KR102420818B1 - Photoisomerization conversion reaction of 9-cis Retinoic acid in all-trans and its application method. - Google Patents

Abstract

Provided is a photoisomerization conversion reacting method for converting all-trans retinoic acid (ATRA) into 9-cis retinoic acid (9CRA) and a photoisomerization conversion reacting device, wherein the method comprises: a step (ga) of preparing a reactant by dissolving, in the ATRA, one or more solvents selected from acetonitrile (ACN), dichloromethane (DCM), ethyl acetate (EA), ethanol (EtOH), and n-hexane (normal hexane); and a UV light irradiation step (na) of inputting the prepared reactant into the photoisomerization reacting device of claim 1, and irradiating the reactant with the light of a wavelength of 385 nm by a UV LED at the light source power of 300 to 1400 mW/cm^2, thereby enhancing efficiency in converting the ATRA into the 9CRA.

Description

Photoisomerization conversion reaction apparatus and isomer conversion method using the same from all-trans to 9-cis Retinoic acid {Photoisomerization conversion reaction of 9-cis Retinoic acid in all-trans and its application method.}

The present invention relates to a photoisomerization conversion method from All-trans to 9 ^- cis Retinoic acid and a conversion reaction apparatus using the same. It relates to a conversion reaction apparatus capable of converting to 9-cis Retinoic acid (9CRA) and a conversion method using the same.

In the United States, not only schools and health research institutes such as Western Reserve University, Cleveland, Ohio, USA and National Institutes of Health (NIH), but also research institutes of ophthalmic companies such as Alcon Research Institute, research on diseases using light has received a lot of attention. have.

Z-isomerization of retinoids and catalytic synthesis of 9-cis-retinoids via a combination of monochromatic light wavelengths and metal catalysts: mechanistic insight into all-trans retinal, retinol, retinoic acid, and all-trans retinoids such as retinyl acetate ), much effort has been devoted to the thermodynamically stable regioselective Z-isomerization of

These studies suggest a new and direct approach to the method of catalytic Z-isomerization of retinoids using heat treatment or microwave irradiation, and a screen of 20 transition metal-based catalysts is the optimal approach for the regioselective production of Z-retinoids. method was confirmed.

And it is known that the most effective catalytic system consists of an unstable ligand and a palladium complex. In particular, several kinetic studies, including isotopic H/D exchange and state-of-the-art quantum chemical calculations using bond cluster methods, have shown that isomerization is initiated by catalytic dimerization followed by cyclic 6-membered chloropalladate ( It is known to be initiated by the formation of six-membered chloropalladate) catalyst-substrate adducts.

All-trans retinoic acid (Tretinoin) is a vitamin A derivative that acts by binding to two nuclear receptor families (retinoic acid receptors (RAR) and retinoid X receptors (RXR (RXR)) within cells. Normalization of follicular keratinization and keratinization Reduced cell cohesion reduces follicle occlusion and micro-comedon formation In addition, all-trans retinoic acid suppresses inflammation and platelet activation, and reduces the expression of P-selection and fibrinogen.

9-cis retinoic acid (Alitretinoin) is known to treat severe/recalcitrant chronic hand eczema. For muscle efficacy and effectiveness, it is prescribed to patients with chronic severe eczema on the hands (PGA) in adults who do not respond to strong topical corticosteroid therapy for at least 4 weeks, 10-30 mg once daily with or immediately after a meal. have.

Photoisomerization reaction of 9-cis-retinoids without catalyst is expressed as mWh ^-1 according to the "mechanical insight" literature, which is the change in isomerism with exposure to a certain wavelength for time. In this case, mWh ^-1 refers to the exposure of the wavelength for one hour for one hour.

However, in the above expression, it is difficult to confirm the change of isomers according to cm ² with the amount of wattage over time, so the present invention confirmed the change of isomers with the amount of wattage according to mW/cm ² , and the time inflection point of isomer change according to exposure was confirmed.

