Chemical synthesis of 3(beta)-hydroxy-25,26,26,26,27,27,27-heptafluorocholest-5en-7-one via 25,26,26,26,27,27,27-heptafluorocholest-5-en-3(beta)-ol and its effects on sterol metabolism
Carroll, Jeffery Neal
Master of Arts
3$\beta$-Hydroxy-cholest-5-en-7-one (15) has been reported to lower 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in both mouse liver cells and whole animals. In experiments with rats, studies have shown that 15 is rapidly metabolized and excreted from the body. We synthesized 3$\beta$-hydroxy-25,26,26,26,27,27,27-heptafluorocholest-5-en-7-one (19) with the hope that blocking the sidechain metabolism at C-25 and C26 would allow sufficient quantities to accumulate in vivo and possibly lower serum cholesterol levels. 19 was synthesized via 25,26,26,26,27,27,27-heptafluorocholest-5-en-3$\beta$-ol (3) by employing the reagents chromic anhydride and 3,5-dimethylpyrazole (DMP) in methylene chloride (66% yield; $>$99% pure by NMR). A thorough characterization of 19 and its nonfluorinated counterpart 15 is presented. Several byproducts from the synthesis of 3 and 19 were discovered. Their preliminary characterizations are also reported.