Synthesis of 1α-Hydroxyvitamin D5 using a modified two wavelength photolysis for vitamin D formation

Article abstract of DOI:10.1021/jo050853f

1α-Hydroxyvitamin D₅ (1) is a promising chemopreventive agent for breast cancer and is being developed as a drug. We report a synthesis for this vitamin D analogue which uses a photochemical method for the B-ring opening, leading to the conjugated triene system. The precursor 7-dehydrositosteryl acetate (4) obtained through a one-pot, five-step procedure, was completely free of the 4,6-diene isomer that usually forms in the 5,7-diene synthesis. The pre-vitamin isomer (11) was generated using a modified two-wavelength photolysis procedure that increases the yield for this step more than 3-fold compared to classically used photolysis. The 1α-hydroxylation step was performed on the 3-triethylsilyl-trans-vitamin D₅ (17) obtained via the sulfur dioxide adduct of cis-vitamin D₅, in an overall yield of 48%. Photoisomerization and deprotection completed the synthesis.