In Korea Patent No. 10-2195795, a curved liquid crystal molecule containing an azo group, which causes photo-isomerization by UV irradiation, is used to induce photo-alignment of the azo group by UV irradiation, and magnetism generated as the temperature decreases. A photonic crystal including a photoreactive molecule capable of synthesizing a photonic crystal capable of making a periodic structure in the visible region using assembly phenomenon, realizing a reflected color, and capable of reversible patterning, and a method for manufacturing the same are published. In Korean Patent Registration No. 10-1741358, a photoactive-conductive polymer material, a photoactive-conductive film, and an optoelectronic device including the same, the photoactive-conductive polymer material includes a conductive polymer, a cresol-like functional group, and a photoactive isomerized in response to light. Disclosed are a photoactive-conductive polymer material, a photoactive conductive film, and an optoelectronic device comprising the same, comprising a moiety and a non-polar aliphatic linkage connecting the cresol-like functional group and the photoactive moiety. In Korea Patent No. 10-2311861, azobenzene monomer compound is photoisomerized at a long wavelength, and azobenzene containing nitrogen-containing heteroaromatics including a high birefringence part that can increase the refractive index change even with a small amount of light irradiation Disclosed are a compound and a composition for recording blue holograms including the same. Korean Patent No. 10-0743278 discloses a method for producing 9-cis retinoic acid, characterized in that the alkali metal salt of 3-methyl-4-oxocrotonic acid is converted using a C15-triphenylphosphonium salt is starting

The present invention is to provide a conversion reaction apparatus capable of converting ATRA (All-Trans Retinoic acid) to 9-cis Retinoic acid (9CRA) by confirming a more accurate amount of power for isomerization reaction by light irradiation and a conversion method using the same .

Photoisomerization conversion method of 9-cis retinoic acid in all-trans according to an embodiment of the present invention is ATRA (all-trans retinoic acid) ACN (Acetonitrile), DCM (Dichloromethane), EA (Ethyl acetate), EtOH (Ethanol), preparing a reactant by dissolving one or more solvents selected from n-hexane (Normal hexane) (A); A UV light source irradiation step (b) of putting the reactant prepared in step (a) into a photo-isomerization reaction device and irradiating a UV LED with a wavelength of 385 nm at a light source power amount of 300 to 1400 mW/cm ² for 10 minutes to 3 hours; refrigeration and concentration drying step (c) of slowly cooling the reactant that has undergone step (b) at 0-5° C. and then concentrating and drying it to produce a solid product; It may consist of HPLC analysis and purification step (d) of purifying 9-cis Retinoic acid by analyzing the resultant in solid form through step (c) by HPLC. The UV light source irradiation in step (b) may be made for 10 minutes to 3 hours.

The catalyst used in the conversion method using the photoisomerization conversion reaction apparatus of 9-cis Retinoic acid in All-trans according to another embodiment of the present invention is (CH ₃ CN) ₂ PdCl ₂ , TFA (Trifluoroacetic acid), Toluene One or more of these may be selected, and the irradiation environment in which the UV LED of 385 nm wavelength is irradiated as a light source may consist of an environment in which the inside of the reactor is filled with nitrogen.

The conversion reaction apparatus capable of converting ATRA (All-Trans Retinoic acid) to 9CRA (9-cis Retinoic acid) of the present invention and the conversion method using the same are the solvent concentration, optimal catalyst, light irradiation time, light irradiation wattage, and optimal light It is possible to provide an apparatus and method capable of further increasing conversion efficiency by providing an irradiation standby environment.

