Doxercalciferol → Isoergosterone

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1α-Hydroxy vitamin D2 exhibiting strong vitamin D activity is disclosed in U.S. Pat. No. 3,907,843. A synthetic route to 1α-hydroxy vitamin D2 disclosed therein is shown in the following reaction scheme I, which includes conversion of isoergosterone (compound 1) prepared from ergosterol to ergosta-1,4,6,22-tetraen-3-one (compound 2) followed by reaction with hydrogen peroxide to give 1α,2α-epoxy-ergosta-4,6,22-trien-3-one (compound 3), reaction of this compound with liquid ammonia and metal lithium to give 1α-hydroxy-7,8-dihydroergosterol (compound 4) followed by acetylation to give 1α-acetoxy-7,8-dihydroergosteryl acetate (compound 5), dehydrogenation of this compound to 1α-hydroxyergosteryl diacetate (1α,3β-diacetoxy-ergosta-5,7,22-trien)(compound 6), irradiation of this compound with light, causing cleavage of the ring to give 1α,3β-diacetoxy previtamin D2 (compound 7) and thermal isomerization and deacetylation of this compound to give 1α-hydroxy vitamin D2 (compound 8). The synthesis of 1α-hydroxy vitamin D2 by the above processes, however, gives rise to a number of problems. The reaction yield of the compounds is low including 16% yield in the formation of compound 5 from compound 3 and less than 10% yield in the formation of compound 6 from compound 5, and hence the overall yield through the synthesis of compound 6 from compound 1 amounts to less than 0.4%. In the conversion of compound 3 into compound 4, use of liquid ammonia and metal lithium is highly dangerous. In the conversion of compound 5 into compound 6, there is formed as by-products an isomeric compound 9 (1α,3β-diacetoxy ergosta-4,6,22-trien) which is difficult to separate and is responsible for reducing the purity of 1α-hydroxy vitamin D2. In view of the foregoing problems, the prior processes are not satisfactory for the production of 1α-hydroxy vitamin D2 in industrial scale. ##STR1##

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