- SIDE CHAIN DERIVATIZED 15-OXYGENATED STEROLS, METHODS OF USING THEM AND A PROCESS FOR PREPARING THEM
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Pharmaceutical compositions are provided for lowering the activity of HMG-CoA reductase and/or lowering serum cholesterol, comprising an amount effective to lower the activity of HMG-CoA reductase and/or lower serum cholesterol of a side chain derivatized
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- Inhibitors of sterol synthesis. An efficient and specific side chain oxidation of 3β-hydroxy-5α-cholest-8 (14)-en-15-one. Facile access to its metabolites and analogs
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Treatment of the acetate of 3β-hydroxy-5α-cholest-8(14)-en-15-one (1), a potent regulator of cholesterol metabolism, with a mixture of trifluoroacetic anthydride, hydrogen peroxide, and sulfuric acid at ~-2°C for 3.5 h gave remarkably high yields (~64%) of a mixture of C24 oxygenated products: 3β-acetoxy-24-trifluoroacetoxy-5α-chol-8(14)-en-15-one (6), 3-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one (7), and 3β,24-diacetoxy-5α-chol-8(14)-en-15-one (8). Selective hydrolysis of the trifluoroacetoxy function of 6 in the crude reaction product gave isolated yields of 7 and 8 of 61% and 3%, respectively. The availability of 7, selectively protected at C-3, provides a key intermediate for the synthesis of potential metabolites and analogs of 1. Thus, 7 was readily converted to 3β-hydroxy-15-keto-5α-chol-8(14)-en-24-oic acid (4) and the 25-aza analog of l, 3βhydroxy-24-dimethylamino-5α-chol-8(14)-en-15-one (10).
- Herz, Josef E.,Swaminathan, Shankar,Wilson, William K.,Schroepfer Jr., George J.
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p. 3923 - 3926
(2007/10/02)
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