Back in Person: Frontiers in Medicinal Chemistry 2023.

The Frontiers in Medicinal Chemistry (FiMC) is the largest international Medicinal Chemistry conference in the German speaking area and took place from April 3rd to 5th 2023 in Vienna (Austria). Fortunately, after being cancelled in 2020 and two years (2021-2022) of entirely virtual meetings, due to the COVID-19 pandemic, the FiMC could be held in a face-to-face format again. Organized by the Division of Medicinal Chemistry of the German Chemical Society (GDCh), the Division of Pharmaceutical and Medicinal Chemistry of the German Pharmaceutical Society (DPhG), together with the Division of Medicinal Chemistry of the Austrian Chemical Society (GÖCH), the Austrian Pharmaceutical Society (ÖPhG), and a local organization committee from the University of Vienna headed by Thierry Langer, the meeting brought together 260 participants from 21 countries. The program included 38 lectures by leading scientists from industry and academia as well as early career investigators. Moreover, 102 posters were presented in two highly interactive poster sessions.

Total synthesis of cyclomarins A, C and D, marine cyclic peptides with interesting anti-tuberculosis and anti-malaria activities.

Cyclomarins are cyclic heptapeptides containing four unusual amino acids. New synthetic protocols toward their synthesis have been developed, leading to the synthesis and biological evaluation of three natural occurring cyclomarins. Interestingly, cyclomarins address two completely different targets: Clp C1, a subunit of the caseinolytic protease of Mycobacterium tuberculosis (MTB), as well as PfAp3Ase of Plasmodium falciparum. Therefore, cyclomarins are interesting lead structures for the development of drugs against tuberculosis and malaria.

Total synthesis of desoxycyclomarin C and the cyclomarazines A and B.

Removing the ß-hydroxy group from the prenylated tryptophan moiety of cyclomarins simplifies the synthesis of these interesting natural products significantly, without having a noteworthy effect on the anti-tuberculosis activity of the cyclomarins. In contrast, cyclomarazines did not show biological activity.

Total Synthesis of Cyclomarin A, a Marine Cycloheptapeptide with Anti-Tuberculosis and Anti-Malaria Activity.

An efficient synthetic protocol for the stereoselective synthesis of cyclomarin A is reported. Key steps in the syntheses of the building blocks are an asymmetric chelate-enolate Claisen rearrangement, an asymmetric hydrogenation, and highly diastereoselective additions of organozinc and -titanium reagents.

Synthesis of fully protected, reverse N-prenylated (2S,3R)-3-hydroxytryptophan, a unique building block of the cyclomarins.

Reverse N-prenylated 3-hydroxytryptophan, the rather exotic amino acid of the cyclomarins, is obtained in enantio- and diastereomerically pure and fully protected form by a combination of a highly stereoselective addition of a zincated indole toward protected serinal and subsequent palladium-catalyzed N-prenylation.

Stereoselective synthesis of deuterium-labeled (2S)-cyclohexenyl alanines, biosynthetic intermediates of cinnabaramide.

Dideuterated ß-cyclohexenylalanines, proposed biosynthetic intermediates of the cinnabaramides, can be obtained from chiral alkynols via a sequence of Irland-Claisen rearrangement, ring closing metathesis, and radical decarboxylation. Feeding experiments indicate that both (2S)-ß-cyclohexenylalanines can be incorporated into cinnabaramide, while the configuration at the cyclohexenyl ring does not restrict biosynthetic processing.