In:
Liebigs Annalen, Wiley, Vol. 1996, No. 11 ( 1996-11), p. 1743-1749
Abstract:
HR 916 K ( 5 ), the 1‐( S )‐(pivaloyloxy)ethyl prodrug ester of the cephalosporin cefdaloxime, exhibits a significantly higher oral bioavailability than the 1‐( R ) diastereomer HR 916 J. An efficient synthesis of HR 916 K was developed. The separation of the diastereomers was achieved by precipitation of the 1‐( R )‐hydrochloride 9 followed by crystallization of the 1‐( S )‐amine 10 (de 〉 96%). The 1‐( R ) diastereomer 9 was recycled by acidic saponification or enzymatic cleavage to AMCA ( 7 ). The amine 10 was acylated with mercaptobenzothiazole thioesters or mixed anhydrides, prepared from carboxylic acids 13 and 14 , in almost quantitative yield. Deprotection of the oxime and formation of the tosylate proceeded in one step. Using thioester 18 , we obtained HR 916 K ( 5 ) from AMCA ( 7 ) in 42% yield.
Type of Medium:
Online Resource
ISSN:
0947-3440
DOI:
10.1002/jlac.v1996:11
DOI:
10.1002/jlac.199619961107
Language:
English
Publisher:
Wiley
Publication Date:
1996
detail.hit.zdb_id:
1475010-7
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