Chemo-Enzymatic Synthesis of Unnatural AminoAcids

摘要

A general chemo-enzymatic process has been developed toprepare enantiomerically pure L- and D-amino acids in highyield by deracemisation of racemic starting materials. Themethod has been developed from initial academic studies to bea robust, scalable industrial process. Unnatural amino acids, inhigh optical purity, are a rapidly growing class ofintermediates required for pharmaceuticals, agrochemicals andother fine chemical applications. However, no single methodhas proven sufficiently adaptable to prepare these compoundsgenerally at large scale. Our approach uses an enantioselectiveoxidase biocatalyst and a non-selective chemical reducingagent to effect the stereoinversion of one enantiomer and canresult in an enantiomeric excess of > 99 % from a startingracemate, and product yields over 90 %. The current approachcompares very favourably to resolution methods which have amaximum single pass yield of 50 %. Efficient methods havebeen developed to adapt the biocatalyst used in this processtowards new target compounds and to optimise key factorswhich improve the process efficiency and offer competitiveeconomics at scale.