Chemoenzymatic Synthesis of Hyoscyamine

doi:10. 3969 / j. issn. 2096-2266. 2026. 04. 004

Abstract

Abstract: Objective：To establish an efficient synthetic method for hyoscyamine based on a chemoenzymatic strategy. Methods:
Acetyl-protected 2-phenyl-1,3-propanediol was used as the starting material. A chiral monoalcohol intermediate was constructed
through porcine pancreatic lipase (PPL)-catalyzed desymmetrization, followed by oxidation in a Fe(NO₃)₃/KCl catalytic system to generate
the tropic acid fragment. The key ester bond was then formed through acyl chlorination and esterification with tropine, followed by
deacetylation to afford the target product, L-hyoscyamine. Results: The PPL-catalyzed desymmetrization exhibited good regioselectivity
and stereoselectivity. The target product was successfully obtained through subsequent oxidation and esterification reactions. The
synthetic route consisted of five steps with an overall yield of 53.6%. Conclusion: The established chemoenzymatic strategy effectively
integrates the high selectivity of biocatalysis with the efficiency of chemical transformation, providing a new approach for the green syn⁃
thesis of tropane alkaloids.

Key words: chemoenzymatic synthesis, hyoscyamine, chiral construction, total synthesis

CLC Number:

R284.3

Wang Xueqian¹, Tian Hongchang, Duan Baozhong, Zhang Lei, . Chemoenzymatic Synthesis of Hyoscyamine[J]. Journal of Dali University, 2026, 11(4): 21-27.

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