Calcitriol derivatives with two different side chains at C-20. II. Diastereoselective syntheses of the metabolically produced 24(R)-hydroxygemini.
Vitamin D derivatives containing two side chains emanating at C-20 are known as gemini. We have recently synthesized two gemini which are related to calcitriol and 19-norcalcitriol containing two identical side chains. The metabolism of these species involves 24(R)-hydroxylation on one of the side chains. To determine the outcome of this diastereospecific transformation, we synthesized both C-20 epimeric pairs containing the 24(R)-hydroxy group in the gemini and 19-norgemini series. On the basis of the availability of these reference compounds, it was shown that the metabolic hydroxylation occurred at the pro-R side chain in both gemini compounds. In comparison to the parent compounds, the 24-hydroxygemini required higher doses to increase blood calcium levels in mice and to suppress INF-gamma release in MLR.
Maehr
Hubert
H
Bioxell, Inc., Nutley, New Jersey 07110, USA. Hubert.maehr@roche.com
Uskokovic
Milan R
MR
Adorini
Luciano
L
Reddy
G Satyanarayana
GS
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006900:Hydroxylation; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D051379:Mice; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007371:Interferon-gamma; D002117:Calcitriol; D002118:Calcium