Guggulsterone
Guggulsterone is a phytosteroid found in the resin of the guggul plant, Commiphora mukul. Guggulsterone can exist as either of two stereoisomers, E-guggulsterone and Z-guggulsterone. In humans, it acts as an antagonist of the farnesoid X receptor, which was once believed to result in decreased cholesterol synthesis in the liver. Several studies have been published that indicate no overall reduction in total cholesterol occurs using various dosages of guggulsterone, and levels of low-density lipoprotein increased in many people. Nevertheless, guggulsterone is an ingredient in many nutritional supplements. Guggulsterone was also found to have interactions with the viral ADP ribose phosphatase enzyme of SARS-CoV-2 and has been proposed as a potential candidate for the development of therapeutics for the treatment of COVID-19.
Guggulsterone is a broad-spectrum ligand of steroid hormone receptors, and is known to possess the following activities:
- Mineralocorticoid receptor antagonist
- Progesterone receptor partial agonist
- Glucocorticoid receptor antagonist
- Androgen receptor antagonist
- Estrogen receptor agonist
- Farnesoid X receptor antagonist
- Pregnane X receptor agonist )
Synthesis
Guggulsterone can be synthesized from 16-DPA, progesterone or DHEA.A synthesis of guggulsterone from 16-DPA is described. Note that for the first step in the patent LiAlH4 is used in THF. Additionally another synthesis patent was found which uses Red-Al for the reduction step:
The reduction of 16-DPA with sodium borohydride leads to 5,16-pregnadiene-3b-20 diol, PC22295555. Acetylation is accompanied by some kind of a bond reorganization to give PC58830759, PC90955911 or PC90960662. Saponification of both the acetyl groups gives PC90795454. Oppenauer oxidation concludes the synthesis.