydroxy - ^ - dimethylbutyric acid, characterized in that the cleavage with a 1-amino- or l-amino-methyl-1,4a-dimethyl-7-isopropyl-octa-, -dodeca- or -tetradecahydro -phenanthrene or one of its acid addition salts as a cleavage reagent. 2. The method according to claim 1, characterized in that the cleavage with l / ?, 4a / 5-dimethyl -la- aminomethyl-7-isopropyl-1,2,3,4,4a, 9,10,10aa - octahydro - phenanthrene (»dehydroabietylamine«) or l / ?, 4a / 3-dimethyl- Ια-amino-7-isopropyl -1,2,3,4,4a, 9,10, lOaa - octahydro - phenanthrene (»dehydroabietan-1 -amine «) or one of these amines with the acetate or a mineral acid salt. 3. The method according to claim 1 or 2, characterized in that the salt of the racemic cijy-dihydroxy-jS.jS-dimethyl-butyric acid, which consists of the racemic a-hydroxy-zS ^ -dimethyl-y-butyro ketone (pantolactone) has been produced by reaction with an alkali metal hydroxide, in aqueous solution with about 0.5 to 0.6 mol of an acid addition salt of the phenanthrene derivative, each Mole of the racemic salt, at room temperature with the addition of a water-miscible organic Reacts solvent or with heating. 4. The method according to claim 3, characterized in that the alkali metal hydroxide is sodium hydroxide and per mole of the racemic salt 0.55 to 0.57 mole of an acid addition salt of the Phenanthrene derivative used.