Synthesis of a-Amino Acids via Hydantoin Intermediate

SCHEME 10.11 Synthesis of PHA-399733E 42 through Bucherer-Bergs hydantoin. 

The authors developed a scalable route for the synthesis of the intermediate core 45 in 12 steps and 0.4% yield and successfully implemented at a pilot plant scale. In this multistep synthesis, racemic hydantoin 43 was obtained after crystallization in 4 1 mixture of diastereomers. Separation of enantiomers by diastereomeric salt formation with (/ )-2-phenylglycerol and further crystallization followed by salt break gave single isomer (-)-44, with the targeted l-glutamic acid configuration. 

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