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CA1180679A - Method of production of vitamin-d - Google Patents

Method of production of vitamin-d

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Publication number
CA1180679A
CA1180679A CA000395862A CA395862A CA1180679A CA 1180679 A CA1180679 A CA 1180679A CA 000395862 A CA000395862 A CA 000395862A CA 395862 A CA395862 A CA 395862A CA 1180679 A CA1180679 A CA 1180679A
Authority
CA
Canada
Prior art keywords
vitamin
product
product containing
irradiating
nanometers
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000395862A
Other languages
French (fr)
Inventor
Vincenzo Malatesta
Clive Willis
Peter A. Hackett
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
National Research Council of Canada
Original Assignee
National Research Council of Canada
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National Research Council of Canada filed Critical National Research Council of Canada
Priority to CA000395862A priority Critical patent/CA1180679A/en
Application granted granted Critical
Publication of CA1180679A publication Critical patent/CA1180679A/en
Expired legal-status Critical Current

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

TITLE
METHOD OF PRODUCTION OF VITAMIN-D

I N V E N T O R S

Vincenzo Malatesta Clive Willis Peter A. Hackett ABSTRACT OF DISCLOSURE
A method of upgrading a product containing a minor proportion of pre-vitamin d2 or pre-vitamin d3 and a major proportion of tachysterol comprising irradiating the product with laser light in the -wavelength range 330-360 nanometers to obtain a product containing ap-proximately 95% pre-vitamin -D2 or pre-vitamin -D3, and heating this product to convert the pre-vitamin -D2 or pre-vitamin -D3 to vitamin -D2 or vitamin -D3.

Description

This invention relates to a method of production of vitamin-D and more particularly to laser photochemical conversion of 7-dehydro-cholesterol ~o vi~min -D3 and ergosterol to vitamin -D2 Vitamin D is not a single substance, but only 2 of 5 the lC or 11 sterols known to have antirachitic properties are of importance medically. These are activated ergosterol and 7-dehydro-cholesterol. The D substances are activated sterols complex substances often closely associated with fats in plants and animals. Cholesterol is an important sterol which is present in the skin; activation`
10 of cholesterol by ultraviolet light changes the compound and produces vitamin D.
The complex photochemistry of 7-dehydro-cholesterol (7-DHC) and ergosterol ~E) is now moderately well understood due to the studies of E. Havinga and his co-workers. See especially the following papers: Loevoet A.L.; Verloop A.; and Havinga E., Red. Trav.
Chim., Pays-Bas, 1955, 74,788 and Boosma F.; Jacobs H.J.C.; and Havinga E.; Vanclès Gen. ~., Tetrahedron Litt. 1975, 7,427.
The present commercial method of vitamin-D production involves a number of fractional crystallizations to isolate the required product. This method is described in French Patent No:
1,378,122, issued 1964 to K.R. Bhaurichter and F.M. Martin.
The use of photolysis with lasers or other light sources to achieve product separation is now well known. The use of photolysis in the production of vitamin-D is known but present methods have had the problem of the production of side products such as tachysterol, lumisterol and other isomers. These methods have required additional process steps such as fractional distillations to obtain the required separation percentages.
It is an object of the present invention to provide a method of producing vitamin-D that gives improved yields and reduced side product contamination.
This and other objects of the invention are achieved by a method involving photolysis at a selected wavelength.
In drawings which illustrate an embodiment of the 40 invention:
Figure 1 is a flow diagram of the process, and 67~

Figure 2 is a cross-sectio~al view of apparatus for carrying out the process.
Referring to figure 1~ the starting material, 7-dehydro-cholesterol (7-D~C) or ergosterol is irradiated with light in the wavelength range 245-260 mm. A low pressure mercury arc which functions at 254 nm. is most suitable for this. This photolysis may also be achieved by the use of an excimer laser ~KrF at 248 nm). Pre-vitamin-D3 or pre-vitamin-D2 (approx. 25%) and tachysterol 3 or tachysterol~ (approx.) 75%) are Eormed. This mixture is then irradiated with laser light in the wavelength range 330-360 nm. A nitrogen laser which functions at 337 nm or a YAG laser at 353 nm are suitable for this step. Other types of lasers that may also be used are XeF lasers at 350 nm, Raman shifted XeCl lasers, and broadband dye lasers pumped by ~eCl or KrF excimer lasers, the last two being tunable to operate as required in the 330-360 nm range. This second photolysis step produces a mixture that is approx. 95% pre-vitamin-D3 or pre-vitamin D2. The remaining 5% (approx.) is lumisterol or other isomers.
The pre-vitamin-D is then~converted to vitamin-D by thermolysis.
Figure 2 shows a suitable apparatus arrangement for carrying out the process and includes a reaction chamber 10 preferably of glass having a quartz end window 11 at one end. The starting -materials ei~her 7-DHC or ergosterol which are normally solid but which are dissolved in a suitable solvent e.g. di-ethyl ether are fed into port 12 and flow down chamber 10 and out port 13 to the second stage irradiation chamber 20. Light at the selected frequency from laser 14 passes through window 11 and irradiates the material flowing therein. The temperature of the material is held in the range 0-20C
by water jacket 15 enveloping chamber 10. This temperature is not critical. The second stage is similar to the first in that the material flowing through chamber 20 is irradiated by a laser beam in the appropriate frequency range from laser 24 passes through quartz window 21 into the flowing mixture. A water jacket 25 maintains the flowing material in the required temperature range. Products from the second stage pass to the thermolysis stage 28 which consists of heating the material to about 60C to convert the pre-vitamin d2 or -d3 to vitamin -d2 or -d3.

