Abstract
Cefcapene pivoxil monohydrochloride monohydrate, a broad spectrum
third-generation cephalosporin for oral administration, was prepared
by reacting three centers of 7β-amino-3-(hydroxymethyl)cephalosporinic
acid (7-HACA), derived from 7β-aminocephalosporanic acid.
The coupling of 7-HACA and (Z )-2-[2-(Boc-amino)thiazol-4-yl]pent-2-enoic
acid, followed by carbamylation with chlorosulfonyl isocyanate,
and precipitation with diisopropylamine gave the key intermediate,
in which thiazole side chain and carbamoyl group had been introduced
into the 7-amino and 3-hydroxymethyl groups of 7-HACA, respectively,
in a continuous procedure. Afterwards, the intermediate was esterified
with pivaloyloxymethyl iodide to complete the modification of the
C4 carboxy group affording Boc-cefcapene pivoxil, from which the desired
product was finally obtained by an economical Boc removal and successive
formation of the hydrochloride in 36% overall yield on
a decagram scale. This synthesis promises an easy entry to cefcapene
pivoxil monohydrochloride monohydrate with convenient manipulation,
simple isolation, and good yields; it is of potential value for
production on an industrial scale.
Key words
antibiotics - cephalosporins - cefcapene pivoxil - 7-ACA - carbamylation - semisynthesis
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