Synthesis of 1alpha-hydroxyergocalciferol

A synthesis of 1alpha-hydroxyergocalciferol (1alpha-hydroxyvitamin D2, a potent analog of vitamin D2, is described. The preparation route involves conversion of ergosterol in two steps (60%) to the known ergosta-4, 6, 22-trien-3-one and dehydrogenation of the triene with SeO2 to ergosta-1,4,6,22-tetraen-3-one (30%). Epoxidation of the tetraenone to the corresponding 1alpha, 2alpha-epoxide followed by Li/NH3 reduction gave ergosta-5,22-diene-1alpha, 3beta-diol in 26% yield from the tetranone. After conversion to the corresponding diacetate and allylic bromination/dehydrobromination 1alpha-acetoxyergosteryl acetate was obtained. Irradiation of this intermediate gave the previtamin which was converted to the new vitamin analog by thermal equilibration and hydrolysis of the acetates. Charcteristic uv, nmr and mass spectral patterns confirmed the structure of the product.