Synthesis of cholesterol analogues and comparison on their effect on plasma cholesterol with β-Sitosterol

The application of plant sterols in the treatment of hypercholesterolemia is promising. We hypothesize that plant sterols can reduce blood cholesterol because they have a side chain of at least three branches. Three cholesterol analogues were synthesized: CA0 (no side chain), CA3 (a 3-carbon chain with one branch), and CA14 (a 14-carbon side chain with two branches), and then compared their effect on blood cholesterol with that of (3-sitosterol. Structurally, (3-sitosterol has a 10-carbon side chain with three branches. Results demonstrated that (3-sitosterol could effectively reduce plasma total cholesterol (TC) by 20.3%, whereas CA0, CA3 and CA14 did not affect plasma TC in hypercholesterolemia hamsters. (3-Sitosterol was absent in the plasma and liver, indicating it was not absorbed. We concluded that (3-sitosterol with three branches had plasma TC-lowering activity. In contrast, cholesterol analogues with a side chain of two or fewer branches did not affect plasma cholesterol.