A method for the photocatalytic production of vitamin d3

Abstract

The application discloses a method for preparing vitamin D3 by visible light catalysis and belongs to the field of biological medicine product manufacturing. The method uses 7-dehydrocholesterol (7-DHC) as raw material, selects tetrabromofluorescein as a catalyst under visible light with a wavelength of 400-780 nm, and 7-DHC is selectively opened to form previtamin D3 (P3) and then isomerized to vitamin D3 by heat. The method can obtain a high-yield (84%) vitamin D3 product by irradiation for only 90 seconds. The method for preparing vitamin D3 by visible light catalysis overcomes the technical bottleneck of the previous ultraviolet light catalysis, avoids the damage to the human body and the environment caused by ultraviolet light irradiation, is more green and environmentally friendly, has high selectivity, short reaction time and high efficiency, and has a wide industrialization prospect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine product manufacturing, and particularly relates to a method for preparing vitamin D3 through visible light catalysis. BACKGROUND

[0002] Vitamin D3 is a fat-soluble vitamin, which is closely related to sunlight, so it is also called'sunlight vitamin'. Vitamin D3 is converted from 7-dehydrocholesterol contained in the epidermis and dermis of most higher animals through ultraviolet irradiation. Vitamin D3 can improve the absorption of calcium and phosphorus in the body, promote growth and bone calcification, and promote the health of teeth and bones. Clinical experimental studies have shown that vitamin D3 also plays a positive role in the treatment of tumors, cardiovascular diseases and diabetes. In addition to the important role in the human body, vitamin D3 is also widely used in feed additives. Vitamin D3 plays an important role in preventing rickets and rickets in young animals, osteoporosis in adult animals, and congenital bone deformities in newborns caused by pregnant mothers.

[0003] The chemical synthesis of vitamin D3 was developed by organic chemist Havings in the 1960s (The photochemical interconversions of provitamin D, lumisterol, previtamin D and tachysterol, Tetrahedron, 1960, 11, 276-284). 7-dehydrocholesterol (7-DHC) is ring-opened to form previtamin D3 (P3) under ultraviolet irradiation at a wavelength of 254-310 nm, and then isomerized to form vitamin D3 by heating. The photochemical reaction process is prone to side reactions, generating byproducts such as lumisterol (L3) and tachysterol (T3).

[0004]

[0005]

[0006] To avoid the formation of byproducts, the initial industrial production used a short-time light irradiation method, and then multiple photochemical reactions were used to improve the yield, but the P3 yield of this method was only about 30%, and the actual total yield of vitamin D3 was only 10%. Although chemists have been looking for suitable methods to improve the yield of the photochemical reaction process, but all of them use ultraviolet light source, still have the disadvantages of many side reactions, low controllability, environmental unfriendliness, low yield, etc. Therefore, it is of great significance to find a substitute for ultraviolet irradiation to realize the production of vitamin D3. SUMMARY

[0007] In order to overcome the above-mentioned defects of the prior art, the present application aims to provide a method for preparing vitamin D3 by visible light catalysis, so as to solve the technical problems of multiple side reactions, low controllability, environmental unfriendliness and low yield in the synthesis of vitamin D3 by ultraviolet light irradiation.

[0008] In order to achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0009] The method for preparing vitamin D3 by visible light catalysis disclosed by the present application comprises the following steps:

[0010] 1) Dissolving 7-dehydrocholesterol in one or more polar organic solvents, and adding an organic small molecule catalyst under stirring to prepare a mixed solution;

[0011] 2) Placing the mixed solution under visible light irradiation for a certain time under the conditions of stirring and circulating water cooling to obtain a vitamin D3 product.

[0012] Preferably, in step 1), the organic small molecule catalyst is tetrabromofluorescein.

[0013] Further preferably, the mass ratio of tetrabromofluorescein to 7-dehydrocholesterol is 1:1-1:40.

[0014] Preferably, in step 2), the circulating water cooling temperature is 5-20℃.

[0015] Preferably, in step 2), the wavelength range of the visible light is 400-780nm.

[0016] Preferably, in step 2), the irradiation time is 5-200 seconds.

[0017] Further preferably, the irradiation time is 30-120 seconds.

[0018] More preferably, the irradiation time is 90 seconds.

[0019] Preferably, in step 1), the polar organic solvent is ethanol.

[0020] Further preferably, the concentration of 7-dehydrocholesterol in ethanol is 5-100mg / mL.

[0021] Preferably, in steps 1) and 2), the stirring is performed by magnetic stirring.

[0022] Compared with the prior art, the present application has the following beneficial effects:

[0023] The application discloses a method for preparing vitamin D3 by visible light catalysis, and the method comprises the following steps: dissolving 7-dehydrocholesterol in a polar organic solvent, taking tetrabromofluorescein as a catalyst, and irradiating under visible light to prepare vitamin D3. The method can induce 7-dehydrocholesterol to react to generate vitamin D3 in the visible light band, and can avoid the damage caused by ultraviolet light synthesis to the human body. The method breaks through the technical bottleneck of the existing ultraviolet light preparation of vitamin D3, does not need ultraviolet light irradiation equipment, does not exist potential ultraviolet damage to the human body and influence on the environment, has low requirements on a production device, and raw materials are cheap and easy to obtain. The method has the characteristics of mild reaction condition, high reaction selectivity, few side reactions, short reaction time and high efficiency, is simple in operation, is more environmentally friendly and safe, can be expected to produce a revolutionary change and promotion to a vitamin D3 preparation industry, and has great industrialization prospects.

