Synthesis of Strophasterols C, E, and F

Abstract

The synthesis of strophasterols C, E, and F has been accomplished from a 14,15-secoergostane derivative via a 1,3-dipolar cycloaddition of a nitrile oxide intermediate to simultaneously install an isolated cyclopentane ring and a C23 oxygen functionality in a diastereoselective manner and a regio- and diastereoselective selenohydroxylation of an olefinic intermediate under thermodynamic conditions. This synthesis also enabled the stereochemical confirmation of strophasterol C.

Biogenetic space-guided synthesis of rearranged terpenoids

“…26 Following their initial studies, optimisation of their cyclisation step allowed them to synthesise strophasterols A–F ( 27 , 32–36 ) in 2017–2020. 26–28 Additionally, their work provided proof for the identity of glaucoposterol A and strophasterol F ( 36 ). 28…”

“…Strophasterols A-D (27,(32)(33)(34) were first isolated from Stropharia rugosoannulata in 2012 by Kawagishi and co-workers, 19 while strophasterols E (35) and F (36) were discovered later in 2019 by the group of Kikuchi from Pleurotus eryngii. 20 Especially, strophasterol A (27) gained attention due to its mitigating effects on Alzheimer's disease.…”

“…The latter would react in the 5-exo-trig radical cyclisation to furnish cyclopentane 31 with a radical at C23. A reductive quench of this radical would lead to either strophasterol A (27) or B (32), while an oxidative quench could lead to the formation of strophasterols C-F (33-36). Assuming an oxidative quench could also happen with the C15 radical 30, the formation of aldehyde 37 became a possibility.…”

“…When treated with m-chloroperbenzoic acid (mCPBA), the 5a,6-epoxide was formed by first oxidation of the iodide to iodosyl M, elimination of the latter giving the 5,6-double bond, which, in turn, was epoxidised by mCPBA. 31 Finally, global deprotection under basic conditions gave strophasterol A (27) or B (32), respectively, in a total of 17 steps each. The route of Kuwahara, thus, proves a similar radical cyclisation to be competent to forge the desired cyclopentyl motif.…”

Structure and Biological Activity of Ergostane-Type Steroids from Fungi

“…Structure of strophasterol C ( 200 ) was proposed based on NOE correlations by Aung et al, who isolated it from the basidiomycete Cortinarius glaucopus together with glaucoposterol A ( 203 ) [ 195 ]. Additional evidence for the structure of 200 was obtained by its chemical synthesis [ 308 ]. Two more steroids with a strophastane skeleton, strophasterol E ( 202 ) and strophasterol F ( 203 ), were isolated from the fruiting bodies of Pleurotus eryngii [ 201 ].…”