Convenient Synthesis of the Antibiotic Linezolid via an Oxazolidine-2,4-dione Intermediate Derived from the Chiral Building Block Isoserine

We describe a new synthesis of the 5‐(aminomethyl)oxazolidin‐3‐one core of linezolid in enantiomerically pure form. The expedient cyclization of the α‐hydroxy amide derived from isoserine and 3‐fluoro‐4‐morpholinoaniline to give the corresponding (aminomethyl)oxazolidine‐2,4‐dione, followed by its m...

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Bibliographic Details
Published in:European journal of organic chemistry 2014-12, Vol.2014 (34), p.7614-7620
Main Authors: Greco, Arianna, De Marco, Rossella, Tani, Sara, Giacomini, Daria, Galletti, Paola, Tolomelli, Alessandra, Juaristi, Eusebio, Gentilucci, Luca
Format: Article
Language:English
Subjects:
Amino acids
Antibiotics
Asymmetric synthesis
Medicinal chemistry
Nitrogen heterocycles
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Summary:We describe a new synthesis of the 5‐(aminomethyl)oxazolidin‐3‐one core of linezolid in enantiomerically pure form. The expedient cyclization of the α‐hydroxy amide derived from isoserine and 3‐fluoro‐4‐morpholinoaniline to give the corresponding (aminomethyl)oxazolidine‐2,4‐dione, followed by its mild selective reduction at the C(4)‐position, gave linezolid in almost quantitative overall yield. The 1,3‐oxazolidin‐2‐one core of linezolid was obtained from isoserine in just three steps and with almost quantitative overall yield; the key features of the protocol are the expedient formation of the intermediate oxazolidine‐2,4‐dione, and its regioselective reduction at the 4‐position.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201402888