Skip to ContentSkip to Navigation
About usNews and EventsNews articles

Synthesis of Methyl-Branched lipids from mycobacterium tuberculosis.

15 January 2010

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:15 September 2017 3.40 p.m.
printView this page in: Nederlands

More news

  • 11 July 2019

    Major companies’ annual reports too vague about climate impact

    Many major Dutch companies publish extensive information about climate impact in their annual reports. However, very few companies provide concrete, detailed information about their own CO2 emissions, the impact of climate change on their business...

  • 08 July 2019

    UG permanently closes Yantai project

    The University of Groningen (UG) has permanently closed the project aimed at creating a branch campus in Yantai. Discussions were held with China Agricultural University, the city of Yantai and the Province of Shandong.

  • 03 July 2019

    Cheap train tickets boost public transport use but reduce customer satisfaction

    Offers of cheap single train tickets through retailers such as Kruidvat or Etos have a positive impact on the number of kilometres travelled by rail. This impact is much bigger than that of more general TV, newspaper or magazine advertising. However,...