Asymmetric synthesis of 14-A4t-neuroprostane: hunting for a suitable biomarker for neurodegenerative diseases.
Oxidative stress has long been associated with aging and age-related pathologies, such as neurodegenerative diseases. One of the direct effects of oxidative stress in vivo is the formation of prostaglandin-like compounds, named isoprostanes, by the action of reactive oxygen species on membrane phospholipids. A particular subclass of isoprostanes, named neuroprostanes, is formed from docosahexaenoic acid (C22:6omega3, DHA) and is considered to be specific for neuronal oxidative stress. Since isoprostanes are considered as golden standards for oxidative stress, and due to the specificity of neuroprostanes for this condition in neurons and their relation with Alzheimer's and Parkinson's diseases, they are envisioned to be suitable biomarkers for these pathologies. Herein we describe the first total synthesis of 14-A4t-NeuroP in an enantioselective and stereoselective fashion, by means of a new and rapid approach for the installation of the omega chain based on a chemoselective Julia-Kocienski olefination. Furthermore, the construction of the 4,5-cis-disubstituted cyclopentenone moiety characteristic of class A neuroprostanes is achieved in a stereospecific fashion, and suitable reaction conditions have been tuned to avoid epimerization of the labile stereogenic centers.
Zanoni
Giuseppe
G
Department of Organic Chemistry, University of Pavia, Viale Taramelli, 10-27100 Pavia, Italy. gz@unipv.it
Brunoldi
Enrico M
EM
Porta
Alessio
A
Vidari
Giovanni
G
D015415:Biomarkers / Q000737:chemistry; D004281:Docosahexaenoic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000175:diagnosis*; D013237:Stereoisomerism
C526483:14-A4t-neuroprostane; D015415:Biomarkers; D004281:Docosahexaenoic Acids