We report on the covalent immobilization of the (S)-selective amine transaminase from Vibrio fluvialis (Vf-ATA) and its use in the synthesis of (S)-1-(5-fluoropyrimidin-2-yl)-ethanamine, a key intermediate of the JAK2 kinase inhibitor AZD1480. Immobilized Vf-ATA on glyoxyl-agarose (activity recovery: 30 %) was used in a packed-bed reactor to set-up a continuous flow biotransformation coupled with a straightforward in-line purification to circumvent the 2-step process described in literature for the batch reaction. The newly developed biotransformation was run in a homogeneous system including dimethyl carbonate as a green co-solvent. Optically pure (S)-1-(5-fluoropyrimidin-2-yl)-ethanamine (ee >99 %) was isolated in 35 % yield.
Use of Immobilized Amine Transaminase from Vibrio fluvialis under Flow Conditions for the Synthesis of (S)-1-(5-Fluoropyrimidin-2-yl)-ethanamine
Ferrandi EE;Vanoni M;Monti D;
2020
Abstract
We report on the covalent immobilization of the (S)-selective amine transaminase from Vibrio fluvialis (Vf-ATA) and its use in the synthesis of (S)-1-(5-fluoropyrimidin-2-yl)-ethanamine, a key intermediate of the JAK2 kinase inhibitor AZD1480. Immobilized Vf-ATA on glyoxyl-agarose (activity recovery: 30 %) was used in a packed-bed reactor to set-up a continuous flow biotransformation coupled with a straightforward in-line purification to circumvent the 2-step process described in literature for the batch reaction. The newly developed biotransformation was run in a homogeneous system including dimethyl carbonate as a green co-solvent. Optically pure (S)-1-(5-fluoropyrimidin-2-yl)-ethanamine (ee >99 %) was isolated in 35 % yield.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
