Synthesis and structure-activity relationships of 14 beta-hydroxy-5 alpha-pregnanes: pregnanes that bind to the cardiac glycoside receptor.
5 alpha-pregnane-3 beta,14 beta,20 beta-triol 3-alpha-L-rhamnopyranoside (8) and 3 beta-(alpha-L-rhamnopyranosyloxy)-5 alpha-pregn-14-en-20-one (14) were prepared from uzarigenin by ozonolysis followed by zinc and acetic acid reduction and glycosidation. During the glycosidation reaction leading to (8) the corresponding ortho ester (9) was also obtained. Uzarigenin alpha-L-rhamnopyranoside (15) also was prepared. Synthesis of 5 alpha-pregnane-3 beta,14 beta,20 beta-triol (20) is described. Structures were established by analysis of their NMR spectra. The binding affinity of 5 alpha and 5 beta cardenolide and pregnane derivatives as measured in a radioligand binding assay was determined and their structure-activity relationships compared. The receptor binding affinity of the 5 alpha derivatives is less than that of the corresponding 5 beta derivatives.
Templeton
J F
JF
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
Ling
Y
Y
Kumar
V P
VP
LaBella
F S
FS
D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D002298:Cardenolides / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D006027:Glycosides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008861:Microsomes / Q000378:metabolism; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010042:Ouabain / Q000378:metabolism; D010084:Oxidation-Reduction; D010126:Ozone; D011278:Pregnanes / Q000737:chemistry* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015032:Zinc
D000085:Acetates; D002298:Cardenolides; D006027:Glycosides; D011278:Pregnanes; C028996:cardiac glycoside receptors; D010042:Ouabain; D010126:Ozone; D000254:Sodium-Potassium-Exchanging ATPase; D015032:Zinc; D019342:Acetic Acid