Synthesis of 1alpha-hydroxyvitamin D5 using a modified two wavelength photolysis for vitamin D formation.
[reaction: see text] 1Alpha-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 1alpha-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.
Moriarty
Robert M
RM
Department of Chemistry (M/C 111), University of Illinois at Chicago, Chicago, Illinois 60607, USA. moriarty@uic.edu
Albinescu
Dragos
D
D016588:Anticarcinogenic Agents / Q000138:chemical synthesis*; D006887:Hydroxycholecalciferols / Q000138:chemical synthesis*; D010782:Photolysis; D014807:Vitamin D / Q000138:chemical synthesis
C103958:1-hydroxyvitamin D5; D016588:Anticarcinogenic Agents; D006887:Hydroxycholecalciferols; D014807:Vitamin D