Clarifying Problems in the Synthetic Pathway Towards Methylene-Type Levodopa Acylals as Potential Prodrugs

Here, we report a practical synthetic pathway towards levodopa (l-DOPA) acylals with a special emphasis on problems occurring during preparation, low yields or unmanageable side reactions, and how to circumvent them. The key step can be performed rapidly by microwave irradiation in a green chemistry manner. Final compounds can be achieved after deprotection approaches but exhibit inadequate properties in terms of stability, thwarting the adaptation of the double ester concept discussed here to the important active pharmaceutical ingredient levodopa. However, a future outlook is provided, discussing potential structural and chemical changes for stable levodopa acylals.