engleski

SYNTHETIC APPROACHES TOWARDS BIOACTIVE COMPOUNDS PRODUCED DURING OXIDATIVE STRESS

Polyunsaturated fatty acids (PUFAs) have for long been recognized for their essential role in living organisms. It has been demonstrated that they undergo a large number of enzymatic transformations leading to compounds with potent anti-inflammatory and neuroprotective properties. Neuroprotectin D1 (NPD1) belongs to the family of still inadequately explored lipid-derived mediators. It is produced from docosahexaenoic acid (DHA) in retinal and neural cells during oxidative stress induced diseases and shows substantial neuroprotective, anti-inflammatory, regenerative and anti-apoptotic abilities. Due to these properties, NPD1 has become an interesting target molecule for the treatment of brain stroke and Alzheimer’s disease and synthetic approaches have been devised. , Nevertheless, new methods for very efficient, stereoselective and versatile syntheses of NPD1 and analogs are needed. We present results of our efforts to design a short and modular synthesis of NPD1 and analogs for various biological investigations. On the other hand, in cell membranes which incorporate PUFAs, highly reactive intermediates are also produced during oxidative stress. Their activity is known to affect a number of important biological processes, leading to possible neurodegenerative diseases and cell apoptosis. Besides the widely recognized 4-hydroxynonenal (HNE), 4-hydroxyhexenal (HHE) and 4-hydroxydodeca-(2E, 6Z)-dienal (HDDE) were also detected, but their behaviour in the membrane bilayer is so far not well understood. We extend our synthetic efforts towards HHE and HDDE using synthetic protocols established in the group in order to help elucidate their role in the cell membrane.

neuroprotectins; total synthesis

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