DD297812A5 - PHOTOISOMERIZATION OF 5.7-DIEN-STEROIDS USING FILTER SOLUTIONS - Google Patents

Abstract

The invention relates to the photoisomerization of 5.7-diene steroids using filter solutions which are important in the preparation of pravitamin or pravitamin metabolites as precursors of the vitamins and vitamin metabolites of the D series. With the invention filter solutions are to be found that are very stable against UV light, do not require the addition of metal salts and therefore lead to a high intensity of the irradiation light and allow the formation of a high proportion of pravitamin or previtamin metabolite in the irradiation mixture. This is achieved according to the invention by dissolving trimethine cyanine salts of the formulas II or III which contain at least one aryl substituent on the trimethine cyanine cation or anions, arylsulfonates or benzoates in water, alcohol or water / alcohol mixtures and these solutions as a filter or at the same time as a filter and cooling liquid can be used in a photoreactor or in a simple irradiation apparatus.

Description

The invention relates to the photoisomerization of 5,7-diene steroids using filter solutions. 5,7-Diene steroids are of great importance as provitamins and provitamin metabolites of the D series as starting materials for the production of the biologically active D-series vitamins and their metabolites. By irradiation with UV light, the respective previtamin is produced from the provitamin, which can be thermally converted into the corresponding vitamin D. The filter solutions according to the invention can be used to select the wavelengths necessary for effective shaping of the irradiation process in a photoreactor or in a simple irradiation apparatus ν.

The conventional irradiation with high-, medium- and low-pressure mercury lamps, xenon / mercury or thallium / mercury lamps without or with the use of filter glasses or filter solutions of aqueous quinine salt, copper or nickel sulfate solutions generally only leads to a small proportion of previtamin or Previtamin metabolites in irradiation: · Mixture. For improved product yield, therefore, the separated, unreacted starting material is again supplied to the irradiation process, or the irradiation is carried out in a two-step process in the presence of an additive (sensitizer), or the irradiation process is performed at two different wavelengths in succession, or both irradiation wavelengths used simultaneously in a defined intensity ratio.

The disadvantage is that in these methods either no appreciably higher degree of conversion to previtamin is achieved or the separation of the additive is costly and associated with yield losses, or the multi-stage process is linked except with an increased workload with an increased formation of by-products, or is the method not suitable for a photoreactor, or the course of the irradiation requires a very precise monitoring of the photoisomerization in order to minimize the formation of over-irradiation products. It has proved advantageous to use two irradiation wavelengths in the range from 270 to 310 and 330 to 350 nm, since in this way a very high proportion of the respective previtamin or previtamin metabolite in the photoisomer mixture can be achieved in a single irradiation step with little effort. However, it is disadvantageous that the necessary generation of the required irradiation light at two different wavelengths with the aid of two monochromocarriers permits only the photoisomerization in a small volume, for example in a cuvette or in a quartz cube, but not in a photoreactor.

Requires carrying out the irradiation in a photoreactor by using a single light source to separate out with the aid of filter solutions having a high Produktu ¹ set favorable radiation wavelengths. The previously proposed filter solutions for simultaneous two-wavelength irradiation, such as alkyl-substituted Trimethincyaninsalze with inorganic anions or nitrophenols, disadvantageously require to achieve a high previtamin in the irradiation mixture generally the addition of metal salts, such as copper, nickel or cobalt sulfate in very high concentrations. A further disadvantage is that a considerable loss of intensity of the irradiation light is associated with the high metal salt concentrations. This requires an uneconomical utilization of the irradiation light and therefore requires long exposure times.

The object of the invention is to find for the photoisomerization of 5,7-diene steroids using filter solutions such substances that can be used as aqueous solutions, do not require the addition of metal salts and therefore lead to a high intensity of the irradiation light and which allow the formation of a :) high proportion of previtamin or previtamin Mstaboliten in Strahlungsgtimisch.

It is the object of the invention to find for the photoisomerization of 5,7-diene steroids using filter solutions against UV light stable and safe to handle filter solutions with steep absorption edges, which are suitable for use in a photoreactor or in a simple irradiation apparatus ensure a high intensity of the irradiation light and lead to a high proportion of previtamin or prjvitamin metabolite in the irradiated solution, which bypass the simultaneous use of two or more ^ n separate filter solutions, an addition of metal salts and additional cooling do not require and their use only a single light source is needed.

The object is achieved in that for the photoisomerization of 5,7-diene steroids of the general formula I.

H ₄ C VR ^:

Formula I

R ^{1 is} hydrogen, alkyl, acyl, Si (alkyl) ₃ R ^{2 is} hydrogen, OH, O acyl, O alkyl, OSi (alkyl) ₃ -CH = CH-CH (CH ₃ > -CH (CH ₃ ) 2, -CH ₂ -CH ₂ -CHR ⁴ -C (CH 3) ₂ R ^{5 is} hydrogen, OH, O-acyl, O-alkyl, OSi (alkyl) _{3 is} hydrogen, OH, O-acyl, O-alkyl, OSilAlkyDa

R ⁴ -R ⁵ G (GH ₃ )

mean, as filter solutions salts of Trimethincyaninen dei general formula II,

R ²

NH

Formula Il

NH ¹

R ^ R '

or the general formula III,

o2

G NH

"? ^Η Λ

NH ⁺ X "

Formula III

Aryl aryl

with η = 1 to

fl ¹ and R ^{3 may be the} same or different and are alkyl, oalkyl, aryl

R ^{2 is} hydrogen, alkyl, aryl

R ⁴ and R ^{5 may be the} same or different and alkyl, aryl, alkylene

X "halide, CIO ₄ ", NO ₃ ", VjSO ₄ ", BF ₄ ", R'-C _e H" -SO ₃ ", FV-C ₆ H ₄ -SO ₂ - R "is hydrogen, haloalkyl

mean,

be used as aqueous or alcoholic / aqueous solutions.

