Cephalosporin 3-deacetoxy

Cephalosporanic acid, 3 -deacetoxy-, 7, 289 Cephalosporin, 3 -deacetoxy-absorption, 7, 293 synthesis, 7, 293 Cephalosporin, 3,4-dihydro-synthesis, 7, 292 Cephalosporin, 7a-hydroxy-synthesis, 7, 290 Cephalosporin C, 7, 288 as pharmaceutical, 1, 152 total synthesis, 7, 294 Woodward s total synthesis, 7, 294 Cephalosporin C, deacetoxy-synthesis, 7, 292 Cephalosporins, 7, 267, 285-298 7-acylamino substituent configuration, 7, 290 analogues synthesis, 7, 288 as antibiotics, 2, 519 3, 1038 application, 7, 296... 

Figure 13.20 The 2-His-l-carboxylate facial triad illustrated for the resting state of deacetoxy-cephalosporin C synthase, an a-ketoglutarate-dependent mononuclear non-haem iron enzyme. (From Koehntop et al., 2005. With kind permission of Springer Science and Business Media.)... 

Deacetoxy/deacetylcephalosporin C synthase (DAOC/DACS), the enzyme isolated from Cephalosporium acremonium catalysing587 the ring expansion of penicillin N, 473, to deacetoxycephalosporin (DAOC), 474, and the hydroxylation of 474 to deacetylcephalosporin C(DAC), 475, which in vivo is acetylated by a different enzyme to give cephalosporin C, 476 (equation 284), converts also the unnatural substrate exomethylene cephalosporin C, 477a, directly to DAC, 475 (equation 285). 

SE Jensen, DWS Westlake, S Wolfe. Deacetoxy cephalosporin C synthetase and deacetoxycephalosporin C hydroxylase are two separate enzymes in Streptomyces clavuligerus. J Antibiot 38 263-265, 1985. 

MJ Rollins, SE Jensen, S Wolfe, DWS Westlake. Oxygen derepresses deacetoxy-cephalosporin C synthase and increases the conversion of penicillin N to cepha-mycin C in Streptomyces clavuligerus. Enzyme Microb Technol 12 40-45, 1990. 

S Kovacevic, BJ Weigel, MB Tobin, TD Ingolia, JR Miller. Cloning, characterization and expression of the Streptomyces clavuligerus gene encoding deacetoxy cephalosporin C synthase. J Bacteriol 171 754-760, 1989. 

S Kovacevic, MB Tobin, JR Miller. The (3-lactam biosynthesis genes for isopenicillin N epimerase and deacetoxy cephalosporin C synthase are expressed from a single transcript in Streptomyces clavuligerus. J Bacteriol 172 3952-3958, 1990. 

Deacetoxy cephalosporin C synthase (DAOCS) from Streptomyces ciavoiigerus... 

Ring expansion of penicillin N into deacetoxy cephalosporin C... 

HsC6-o-ch2-c-nh-M i COOCh3 0,1 N NaOH, Pvridin/Wasser 0 3 A 2-Deacetoxy-cephalosporin 45-60 273... 

Ospina S, Lopez-Munguia A, Gonzalez R et al. (1992) Characterization and use of a penicillin acylase biocatalyst. J Chem Technol Biotechnol 53 205-214 Ospina S, Barzana E, Ramirez O et al. (1996) Effect of pH in the synthesis of ampicilfinby penicillin acylase. Enzyme Microb Technol 19 462-469 Palazzi E, Converti A (2001) Evaluation of diffusional resistances in the process of glucose isomerization to fructose by immobilized glucose isomerase. Enzyme Microb Technol 28 246-252 Pan JL, Syu MJ (2004) A thermal study on the use of immobilized penidllin G acylase in the formation of 7-amino-3-deacetoxy cephalosporanic acid from cephalosporin G. J Chem Technol Biotechnol 79(10) 1050-1056... 

Pan JL, Syu MJ (2004) A thermal study on the use of immobilized penicillin G acylase in the formation of 7-amino-3-deacetoxy cephalosporanic acid from cephalosporin G. J Chem Technol Biotechnol 79(10) 1050-1056... 

This reaction has important application in the preparation of antibiotics containing deacetoxy-cephalosporin moiety. 

Figuic I The common pathway for biosynthesis of penicillins, cephalosporins, and cephamycins in bacteria and fungi. Abbreviations ACV, 5-(L a aminoadipyl) L CYsteinyl l>valine IPN, isopeni-cillin N 6-APA 6-aminopenicillanic add DAC, deacetylcephalosporin C DAOC. deacetoxy cephalosporin C OCDAC, o-carbamoyl-deacetoxycephalosiwrin C. The genes ate indicated in parentheses. 

Kovacevic S, Weigel BJ, Tobin MB, Ingolia TD, Miller JR. Oonir, chatacterization, and expression in Escherichia cofi of the Strepiomyces clasoiligerus gene encoding deacetoxy-cephalosporin C synthetase. J Bacterial 1989 171 754-756. 

Cantwell C, Beckmann R, Whiteman P, Queener SW, Abraham EP. Isolation of deacetoxy cephalosporin C from fermentation broths of PeninUium chntsogenum tTansformanls Con> struction of a new fungal Nosynthetic pathway Pioc R Soc Lond B 1992 248 283-289,... 

Similarly, deacetoxy-Zdeacetylcephalosporin synthase C (DOAC/DAC synthase) catalyzes enzymatic ring expansion of penicillin N to deacetoxy- and deacetyl-cephalosporin C as shown in eq. (21) in the presence of Fe, a-ketoglutaric acid. The enzyme has been purified from stereptomyces clavuligerus, Mr 36 kDa [346, 347] and recombinant streptomyces clavulgerus [348]. A mechanism involving iron(IV) oxene formed from ferrous iron has been proposed [349,350]. 

Fujisawa et al. (304) provided further evidence that deacetoxy-cephalosporin C was converted to deacetylcephalosporin C by isolating the latter compound from a cell-free system of C. acremonium to which deacetoxycephalosporin C had been added. After purification by chromatography and electrophoresis the product was examined by t.l.c. and u.v. and i.r. spectroscopy. It was found to be indentical with authentic deacetylcephalosporin C. 

Yoshida, M.,T. Konomi, M. Kohsaka, J. E. Baldwin, S. Herchen, P. D. Singh, N. A. Hunt, and A. L. Demain Cell-Free Ring Expansion of Penicillin N to Deacetoxy-cephalosporin C by Cephalosporium acremonium CW-19 and its Mutants. Proc. Natl. Acad. Sci. USA 75, 6253 (1978). 

No significant ring expansion to deacetoxy-cephalosporin occurred, presumably because Fe, ascorbic acid, and ATP are needed for this reaction). 

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