Synthetic antibiotics

Fig. 1. Mode of action on selected antibiotics. Synthetic antibiotics are underlined.

Quinone antitumor antibiotics, synthetic studies of 88YGK801. Synthetic studies toward CC-1065, PDE-I, and PDE-II 87H(25)701. 

Antibacterial antibkitics. 299-.364. See also Antibiotics synthetic. 247-252 Antibiotics... 

Monocyclic -lactam antibiotics, synthetic approaches to 84BSB571. 

Enzymatic Formation of Semi-synthetic Antibiotics Synthetic Processes... 

Either neutral or charged carrier molecules (e.g. crown ethers, natural antibiotics, synthetic ionophores, etc.) can be doped into polymeric membranes to achieve desired selectivities. However, despite successes in the fabrication of selective and stable cation electrodes (1-5), the development of analogous devices for anions has thus far been limited by the inability to identify appropriate anion-selective ionophores. 

Turanek J, Zaluska D, Neca J. Link of a fast protein liquid chromatography system with a stirred thermostated cell for sterile preparation of liposomes by the proliposome-Uposome method appUcation to encapsulation of antibiotics, synthetic peptide immu-nomodulators, and a photosensitizer. Anal Biochem 1997 249 131-9. 

Nucleoside antibiotic. Synthetic. Inhibits bacterial ribosomal binding. Micro-cryst. Mp 205-207° dec. [a]o +4.5 (c, 0.7 in CHCI3). Log P -1.47 (uncertain value) (calc). 

Nucleoside-type antibiotic. Synthetic. Antineoplastic and antiviral agent. Cryst. (2-propanol). Mp 131-133 . 

The modular and elegant programming characteristic of antibiotics synthetic process has provided us varieties of functional elements gathered from natural product biosynthetic pathways. Based on type of catalyzed reaction or specificity of substrate and product, all natural and artificial modified elanents can be categorized in synthetic... 

Methyl acetoacetate (MAA) and ethyl acetoacetate (EAA) are the most widely used esters they are found ia the pharmaceutical, agricultural, and allied industries. Both esters are used extensively as amine protecting agents ia the manufacture of antibiotics and synthetic sweeteners (Dane Salts) (147). Principal outiets for MAA are the manufacture of the organophosphoms insecticide dia2inon [33341-5] (148,149) and the uracil herbicides bromacil [31440-9] and terbacil [5902-51-2] (150,151) (see Insect conztiol technology Herbicides). 

A Acetylation, O-Phosphorylation, and O-Adenylylation. A/-Acetylation, O-phosphorjiation, and O-adenyljiation provide mechanisms by which therapeutically valuable aminocyclitol antibiotics, eg, kanamycia [8063-07-8] gentamicin [1403-66-3] sisomicin [32385-11-8], streptomycia [57-92-1], neomycin, or spectinomycin are rendered either partially or completely iaactive. Thus, eg, kanamycia B [4696-78-8] (50) can be iaactivated by modification at several sites, as shown. The elucidation of these mechanisms has allowed chemical modification of the sites at which the iaactivation occurs. Several such bioactive analogues, eg, dibekacia and amikacin have been prepared and are not subject to the iaactivation hence, they inhibit those organisms against which the parent antibiotics are iaeffective (96) (see Antibacterial agents, synthetic). 

The number of naturally occurring antibiotics increased from about 30 known in 1945, to 150 in 1949, 450 in 1953, 1200 in 1960, and to 10,000 by 1990 (1,9). Table 1 Hsts the years of historical importance to the development of antibiotics used for treatment in humans. Most of the antibiotics introduced since the 1970s have been derived from synthetic modifications of the P-lactam antibiotics (qv). 

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. 

The development of new antibiotics to combat resistance, and to provide easier oral administration and improved pharmacokinetics has been successful through synthetic modifications. This approach has been particularly rewarding in the area of P-lactams. The commercial importance of the P-lactams is evident from Table 3 which gives the market share of antibacterials. Fully 62% of the 1989 world antibacterial market belonged to the cephalosporin and penicillin P-lactams (20). 

Quinones of various degrees of complexity have antibiotic, antimicrobial, and anticancer activities, eg, a2iddinornitosene [80954-63-8] (36), (-)-2-methyl-l,4-naphthoquinone 2,3-epoxide [61840-91 -3] (37), and doxombicin [23214-92-8] (adriamycin) (38) (see Antibiotics Chemotherapeutics, anticancer), ah of these natural and synthetic materials have stimulated extensive research in synthetic chemistry. 

In seeking a synthetic route to an antibiotic antitumor agent, the Thiele-Winter synthon, with 2,3-bis(methoxycarbonyl)-l,4-ben2oquinone [77220-15-6] (60), was used to introduce a required third oxygen linkage (57). A 67% yield of (61) was obtained. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

In the period up to 1970 most P-lactam research was concerned with the penicillin and cephalosporin group of antibiotics (1). Since that time, however, a wide variety of new mono- and bicychc P-lactam stmctures have been described. The carbapenems, characterized by the presence of the bicychc ting systems (1, X = CH2) originated from natural sources the penem ring (1, X = S) and its derivatives are the products of the chemical synthetic approach to new antibiotics. The chemical names are 7-oxo-(R)-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxyhc acid [78854-41-8] CyH NO, and 7-oxo-(R)-4-thia-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxylic a.cid [69126-94-9], C H NO S, respectively. 

Rapid inactivation of added lincomycin was found to result from the growth of Streptomjces rochei in a synthetic medium the antibiotic was converted into lincomycin 3-phosphate [23670-99-7] (5, R = CH3, R = PO3H2, R = SCH3), C2gH33N202PS, readily cleaved back to the antibiotic upon treating with alkaline phosphatase (53). 

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