Synthesis of Leningosterol and Saringosterol: A Study on Chimeric Sterols and Antitubercular Activity

Abstract Saringosterol (15), a phytosterol isolated as an epimeric mixture from the brown algae Sargassumringgoldianum and Lessonia nigrescens, is a potent antitubercular agent with a minimum inhibitory concentration (MIC) of 0.25 μg/mL and low cytotoxicity toward the Vero cell line. Likewise, several 5(6→7) abeo-sterols such as parguesterol A (18) are typically endowed with low cytotoxicity while displaying promising antitubercular activity with MICs ranging from 3.8 to 15 μg/mL. Based on these observations, we designed a chimeric sterol, hereafter known as leningosterol (30), which combines the most salient structural features of 15 and 18 believed to be responsible for antitubercular activity. Leningosterol (30) was synthesized in 10 steps from commercially available 3β-hydroxy-5-cholenic acid (32) with an overall yield of 7% and minimal utilization of protecting groups. When screened in vitro against Mycobacterium tuberculosis H37Rv, the MIC of 30 was unexpectedly higher than either 15 or 18. We also present a semi-synthesis of saringosterol (15) and reassess its purported potent antitubercular activity.