Abstract EN:

In the context of Al Mourabit biogenetic hypothesis for the marine pyrrolimidazoles alkaloids, and in order to address their biomimetic syntheses in the best conditions, I was assigned to prepare substancial amounts of four of them, namely oroidine, clathrodine, hymenidine and 3-amino-1-(2-aminoimidazolyl)-prop-1-ene by having recourse to a disclosed procedure (Lindel protocol) as the first stage of the venture. Instead, I formulated a new, general vision for their preparation which contemplates resort to the unknown and quite daunting coupling between a 1,2-dihydropyridine and a guanidine derivative under oxidative conditions followed by a challenging aromatisation. Efforts met with success, rendering this strategy the most robust way to reach these four molecules. Concerning my work in Sinaÿ’s laboratory, the goal was the assignment of the stereochemistry at C6’ of the nucleoside antibiotic Miharamycine B. In this regard, my efforts were directed toward the synthesis of the two diastereomers with respect to C6’. Early before my arrival, the necessary chemistry for fashioning the tetrahydrofuran sector of Miharamycine B had been implemented. The remaining issues that had to be addressed in this project were the installation of the purine base by a carefully regiocontrolled N-glycosylation, followed by an amidic coupling with an arginine. These two reactions were successfully conducted on one epimer, setting the stage for the final hydrogenolysis step which unfortunately turned out to be problematic. Among many other impedimenta, unsufficient quantities of the final dipeptide intermediate thwarted the success of the enterprise.