DE2159007C3 - Process for the preparation of cis-zearalenone or cis-zearalenol - Google Patents

Description

From the USA patent specification 3 196 019 it is known Iran's zearalenone [6- (10-hydroxy-6-oxo-1-undecnyl) - * u / f-resorcylic acid ^ -lactonj dutch cultivation of the microorganism Manufacture Gibberella zeae. US Pat. No. 3,239,348 describes how from US Pat Irans-zearalenone the trans-zearalenol [6- (6,10-dihydroxy-l-undecenyl) - /? - resorcylic acid ^ -lactone] can be obtained by reducing the keto group. The invention now relates to a process from these compounds the corresponding ice connections too obtain.

From "Basic Principles of Organic Chemistry" (1967), On p. 1071 it is generally known that in certain cases cis-trans isomerizations are caused photochemically can be. The reference also shows that this method is not generally applicable, but with regard to the starting materials is specific and that, for example, in the case of stilbene, the photochemical Isomerization of the cis compound leads to the trans compound. The literature also leaves nothing recognize the influence of oxygen on such photochemical isomerizations.

The object on which the invention is based now consists in the known trans-zearalenone or trans-zearalenol into cis-zearalenone or cis-zearalenol to convert under the simplest possible working conditions and thereby the highest possible yields and To achieve purity of the products.

The inventive method for the preparation of cis-zearalenone or cis-zearalenol is thereby , characterized in that one trans-zearalenone or trans-zearalenol with ultraviolet rays of one wavelength from 2800 to 3500 A and with a radiation dose of at least 10 kWh / hour. per kilogram of raw material in a practically oxygen-free inert oiganic solvent and under an inert gas atmosphere irradiated.

The cis isomers differ in their nuclear magnetic properties Resonance spectrum clearly of the corresponding trans isomers. The cis-zearalenol just like the corresponding trans compound, occurs in the form of two diastereoisomers.

Typical light sources for the ultraviolet rays used in the claimed method are mercury vapor lamps, carbon arc lamps, and tungsten arc lamps. The preferred one used Radiation dose is 20 to 500 kWh / hour. per kilogram of raw material. The exposure time varies depending on the wavelength, the radiation dose and the amount of starting material.

The inert organic solvent used for the process according to the invention can be, for example, low molecular weight monohydric alkanols, acetonitrile or dichloromethane, methane being preferred. Favorable solution concentrations are around 0.5 to 2.5, preferably around 1 to 1 percent by weight. The solvent should be practically free of oxygen, since oxygen may inhibit isomerization and / or oxidize the reactants. For this reason, it is appropriate to purge the solution of the trans compound with an inert gas such as nitrogen, argon or helium before irradiation, and the irradiation itself is carried out under an inert gas atmosphere.

The inventive method can at room temperature, elevated temperature or lower Temperature, such as at about 15 to 45 C, at atmospheric pressure, above atmospheric pressure or Unleratospheric pressure can be carried out. For reasons of economy, however, one usually works at ambient temperature and atmospheric pressure. .

The isomerization yields are generally over 90%, for example at about 97 ⁿ ", and the Isomerisierüngsprodukte can then be further purified. In the case of zearalenone may be about * / ₃ of the unisomerized trans-isomer can be removed by recrystallization from the process product, so that one can obtain a 99 "" ig pure cis zearalenone. Suitable solvent systems for the recrystallization are for example, mixtures of low molecular weight monohydric alkanols having Water, such as a mixture of isopropanol and water or methanol and water, a mixture of methanol and water with about 20 to 50 volume percent water being particularly preferred. In the case of zearalenol, the isomerization product can be purified by column chromatography over silica or alumina it is advantageous to treat the reaction solution with activated carbon to increase the purity of the process product.

