Stereoselective synthesis of γ-hydroxynorvaline through combination of organo- and biocatalysisElectronic supplementary information (ESI) available: Detailed description of each experiment, full characterisation of all compounds and copy of HPLC traces and NMR data. See DOI: 10.1039/c4cc06230b

• Main Authors: Simon, Robert C, Busto, Eduardo, Schrittwieser, Joerg H, Sattler, Johann H, Pietruszka, Jörg, Faber, Kurt, Kroutil, Wolfgang
• Format: Journal Article
• Language: English
• Published: 18.11.2014
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c4cc06230b

An efficient route for the synthesis of all four diastereomers of PMP-protected α-amino-γ-butyrolacton to access γ-hydroxynorvaline was established. The asymmetric key steps comprise an organocatalytic Mannich reaction and an enzymatic ketone reduction. Three reaction steps could be integrated in a one-pot process, using 2-PrOH both as solvent and as reducing agent. The sequential construction of stereogenic centres gave access to each of the four stereoisomers in high yield and with excellent stereocontrol. Stereoselective synthesis of all four diastereomers of PMP-protected γ-hydroxynorvaline via an organocatalytic Mannich reaction and an enzymatic ketone reduction.