Synthesis and biological activity of 2-hydroxy and 2-alkoxy analogs of 1 alpha,25-dihydroxy-19-norvitamin D3.
1 alpha, 2 alpha,25-Trihydroxy-19-norvitamin D3, 1 alpha, 2 beta,25-trihydroxy-19-norvitamin D3, and their alkoxy analogs were efficiently prepared in a convergent synthesis, starting with (-)-quinic acid and a Windaus--Grundmann type ketone. Configurations of the A-ring fragment substituents were determined by 1H,1H COSY 2D spectra and 1H NOE difference spectroscopy. The new analogs exhibited selective activity in stimulating intestinal calcium transport while having little or no activity in mobilizing bone calcium. They also showed HL-60-differentiating activity equal to or 10 times lower than that of 1 alpha,25-dihydroxyvitamin D3.
Sicinski
R R
RR
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, 53706.
Perlman
K L
KL
DeLuca
H F
HF
D000818:Animals; D001692:Biological Transport; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
C083610:1,25-dihydroxy-19-norvitamin D3; D002117:Calcitriol; D002118:Calcium