The Combination of Hydroformylation and Biocatalysis for the Large-Scale Synthesis of (S)-Allysine Ethylene Acetal

The compound, (S)-2-amino-5-[1,3]dioxolan-2-yl-pentanoic acid [(S)-allysine ethylene acetal], is a key intermediate in a number of angiotension-I converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors currently in clinical trials. Through a combination of our hydroformylation and biocatalysis technologies we have developed an efficient five-step synthetic route to this material starting from crotonaldehyde. The development of this process, leading to a large-scale commercial manufacturing campaign, is described in this paper.