The biosynthesis of tropic acid: the stereochemical course of the mutase involved in hyoscyamine biosynthesis in Datura stramonium

Abstract

Incubation of (R,S)-DL-phenyl[2-³H]lactic acid with Datura stramonium generates hyoscyamine 2 with the tritium isotope located at C-3′ of the tropic acid ester moiety; the C-3′ hydroxymethyl group of 2 is converted into a chiral methyl group and is oxidised to generate chiral sodium acetate, with the (R) configuration (96% ee); the tritium is therefore located at the 3′-pro-S site of 2; it follows that the 3′-pro-R hydrogen is introduced with inversion of configuration by the mutase operating during hyoscyamine biosynthesis.