1 shows an experimental schematic diagram according to Experimental Example 1 of the present invention.
Figure 2 shows the HPLC analysis data of the standard 9-cis-retinoic acid reagent and the standard all trans retinoic acid reagent.
3 shows the HPLC analysis results of the reactants according to the solvent of Experimental Example 1 of the present invention.
4 shows the results of HPLC analysis of the reactants according to the solvent of Experimental Example 1 of the present invention.
Figure 5 shows the HPLC analysis results of the ACN low concentration (100 ~ 1000ppm) group after irradiation for 10 minutes with a light source power amount (300mW/cm ² ) according to Experimental Example 2 of the present invention.
6 is an ACN medium concentration (5000ppm) light source wattage (300mW/cm ² ) according to Experimental Example 2 of the present invention after irradiation for 20 minutes, HPLC analysis results and ACN medium concentration (10000ppm) light source wattage (640mW / cm) ² ) after irradiation for 60 minutes, HPLC analysis results are shown.
7 shows the results of HPLC analysis after irradiation for 180 minutes with a light source wattage (640mW/cm ² ) of high ACN concentration (20000-30000ppm) according to Experimental Example 2 of the present invention.
8 shows the results of HPLC analysis after irradiation for 120 minutes with a light source wattage (1400mW/cm ² ) of high ACN concentration (30000 ppm) according to Experimental Example 2.
9 is a graph showing the isomerization conversion rate according to the change in the reactant concentration and output amount of the ACN high concentration (20,000 to 30000 ppm) group according to Experimental Example 2 of the present invention.
10 shows the results of HPLC analysis according to Experimental Example 3 of the present invention.
11 shows the results of HPLC analysis in a nitrogen environment and a general atmospheric environment after 180 minutes of irradiation according to Experimental Example 4 of the present invention.
12 shows a schematic diagram of a photoisomerization reaction apparatus of the present invention.

The present invention confirmed the relationship between light intensity and time in the photoisomerization conversion of 9-cis Retinoic acid in all-trans, and what is the solvent for accelerating the 9-cis Z-isomerization process in the large-scale? In addition to confirming the optimized concentration, it was intended to apply to industrial applications by identifying the limits of the reaction regardless of the presence or absence of a catalyst for industrialization of 9-cis-retinoids (Alitretinoin).

The photoisomerization conversion reaction apparatus of 9-cis Retinoic acid in the All-trans of the present invention and the conversion method using the same are performed by irradiating 300 ~ 1400mW/cm ² (value measured at the outer wall of the reaction glass) with a UV light source of 385nm and ATRA ( A method for converting All-Trans Retinoic acid) to 9-cis Retinoic acid (9CRA) is provided.

Hereinafter, for a specific experimental example, the photoisomerization conversion reaction apparatus of 9-cis Retinoic acid in All-trans of the present invention and the conversion method using the same will be described in detail with reference to the drawings.

<Experimental Example 1> Confirmation of optimal solvent

In Experimental Example 1 of the present invention, an experiment was conducted by applying ATRA (All-Trans Retinoic acid) to a short-wavelength UV light of 385 nm for 10 minutes in order to clarify the relationship between wattage and time, mWh ^-1 .

1 shows an experimental schematic diagram according to Experimental Example 1 of the present invention. The conversion method using the photoisomerization conversion reaction apparatus of 9-cis retinoic acid in all-trans of the present invention is ATRA (all-trans retinoic acid) to ACN (Acetonitrile), DCM (Dichloromethane), EA (Ethyl acetate), EtOH (Ethanol), preparing a reactant by dissolving one or more solvents selected from n-hexane (Normal hexane) (A); A UV light source irradiation step (b) of putting the reactant prepared in step (a) into a photo-isomerization reaction device and irradiating a UV LED with a light source power of 300 to 1400 mW/cm ² of a wavelength of 385 nm; refrigeration and concentration drying step (c) of slowly cooling the reactant that has undergone step (b) at 0-5° C. and then concentrating and drying it to produce a solid product; It consists of HPLC analysis and purification step (d) of purifying 9-cis Retinoic acid by analyzing the solid product through step (c) by HPLC.

(A) reactant preparation step

In the reaction preparation step (A) according to Experimental Example 1 of the present invention, the reaction solvent was ACN (Acetonitrile), DCM (Dichloromethane), EA (Ethyl acetate), EtOH (Ethanol), n-hexane (Normal) to confirm the optimal solvent. hexane) was prepared at a concentration of 5000 ppm, respectively, and dissolved in ATRA (all-trans retinoic acid) to prepare a reaction product.

