DD279668A1 - PROCESS FOR SENSITIZED PHOTOISOMERIZATION OF 5.7-DIEN-STEROIDS - Google Patents

Abstract

The invention relates to a method for the sensitized photoisomerization of 5.7-diene steroids (provitamins and provitamin metabolites of the D series). It has been found that provitamins and provitamin metabolites of the D series, when irradiated in admixture with a sensitizer whose triplet energy is in the range of 150 to 250 kJ / mol, achieve very high product yields of previtamin or previtamin metabolites, respectively Irradiation with light in the wavelength range of 240 to 320 nm is performed, or when simultaneously irradiated with two different wavelengths, wherein the wavelength range of a light source between 240 and 310 and the second light source is greater 330 nm. The yield of previtamin can be over 90%.

Description

Field of application of the invention

The invention relates to a method for the sensitized photoisomerization of 5.7-diene steroids. 5.7-diene steroids are of great importance as provitamins and provitamin metabolites of the D series, as they are the starting materials for the production of the biologically active vitamins of the D series and their metabolites.

Characteristic of the known technical solutions

To represent the vitamins of the D series, the respective provitamin is photochemically converted into the corresponding previtamin and subsequently thermally isomerized. The achievable yield of vitamin D or vitamin D metabolite is ostensibly determined by the proportion of the previtamin or previtamin metabolite formed during the photoisomerization. The conventional irradiation of provitamins with high, medium or low pressure mercury lamps, xenon / mercury lamps without or with the use of filter glasses or filter solutions of aqueous quinine or metal salt solutions leads only to a low yield of previtamin or previtamin metabolite , To increase the product yield, therefore, the separated, unreacted starting material is again supplied to the irradiation process, or in the irradiation process is performed with two different wavelengths in succession, or both Irstrahlweillängen be used simultaneously in a certain intensity ratio, or the irradiation is in a two-stage process in the presence of a Additive carried out, wherein the by-product tachysterol formed in the first irradiation process with a high proportion is sensitized in a subsequent irradiation in the previtamin is transferred.

The disadvantage is that in these methods either no significantly higher degree of conversion is achieved to previtamin, or the multi-stage process is connected except with an increased workload with an increased formation of by-products, or the method is not suitable for a photoreactor, or the irradiation ' It requires very careful monitoring of the photoisomerization in order to minimize the formation of unwanted marrow products.

It is advantageous for the photoisomerization, the simultaneous use of two irradiation wavelengths and various filter solutions for generating these irradiation conditions. However, disadvantageously, only a maximum yield of about 80% of previtamin D in Photoisomerenge.nisch is achieved.

Object of the invention

The object of the invention is to find a method for the sensitization of sensitized 5.7-dienes steroids, which allows a high yield of previtamin D or previtamin D metabolites.

Explanation of the nature of the invention

It is the object of the invention to achieve a very high yield of the respective previtamin or previtamin metabolite of the D series by sensitized photoisomerization of 5.7-diene steroids in a single irradiation step. The object is achieved daduch that the Photoisomierisierung of 5.7-diene steroids of the general formula I.

Formula I

R ¹ = H, alkyl, acyl, Si (alkyl) j, alkoxylalkyl

R ² = H, OH, O acyl, OAlkyl, OSi (alkyl) ₃ , OAlkoxyalkyl

r3 = -CH = CH-CH (CH ₃ I-CH (Ch ₃ I ₂ , -CHz-CHjCH '

R ⁴ = H, OH, O acyl, OAlkyl, OSi (alkyl) ₃ , OAlkoxyalkyl

R ⁵ = H, OH, O acyl, OAlkyl, OSi (alkyl) ₃ , OAlkoxyalkyl

R ⁴ -R ⁵ = O ₂ C (CH ₃ I ₂

mean,

in the presence of a triplet sensitizer using irradiation wavelengths in the range of 240 to 320 nm or with simultaneous irradiation with light in the wavelength range of 240 to 310 nm and greater than 330 nm.

