Synthesis And Process Optimization Of The Skeleton Reserved Vitamin D Derivatives’Intermediates

The skeleton reserved vitamin D derivatives are be widely usded in the field of food, drug and so on. Researches of these derivatives and their common intermediates have very important significance.1(S),3(R)-bis(tert-butyldimethylsilyloxy)-9,10-sco-ergosta-5(E),7(E),10(19),22(E)-tetraene which has been widely used, is an important intermediate of skeleton reserved vitamin D derivatives. Tacalcitol, calcipotriol which are derivatives of the skeleton reserved vitamin D, they can both be synthesised from the intermediate which is the the target product of this paper, at the same time they are drug for the treatment of psoriasis.In this thesis, the preparative methods of1(S),3(R)-bis(tert-butyldimethylsilyloxy)-9,10-sco-ergosta-5(E),7(E),.10(19),22(E)-tetraene were briefly reviewed, and then the synthesis route was designed.1(S),3(R)-Bis(tert-butyldimethylsilyloxy)-9,,10-sco-ergosta-5(E),7(E),10(19),22(E)-tetraene was synthesized from Vitamin D2, through the Diels-Alder Addition reaction with SO2, then the hydroxyl at C-3was protection by TBS, deprotection of SO2, Riley oxidation reactions at C-1, followed by protection of hydroxyl by TBS at C-1, Also according to the phenomenon and data, the reasonable mechanism of the reactions was presumed respectively, and factors which may affect the yield were found. The reactive conditions were optimized with a overall yield of38%.We completed the the calcipotriol content’s detection.Literature research found that there were no reports of the use of HPLC to analysis tacalcitol. This paper found the separation conditions of tacalcitol using preparative high performance liquid chromatography technolog.At the time using the ordinary C18column finished its chiral separation according to the separation conditions.