Acylation amino groups with acidic chains

Glycine (Gly or G) (aminoacetic acid, aminoethanoic acid) is a nonpolar, neutral, aliphatic amino acid with the formula HOOCCH(NH2)H. Gly is the simplest amino acid and plays important roles in peptide and protein chains. It does not contain a side chain and can thus fit into secondary structures where larger amino acids cannot. Gly acts as a transmitter in the CNS where it accomplishes several functions. Gly is a precursor of porphyrins. Gly, Pro, aspartate, Ser, and Asn enable reverse turns. The acylated amino group of Gly can accept a second acyl group to give rise to a diacylamide. ... 

The incorporation of complex side chains at the 7 position based on alkyloximes of 2-amino-thiazole-5-gyloxylamides has provided drugs with very wide antibacterial activity that extend to hitherto resistant species such as pseudomonas. The preparation of one of the simpler side chains involves, first, the formation of the methyl ether from the oxime obtained by the nitrosation of methyl acetoacetate. Chlorination of the product, for example with sulfuryl chloride, gives the intermediate (21-1). The aminothiazole ring is then formed by reaction of that with thiourea to give (21-2). The free acid (21-3) is obtained by saponification of the product. The protected acid chloride (21-5) is obtained by sequential acylation of the amino group with chloroacetyl chloride and then reaction with thionyl chloride. 

Since lysinoalanine and at least one D-amino acid are toxic to some animals (35), we wished to distinguish their effects in alkali-treated proteins. Such discrimination is possible, in principle, since we have found that acylating the e-amino group of lysine proteins seems to prevent lysinoalanine formation. Since lysinoalanine formation from lysine requires participation of the e-amino group of lysine side chains, acylation of the amino group with acetic anhydride is expected to prevent lysinoalanine formation under alkaline conditions if the protective effect survives the treatment. This is indeed the case (16). 

Penicillium chrysogenum on complex solid media, with the result that they were mixtures differing from one another in the identity of the side-chain moiety. When a sufficient supply of phenylacetic acid is present in liquid media, this is preferentially incorporated into the molecule to produce mainly benzylpenicillin (penicillin G in the old nomenclature). Use of phenoxyacetic acid instead leads to phenoxymethyl penicillin (penicillin V). More than two dozen different penicillins have been made in this way, but these two are the only ones that remain in clinical use. The bicyclic penicillin nucleus itself is prepared biosynthetically via a complex process from an acylated cysteinyl valyl peptide. The complete exclusion of side chain precursor acids from the medium produces the fundamental penicillin nucleus, 6-APA, but in poor yield. By itself, 6-APA has only very weak antibiotic activity, but when substituted on its primary amino group with a suitable... 

It is difficult to anticipate all possible imperfections of the chain-building process and even more problematic to find perfect remedies for undesired side reactions. Therefore, one has to resort to monitoring the completion of the individual steps. Titration of unblocked amino groups with a strong acid, for instance perchloric acid, has been proposed as a method by which the process of deprotection and the progress of acylation can be followed. In acylation with active esters the absorption of the eliminated material (e.g. / -nitrophenol) in the ultraviolet can be used for monitoxing. Esters of 3-hydroxy-3,4-dihydro-l,2,3-... 

N-acylation with a fatty acid radical was historically the first useful and successful protein derivatization for cosmetic purposes and still remains one of the most important. As a result of the reaction, each amino group with its potentially positive charge is masked by conversion into an amide, nonprotonable at neutral or lower pH value, while an additional lipophilic chain is added. The resulting molecule has an enhanced anionic character and gains amphiphilic properties when suitable-size hydrophilic and lipophilic moieties are involved (Fig. 9). 

The amino group of sphingosine is acylated with long-chain fatty acids and the N-acylated product is termed a ceramide (Fig. 3-3). C-l of ceramide is linked to different... 

FIGURE 6.10 The side chain of histidine is readily acylated (A) by activated residues. The imidazolide produced is an activated species similar to the intermediate generated by reaction (B) of a carboxylic acid with coupling reagent carbonyldiimidazole. (Staab, 1956). Imida-zolides acylate amino and hydroxyl groups. Isomerization of histidyl during activation results from abstraction (C) of the a-proton by the 7t-nitrogen. 

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