Suitable sensitizers are compounds whose triplet energy is in the range from 150 to 250 kJ / mol. Such sensitizers effect under these irradiation conditions a virtually quantitative conversion of the by-product formed during the irradiation in tachysterol previtamin D. The Konzentrationsb ^ rich of sensitizer may vary depending on its absorption characteristics 10 ^"4 to 1G ~ ² mol / l.

The sensitizers used may preferably be fluorenone, benzanthrone, 1,2-benzanthracene, pyrene, chrysene, benzil, diacetyl, phenanthrene or acridine. The photoisomerization can be carried out in the usual inert solvents, such as pentane, hexane, heptane, cyclohexane, isooctane, ether, THF, ethanol, isopropanol, benzene or mixtures thereof. Suitable irradiation lamps are high-, medium- or low-pressure mercury radiators or xenon / mercury lamps, wherein the irradiation wavelengths can be generated by means of monochromators, filters or filter solutions, or lasers of suitable emission wavelengths can be used as irradiation sources.

The yield achieved by the process according to the invention on the respective previtamin in the irradiation mixture can be up to 95%. The isolation of the previtamin or previtamin D metabolite can be carried out in a manner known per se.

embodiments

example 1

An oxygen free solution of 7-dehydrocholesterol (pro-vitamin D ₃₎ (C = 0.4 x 10 ~ ⁴ mol / l) undFluoren-9-one (c = 4 x 10 ^-4 mol / l) was dissolved in dry ethanol at 0 ⁰ C irradiated simultaneously with two 200 W high-pressure mercury lamps (HBO 200) in a simple irradiation apparatus. By means of monochromators, the irradiation wavelengths 256.5 and 405 nm were generated. After an irradiation time of 5 h, the reaction mixture contained 89% previtamin D ₃ , 4% provitamin D ₃ , 3% tachysteroi ₃ and 4% lumisterol.

Example 2

Under the same experimental conditions as specified in Example 1, the composition of the irradiation mixture when using benzanthrone is as a sensitizer (c = 3 · 10 ^-4 mol / l): 92% previtamin D _3, 2% provitamin _D: 2% Tachysterols , 4% lumisterol.

Claims (7)

Invention claim: A process for the sensitization of photo-isomerization of 5.7-diene steroids, characterized in that provitamins or provitamin metabolites of the D-series of the general formula H ₃ C Formula I R ¹ = H, alkyl, acyl, Si (alkyl) ₃ , alkoxyalkyl R ² = H, OH, O acyl, OAlkyi, OSi (alkyl) ₃ , OAlkoxyalkyl r ₃ = -CH = CH-CH (CH 3) -CH (CH 3) ₂ , -CH ₂ -CH ₂ -CHR ⁴ -C (CH 3) ₂ R ⁵ R ⁴ = H, OH, O acyl, OAlkyi, OSi (alkyl) ₃ , OAlkoxyalkyl R ⁵ = H, OH, O acyl, OAlkyi, O 3i (AlkyM ₃ , OAlkoxyalkyl R ⁴ -R ⁵ = O ₂ C (CH ₃ J ₂ mean, in admixture with a sensitizer to form previtamins of the general formula II Formula Il, wherein R ¹ to R ^{3 have} the above meaning, are irradiated in an inert solvent. 2. Method according to item 1, characterized in that sensitisers with a triplet energy in the range from 150 to 250 kJ / mol are used. 3. The method according to item 2, characterized in that are preferably used as sensitizers fluorenone, benzanthrone, 1.2-benzanthracene, benzil, chrysene, diacetyl, phenanthrene or acridine. 4. The method according to item 3, characterized in that are used as light sources high, medium or low pressure mercury radiator or xenon / mercury lamps and with monochromators, filters or filter solutions suitable irradiation wavelengths are generated. 5. The method according to item 3, characterized in that are used to generate the irradiation wavelengths laser. 6. The method according to item 4 and 5, characterized in that light is used in the wavelength range of 240 to 320nm for irradiation. 7. The method according to item 4 and 5, characterized in that the sensitized photoisomerization by simultaneous irradiation with light in the wavelength range of 240 to 310nm and greater 330nm is performed.