[0024] Further, the irradiation time is 5-200 seconds; preferably, the irradiation time is 30-120 seconds, and further preferably, the irradiation time is 90 seconds, and the yield of vitamin D3 is about 84%.

[0025] Further, the amount of tetrabromofluorescein affects the reaction rate and yield, and the use of an appropriate amount of catalyst can quickly and efficiently catalyze the generation of vitamin D3 and improve economic benefits. In combination, the mass ratio of tetrabromofluorescein to 7-dehydrocholesterol is preferably in the range of 1:1-1:40. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 The figure is a product ultraviolet absorption spectrum under different reaction times. DETAILED DESCRIPTION

[0027] In order for those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor should belong to the protection scope of the present application.

[0028] It is to be understood that the terminology "first", "second", and the like used in the specification and the claims of the application as well as the appended drawings is merely used for distinguishing between similar objects and does not necessarily imply a required or a particular order or sequence. It is to be understood that the data used herein can be interchanged, where appropriate, to carry out an embodiment of the application described herein in other than the order described. Additionally, the terms "comprising", "including", "containing", and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, product or apparatus that comprises, includes or contains an item or list of items who have the enumerated process steps, functions, clauses, or elements, but not those excluding any enumerated steps, functions, clauses or elements are also encompassed by the term. It is to be understood that the terminology "comprising", "including", "containing" and / or "having" contains the term "consisting" and / or "consisting essentially of" and the inclusion of the term "consisting" and / or "consisting essentially of" is to be understood as an act of substitution therefore.

[0029] The application will be further described in detail by the following embodiments with reference to the accompanying drawings:

[0030] A method for preparing vitamin D3 by visible light catalysis, comprising the following steps:

[0031] 7-dehydrocholesterol is dissolved in ethanol, and tetrabromofluorescein is added under magnetic stirring to prepare a mixed solution; the mixed solution is irradiated under visible light for a certain time under the conditions of magnetic stirring and circulating water cooling to obtain a vitamin D3 product.

[0032] The mass ratio of tetrabromofluorescein to 7-dehydrocholesterol is 1:1-1:40; preferably, the mass ratio of tetrabromofluorescein to 7-dehydrocholesterol is 1:1-1:10. The circulating water cooling temperature is 5-20°C; preferably, the circulating water cooling temperature is 5-10°C.

[0033] The wavelength range of visible light is 400-780 nm.

[0034] The irradiation time is 5-200 seconds; preferably, the irradiation time is 30-120 seconds.

[0035] Example 1

[0036] 0.5 g of 7-dehydrocholesterol (7-DHC) is dissolved in 40 mL of an ethanol solution, and 75 mg of tetrabromofluorescein is added under magnetic stirring within 10 minutes. The mixture is irradiated under visible light with a wavelength of 400-780 nm under the condition of circulating water cooling (5°C) for 90 seconds under magnetic stirring, and the reaction is basically completed (as shown in FIG. 1). The standard curve of a vitamin D3 standard is drawn by high performance liquid chromatography (HPLC), and the solution after the reaction is analyzed by HPLC. It is calculated according to the standard curve that the yield of vitamin D3 is about 84%. Figure 1

[0037] Example 2

[0038] ​Example 1

[0039] Example 2

[0040] Example 3

[0041] Example 4

[0042] Example 5

[0043] Example 6

[0044] Example 7

[0045] In summary, the present application provides a method for preparing vitamin D3 by visible light catalysis. Under the condition of circulating water cooling, the method uses tetrabromofluorescein as a catalyst, and irradiates for only 90 seconds under visible light with a wavelength of 400-780 nm, so that 7-dehydrocholesterol is selectively ring-opened and isomerized into vitamin D3, with a yield of 84%. The method uses a visible light source, overcomes the technical bottleneck of preparing vitamin D3 by ultraviolet light catalysis, eliminates the damage to the human body caused by ultraviolet light under the operation condition, and is more green and environmentally friendly. In addition, the reaction of the method only takes 90 seconds, greatly reducing the time cost and being more efficient. Meanwhile, the visible light catalysis is more selective, the by-products are reduced, and the production cost is greatly reduced. In addition, the experimental operation and device are relatively simple, and have great industrialization prospects.

[0046] The above content only illustrates the technical idea of the present application, and cannot limit the protection scope of the present application. Any modification made according to the technical idea of the present application on the basis of the technical scheme falls within the protection scope of the claims of the present application.

Claims

1. A method for preparing vitamin D3 by visible light photocatalysis, characterized in that, Includes the following steps: 1) Dissolve 7-dehydrocholesterol in one or more polar organic solvents, and add tetrabromofluorescein as a small molecule catalyst under stirring to prepare a mixed solution; 2) Under stirring and circulating water cooling conditions, the mixed solution was irradiated under visible light for a certain period of time to obtain vitamin D3 product; The mass ratio of tetrabromofluorescein to 7-dehydrocholesterol is 1:1 to 1:

40. The circulating water cooling temperature is 5℃~20℃, the visible light wavelength range is 400 nm~780 nm, the irradiation time is 90 seconds, and the vitamin D3 yield reaches 84%.

2. The method for preparing vitamin D3 by visible light photocatalysis according to claim 1, characterized in that, In step 1), the polar organic solvent is ethanol.

3. The method for preparing vitamin D3 by visible light photocatalysis according to claim 2, characterized in that, The concentration of 7-dehydrocholesterol in ethanol is 5-100 mg / mL.

4. The method for preparing vitamin D3 by visible light catalysis according to claim 1, characterized in that, In both steps 1) and 2), magnetic stirring is used.

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