Enantioselective resolution of (R,S)-α-methyl-4-pyridinemethanol using immobilized biocatalyst: Optimization and kinetic modeling

- Kinetic resolution transesterification of (R,S)-α-methyl-4-pyridinemethanol.
- Vinyl acetate (acylating agent); conversion- 49.76% and 100% eep of R.
- Ping-pong bi-bi mechanism; (±)-α-methyl-4-pyridinemethanol inhibition.
- Activation energy 3.5 kcal/mol.

Being a valuable pharmaceutical intermediate, (R,S)-α-methyl-4-pyridinemethanol has remarkable significance in the formation of spiral structures and in their role as chiral auxiliary compounds. The kinetic resolution and mechanism of transesterification of (R,S)-α-methyl-4-pyridinemethanol were investigated using vinyl acetate as acyl donor and Novozym 435 as catalyst. The operational parameters were optimized using one factor at a time. The meticulous study of initial rate as well as progress curve of reaction has proven that the reaction follows the ping pong bi bi mechanism with negative association of α-methyl-4-pyridinemethanol-lipase dead end inhibitory complex which was then validated with parity plot of theoretical and experimental rate data. The developed process showed high stability of catalyst on the basis of its ease of separation and reusability.

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