Synthesis and biological activity of 1.ALPHA.-hydroxy-24,24-dimethyl-22E-dehydrovitamin D3 and 1.ALPHA.,25-dihydroxy-24,24-dimethyl-22E-dehydrovitamin D3.

Abstract

Two new vitamin D3 analogues, 1.alpha.-hydroxy-24,24-dimethyl-22E-dehydrovitamin D3(13) and 1.alpha.,25-dihydroxy-24,24-dimethyl-22E-dehydrovitamin D3 (17), which are blocked for 24-hydroxylation by the methyl groups, were synthesized from 1.alpha.,3.beta.-bismethoxymethoxymegan-5-ene-20S-carbaldehyde (6) by using the orthoester Claisen rearrangement for construction of the carbon skeleton of their side chains. These compounds (13 and 17) elicited a rise in serum calcium, but not in serum inorganic phosphorus in rats. In a bioassay for alkaline phosphatase, they were found to show much weaker activity than 1.alpha.-hydroxy vitamin D3 (5).