Synthesis of Methyl-Branched lipids from mycobacterium tuberculosis.
PhD Ceremony: dhr. B. ter Horst, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Synthesis of Methyl-Branched lipids from mycobacterium tuberculosis.
Promotor(s): prof.dr. B.L. Feringa, prof.dr.ir. A.J. Minnaard
Faculty: Mathematics and Natural Sciences
Contact: Bjorn ter Horst, tel. 06 1449 5743, e-mail: bjornter.horst@gmail.com
For physiological and, especially, immunological studies, access to pure cell wall lipidic compounds is of paramount importance. However, next to being severely restricted, culturing of Mycobacterium tuberculosis (M. tuberculosis) is difficult and purification of components from the lipid fraction is very complicated. An effective synthetic route to these lipids is therefore highly desirable.
This thesis describes to synthesis of the following methyl-branched fatty acids from M. tuberculosis; mycocerosic, phthioceranic, hydroxyphthioceranic, mycolipenic, mycolipanolic and tuberculostearic acid. Moreover, the absolute configuration of the until now unknown C-17 hydroxy stereocenter is elucidated in the synthesis of hydroxyphthioceranic acid. Direct comparison between the two possible (synthetic) diastereomers and the natural product isolated from M. tuberculosis allowed us to unambiguously determine the absolute configuration of the C-17 stereocenter. The configuration was established as R. The first total synthesis of PDIM A and a newly isolated phospholipid (collaboration with Prof. Moody, Harvard Medical School, VS) from M. tuberculosis are also described. The structure of this newly isolated phospholipid was elucidated by asymmetric synthesis and MS/MS analysis.
The enantioselective copper-catalyzed 1,4-addition reaction with MeMgBr to unsaturated thioesters was used as a key synthetic strategy for the synthesis of the methyl-branched fatty acids. The efficiency and selectivity of this methodology in combination with newly developed synthetic methodologies allowed us to isolate and fully characterize these components from M. tuberculosis for the very first time.
Last modified: | 13 March 2020 01.14 a.m. |
More news
-
06 June 2025
India-Netherlands Hydrogen Valley Fellowship Programme announced
To coincide with World Environment Day, 5 June 2025, the Indian Department of Science and Technology and the University of Groningen yesterday announced a Hydrogen Valley Fellowship Programme Partnership, allowing talented Indian scholars working on...
-
24 March 2025
UG 28th in World's Most International Universities 2025 rankings
The University of Groningen has been ranked 28th in the World's Most International Universities 2025 by Times Higher Education. With this, the UG leaves behind institutions such as MIT and Harvard. The 28th place marks an increase of five places: in...
-
05 March 2025
Women in Science
The UG celebrates International Women’s Day with a special photo series: Women in Science.