Total Synthesis, Structure Revision, and Neuroprotective Effect of Hericenones C-H and Their Derivatives.
J Org Chem
; 86(3): 2602-2620, 2021 02 05.
Article
em En
| MEDLINE
| ID: mdl-33492133
ABSTRACT
The first total syntheses of hericenones C-H and "putative 3-hydroxyhericenone F" were achieved. Highlights of the synthesis include the straightforward construction of the resorcinol core and geranyl side chain, assembly of the natural product skeleton by sequential O-geranylation and a clay/zeolite-mediated O â C rearrangement reaction, and a biomimetic cyclization to form a variety of bicyclic natural hericenones and their congeners. The structure of the "putative 3-hydroxyhericenone F" was revised as the 5-exo cyclization product (named hericenone Z) of epoxyhericenone C through in-depth analyses of the cyclization modes in addition to NMR spectroscopic studies. To gain insights into the biological functions of geranyl-resorcinols in Hericium erinaceus, potential neuroprotective effects against endoplasmic reticulum (ER) stress-dependent cell death were evaluated systematically to clarify a fundamental structure-activity relationship. Among the compounds assayed, the linoleate-containing hericenone analogue, i.e., the regioisomer of hericene D, was found to possess the most potent neuroprotective effect against tunicamycin and thapsigargin-induced ER stress-dependent cell death.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Fármacos Neuroprotetores
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2021
Tipo de documento:
Article