Amino protection

A second, conceptually distinct chiral synthesis of monobactams was developed from P-hydroxy amino acids. As shown in Figure 2, cycli2ation of the acylsulfamate of an amino-protected 0-mesylserine derivative (14, R = H) leads directiy to the monobactam (15). This methodology was also appHed to the synthesis of 4a- (15, R = CH ) and 4P-methyl monobactams from L-threonine and aHothreonine, respectively (17). The... 

Fig. 2. Synthesis of clinically useful monobactams where R = H, CH P is an amino protecting group, and Mes = mesyl is methanesulfonyl.

Fig. 7. Synthesis of monocarbams where P is an amino protecting group and CSI is chlorosulfonyl isocyanate. TFA is trifluoroacetic acid...

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. 

Amino-protecting groups include benzyloxycarbonyl (Z) and ten-btitoxy-carbonyl (Boc). 

For a review of the use of Fmoc protection in peptide synthesis, see E. Atherton and R. C. Sheppard, The Fluorenylmethoxycarbonyl Amino Protecting Group, in The... 

The choice of the acyl substituent X for Diels-Alder reactions of l-N-acylamino-l,3-butadicnes depends on the particular synthetic problem. The acyl substituent has a moderate effect on the cycloaddition reactivity of these dienes, and also determines what amine unmasking procedures are required. As a result of their stability and the variety of amine deprotection procedures available, " the diene carbamates are the components of choice in most cases. A particularly attractive aspect of the diene synthesis detailed here is the ability to tailor the amino-protecting group... 

The t-butoxycarbonyl (rBoc) group is another valuable amino-protecting group. The removal in this case is done with an acid such as trifluoroacetic acid or /Moluenesulfonic acid.218 r-Butoxycarbonyl groups are introduced by reaction of amines with f-butoxypyrocarbonate or a mixed carbonate-imidate ester known as BOC-ON. 219... 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

The first version of SPPS to be developed used the t-Boc group as the amino-protecting group. f-Boc can be cleaved with relatively mild acidic treatment and TFA is usually used. The original coupling reagents utilized for SPPS were carbodiimides. In addition to dicyclohexylcarbodiimide (DCCI), N, (V -diisopropylcarbodiimide (DIPCDI) is often used. The mechanism of peptide coupling by carbodiimides was... 

Rosenau, T. Chen, C. L. Habicher, W. D. A vitamin E derivative as a novel extremely advantageous amino-protecting group. J. Org. Chem. 1995, 60, 8120-8121. 

Carbamates by Reaction of Imidazole- or Imidazolium-iV-carboxylates. Introduction of Amino Protecting Groups... 

A variant of this method for the introduction of amino protecting groups into amino acids via the alkoxycarbonylimidazolium salts starts from the more reactive carbonyl-bis(methylimidazolium) salts [105]... 

Some examples for the introduction of amino protecting groups such as 2-(4-nitro-phenyl)ethoxycarbonyl (npeoc) or benzyloxycarbonyl (Z) were already given in the compilation of carbamates produced with imidazolium caiboxylates in Section 4.6.1. 

Analogously to these reactions of imidazolium carboxylates, the introduction of urethane-type amino-protecting groups can be accomplished with the following mesoionic azolides [194]... 

In brief, the use of acetonitrile as solvent and the selection of an appropriate C-5 amino protecting group and reactive promoter system are critical for achieving high a-selectivities and yields in the synthesis of sialosides. 

To overcome these difficulties in the selective deprotection and chain extension, several carboxyl-protecting groups, namely, allyl (16,32), benzyl (43,44), tert-butyl (42), 2-bromoethyl (45), 2-chloroethyl (45), heptyl (46), 4-nitrophenyl (47,48), and pentafluorophenyl (49) for L-serine/L-threonine have been introduced or applied. Similarly, amino-protecting groups for L-serine/L-threonine that have proved useful for the synthesis of glycopeptides are tm-butyloxycarbonyl (50), 9-fluorenylmethoxycarbonyl (43,44,48), 2-(2-pyridyl)ethoxycarbonyl (51), 2-(4-pyridyl)ethoxycarbonyl (44,52), and 2-triphenylphosphonioethoxycarbonyl (53). Some applications of these groups have been discussed in earlier reviews (7-11). 

The allylic HYCRAM derivative was subsequently modified by insertion of a standard amino acid between the aminomethyl resin and the hydroxy butenoic acid moiety. Using this allylic anchor, the resin-linked, glycosylated HIV peptide T-derivative 164 was synthesized by application of Fmoc amino protection and sidechain protection with lert-butyl groups. The lac-tosamine peptide T (165) could be released from the resin by application of the palladium(0)-catalyzed allyl-transfer reaction to V-methyl aniline as the allyl acceptor. 

Liming and coworkers (56) also used the Fmoc group for temporary amino protection and employed a commercial resin (SASRIN , trademark of Bachem, Switzerland) having a dialkoxybenzyl anchoring group. The synthesized glycopeptide could be cleaved from the resin with 1% trifluoroacetic acid in dichloromethane. 

G Barany, RB Merrifield. A new amino protecting group removable by reduction. 

CGJ Verhardt, GI Tesser. New base-labile amino-protecting groups for peptide synthesis. Rec Trav Chim Pays-Bas 107, 621, 1988. 

VV Samukov, AN Sabirov, PI Pozdnyakov. 2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) group as a base-labile a-amino protection for solid phase peptide synthesis. Tetrahedron Lett 35, 7821, 1994. 

H Kuntz, C Unverzagt. The allyloxycarbonyl (Aloe) moiety — conversion of an unsuitable into a valuable amino protecting group for peptide synthesis. Angew Chem Int Edn Engl 23, 436, 1984. 

A Paquet. Introduction of 9-fluorenylmethoxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amino protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates. Can J Chem 60, 976, 1982. 

P Sieber, B Iselin. Peptide synthesis using the 2-(p-diphenyl)-isopropoxycarbonyl (Dpoc) amino protecting group. Helv Chim Acta 51, 622, 1968. 

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