Scalable and Cost-Effective Synthetic Process for the Preparation of l-3,4-Dihydroxyphenylalanine─Levodopa

Abstract

We reported the development of a novel synthetic process for Levodopa (1), which involves two simple chemical steps. The first step includes the reaction of L-tyrosine (18) with aqueous hydrogen bromide (HBr) to yield 3-bromo-L-tyrosine (19). The second step involves hydroxylation using an alkali base and copper iodide as a catalyst to produce Levodopa (1) with good quality and an overall yield of 41.75%. This new synthetic approach offers several advantages, including good reactivity, low cost, mitigation of the poor solubility issues associated with the reported process, and finally, it is industrially viable and capable of controlling the quality of the final Levodopa drug substance.