~8~7~

IE in stage l, a mercury arc lamp is used rather than a laser, then this can readily be achieved by lamp tube 16 helically surrounding chamber 10. In addition it might be convenient to carry out both stages of irradiation in a single chamber. This 5 is done by a second laser 17 at the appropriate Erequency irradiating the mixture through quart~ end window 18.
In the above description of ~he process the starting materials are 7-dehydro-cholesterol or ergosterol, The di-hydroxy form oE these materials may also be used as starting materials and 10 with the same process as outlined above will ~r~ee~ee the di-hydro~y version of the vitamin -D3 or vitamin -D2. It is therefore pointed out that wherein the terminology: 7-dehydro-cholesterol; ergosterol;
pre-vitamin-D2 or -D3; and vitamin -D2 or -D3 is used in this disclosure and claims that these terms include the di-hy.droxy form 15 of these materials.
The second stage of the two step irradiation process mentioned above may be readily applied to present methods that produce vitamin -D but with large percentages of tachysterol, lumisterol, or other isomers also produced. The photolysis step 20 us:Lng laser light in the 330-360nm range provides an efficient and economic method of upgrading the product produced by present methods and a,voids the need for derivativi~.ation and fractional re-crystalli-zation.

Claims (4)

Claims
1. A method of production of vitamin-D2 or vitamin-D3 using ergosterol or 7-dehydro-cholesterol or their dihydroxy derivatives as the starting materials, comprising:
a) irradiating the starting material with light in the wavelength range 245-260 nanometers to obtain a product containing pre-vitamin-D2 or pre-vitamin-D3 as a minor proportion and tachysterols as a major pro-portion, b) irradiating this product with light in the wavelength range 330-360 nanometers to obtain a product containing pre-vitamin-D2 or pre-vitamin-D3 as a major proportion, and c) heating this product to convert the pre-vitamin-D2 or pre-vi-tamin-D3 to vitamin-D2 or vitamin-D3, the intermediates and final pro-ducts being the dihydroxy derivatives when the starting material is in this form.
2. A method of upgrading a product containing a minor proportion of pre-vitamin-D2 or pre-vitamin-D3 or their dihydroxy deri-vatives and a major proportion of tachysterols comprising:
a) irradiating the product with light in the wavelength range 330-360 nanometers to obtain a product containing pre-vitamin-D2 or pre-vitamin-D3 as a major proportion, and b) heating this product to convert the pre-vitamin-D2 or pre-vita-min-D3 to vitamin-D2 or vitamin-D3 , the intermediates and final products being the dihydroxy derivatives when the starting material is in this form.
3. A method of production of vitamin-D2 or vitamin-D3 u-sing ergosterol or 7-dehydro-cholesterol as the starting materials com-prising:

a) irradiating the starting material with light in the wavelength range 245-260 nanometers to obtain a product containing pre-vitamin-D2 or pre-vitamin-D3 as a minor proportion and tachysterol2 or tachyste-rol3 as a major proportion, b) irradiating this product with light in the wavelength range 330-360 nanometers to obtain a product containing approximately 95% pre-vitamin-D2 or pre-vitamin-D3, and c) heating this product to convert the pre-vitamin-D2 or pre-vitamin-D3 to vitamin D2 or vitamin D3.
4. A method of upgrading a product containing a minor proportion of pre-vitamin D2 or pre-vitamin D3 and a major proportion of tachysterols comprising:
a) irradiating the product with light in the wavelength range 330-360 nanometers to obtain a product containing approximately 95%
pre-vitamin-D2 or pre-vitamin-D3, and b) heating this product to convert the pre-vitamin-D2 or pre-vitamin-D3 to vitamin-D2 or vitamin-D3.
CA000395862A 1982-02-09 1982-02-09 Method of production of vitamin-d Expired CA1180679A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA000395862A CA1180679A (en) 1982-02-09 1982-02-09 Method of production of vitamin-d

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA000395862A CA1180679A (en) 1982-02-09 1982-02-09 Method of production of vitamin-d

Publications (1)

Publication Number Publication Date
CA1180679A true CA1180679A (en) 1985-01-08

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA000395862A Expired CA1180679A (en) 1982-02-09 1982-02-09 Method of production of vitamin-d

Country Status (1)

Country Link
CA (1) CA1180679A (en)

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