Stereocontrolled Synthesis of α-Branched Tetrahydropyrans by a One-Pot-Two-Step Photobiocatalytic Cascade of Citronellol

Journal Article (2026)
Author(s)

Claudio Zippilli (University of Tuscia)

Elisa De Marchi (University of Tuscia)

Beatrice Di Maio (University of Tuscia)

Raffaele Saladino (University of Tuscia)

Greta Donati (Università degli Studi di Napoli Federico II)

Francesco Saverio Di Leva (Università degli Studi di Napoli Federico II)

Frank Hollmann (TU Delft - BT/Biocatalysis)

Lorenzo Botta (University of Tuscia)

DOI related publication
https://doi.org/10.1021/acs.jnatprod.5c01352 Final published version
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Publication Year
2026
Language
English
Journal title
Journal of Natural Products
Issue number
2
Volume number
89
Pages (from-to)
539-547
Downloads counter
13
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Abstract

The monoterpene citronellol often represents the substrate for the synthesis of other natural products and fragrances bearing α-branched tetrahydropyran moieties. In this contribution, we developed a process that combines in one-pot condition photocatalytic Schenck-ene reaction and biocatalytic halocyclization to synthesize enantiopure α-branched tetrahydropyrans starting from natural monoterpene citronellol. The reaction pathway of the enzymatic haloetherification, studied by combining experimental and theoretical studies, showed for the first time the key role played by the hydroperoxide functional group in the control of the regioselectivity of the cyclization step. Overall, a novel and sustainable synthetic procedure is reported as a new approach for α-branched tetrahydropyrans.

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