Synthesis and Photophysical Properties of 7-Azaserotonin and 7-Azamelatonin
Date Issued
2006
Date
2006
Author(s)
Wu, Pei-Wen
DOI
en-US
Abstract
Perhaps, the most prominent neurotransmitters can be ascribed to serotonin and melatonin. In many neuropsychiatric disorders, the serotonin or melatonin system may play a key modulatory role. Although the pathophysiology of many neuropsychiatric disorders remains enigmatic, the abnormalities in serotonin or melatonin signaling have been strongly implicated.
Such a small molecule like serotonin or melatonin acting as a vital element in brain function has attracted much attention in the synthetic chemistry. Focus on derivatization of serotonin or melatonin has been one of the intensive areas in the medicinal chemistry. While most of the approaches lie in the substitution effect on the parent serotonin or melatonin, we have long been interested in replacing the parent indole moiety by the 7-azaindole chromophore, forming 7-azaserotonin, 7-azamelatonin.
Herein, we elaborated first synthesis of 7-azaserotonion in ~10 % total yield and rose up the yield of 7-azamelatonin by the synthetic route different from the synthetic pathway of Guillaumet in ~6 % total yield. Subsequently, we further investigated the photophysical properties of 7-azaserotonin and 7-azamelatonin, namely the excited state proton transfer reaction. Differentiation of photophysics between alcohol and water are intriguing. In view of bio-application, we suspect that once 7-azaserotonin and 7-azamelatonin are in the hydrophobic medium, water catalyzed proton transfer reaction may take place, serving as suitable molecular probes. We also performed the molecular dynamic approaches for 7-azaserotonin (and 7-azamelatonin) to investigate the difference of interaction to the 5-HT1B receptor (and calmodulin) between serotonin (melatonin) and 7-azaserotonin (7-azamelatonin). Our preliminary data indicate that 7-azaserotonin (7-azamelatonin) has larger association strength than that of serotonin (melatonin). Thus, 7-azaserotonin may serve as a powerful 5-HT1B agonist or antagonist to treat aggression or depression, respectively. 7-azamelatonin could be taken to treat estrogen responsive cancers more efficiently. We believe that exploration of 7-azaserotonin and 7-azamelatonin may spark a broad spectrum of interest in the fields of medicinal chemistry and biophysics.
Subjects
褪黑激素
血清激素
melatonin
serotonin
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-95-R93223002-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):cb2cd04299e78bd2f97b4c17b44d984c