Enzyme-like polyene cyclizations catalyzed by dynamic, self-assembled, supramolecular fluoro alcohol-amine clusters

Abstract

Terpene cyclases catalyze one of the most powerful transformations with respect to efficiency and selectivity in natural product (bio)synthesis. In such polyene cyclizations, structurally highly complex carbon scaffolds are built by the controlled ring closure of linear polyenes. Thereby, multiple C,C bonds and stereocenters are simultaneously created with high precision. Structural pre-organization of the substrate carbon chain inside the active center of the enzyme is responsible for the product- and stereoselectivity of this cyclization. Here, we show that in-situ formed fluorinated-alcohol-amine supramolecular clusters serve as artificial cyclases by triggering enzyme-like reactivity and selectivity by controlling substrate conformation in solution. Because of the dynamic nature of these supramolecular assemblies, a broad range of terpenes can be produced diastereoselectively. Mechanistic studies reveal a finely balanced interplay of fluorinated solvent, catalyst, and substrate as key to establishing nature’s concept of a shape-selective polyene cyclization in organic synthesis.

Controlling the regioselectivity of the bromolactonization reaction in HFIP

“…S6 in the ESI† for more details). This result is in agreement with the fact that HFIP has an exceptional cation stabilization ability 6 a ,20 due to the low nucleophilicity and high dielectric constant, and, thus, the stepwise mechanism is supposed to be the preferable pathway. 16 b…”

Integrating Enzymes with Supramolecular Polymers for Recyclable Photobiocatalytic Catalysis

“…[6] To date, the concepts of supramolecular chemistry have been widely utilized for a diverse range of applications, including molecular selfassembly for the development of smart materials and molecular recognition for catalysis. [7] A significant advantage of supramolecular systems is their inherent multifunctionality, which can be precisely controlled through bottom-up molecular design. [8] These distinctive characteristics have spurred the integration of synthetic supramolecules with biomolecules to create novel functionalities.…”

Biomimetic chlorine-induced polyene cyclizations harnessing hypervalent chloroiodane–HFIP assemblies

“…Unfortunately, most transformations lacked any diastereoselection. Our group recently published a haliranium-mediated polyene cyclization protocol 8 n using HFIP 13 emulating the intrinsic features of terpene cyclases. 1,14 This method is in principle applicable to chlorine-assisted ring closures but here we were able to target just a small set of electron-rich alkenes 1 (6 examples) albeit with good diastereomeric excess.…”