(B) UV light source irradiation step

In the UV light source irradiation step (b) according to Experimental Example 1 of the present invention, the reactants of step (a) were put into the photoisomerization reaction apparatus of the present invention, and a short wavelength UV light of 385 nm was applied for 10 minutes. At this time, all light irradiation conditions were light sources under dark conditions without interference of other wavelengths.

12 shows a schematic diagram of a photoisomerization reaction apparatus of the present invention. The photoisomerization reaction apparatus of the present invention includes a reaction tank that stores reactants and provides a dark space where light other than a light source does not penetrate, and at least one UV LED light source is installed on the outer wall of the reaction tank to surround the reaction tank, and as the light source A water-cooled reflux cooler is installed to control the generated heat. The UV LED light source can emit light with a power amount of 300 to 1400 mW/cm ² of a single wavelength of 385 nm.

The light irradiator used a UV 385nm LED curing machine from Uber Co., Ltd. of Korea, and a water-cooled COB (C type-chip on board curing system) output amount of 600mW/cm ² (measured from the outer wall of the reaction glass) for 10 minutes. investigated.

(C) refrigeration and concentration drying step

In the refrigeration and concentration drying step (c) according to Experimental Example 1 of the present invention, the reactant that has undergone the step (b) is slowly cooled at 0-5° C. and then concentrated and dried to produce a solid product. .

(D) HPLC analysis and purification steps

The HPLC analysis and purification step (d) according to Experimental Example 1 of the present invention is a step of analyzing the solid product according to step (c) by HPLC.

It was compared with Sigma-Aldrich's Standard 9-cis-retinoic acid (9CRA). Figure 2 shows the HPLC analysis data of the standard 9-cis-retinoic acid reagent and the standard all trans retinoic acid reagent. Purification was performed using Recycle HPLC to purify 95% or more of purity.

Recycle HPLC was performed using JAI's LaboACE, Column: Cholester 5㎛, Mobile phase (isocratic: Water (0.1% formic acid) vs. Acetonitrile (0.1% formic acid) = 3:7. Power of light source 1400mW/cm ² , after photoisomerism reaction for 3 hours in a 20L reaction tank in which ATRA is dissolved in ACN at 30000ppm, the weight of 9CRA to be purified was about 225.80g (purity 98%) when 1kg of crystallized 1kg was purified for about 42 minutes.

As for HPLC analysis conditions, Standard was analyzed based on Sigma-Aldrich, and 9-cis Retinoic Acid before and after purification was analyzed through Waters e2695 HPLC. Condition settings were Flow rate: 1 ml/min, UV: 352 nm, Injection volume: 20 ul, Column: Agilent Polaris Si-A 250 x 4.6 mm 3 um, Column temperature: 25 ℃, HPLC solvent composition (Isocratic) is Iso-octane 99.65%, Isopropanol 0.25%, Acetic acid 0.1%, After irradiation with light, the resultant was concentrated and analyzed by HPLC. It was compared with Sigma-Aldrich's Standard 9-cis-retinoic acid (9CRA).

3 to 4 show the HPLC analysis results of the reactants according to the solvent of Experimental Example 1 of the present invention. Looking at the above results, it was confirmed that 9CRA was generated in all of the above solvents as a result of the experiment. In addition, it was confirmed that the UV wavelength is isomerized at 365 nm, and the wattage (600 mW/cm2) and the conversion time of the wavelength were correlated with 10 min. In solvents other than ACN solvents, 7-cis, 11-cis, 13 Since isomers such as -cis are also isomerized together, preferably, ACN solvent is considered to be the most effective.