The cis-zearalenone or cis-zearalenol obtained by the process according to the invention can be used for Growth stimulation can be used by animals given it orally, parenterally, or by planting below the skin, such as on the animal's ear, can be administered. For oral administration it can be used with usual Animal feed can be mixed, for example for parenteral injection it can be suspended in peanut oil.

example 1

3 g of trans-zearalenone are dissolved in 500 ml of methanol and the solution is placed in a 500 ml photochemical reactor (Ace Glass Model 6515) equipped with a borosilicate glass dip tube (Ace Glass Model 6517-05). The solution is flushed with nitrogen overnight (about 12 hours) and then irradiated under a nitrogen atmosphere with a 450 watt medium pressure mercury vapor lamp (Ace Glass Model 6515-34) for 41 hours. The reaction solution is slurried with 1 g of activated charcoal, filtered, and the filtrate is evaporated to dryness under vacuum on a rotary evaporator to give 2.98 g of a very pale yellow solid substance, which is obtained twice from a mixture of 25 ml of methanol and 15% ml of water is recrystallized. There are 2.2 g (73.5 % of theory) of white crystals. M.p. 133 to 134.5 ° C obtained the

3 4

as about 99% pure by NMR spectroscopy. The same mixture of cis-zearalenone will be identified as the eluent. Methanol and chloroform used. According to weight analysis in% for C ₁₈ H ₂₈ O ₅ : The evaporation rate of the eluate is calculated to be 8.1 g of a white sub-C 67.92, H 6.92%; found C 68.19, H 7.23%. punch obtained from m.p. 124 to 128 ° C, which by NMR-

5 Spectroscopy as approximately 97% pure cis-zearalenol

Example 2 is identified.

The procedure of Example 1 is carried out using% weight analysis for C ₁₈ H ₂₁ O ₅ : Calculated

preparation of a solution of lOgtrans-zearalenone in 500ml 67.50, H 7.50%; found 67.38, H 7.62%.

_N methanol and with an irradiation time of 72 hours. . . .

the repeated, whereby 9.9 g of crude product are obtained. io example <*

After the recrystallization, 8.8 g of cis-zearalucis-zearalenol are made from the low-melting dia-

non (88% of theory) obtained from m.p. 134 to 135 "C. stereoisomer of trans-zearalenol. 5 g of the low

melting diastereoisomer of trans-zearalenol

Example 3 is dissolved in 500 ml of methanol, and the solution of 10 g of the higher melting diastereoisomer of 15 is placed in a photochemical reactor of 500 ml of trans-zearalenol are dissolved in 500 ml of methanol. Contents (Ace Glass Model 6515), which is equipped with a and the solution is placed in a photochemical reactive borosilicate glass dip tube (Ace Glass Model 6517-05) with a capacity of 500 ml (Ace Glass Model 6515). The solution is rinsed with nitrogen overnight (approximately the one with a borosilicate glass dip tube (Ace Glass 12 hours) and then fitted under Model 6517-05). The solution is flushed with nitrogen over ao nitrogen atmosphere with a 450 watt midnight (about 12 hours) and irradiated with a pressure mercury vapor lamp (Ace Glass Model 6515 - then under a nitrogen atmosphere with a 450 34) for 48 hours. The solution obtained is irradiated for 91 hours by a Watt medium pressure mercury vapor lamp (Ace Glass slurried with 1 g of activated charcoal and filtered, and Model 6515-34). The resulting filtrate is then evaporated to dryness under vacuum on a light yellow solution with 1 g of activated charcoal, with slurrying and then filtered. The filtrate is obtained under 4.65 g of a light yellow solid cooling substance. Vacuum on a rotary evaporator to dryness. This is in accordance with säulenchromatoeingedampft Example 3, 9.42 g of a pale-yellow solid g ^r aphisch purified and yields 4.3 g of a white SubSubstanz be obtained. This is in the smallest amount of m.p. 126 to 131 ° C, which is identified by NMR spectrometry of a mixture of 3 weight scopes as about 97% pure cis-zearalenol percent methanol and 97 percent by weight chloroform.

dissolved and on a silica column of 5 cm diameter weight analysis in% for Ci ₈ H ₂₄ O ₅ : Calculated

knife (»Silicar CC-7«, 200 g) chromatographies. 67.50, H 7.50%; found 67.51, H 7.53%.

Claims (1)

Claim: Process for the production of cis-zearalenone or cis-zearalenol, characterized in that that one trans-zearalenone or trans-zearalenol with ultraviolet rays having a wavelength of 2800 to 3500 A and with a Radiation dose of at least 10 kWh / hour. per kilogram of raw material in a practical oxygen-free inert organic solvent and irradiated under an inert gas atmosphere.