Dissolving salts of the formula type II or III, which contain at least one aryl substituent on Trimethincyaninkation or

Any Trimethincyaninsalze with arylsulfonates or benzoates as anions of suitable concentration in water, alcohol or alcohol / water mixtures, we obtain solutions that are extremely stable against UV light, can be safely handled, simultaneously used as a cooling fluid for the photoreactor and as filter solutions for one

Multi-wavelength irradiation with narrow steep-edged transmission curves in the spectral range from 270 to 310 and 330 to

350nm can be used.

When using Trimethincyaninsalzen of the formulas II or III in the concentration range of 0.001 g to 10g per liter Solvents as filter solutions can easily irradiation conditions without the addition of metal salts

be created, which is practically a largely monochromatic irradiation with light of two different

Wavelengths correspond, which due to relatively high transmission properties high irradiation intensities

and which result in a high yield of previtamin or previtamin moitites in the radiation mixture.

If suitable filter solutions are selected, this proportion can be up to 80%. The advantage in the application of the filter solutions according to the invention over the previously known in particular

in that small steep-edged transmission curves of high permeability are obtained without metal salt addition, the high

Irradiation intensities and thus short irradiation times and allow for a very high proportion of previtamin

or previtamin metabolites in the diet.

The use according to the invention of dimethyl-phenyl-diaza-cycloheptadiene-1DPCH) and N, N'-dibenzyl-dimethyl-trimethine-cyanine (DTC) salts as resolubilizers for the photoisomerization of 7-dehydrocholesterol (7-DHC) is explained below without the use restrict in any way.

example 1

An argon-saturated solution of 7-DHC in dry ethanol (c = 1 x 10- ⁴ mol / l) is irradiated in a quartz cuvette at ⁰ ° C with a 150Watte high pressure mercury lamp. The filter solution used is an aqueous solution of DTC tetrafluoroborate (1 mg / l to 0.8 g / l). After an irradiation time of 15 minutes, the proportion of previtamin D ₃ in the irradiation mixture, depending on the concentration used, is 45 to 73%.

Example 2

When using an aqueous solution of DTC tosylate (0.005 g to 1 g / l) as a filter solution for the photoisomerization of 7-DHC is be. the unteil example 1 given experimental conditions, the proportion of previtamin D ₃ in the isomer mixture 70 to 80%.

Example 3

If DPCH tosylate is used in water (0.005 g / l to 1 g / l) as filter solution and 7-DHC irradiated with the irradiation arrangement indicated in Example 1, after 10 to 15 minutes irradiation time, a proportion of previtamin D ₃ in the range of 60 up to 75% can be achieved.

Claims (1)

1. Photoisomerization of 5,7-diene-3-teroids using one of filter solutions, characterized in that for the photochemical production of the respective previtamin or previtamin metabolite from the provitamin or provitamin metabolite of the D series of the general formula I. R ^{1 is} hydrogen, alkyl, acyl, Si (alkyl) ₃ R ^{2 is} hydrogen, OH, O-acyl, O-alkyl, OSi (alkyl) ₃ 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 is} hydrogen, OH, O-acyl, O-alkyl, OSi (alkyl) ₃ R ^{5 is} hydrogen, OH, O-acyl, O-alkyl, OSi (alkyl) ₃ Formula I mean, Solutions of the salts of aryl-substituted trimethycyanines of the general formula II _π 2 NH * NH Formula Il IT B ' or the general formula III, R ² formula Kii ⁺ χ ' (CH ₂ ) _n (0H ₂ ) _n Aiyl aryl with n = 1 - 6 R ¹ and R ^{3 may be the} same or different and alkyl, OAalkyl, aryl R ^{2 is} hydrogen, alkyl, aryl R ⁴ and R ^{5 may be the} same or different and alkyl, aryl, alkylene Χ "halide, CIO ₄ -, NO ₃ ", V ² SO ₄ 2-, CH ₃ SO ₃ ", BF ₄ ", R ^e -C ₆ H ₄ -SO ₃ -, R ⁶ --C ₆ H ₄ -CO ₂ - R ^{6 is} hydrogen, halogen, alkyl mean, be used as filter solutions. Photoisomeiisierung of 5,7-diene steroids using όπ filter solutions according to claim 1, characterized in that are used as the solvent water, alcohol or water / alcohol mixtures. Photoisomerization of 5,7-diene steroids using filter solutions according to claim 2, characterized in that these solutions are used as a filter or at the same time as a filter and cooling liquid in a photoreactor or a simple irradiation apparatus.