<Experimental Example 2> Confirmation of optimal solvent concentration

Experimental Example 2 of the present invention is dissolved in ATRA by varying the concentration of ACN identified as an optimal solvent according to Experimental Example 1 to low (100 to 1000 ppm), medium (5000 to 10000 ppm), and high (20000 to 30000 ppm), and By checking the 9CRA Peak Area (%) converted by UV 385nm LED irradiation time, the conversion ratio for each time at low, medium and high concentrations was confirmed.

UV light source irradiation was irradiated with the light source wattage (300mW/cm 2 ) in the low concentration group, the light source wattage (300mW/cm ² ) and the light source wattage (640mW/cm ² ) in the medium concentration group, and the light source wattage (300mW/cm ² ) in the high concentration group cm ² ), light source wattage (640mW/cm ² ), and light source wattage (1400mW/cm ² ) were irradiated. Irradiation time was 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 180 minutes, etc. after each hour of irradiation, HPLC analysis was performed in the same manner as in Experimental Example 1.

Figure 5 shows the HPLC analysis results of the ACN low concentration (100 ~ 1000ppm) group after irradiation for 10 minutes with a light source power amount (300mW/cm ² ) according to Experimental Example 2 of the present invention. As a result of dissolving ACN at 100ppm in ATRA and irradiating the light source wattage (300mW/cm ² ) for 10 minutes and analyzing by HPLC, about 28.4% of 9CRA was generated in the peak area in ATRA. cm2) After 10 minutes of irradiation, analysis by HPLC showed that the peak area of ATRA was about 20.31% of 9CRA.

Table 1 below shows the 9CRA Peak Area converted by UV LED irradiation time at low concentration (100 ~ 1000ppm). The wavelength mismatch in Table 1 means that the wavelength value of the 9-cis Retinoic acid cannot be found in the HPLC analysis.

9CRA Peak Area converted by UV LED irradiation time at low concentration (100 ~ 1000ppm) ACM concentration (ppm) Output (mW/cm ² ) 9CRA Peak Area (%) converted by UV LED irradiation time 10 minutes 20 minutes 30 minutes 1 hours 2 hours 3 hours 100 300 28.4 - Wavelength mismatch* Wavelength mismatch* Wavelength mismatch* - 1000 300 20.31 - 16.47 14.7 6.65 -

UV 385nm, 300mW/cm ² The conversion of 9CRA according to the concentration versus time at a low concentration (100 ~ 1000ppm) was confirmed that the 9CRA conversion rate was rather decreased after 10 minutes as shown in the table above.

6 is an ACN medium concentration (5000ppm) light source wattage (300mW/cm ² ) according to Experimental Example 2 of the present invention after irradiation for 20 minutes, HPLC analysis results and ACN medium concentration (10000ppm) light source wattage (640mW / cm) ² ) after irradiation for 60 minutes, HPLC analysis results are shown.

After dissolving ACN at 5000 ppm in ATRA and irradiating the light source wattage (300mW/cm2) for 20 minutes, analysis by HPLC showed that 9CRA of peak area: about 22.58% was generated in ATRA. After dissolving ACN at 10000 ppm in ATRA and irradiating the light source wattage (640mW/cm ² ) for 60 minutes, analysis by HPLC resulted in 9CRA of peak area: about 26.31% in ATRA.

Table 2 below shows the 9CRA Peak Area converted by UV LED irradiation time at medium concentration (5000 ~ 10000ppm). The wavelength mismatch in Table 2 means that the wavelength value of the 9-cis Retinoic acid cannot be found in HPLC analysis.

As shown in Table 2, the conversion of 9CRA according to the time-to-concentration at 385nm, 300mW/cm2 ^double concentration of 5000ppm, the 9CRA conversion rate decreased after 30 minutes, and UV 385nm, 640mW/cm2 double concentration At 10000 ppm, it was confirmed that the decrease was after 60 minutes, and it was confirmed that the conversion rate gradually decreased after 1 hour.

