7 LanosterolからのCholesterol生合成 : Lanosterol同族体の生合成に及ぼす影響とその代謝

抄録

The effects of lanosterol analogues on cholesterol biosynthesis and their metabolisms were examined. The lanosterol analogues (3), (4), (5), (6), (8), (11), (14). (16), (18) and [24-^3H]-lanosterol (22) were synthesized from lanosteryl acetate (1b) (Scheme 1 and 2). [24-^3H]-Lanosterol (19μM) was incubated in the presence of lanosterol analogues (45 μM) with S-10 from rat liver. It was found that the side chain analogues of lanosterol have the inhibitory activities and that 27-nordihydrolanosterol (4) and 23,24,25,26,27-pentanordihydrolanosterol (14) exhibit high activities (Table II). Furthermore, tritium labeled lanosterol analogues (24 and 25) were synthesized (Scheme 2) and their metabolisms were examined. After the incubation of [24,25-^3H]-27-nordihydrolanosterol (25) with S-10, its nonsaponifiable fraction was chromatographed on t.l.c. plate followed by radioautography (Fig. 1a). The results indicated that (25) was transformed to tritium labeled 27-norcholesterol in the yield of 6.4%. On the other hand, the incubation experiments proved that [22-^3H]-23,24,25,26,27-pentanordihydrolanosterol (24) is not transformed into the corresponding demethylated sterol, 23,24,25,26,27-pentanorcholesterl.