Protection for the Amino Group Carbamates

Reactivity Chart 8. Protection for the Amino Group Carbamates 

Methyl Carbamate 5. 9-Fluorenylmethyl Carbamate 8. 2,2,2-Trichloroethyl Carbamate 11. 2-Trimethylsilylethyl Carbamate 16. 1,1 -Dimethylpropynyl Carbamate 20. 1-Methyl-1-phenylethyl Carbamate 22. 1 -Methyl-1 -(4-biphenylyl)ethyl Carbamate 24. 1,1 -Dimethyl-2-haloethyl Carbamate 26. 1,1 -Dimethyl-2-cyanoethyl Carbamate 28. r-Butyl Carbamate 

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Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

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-... 

Only a restricted selection of the very great number of methods for the protection of the amino and imino groups is possible here. These have often been developed for the protection of the amino group in an amino acid for the purpose of peptide synthesis. Those considered below are (a) AT-acyl derivatives (b) carbamates and (c) phthalimides. 

Carbamate-protected amino alcohols also yield oxazolidinones upon treatment with base (eq 4) orp-Toluenesulfonyl Chloride (eq 5). The latter reaction requires the protection of the amino group as the A-methylated carbamate for selective inversion of the hydroxyl-bearing center. 

C—X) for the application at hand. Benzyl trans-l,3-butadiene-l-carbamate has the amino group protected with the benzyloxycar-bonyl group. The ability to remove this functionality by catalytic... 

To prevent side reactions, the amino group of alanine must be protected to make it nonnucleophilic. In Section 24-7B, we saw that an amino acid reacts with benzyl chlo-roformate (also called benzyloxycarbonyl chloride) to form a urethane, or carbamate ester, that is easily removed at the end of the synthesis. This protecting group has been used for many years, and it has acquired several names. It is called the benzyloxycarbonyl group, the carbobenzoxy group (Cbz), or simply the Z group (abbreviated Z). 

The carbamates represent the single most important family of protecting groups for all types of amines. All of the members of the carbamate family are easy to introduce by reaction of the amino group with chloroformates or various deri-... 

In peptide synthesis the use of a suitable protection for the N-terminal amino group is required not only to prevent the formation of a complex mixture of oligo- and cyclo-peptides, but an additional demand on the functionality applied for this purpose is that it should prevent possible racemization of the activated amino acid. Racemization usually takes place via an intermediate oxazolone (7) that forms readily from A -acyl-protected amino acids (Scheme 2). This side reaction can be mostly suppressed by using a carbamate as an N-terminal-protecting group. Therefore, nearly all blocking functions currently applied in this field are of the urethane type. 

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