Total synthesis of 25-hydroxy-16,23E-diene vitamin D3 and 1 alpha,25-dihydroxy-16,23E-diene vitamin D3: separation of genomic and nongenomic vitamin D activities.
Separation of genomic and nongenomic vitamin D activities was achieved by structural modification of 1,25-dihydroxy vitamin D3 by introduction of 16 and 23E double bonds. The modified compound 3, lacking a 1 alpha-hydroxy group, exhibits only nongenomic activity. Its 1 alpha-hydroxy relative 4 expresses fully both genomic and non-genomic activities. A total synthesis of analogues 3 and 4 is described.
Kabat
M M
MM
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Burger
W
W
Guggino
S
S
Hennessy
B
B
Iacobelli
J A
JA
Takeuchi
K
K
Uskoković
M R
MR
D000818:Animals; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007422:Intestines; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects
C116777:1,25-dihydroxy-16,23-diene vitamin D3; C116776:25-hydroxy-16,23-diene vitamin D3; D015220:Calcium Channels; D007202:Indicators and Reagents; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium