Synthesis of β-Hydroxy-β-methylglutaryl- coenzyme A reductase inhibitors utilizing in-situ and ex-situ recovered phytosterols from Gymnema sylvestre R. Br. Processing waste.

Abstract

Natural product industries are facing challenge in residual waste disposal. To mitigate this concern, an industrial methodology was established utilizing solid herbal waste (SHW) and phytosterol waste (PW_in) generated while preparing commercial hypoglycemic extracts from Gymnema sylvestre. Chromatographic evaluation of SHW and PW_in (HPLC and TLC) discovered them as a potential source of phytosterols. PW_in (4.63 ± 0.04 % (w/w)) was recovered during initial defatting step (Hexane: Herb, 15:1, 50 °C, 6 h) and after the extraction of Gymnemic acids PW_ex (4.49 ± 0.13 % (w/w)) was recovered by extracting the SHW with ethyl acetate (ethyl acetate: Herb, 15:1, 50 °C, 6 h). Stigmasterol (I) (most abundant phytosterol) was isolated from PW_in and PW_ex on an industrial scale and subjected to stigmasteryl acetates modification. Stigmasterol (1 mM) with respective anhydrides/carbonyl chlorides (1.12 mM) was stirred at 40 °C along with 0.5 mM of DMAP in 20 mL DCM. The synthesized stigmasteryl acetates (II-VI) were performed better with respect to Stigmasterol (I) in In-silico docking analysis. Compound VI was found most affinitive with HMGCoAR, attenuates hypercholesterolemia, and improves blood cholesterol profile of experimental animals when tested In-vivo. Findings suggest that recovery of chemical resources could be valuable in providing sustainable waste utilization approach for natural product industry.