Study On Photochemical Synthesis Of Vimtamin D₃

As an important additive in feed,food and drugs,vitamin D3 is indispensable for human and animal growth,development and health maintenance.Its use is more and more widely.Photochemical synthesis of vitamin D3 from 7-dehydrocholesterol is one of key reaction steps for vitamin D3 preparation,which embodies complex reaction mechanism,with various impurities and isomers are given as byproducts.It is difficult to obtain these byproducts with high purity as standards,due to their unstablility.Thus,it has become an important topic how to obtain the standards and reduce or remove the impurities in the vitamin D3 synthesis.The main research contents of this thesis are as follows:1.Impurities A,C and E with high purity are prepared from vitamin D3 crude oil by primary phase preparative chromatography and secondary preparative chromatography.The conditions of primary preparative chromatography are:column length 300 cm,column diameter 50 mm,silica filler particle size 5 μm,eluent flow rate 10.0 mL/min,detecting wavelength 254 nm.The second preparative chromatographic conditions are:column length 250 cm,column diameter 10 mm,silica filler particle size 5 μm,flow rate eluent 2.0 mL/min,detecting wavelength 254 nm.Their structure is characterized by UV-Vis,IR,LC-MS,and NMR.2.A possible mechanism of the photochemical reaction was given and analyzed.Firstly,under ultraviolet light irradiation,7-dehydrocholesterol undergoes a para-electric cyclization reaction of 4n+2π electron system to obtain pre-vitamin D3,and then pre-vitamin D3 is heated to obtain vitamin D3 by σH[1,7]arrangement and the effect of trans-cis-trans isomerization.Under the ultraviolet light,vitamin D3 can be further converted to impurity A.Meanwhile,impurity C was generatend by a para-electric cyclization reaction of 4n+2π electron system of pre-vitamin D3.Through cis-trans isomerization,pre-vitamin D3 was converted to impurity E.3.According to the given reaction mechanism,designed experiments to study the formation of impurities A,C,and E.Cyclohexane and methanol(3:1 mass ratio)was used as solvent to optimize the reaction temperature,the concentration of raw material 7-dehydrocholesterol,the exposure time,and different light sources.The results show that the total amount of impurity A,impurity C,and impurity E can be reduced by shortening reaction time under reaction temperature of 40℃ and concentration of 7-dehydrocholesterol of 20 mg/mL,using excimer lamp(282 nm)as light resource.