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Desacetyl cephalosporin

A microorganism with the required activity was found as Glaxo were already developing esterases to convert cephalosporin C into desacetyl cephalosporin C and some of these proved able to prodnce cefuroxime and to be cost effective on a process scale (Figure 4.9). [Pg.131]

Desacetylation of cephalosporins occurs in liver and kidney via the activity of acetylesterases. Desacetylated cephalosporins all maintain some antibacterial activity. Desacetylcefotaxime penetrates well extra vascular body sites, achieves high tissue concentrations and acts synergistically with cefotaxime [94,95]. Desacetylation of cephaloglycin, cephalothin and cephapiiin resulted in formation of less active desacetyl forms [94] and less toxicity [64]. About 50% of cephaloglycin is metabolized to desacetylcephloglycin, which is less nephrotoxic at... [Pg.305]

The structure of cephalosporin C, a 3-lactam antibiotic, is shown in Figure 1. Under neutral, but especially basic conditions, it is hydrolyzed to desacetyl cephalosporin C. In acid cephalosporin C lactone is formed (1,2) (both of these are shown in Figure 1). In order to minimize these degradations, it is important that cephalosporin C broth be processed rapidly, avoiding extremes of pH and keeping temperatures low. [Pg.158]

Substitution of the 7 -amino side chain is accomplished by non-aqueous cleavage of the a-aminoadipyl group to yield 7-aminocephalos-poranic acid (7ACA). Reacylation at the 7-amino site by the desired substituent is carried out in a subsequent step. By contrast, substitution at C 3 is usually accomplished by a direct displacement of the acetoxy by the new group. Obviously, neither desacetyl cephalosporin C nor cephalosporin C lactone can participate in that substitution reaction. [Pg.163]

No discussion of cephalosporin C isolation would be complete without some comment on desacetyl cephalosporin C. This compound, always present in significant quantity in broth, besides being a neutral and high pH degradation product of cephalosporin C (2,61), is also produced enzymatically by endogenous or contaminant esterases. [Pg.170]

Figure 14 depicts the final step in cephalosporin C synthesis as being the enzymatic acetylation of desacetyl cephalosporin C with acetylcoenzyme A. This step, however, only occurs intracellularly, and exogenous desacetyl cephalosporin C is not reabsorbed (62,63). [Pg.172]

Chemical acetylation of the 3-hydroxymethyl to reform cephalosporin C is complicated by the competing lactonization reaction. This problem is avoided by reacting a desacetyl cephalosporin C derivative salt with acetic anhydride in a non-aqueous system. In the example shown in Figure 15, the triethylamine salt of N-phthaloyl desacetyl cephalosporin C is converted to N-phthaloyl cephalosporin C in dimethylformamide. If the acetoxy group is to be subsequently displaced, other acid anhydrides can be used to prepare other C-3 esters (64). A variation of this approach, also shown in Figure 15, is to react the desacetyl derivative with diketene, which yields the acetoacetate ester (65). [Pg.172]

The extractive esterification method mentioned earlier allows the desacetyl cephalosporin C derivative to be reacylated without lactone formation since the C-4 carboxyl ester does not readily participate in the lactonization reaction. For the same reason, it is possible to form a 3-halomethyl derivative of cephalosporin C from desacetyl cephalosporin ester, with the resulting halide readily displaced by the desired C-3 substituent. These reactions are shown in Figure 16. (41)... [Pg.172]

Figure 14. Last step in biosynthesis of cephalosporin C and exogenous derivation of desacetyl cephalosporin C. Figure 14. Last step in biosynthesis of cephalosporin C and exogenous derivation of desacetyl cephalosporin C.
Figure 15. Non-aqueous acylation of 3-hydroxymethyl group of N-substituted desacetyl cephalosporin C. Figure 15. Non-aqueous acylation of 3-hydroxymethyl group of N-substituted desacetyl cephalosporin C.
Wildfeuer ME. Aqueous acetylation of desacetyl glutaryl 7-amino-cephalosporanic acid (7ACA) and speculation on the origin of desacetyl cephalosporin C in fermentatitm broth. J Arttibiot 1994 47 64-71. [Pg.750]

Urinary excretion is the major elimination path for most cephalosporins. When prescribing cephalosporins to patients with renal failure, practitioners must consider dose reduction or dose interval extension (Table 45.2). Renal tubular secretion contributes to the elimination of some cephalosporins, and an increase in cephalosporin plasma concentrations may occur when probenecid blocks renal tubular secretion of cephalosporins. Biliary elimination is important for some cephalosporins. Cefmetazole, cefoperazone (Cefobid), cefoxitin, and ceftriaxone achieve biliary concentrations greater than those in plasma. After parenteral administration of cefoperazone, 70% of the dose appears in the bile within 24 hours. Practitioners should decrease the dose of cefoperazone when prescribing for patients with hepatic failure or biliary obstruction. Metabolism is not a major elimination path for most cephalosporins. Cefotaxime is one of the few cephalosporins having an active metabolite, desacetyl cefotaxime. [Pg.533]

Initially we evaluated potential routes via the desacetyl derivative of II, namely 7-glutaroylamino-3-hydroxymethylceph-3-em-4-carboxylic acid. It was known that several microorganisms deacetylate cephalosporins in high yield. However, evaluation of the literature and review of the production plant requirements to adopt a route to convert 3-hydroxymethyl cephalosporins to 3-H cephalosporins dissuaded us from this option.28... [Pg.222]

Pharmacokinetics. Usually, cephalosporins are excreted unchanged in the urine, but some, including cefotaxime, form a desacetyl metabolite which possesses some antibacterial activity. Many are actively secreted by the renal tubule, a process which can be blocked with probenecid. As a rule, the dose of cephalosporins should be reduced in... [Pg.221]

Cephalosporins such as cephalothin, cephalogly-cin, cephapirin, cephacetrile and cefotaxime share an acetoxymethyl group at the position 3 (Figure 2) and are all metabolically converted to desacetyl derivatives and to the antibacterially inactive lactone of these substances. [Pg.177]

N-ACYLAMINOCEPHALOSPOR-ANIC ACIDS O-DESACETYL DERIVATIVES (cf., cephalosporins)... [Pg.33]

Cephalosporin derivatives and their desacetyls and lactones moved however, cephalosporin C itself and its desacetyl and lactone derivatives failed to move in this system... [Pg.89]


See other pages where Desacetyl cephalosporin is mentioned: [Pg.135]    [Pg.160]    [Pg.170]    [Pg.183]    [Pg.108]    [Pg.135]    [Pg.160]    [Pg.170]    [Pg.183]    [Pg.108]    [Pg.306]    [Pg.120]   
See also in sourсe #XX -- [ Pg.87 , Pg.103 , Pg.108 ]




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