Antibiotics semisynthetic

Use antibacterial in combination with 3-lactam antibiotics, semisynthetic P-iactamase inhibitor... 

Figure 6.37 shows the two-dimensional structure of cephalosporin C, a compound first isolated from mold cultures of Cephalosporium acremonium in 1948. Cephalosporin C exhibits weak antibacterial effect, but the modification of side chains of the molecule generates cephalosporins having diverse antibacterial activity [105]. Cephalosporins are p-lactam antibiotics, semisynthetically produced from cephalosporin C. 

C22H45N50j2 571.624 Aminoglycoside antibiotic. Semisynthetic. Active against a wide range of pathogenic bacteria, including many gentimicin-resistant strains. Log P -8.99 (uncertain value) (calc). 

CisHjjNjOii 461.385 Nucleoside antibiotic. Semisynthetic. Antifungal agent. Sol. H2O poorly sol. MeOH, hexane. Mp 190° dec. [a] ... 

Other Reactions. The reaction of Thydioxybenzaldehyde with sodium cyanide and ammonium chloride, Strecker synthesis, yields /J-hydroxyphenylglycine [938-97-6] a key intermediate in the manufacture of semisynthetic penicillins and cephalosporins (see Antibiotics, p-LACTAMs). 

Pharmaceuticals. -Hydroxybenzaldehyde is often a convenient intermediate in the manufacture of pharmaceuticals (qv). For example, 2-(p-hydroxyphenyl)glycine can be prepared in a two-step synthesis starting with -hydroxybenzaldehyde (86). This amino acid is an important commercial intermediate in the preparation of the semisynthetic penicillin, amoxicillin (see ANTIBIOTICS, P-LACTAMs). Many cephalosporin-type antibiotics can be made by this route as well (87). The antiemetic trimethobenzamide [138-56-7] is convenientiy prepared from -hydroxybenzaldehyde (88) (see Gastrointestinal agents). 

The sulfa dmgs are stiH important as antimicrobials, although they have been replaced in many systemic infections by the natural and semisynthetic antibiotics. They are of great value in third world countries where problems of storage and lack of medical personnel make appropriate use of antibiotics difficult. They are especially useful in urinary tract infections, particularly the combination of sulfamethoxazole with trimethoprim. Their effectiveness has been enhanced by co-adniinistration with dihydrofolate reductase inhibitors, and the combination of sulfamethoxazole with trimethoprim is of value in treatment of a number of specific microbial infections. The introduction of this combination (cotrimoxazole) in the late 1960s (1973 in the United States) resulted in increased use of sulfonamides. 

Most of the new commercial antibiotics have resulted from semisynthetic studies. New cephalosporkis, a number of which are synthesized by acylation of fermentation-derived 7-amkiocephalosporanic acid, are an example. Two orally active cephalosporkis called cefroxadine and cephalexin are produced by a synthetic ring-expansion of penicillin V. 

G. Lancini and W. ZanicheUi, in Structure-Activity Relationships Among Semisynthetic Antibiotics, Academic Press, New York, 1977, pp. 531—600. 

Worldwide retail antibiotic sales in 1986 were approximately 11 biUion of which penicillins comprised approximately 2.5 biUion (66). Preparations containing ampicillin are estimated at 800 million whereas those containing amoxicillin are estimated at 1,020 million. Total sales include sales of ampicillin esters and the iireidopenicillins derived from ampicillin. Total sales of penicillins, including semisynthetic penicillins in the United States in 1987, were 25 million (67). Sales of amoxicillin, the largest single selling penicillin, were approximately 350 million. 

The cost of 6-APA, ampicillin, and amoxicillin is invariably linked to that of penicillin G. 6-APA remains one of the cheapest raw starting materials available for the preparation of semisynthetic penicillins and other related P-lactam antibiotics. 

Semisynthetic Derivatives. No significant improvements in activity have resulted from modifications of the 3-, 9-, 2and/01 4"-hydioxyl groups (314). 3 -0-Acyl derivatives have not been found via fermentation, but chemical acylation of the 3 -hydroxyl group yields products having good antibiotic activity and better pharmacokinetics than the patent macroHdes. Two such compounds have been developed (315,316) ... 

The total U.S. antibiotic market for 1990 was about 4.73 biUion, 233 million of that was tetracyclines. The development of the semisynthetic P-lactam antibiotics (see Antibiotics, P-LACTAMs) and emergence of resistance to the tetracyclines has steadily diminished the clinical usefulness of tetracyclines. 

Antimicrobial spectrum, pharmacodynamic and phamacokinetic characteristics of rifabutin, a long-acting antituberculosis semisynthetic antibiotic of rifam-icin group 99MI13. 

Use antibacterial, semisynthetic p-lactam antibiotic, derivative of ampicillin (prodrug for ora application)... 

There are several clinically important tetracyclines, characterized by four cyclic rings (Fig. 5.7). They consist of a group of antibiotics obtained as by-products horn the metabohsm of various species of Streptomyces, although some members m now be thought of as being semisynthetic. Thus, tetracycline (by catalytic hydrogenation) and... 

The manufacture of benzylpenicillin (penieillin G, originally just penicillin ) is chosen as a model for the antibiotic production process. It is the most renowned of antibioties and is the first to have been manufactured in bulk. It is still universally prescribed and is also in demand as input material for semisynthetic antibiotics (Chapter 5). Developments associated with the penicillin fermentation process have been a significant factor in the development of modem bioteehnology. It was a further 30 years, i.e. not until the 1970s, before there were signifieant new advances in industrial fermentations. 

Benzylpenicillin is produced as various salts according to its intended use, whether as an input to semisynthetic /3-lactam antibiotics manufacture or for clinical use in its own right. 

Fig. 2.2 illustrates the three types of chemicals by reference to the production of the semisynthetic penicillin antibiotic, ampicillin. 

Suloff, E. C Comparative study of semisynthetic derivative of natamycin and the parent antibiotic on the spoilage of shredded cheddar cheese. Thesis, Virginia Polytechnic Institute and State University, Blacksburg, VA, 1999, http // scholar. lib. vt.edu/theses/available/etd-... 

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