Protection for the Amino Group Amides

Reactivity Chart 9. Protection for the Amino Group Amides... 

Many protective groups have been developed for the amino group, including carbamates (>NCO,R), used for the protection of ammo acids in peptide and protein syntheses, and amides (>NCOR). used more widely in syntheses of alkaloids and for the protection of the nitrogen bases adenine, cytosine, and guanine in nucleo-... 

The bases adenine, guanine, and cytosine all contain exocyclic amino substituents that require protection, since these are potential nucleophiles. They are converted into amides that are stable to the other reagents used in the process, yet can be removed readily by basic hydrolysis. The most effective protecting groups have been found to be isobutyryl for the amino group of guanine, and benzoyl for adenine and cytosine. Thymine has no exocyclic nitrogen and does not need protection. 

The monoaminomonophosphonic acids, either in the free state or, very often, as their diethyl esters, have been resolved by the usual techniques of repeated crystallization of appropriate salts those of L-(+)-tartaric acid (2,3-dihydroxybutanedioic acid) or its mono-or di-benzoyl derivativesor of D-(-)-mandelic acid, have been widely employed the use of di-O-benzoylated L-tartaric anhydride, which is based on the separation of diastereoisomeric amides (111), has also been employed to a limited extent. In selected cases, such as the monoaminomonophosphonocarboxylic acids or A -acylated (aminoalkyl)phosphonic acids, resolution following salt formation with organic bases has also been carried out ephedrine, quinine and both enantiomers of l-phenylethylamine have all been used. In many cases, only one enantiomer of the (aminoalkyl)phosphonic acid (or diester) has been isolated in optically pure form. Sometimes, the acidity of the substrate, and hence choice of base for resolution, can be modified by using a mono- (as opposed to di-) ester or (or even in addition to) protection of the amino group as, for example, the phthalimido, benzyloxycarbonyl (cbz) or r r -butyloxycarbonyl (boc) derivative. Resolved di- and mono-esters can be hydrolysed to the free acids under acidic conditions, and A -protection can also be removed through the customary procedures. 

Examples are given in Table 4—1 for the synthesis of amides of AT-protected amino acids by means of imidazolides and triazolides (where Z and Boc represent the protecting groups benzyloxycarbonyl and terf-butoxycarbonyl) ... 

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