Convenient Synthesis of the Antibiotic Linezolid via an Oxazolidine‐2, 4‐dione Intermediate Derived from the Chiral Building Block Isoserine1. Issue 34 (28th October 2014)

• Record Type: Journal Article
• Authors: Greco, Arianna; De Marco, Rossella; Tani, Sara; Giacomini, Daria; Galletti, Paola; Tolomelli, Alessandra; Juaristi, Eusebio; Gentilucci, Luca
• Is Part Of: European journal of organic chemistry. Issue 34(2014)
• Page Start: 7614
• Page End: 7620
• Publication Date: 2014-10-28
• Subjects: Medicinal chemistry -- Asymmetric synthesis -- Antibiotics -- Amino acids -- Nitrogen heterocycles; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402888
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: 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. Abstract : 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.