On the total synthesis of terpenes containing quaternary stereocenters:Stereoselective synthesis of the taiwaniaquinoids, mastigophorene A, and tuberculosinyl adenosine

Dit proefschrift beschrijft de stereoselectieve synthese van natuurstoffen. Allereerst is de synthese van mycoketide beschreven, en de daaropvolgende analyse met NMR-spectroscopie. De analyse heeft bijgedragen aan het opstellen van een voorspelmodel voor natuurproducten die het 1,5-methyl raamwerk bevat. De twee volgende hoofdstukken staan in het teken van de synthese van 1-tuberculosinyladenosine (1-TbAd), dit in samenwerking met het Moody lab (Harvard medical school). 1-TbAd is geïsoleerd uit Mycobacterium tuberculosis en bleek specifiek geproduceerd door dit organisme. Het virulentie-geassocieerde enzym (Rv33878c) is verantwoordelijk voor de productie van 1-TbAd en is daarom verdacht betrokken te zijn in virulentie van de tubercuosis bacterie. De synthese van 1-TbAd leverde product dat gebruikt is in de ontwikkeling van een diagnostische test voor de tuberculose ziekte. Meer materiaal was geproduceerd in de eerste, multi-gram, stereoselective synthese van 1-TbAd. Naast de synthese is ook de stereocentra introducerende stap, de Diels-Alder reactie, onderzocht met behulp van in silico studies. Het tweede deel van dit proefschrift staat in het teken van de Pd-gekatalyseerde geconjugeerde additie van ortho-gesubstitueerde arylboorzuren voor de constructie van benzillische quartenaire stereocentra. Allereerst is de reactie ontwikkeld en daarna toegepast in de kortste syntheses van herberteendiol en enokipodine A en B. Het daaropvolgende hoofdstuk beschrijft de ontwikkeling van de Pd-gekatalyseerde homo-koppeling van aryllithium reagentia met de directe toepassing in de kortste asymmetrische synthese van mastigophoreen A. Het proefschrift is afgesloten met initieel onderzoek naar de synthese van natuurstoffen uit de tainwaniaquinoide familie

Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis

The pathogen Mycobacterium tuberculosis (Mtb), causing tuberculosis disease, features an extraordinary thick cell envelope, rich in Mtb-specific lipids, glycolipids, and glycans. These cell wall components are often directly involved in host-pathogen interaction and recognition, intracellular survival, and virulence. For decades, these mycobacterial natural products have been of great interest for immunology and synthetic chemistry alike, due to their complex molecular structure and the biological functions arising from it. The synthesis of many of these constituents has been achieved and aided the elucidation of their function by utilizing the synthetic material to study Mtb immunology. This review summarizes the synthetic efforts of a quarter century of total synthesis and highlights how the synthesis layed the foundation for immunological studies as well as drove the field of organic synthesis and catalysis to efficiently access these complex natural products

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

Virgin females of the parasitoid wasp Trichogramma turkestanica produce minute amounts of a sex pheromone, the identity of which has not been fully established. The enantioselective synthesis of a putative component of this pheromone, (6S,8S,10S)-4,6,8,10-tetramethyltrideca-2E,4E-dien-1-ol (2), is reported as a contribution to this identification. Catalytic asymmetric conjugate addition of methylmagnesium bromide and stereoselective Horner–Wadsworth–Emmons olefinations are used as the key steps, and 2 was obtained in 16 steps with an overall yield of 4.4%

Pd-catalyzed sp-sp³cross-coupling of benzyl bromides using lithium acetylides

Organolithium-based cross-coupling reactions have emerged as an indispensable method to construct C-C bonds. These transformations have proven particularly useful for the direct and fast coupling of various organolithium reagents (sp, sp2, and sp3) with aromatic (pseudo) halides (sp2). Here we present an efficient method for the cross-coupling of benzyl bromides (sp3) with lithium acetylides (sp). The reaction proceeds within 10 min at room temperature and can be performed in the presence of organolithium-sensitive functional groups such as esters, nitriles, amides and boronic esters. The potential application of the methodology is demonstrated in the preparation of key intermediates used in pharmaceuticals, chemical biology and natural products

Novel compositions and methods for trehalose phospholipids

Provided herein are compositions of trehalose phospholipids and uses thereof, e.g., compounds and compositions comprising 6,6'-diphosphatidyltrehalose (diPT) and analogs thereof with modifications of the diPT chemical scaffold, that bind and agonize Mincle, and the use thereof as adjuvants