9CRA Peak Area converted by UV LED irradiation time at medium concentration (5000 ~ 10000ppm) ACN concentration (ppm) Output (mW/cm ² ) 9CRA Peak Area (%) converted by UV LED irradiation time note 10 minutes 20 minutes 30 minutes 1 hours 2 hours 3 hours 5000 300 2.27 22.58- 28.22 - - - 640 2.29 23.19 30.64 15.94 - - 2.5h, 3.5h wavelength mismatch* 10000 300 Wavelength mismatch* Wavelength mismatch*- 13.04 - - - 640 26.31 25.56 - 3.5h Wavelength Mismatch*

At 5000 ppm of ACN (Acetonitrile), ATRA (All-Trans Retinoic acid) was converted to 9CRA (9-cis Retinoids acid) in 30 minutes by applying 300 mW/cm ² ((measured from the outer wall of the reaction glass) with a wattage of 385 nm of UV light source. In addition, at 10000 ppm of ACN (Acetonitrile), 640 mW/cm ² ((measured from the outer wall of the reaction vessel) was applied to reduce ATRA (All-Trans Retinoic acid) to 9CRA (9- It is thought that conversion to cis Retinoids acid) can be maximized.

Figure 7 shows the HPLC analysis result after irradiation for 180 minutes with a light source wattage (640mW/cm ² ) of ACN high concentration (20000-30000ppm) according to Experimental Example 2 of the present invention, Figure 8 is ACN high concentration according to Experimental Example 2 (30000ppm) of light source power (1400mW/cm ² ) After irradiation for 120 minutes, HPLC analysis results are shown. 9 is a graph showing the isomerization conversion rate according to the change in the reactant concentration and output amount of the ACN high concentration (20,000 to 30000 ppm) group according to Experimental Example 2 of the present invention.

9CRA Peak Area converted by UV LED irradiation time at high concentration (20000~30000ppm) ACN concentration (ppm) Output (mW/cm ² ) 9CRA Peak Area (%) converted by UV LED irradiation time note 10 minutes 20 minutes 30 minutes 1 hours 2 hours 3 hours 20000 300 Wavelength mismatch* Wavelength mismatch* 2.69 - - - 640 15.14 - Wavelength mismatch* 3.5h, 4h wavelength mismatch* 30000 300 Wavelength mismatch* Wavelength mismatch* 3.98 - - - 640 - - 19.19 - 23.38 1400 20.97 22.24 24.18

Table 3 above shows the 9CRA Peak Area converted by UV LED irradiation time at high concentration (20000 ~ 30000ppm). The wavelength mismatch described in Table 3 means that the wavelength value of the 9-cis Retinoic acid cannot be found in the HPLC analysis.

From the above results, when the concentration of the sample exceeds 10000 ppm, it is difficult to convert ATRA (All-Trans Retinoic acid) to 9CRA (9-cis Retinoids acid) with UV 385 nm and 300 mW/cm ² light irradiation wattage, and at least 640 mW It was found that an amount of power of /cm ² or more was required, and light irradiation of at least 1 hour was required.

<Experimental Example 3> Catalyst confirmation

As TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy), the compound of _formula (CH₂) _₃ (CMe₂) _₂ NO with oxyl or oxydanyl promotes the change to 13-cis. In Experimental Example 3 of the present invention, conversion to 9-cis was confirmed by applying a catalyst such as palladium chloride (CH ₃ CN) ₂ PdCl ₂ , TFA (Trifluoroacetic acid), and Toluene.

10 shows the results of HPLC analysis according to Experimental Example 3 of the present invention. Experimental Example 3 of the present invention was dissolved in ATRA at a concentration of 400 ppm of solvent ACN, (CH ₃ CN) ₂ PdCl ₂ 1.6 equivalents of TFA were added to 0.2 equivalents, and the wattage of the light source (300mW/cm ² ) was irradiated for 10 minutes. After that, HPLC analysis was performed (phase in FIG. 10). In addition, ATRA was dissolved at a concentration of 1000 ppm of the solvent ACN, 1.1 equivalents of toluene were added, and the wattage (640 mW/cm ² ) of the light source was irradiated for 30 minutes, followed by HPLC analysis (bottom of FIG. 10).

