Semisynthetic

Starch is a polysaccharide found in many plant species. Com and potatoes are two common sources of industrial starch. The composition of starch varies somewhat in terms of the amount of branching of the polymer chains (11). Its principal use as a flocculant is in the Bayer process for extracting aluminum from bauxite ore. The digestion of bauxite in sodium hydroxide solution produces a suspension of finely divided iron minerals and siUcates, called red mud, in a highly alkaline Hquor. Starch is used to settle the red mud so that relatively pure alumina can be produced from the clarified Hquor. It has been largely replaced by acryHc acid and acrylamide-based (11,12) polymers, although a number of plants stiH add some starch in addition to synthetic polymers to reduce the level of residual suspended soHds in the Hquor. Starch [9005-25-8] can be modified with various reagents to produce semisynthetic polymers. The principal one of these is cationic starch, which is used as a retention aid in paper production as a component of a dual system (13,14) or a microparticle system (15). 

Petro-Canada Oils. Petro-Canada manufactures three oils specially refined for use as heat-transfer fluids. Calflo EG is a semisynthetic, paraffinic heat-transfer fluid specifically developed for use in systems where incidental contact with food may result. Calflo AE is a saturated paraffinic oil containing inhibitors to minimise oxidation. Calflo HTE is a saturated paraffinic oil inhibited to minimise oxidation. 

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). 

Avermectins and Ivermectin. The avermectias are pentacycHc lactones isolated from fermentation products of Streptomjces avermitilis and ivermectin is a semisynthetic chemical, 22,23-dihydroavermectia (46). Ivermectin is effective in very low doses for the control of red spider mites on deciduous fmits, in baits for the control of imported fire ants, and as a parasiticide for Onchocerca volvulus in humans and for catde gmbs. These insecticides appear to function as agonists for the neuroinhibitory transmitter y-aminobutyric acid (GABA) (see Antiparasitic agents, avermectins). 

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. 

Antituberculin Agents. Rifampin [13292-46-17, a semisynthetic derivative of rifamycin SV, is a most valuable dmg for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve dmg. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4] both of which are peptides, have also been used for treatment of this disease. 

Derivatives Containing a Modified 4,6-Disubstituted-2-deoxystreptamine Moiety. Mutasynthesis is the term used to refer to the process of employing mutated intermediate-requiring organisms to prepare derivatives that would be difficult to obtain by synthetic or semisynthetic means (117,185—188). Whereas this approach has been used to obtain amiaoglycoside analogues, the primary contribution has been as a means to vary the 2-deoxystreptamiae portion of the molecule. The most significant compound found by this approach is 5-episisomicin, which is produced by a... 

The biosynthesis of the fortimicins has received some initial study (220—222) and a significant amount of semisynthetic modification has been carried out in this series. 3-0-Demethylfortimicin A (223,224) was found to be significantly more potent than the parent fortmicin A, especially against P aeruginosa 3-0-Demethyl-2-epi-, 2,3-di-epi-, and 3-0-demethyl-2,3-di-epi-fortimicin A are somewhat less active than fortimicin A, but the... 

Several semisynthetic maytansinoids have been prepared by acylating the C-3 hydroxyl group of maytansinol. Some of these derivatives have antiprotozoal and antitumor activity similat to maytansine (104) and ansamitocin P-3 (127) (52,254). 3-Epimaytansinoids have been synthesized and were not biologically active (255). 

Biological Activity. The maytansinoids possess antitumor activity, particulady against P 388 lymphocytic leukemia, B 16 melanocarcinoma, and Lewis lung carcinoma. A number of semisynthetic esters of maytansinol have been prepared and exhibit good antileukemic activity (52,255). The maytansides lack antitumor activity, indicating that the ester at C-3 is a requirement for activity (50,52). The carbinolamide also appears to be necessary for... 

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

Many labeling systems have been used for dalbaheptide stmctures. The one used herein, where each of the seven amino acids is identified by a number (see Table 2) and each atom by a letter, is widely appHed because it permits easy comparison of and nmr data (31). The lUPAC system, utilised in Chemicaly hstracts and generally in the description of semisynthetic derivatives, requires decodification for comparison of different dalbaheptides (83). 

The -NH(CH2)3N(CH2)2 amide of teicoplanin factor A2-2, coded MPT. 62,873 [122173-74-4] was also prepared. The combined effect of a moderate basicity and a slightly increased lipophilicity at neutral pH probably led to a better penetration through the cell wall. MDL 62,873 was consistentiy more active than teicoplanin against CNS clinical isolates (119,120). No semisynthetic dalbaheptide is under clinical evaluation at this writing. 

The penicillins as natural and semisynthetic agents are used primarily against susceptible Pasteurella sp., staphylococci, streptococci, clostridia, and CoTynebacterium sp. Penicillin is widely used for therapeutic purposes against these organisms and in animal feeds as a growth promoter. The latter effect is considered to be a result of subtie and reversible effects on the gastrointestinal microflora. 

AH cephalosporins found in nature (Tables 1 and 2) have the D-a-aminoadipic acid 7-acyl side chain (21). AH of these compounds can be classified as having rather low specific activity. A substantial amount of the early work in the cephalosporin area was unsuccessfiiHy directed toward replacing the aminoadipic acid side chain or modifying it appropriately by fermentation or enzymatic processes (6,22). A milestone ia the development of cephalosporins occurred in 1960 with the discovery of a practical chemical process to remove the side chain to afford 7-ACA (1) (1). Several related processes were subsequendy developed (22,23). The ready avaHabHity of 7-ACA opened the way to thousands of new semisynthetic cephalosporins. The cephalosporin stmcture offers more opportunities for chemical modification than does that of penicillins There are two side chains that especiaHy lend themselves to chemical manipulation the 7-acylamino and 3-acetoxymethyl substituents. 

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