Synthesis and Biological Evaluation of Polyunsaturated Natural Products and Derivatives
Appears in the following Collection
- Farmasøytisk institutt 
AbstractIn recent years, marine natural products have gained attention from scientists within diverse research fields, such as biology, pharmacology, medicine and chemistry. Among those natural products, several polyunsaturated fatty acids (PUFAs) and their metabolites have been isolated.
This prompted us to develop an efficient synthesis of analogs of the two PUFA marine natural products mycalazol 5 and mycalazal 2 starting from eicosapentaenoic acid (EPA) and eicosanoic acid (EA). The biological studies revealed that all synthesized analogs displayed potent cytotoxic effect against several human cancer cell lines.
In continuation of this study, another PUFA derived marine natural product was used as a lead compound for making analogs that were subjected to biological testing as antioxidants. The analogs with a polyunsaturated alkyl chain exhibited more potent effects than the analogs possessing a saturated alkyl chain.
Bosseopentaenoic acid (BPA) and its methyl ester have been isolated from different algae.This PUFA contains a (Z,E,E,Z)-conjugated polyene moiety with five double bonds in total. An efficient stereocontrolled synthesis of this natural product has been achieved. During the work towards the total synthesis of BPA, a Z-stereoselective Boland reduction reaction was needed. The Boland reduction procedure was modified by the addition of TMSCl, which resulted in shorter reaction times. This procedure was applied for the preparation of several Z-alkenes.
As a continuation of the synthetic work towards BPA, the synthesis of α-parinaric acid was also investigated. As in the case with BPA, this naturally occurring PUFA also contains a Z,E,E,Z-conjugated polyene moiety, that we attempted to prepare via iterative palladiumcatalyzed cross coupling reactions.
List of papers
|Paper I Synthesis of mycalazol and mycalazal analogs with potent antiproliferating activities. Mohamed, Y. M. A.; Hansen T. V. Pure and Applied Chemistry 2011, 83, 489-493. http://dx.doi.org/10.1351/PAC-CON-10-09-27|
|Paper II Polyunsaturated fatty acid-derived chromones exhibiting potent antioxidant activity. Mohamed, Y. M. A.; Vik, A.; Hofer, T.; Andersen, J. H.; Hansen, T. V. Chem. Phys. Lipids 2013, submitted. The paper is removed from the thesis in DUO.|
|Paper III First total synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate. Mohamed Y. M. A.; Hansen T. V. Tetrahedron Lett. 2011, 52, 1057-1059. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1016/j.tetlet.2010.12.078|
|Paper IV Z-Stereoselective semi-reduction of alkynes: Modification of the Boland protocol. Mohamed, Y. M. A.; Hansen, T. V. Tetrahedron 2013, 69, under revision. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1016/j.tet.2013.03.038|