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5-(2-Oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) is a natural product formed during bacterial synthesis of vitamin B2. It potently activates mucosal associated invariant T (MAIT) cells and has immunomodulatory, inflammatory, and anticancer properties. This highly polar and unstable compound forms a remarkably stable Schiff base with a lysine residue in major histocompatibility complex class I-related protein (MR1) expressed in antigen-presenting cells. Inspired by the importance of the ribityl moiety of 5-OP-RU for binding to both MR1 and the T cell receptor (TCR) on MAIT cells, each OH was removed in silico. DFT calculations and MD simulations revealed a very stable hydrogen bond between the C3'-OH and uracil N1H, which profoundly restricts flexibility and positioning of each ribityl-OH, potentially impacting their interactions with MR1 and TCR. By using deoxygenation strategies and kinetically controlled imine formation, four monodeoxyribityl and four monohydroxyalkyl analogues of 5-OP-RU were synthesised as new tools for probing T cell activation mechanisms.

The formal cycloaddition adduct of 1,4-benzoquinone with two equivalents of cyclopentadiene is a scaffold with two non-conjugated alkenes. Both alkenes undergo endo [4+2] cycloaddition with a diene to form a rigid U-shaped molecular cleft. Here we show experimental, computational and structural evidence that π interactions between the alkenes affect structural rigidity, Diels–Alder reactivity, cleft formation and host–guest capture.

Vor uber hundert Jahren begann Professor Julius Bredt seine Forschungskarriere auf dem Gebiet der verbruckten bicyclischen Systeme, die durch ein Bruckenkopf-Alken unter Ringspannung stehen. Seine kritischen Betrachtungen mundeten in der Formulierung dessen, was wir heute als die Bredtsche Regel kennen. Seitdem versuchen Physikochemiker, Theoretiker und Synthesechemiker gleichermasen, die Grenzen dieses physikalische Phanomens auszuloten, um es besser kennenzulernen. Der Bauplan der Natur sieht durchaus Bruckenkopf-Doppelbindungen nach der Bredtschen Regel vor. In diesem Aufsatz wird erstmals die Anwendung der Bredtschen Regel auf Naturstoffe umfassend erortert.

The total synthesis of ()-neovibsanin G and ()-14-epi-neovibsanin G has been accomplished, establishing the absolute configurations of these caged diterpenes as 11S, and confirming Fukuyama's postulated biosynthesis of the neovibsanins. Synthetic studies towards 15-O-methylneovibsanin F and 14-epi-15-O-methylneovibsanin F were undertaken based on the hypothesis that these methoxy substituted caged neovibsanins were artifacts of isolation, formed by the addition of methanol to the terminal alkenes of neovibsanin G and 14-epi-neovibsanin G. The results strongly suggest, however, that the methoxy caged neovibsanins are true natural products.

Well over a hundred years ago, Professor Julius Bredt embarked on a career pursuing and critiquing bridged bicyclic systems that contained ring strain induced by the presence of a bridgehead olefin. These endeavors founded what we now know as Bredt's rule (Bredtsche Regel). Physical, theoretical, and synthetic organic chemists have intensely studied this premise, pushing the boundaries of such systems to arrive at a better understood physical phenomenon. Mother nature has also seen fit to construct molecules containing bridgehead double bonds that encompass Bredt's rule. For the first time, this topic is reviewed in a natural product context.

Vibsanins are rare, structurally dense diterpenes, which occur exclusively in the Viburnum species. Despite the first reported isolation thirty one years ago, this natural product family has only attracted synthetic attention within the past decade. The aim of this article is to highlight the key accomplishments in the total synthesis of these unique natural products.

Key step is an EtAlCl2-mediated cascade leading to the bicyclo[3.3.]nonane core in one step.