Synthesis of new nitro and amino sterols; potential inhibitors of 4-methyl sterol oxidase

Abstract

New 4-nitro and 4-amino 5α-steroids were made regioselectively from cholesterol via nitration of 3-acetoxy-5α-cholesta-l,3-diene (2). Nitration of enol acetate (2) gave 4α-nitro-5α-cholest-1-en-3-one (3), which was catalytically reduced to 4α-nitro-5α-cholestan-3-one (4). Sodium borohydride reduction of (4) gave 4α-nitro-5α-cholestan-3β-ol (5). Reduction of 4α-nitro-5α-cholestan-3β-ol with lithium aluminium hydride furnished 4-amino-3,4-seco-5α-cholestan-3β-ol (6), rather than the desired 4α-amino-5α-cholestan-3β-ol (8). The synthesis of compound (8) required prior derivatization of the 4α-nitro sterol as the 3-(tetrahydropyran-2-yl) ether. The related 4α-aminomethyl-5α-cholestan-3β-ol (12) has also been synthesized, via a 4α-formyl intermediate.