High performance liquid chromatography (HPLC) of natural products part VI. Sulfoxides of penicillin N and cephalosporin c and their role in biosynthesis of β‐lactam antibiotics

Abstract

SummaryPure penicillin N a-sulfoxide (1) and penicillin N 8-sulfoxide (2) were obtained by HPLC and tested as substrates for deacetoxycephalosporin C synthetase (DXCS). Neither one of the sulfoxides was utilized under conditions of conversion of penicillin N (8) to deacetoxycephalosporin C (9). The cephalosporin C a-and 8-sulfoxides (3 and 4, resp.) were also prepared. Relative stabilities of the sulfoxidles 3 and 4 are discussed by interpretation of the I3C-NMR spectra.In a series of publications from our laboratories we have shown a convenient way to follow the isolation and identification of different metabolites from the fermentation broth using HPLC [2]. We have applied a similar technique lo the study of cell-free biosynthesis of p-lactam antibiotics [ 11.A penicillin N sulfoxide had been first suggested by Abraham & Newton (1965) [3] and later by Troonen et a/. (1976) [4] as a possible intermediate in the conversion of penicillin N (8) to deacetoxycephalosporin C (9). These assumptions were made on the basis of analogy with the nonbiological conversion of penicillin to cephalosporins first described by Morin et al. (1963) [5]. Baldwin et al. (1980) [6] mentioned, however, that there was no evidence of cephalosporin formation when 8-sulfoxide 2 or 5 of penicillin N and isopenicillin N, respectively, were added to protoplast lysates prepared from Cephalosporium unlike in the case where synthetic samples of (~-2-amino-6-adipyl)-~-cysteinyl-D-valine (6), isopenicillin N (7), or penicillin N (8) were added as precursors of the formation of deacetoxycephalosporin C (9).One of us [7] has suggested that biosynthesis of penicillin N (S), deacetoxycephalosporin C(9), and closely related substances could possibly be explained as proceeding I ) For part V, see [I].