A facile synthesis of 3β, 25-dihydroxy-5α-cholest-7-ene, the precursor to HMG-CoA reductase inhibitor

作者：Jin, Can^*; Liao, Zhibing; Sun, Bin; Xu, Tengwei

来源：Journal of Chemical Research, 2018, 42(3): 156-159.

DOI：10.3184/174751918X15220628915420

• 3 beta,25-dihydroxy-5 alpha-cholest-7-ene
• 5 alpha-cholesta-7,24-diene-3 beta-toluene-sulfonate
• hydroxybromination
• 3-hydroxy-3-methylglutaryl coenzyme A reductase

An efficient four-step procedure is described for the synthesis of 3 beta, 25-dihydroxy-5 alpha-cholest-7-ene from 3 beta-hydroxy-5 alpha-cholesta-7,24-diene in an overall yield of 34%. This product can serve as a precursor for the synthesis of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The 3 beta-toluene-p-sulfonate ester of 5 alpha-cholesta-7,24-diene was obtained from natural lanolin followed by treatment with toluene-p-sulfonyl chloride. The key step in the synthesis is a very mild method for the hydroxybromination of this ester with N-bromosuccinimide in water, followed by reduction with LiAlH4 to obtain the 3 beta-toluene-p-sulfonate ester of 25-hydroxy-5 alpha-cholesta-7-ene. The final product was obtained after desulfonation of 3 beta-toluene-p-sulfonyoxy-25-hydroxy-5 alpha-cholesta-7-ene to afford 3 beta, 25-dihydroxy-5 alpha-cholest-7-ene in excellent yield. The reagents are all relatively cheap, non-toxic and stable.

• 出版日期2018-3
• 单位浙江工业大学