As a catalyst (CH ₃ CN) ₂ PdCl ₂ and TFA Toluene was added to irradiate the light source, it can be seen that the conversion to 9-cis smoothly. That is, it was confirmed that there was no difference in the isomerization change result between the method using the catalyst and the case where the catalyst of the present invention was not used.

<Experimental Example 4> Confirmation of isomerization change according to nitrogen environment

Experimental Example 4 of the present invention is isomerization during light irradiation in a state in which the inside of the reactor is filled with nitrogen and in normal air to confirm 9-cis isomerization through the difference between the normal atmosphere and the nitrogen atmosphere with respect to the light irradiation environment. Check if there is any change in

9CRA Peak Area converted by UV LED irradiation time ACN concentration (ppm) Output (mW/cm ² ) Converted 9CRA Peak Area (%) after 180 minutes of UV LED irradiation note 30000 200 9.4 N2 atmospheric condition 200 6.7 Air Atmospheric Conditions

The atmospheric environment group in which the concentration of solvent ACN in ATRA was dissolved at 30000ppm and nitrogen (N ₂₎ was filled in the reaction tank and the general atmospheric environment group carried out in Experimental Examples 1 to 3 were irradiated with light source power (200mW/cm ² ) for 180 minutes. HPLC analysis was performed.

11 shows the results of HPLC analysis in a nitrogen environment and a general atmospheric environment after 180 minutes of irradiation according to Experimental Example 4 of the present invention. Table 4 shows the 9CRA Peak Area converted for each UV LED irradiation time according to Experimental Example 4. As a result of HPLC analysis in nitrogen environment, 9CRA peak area value was confirmed to be about 9%, and 9CRA peak area value was confirmed to be about 6% in general atmospheric environment. Through the above results, it was confirmed that the photoisomerization reaction was more effective in a nitrogen (N ₂ ) atmospheric environment than in a general atmospheric environment.

The present invention provides a conversion reaction device capable of converting ATRA (All-Trans Retinoic acid) to 9-cis Retinoic acid (9CRA) by light irradiation and a conversion method using the same, thereby improving the production efficiency of 9CRA, known as a treatment for severe chronic hand eczema. It can be increased and has industrial applicability.

Claims (5)

delete Dissolving one or more solvents selected from ACN (Acetonitrile), DCM (Dichloromethane), EA (Ethyl acetate), EtOH (Ethanol), and n-hexane (Normal hexane) in ATRA (all-trans retinoic acid) to prepare a reactant step (a);
All-trans to 9-cis Retinoic acid, characterized in that it consists of a UV light source irradiation step (b) of irradiating the reactant prepared in step (a) with a UV LED having a wavelength of 385 nm at a light source power amount of 300 to 1400 mW/cm ² Photoisomerization Conversion Method The method of claim 2, wherein the UV light source irradiation in step (b) is performed for 10 minutes to 3 hours. Photoisomerization conversion method from all-trans to 9-cis Retinoic acid The method of claim 2, wherein step (a) comprises adding one or more catalysts selected from among (CH ₃ CN) ₂ PdCl ₂ , TFA (Trifluoroacetic acid), and Toluene to a reactant dissolved in a solvent to prepare a reactant. Photoisomerization conversion method from All-trans to 9-cis Retinoic acid characterized The reaction product prepared by dissolving ATRA (all-trans retinoic acid) in one or more solvents selected from ACN (Acetonitrile), DCM (Dichloromethane), EA (Ethyl acetate), EtOH (Ethanol), and n-hexane (Normal hexane) a reaction tank that is stored and provides a dark space through which light other than the light source does not penetrate;
One or more UV LED light sources are installed on the outer wall of the reaction tank to surround the reaction tank, and the inside of the reaction tank can be filled with external atmosphere or nitrogen; Photoisomerization conversion reaction device from All-trans to 9-cis Retinoic acid, characterized in that a water-cooled reflux cooler is installed to control the heat generated by the light source

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