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New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1 n-3 DPA has been achieved using the underutilized sp 3 -sp 3 Negishi cross coupling reaction and an alkyne hydrosilylation-protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthesis of the C10-C32 core structure of spirangien A is reported. The pivotal aldol coupling between both key intermediates provides a synthetic challenge in the synthesis of this complex natural product.

Callystatin A is a prominent member of a class of natural products which display promising growth inhibition of cancer cells in their biological profile. The challenging structure and the interesting biological activity of (-)-callystatin A fueled our interest in the synthesis of this marine natural product. We achieved the total synthesis using a highly convergent approach joining four subunits together with a Wittig olefination, a selective Heck reaction and an aldol reaction as the pivotal steps. The aldol reaction as one of the final transformations during the synthesis opens fast access to a variety of structural analogues and circumvents tedious protecting group manipulations. Here we report an improved synthesis utilizing a modified vinyl iodide which shortens the synthesis by two steps. Additionally, first biological results will be reported.

[reaction: see text] The enantioselective synthesis of callystatin A is described. The pivotal step in the synthesis is the stereoselective aldol reaction that generates the beta-hydroxy ketone moiety. Utilizing the allylic strain within the ethyl ketone precursor, we were able to generate the all-syn configuration of callystatin A. For the construction of the two diene moieties, both a Heck coupling and a Wittig reaction were employed.