Alkylation biological

Antimetabolites. This class of drugs includes purine, pyrimidine, and folic acid analogs that have been successfully used to treat various carcinomas, autoimmune diseases, and dermatological disorders such as psoriasis. Because of their structural similarities to normal components of DNA and RNA synthesis, they are capable of competing with the normal macromolecules and alkylating biological nucleophiles. 

Loveless (1966 v) describes alkylating agents as those compounds possessing the capacity to alkylate biologically functional chemical groups in vivo under normal physiological conditions. ... 

Side Chain Alkylation.—Biological C-alkylation has been reviewed by Lederer. The 24-methyl group of ergosterol (86 R = Me) is derived from a 24-methylene-... 

Some esters of inorganic acids such as dimethyl sulfate are used as reagents m syn thetic organic chemistry Certain naturally occurring alkyl phosphates play an important role m biological processes... 

The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

A wide variety of quaternaries can be prepared. Alkylation with benzyl chloride may produce quaternaries that are biologically active, namely, bactericides, germicides, or algaecides. Reaction of a tertiary amine with chloroacetic acid produces an amphoteric compound, a betaine. 

The alkyl pyridines (6) and (7) can be transformed either to nicotinic acid or nicotinonitrile. In the case of nicotinic acid, these transformations can occur by either chemical or biological means. From an industrial standpoint, the majority of nicotinic acid is produced by the nitric acid oxidation of 2-meth5i-5-ethylpyridine. Although not of industrial significance, the air oxidation has also been reported. Isocinchomeronic acid (10) (Fig. 2) is formed as an intermediate. 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

Caprolactam is an amide and, therefore, undergoes the reactions of this class of compounds. It can be hydrolyzed, Ai-alkylated, O-alkylated, nitrosated, halogenated, and subjected to many other reactions (3). Caprolactam is readily converted to high molecular weight, linear nylon-6 polymers. Through a complex series of reactions, caprolactam can be converted to the biologically and nutritionally essential amino acid L-lysine (10) (see Amino acids). 

The antitumor activity displayed by the mitosanes and many synthetic aziridines stems from their ability to act as alkylating agents which chemically modify (crosslink) DNA. For this reason, a large number have been screened for antitumor activity, the mechanism of which has been the subject of considerable research effort <75CJC289l). An excellent account of the broad spectrum of biological properties of a multitude of compounds containing the aziridinyl moiety has been published [Pg.93]

Isothiazole, 5-acetamido-3-alkyl-nitrosation, 5, 59 6, 148 Isothiazole, 5-acetyl-thiosemicarbazone biological activity, 6, 175 Isothiazole, 4-acetyl-5-amino-3-bromo-synthesis, 6, 166 Isothiazole, 4-acetyl-3-methyl-oxime... 

Isothiazole-4,5-dicarboxylic acid, 3-phenyl-dimethyl ester synthesis, S, 150 Isothiazole-5-glyoxylic acid ethyl ester reduction, 6, 156 Isothiazole-4-mercurioacetate reactions, 6, 164 Isothiazole-5-mercurioacetate reactions, 6, 164 Isothiazoles, 6, I3I-I75 acidity, 6, 141 alkylation, 6, 148 aromaticity, S, 32 6, 144-145 basicity, 6, I4I biological activity, 6, 175 boiling points, 6, I43-I44, 144 bond fixation, 6, 145 bond orders, 6, I32-I34 calculated, 6, 133 bromination, S, 58 6, 147 charge densities, 6, 132-134 cycloaddition reactions, 6, 152 desulfurization, S, 75 6, 152 deuteration, S, 70... 

A -l,3,4-Oxadiazoline-5-thione, 4-alkyl-2-(4-pyridyl)-biological activity, 6, 445 A -l,3,4-Oxadiazoline-5-thione, 2-aryl-reactions... 

A -l,3,4-Oxadiazoline-5-thione, 2-phenyl-alkylation, 6, 440 Oxadiazolinethiones acylation, 6, 432 Mannich reaction, 6, 431 pK 6, 435 ring cleavage, 6, 433 Oxadiazoline-5-thiones acidity, 6, 435 stability, 6, 431 A -Oxadiazoline-5-thiones biological activity, 6, 445 synthesis, 6, 441 A -1,3,4-Oxadiazoline-5-thiones... 

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