Eine Prins‐Cyclisierung eines polymergebundenen Aldehyds mit einem Homoallylalkohol ist der Schlüsselschritt einer Synthese von Tetrahydropyran‐Derivaten. Ein phänotypisches Screening identifizierte Mitose‐Inhibitoren (zu erkennen an der Anreicherung runder Zellen mit verdichteter DNA und Membranbläschen; siehe Bild). Diese erhalten den Namen Tubulexine, da sie an das CSE1L‐Protein und die Bindungsstelle der Vinca‐Alkaloide im Tubulin binden.

Macrocyclic natural products (NPs) and analogues thereof often show high affinity, selectivity, and metabolic stability, and methods for the synthesis of NP-like macrocycle collections are of major current interest. We report an efficient solid-phase/cyclorelease method for the synthesis of a collection of macrocyclic depsipeptides with bipartite peptide/polyketide structure inspired by the very potent F-actin stabilizing depsipeptides of the jasplakinolide/geodiamolide class. The method includes the assembly of an acyclic precursor chain on a polymeric carrier, terminated by olefins that constitute complementary fragments of the polyketide section and cyclization by means of a relay-ring-closing metathesis (RRCM). The method was validated in the first total synthesis of the actin-stabilizing cyclodepsipeptide seragamide A and the synthesis of a collection of structurally diverse bipartite depsipeptides.

A Prins cyclization between a polymer-bound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.