PhD ceremony Mr. D. Geerdink: Total synthesis of enantiopure lipids on mycobacterial glycolipids and a putative sex pheromone of Trichogramma turkestanica

PhD ceremony: Mr. D. Geerdink, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Total synthesis of enantiopure lipids on mycobacterial glycolipids and a putative sex pheromone of Trichogramma turkestanica

Promotor(s): prof. A.J. Minnaard

Faculty: Mathematics and Natural Sciences

Mycobacterium tuberculosis is the bacterium that causes tuberculosis and is responsible for 1.7 million deaths annually. Ac2SGL, one of the glycolipids in the cell enveloppe of M. tuberculosis, stimulates the production of antibodies and is considered as a candidate for a tuberculosis vaccine. To stimulate the research into Ac2SGL and to confirm its structure, Danny Geerdink presents the first total synthesis of this molecule.

The difficult treatment of tuberculosis is caused by its multi-layered cell envelope that consists of a variety of molecular complex (glyco)lipids. These lipids create a waxy (hydrophobic) barrier against antibiotics. Research into these lipids has proven that several have very interesting functions. An important part of Ac2SGL, the molecule hydroxphthioceranic acid, could be prepared stereoselectively using a copper-catalyzed conjugate addition protocol. The same approach had proven to function already earlier in the preparation of phthioceranic acid. After 39 steps, Ac2SGL was obtained and its structure confirmed. Moreover, a biological evaluation of synthetic and natural Ac2SGL showed identical activity. Applying the same strategy as for Ac2SGL, the total synthesis of sulfolipid-1, a closely related, very interesting molecule, could be completed.

In addition, Geerdink‘s thesis describes the synthesis of a putative sex pheromone of a parasitic wasp (Trichogramma turkestanic) and our efforts towards the synthesis of another glycolipid from Mycobacterium tuberculosis (DAT2) and a sulfo-glycopeptidolipid from Mycobacterium avium (S-GPL).