Synthesis of 1 a-Hydroxyvitamin D3

Abstract

(6 R)-6-(1, 3-Benzodithiol-2-yloxy)-3, 5-cyclovitamin D3 (6 a) was prepared from (6 R)-6hydroxy-3, 5-cyclovitamin D3 ( 5 ) and 1, 3-benzodithiolylium tetrafluoroborate. Allylic oxidation of 6 a yielded (6 R)-1 a-hydroxy-6-(1, 3-benzodithiol-2-yloxy)-3, 5-cyclovitamin D3 (6 b)(49% yield from 5). Compound 6 b was hydrolyzed with 12-phosphomolybdic acid catalyst to give 1 a-hydroxyvitamin D3 (1 b) (mp 137-138 °C, isolated in 33% yield). In the cycloreversion of 6 b bearing 6-[(R)-1, 3-benzodithio1-2-yloxyl] group, no 5, 6-trans isomer ( 4 )was given in contrast with that of (6 R)-1a-hydroxy-6-methoxy, -3, 5-cyclovitamin D3 (3 b). Similarly, the acetolysis of 6 b gave only 1 a-hydroxyvitamin D3 3-acetate ( 7 ) (46%yield) without forming the 5, 6-trans isomer ( 8 ). In our method, 1 b (or 7) can be easily isolated and purified because of the absence of 5, 6-trans isomer in the reaction mixtures. Therefore, a large scale synthesis can easily be carried out.