Protection of the Amino Group

Aminopalladation and subsequent carbonylation are also facile reactions. The carbonylation of substituted 3-hydroxy-4-pentenylamine as a carbamate (254) proceeds smoothly via the aminopalladation product 255 in AcOH to give 256[228). The protection of the amino group of the carbamate as tosyl amide is important in the carbonylation of 257 to give 258[229],... 

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. 

Concomitant protection of the amino group and the cis-hydroxyl group of the diol 342 was realized by treatment with formaldehyde to afford the oxazolidine 345, oxidation of which with silver carbonate on Celite gave the... 

The 9-phenylfluoren-9-yl (PhFI) group is very useful for protection of the amino group. Pd/C can remove the Pf group and reduce the amido group,... 

Modification of Neamine Regioselective Protection of the Amino Groups Using Metal Chelation... 

Tertiary electrophiles alkylate bydroxylamines through the SatI mechanism. These reactions (e.g. equation 10) are practically feasible only for compounds forming highly stabilized carbocations such as trityl , or 2-(p-alkoxyphenyl)propyl. All these reactions proceed exclusively on the nitrogen atom and have been used for A-protection of the amino groups in bydroxylamines. 

Minisci and coworkers followed Ishii s procedure, and implemented it in the oxidation of benzyhc alcohols to benzaldehydes in almost quantitative yields" (Table 12). A,Af-dimethylbenzylamines were converted into aldehydes in good yields, by using catalytic amounts of either HPI or A-hydroxysuccinimide (HSI) for the formation of the corresponding aminoxyl radical intermediates. Because the attempted oxidation of primary and secondary amines caused the degradation of catalyst HPI, protection of the amino group in those substrates by acetylation was considered. This led one to develop... 

To allow for the use of the stronger sulfating reagent pyridine/S03, an alternative protection strategy has been proposed by Fujii et al. 55-99 that is based on postsynthetic protection of the amino groups as Fmoc derivatives and of the serine hydroxy groups as terf-butyldiphenylsilyl derivatives as shown in Scheme 12. The histidine side chain is not protected since model studies indicate that sulfated histidine is readily hydrolyzed by water within 60 minutes. 

Similarly, very useful yields and diastereoselectivities were observed on alkylation of (5R)-2,3,5,6,-tetrahydro-5-phenyl-A-(ter/-butoxycarbonyl)-4/f-l,4-oxazin-2-one (7)92, The latter is available from (A)-phenylglycinol and phenyl 2-bromoacetate with subsequent protection of the amino group. The influence of the base, the counterion and the solvent was studied for this example. Sodium hexamethyldisilazanide in tetrahydrofuran/dimethoxyethane turned out to be by far the best conditions for deprotonation. Also, it seems to be essential that the base is added to the chilled solution of 7 and not vice versa. 

Thus, the 1,4-addition of the lactams 72 to nitroolefins provided access to the Michael adducts 73 with good stereoselectivities, which could be improved by recrystallization or chromatography. After reduction and protection of the amino group the y-butyrolactams 74 were converted to the corresponding a-substituted lactams 75 in good overall yields (37-65%) and excellent diastereo- and enantio-... 

The statine-like moiety in one of the first drugs, saquinovir (23-8), comprises a transition state mimic for the cleavage of phenylalanylprolyl and tyrosylprolyl sequences. Constmction starts with the protection of the amino group of phenylalanine as its phthaloyl derivative (Phth) by reaction with phthalic anhydride this is then converted to acid chloride. The chain is then extended by one carbon using a Friedel-Crafts-like reaction. The required reagent (21-2) is prepared by reaction of the enolate obtained from the /7A-silyl ether (21-3) of glyoxylic acid and lithio... 

Introducing the Tau residue into a peptide according to the first approach demands protection of the amino group, usually in the form of a Z-derivative and turning the sulfonic acid into sulfonyl chloride. Synthesis of (j-su Ifonamidopeptides via an iterative process, both in solution and in the solid phase, has been described.11201 Chiral methylene sulfinamide peptides can be synthesized both in solution and in the solid phase using the sulfonyl chlorides derived from enantiomerically pure 2-substituted taurines under mild coupling conditions (DMAP catalysis and excess methyl trimethylsilyl dimethylketene acetal as a proton trap).11261... 

A few methods for the esterification of 1-aminoalkylphosphonic adds have been developed for use when diesters of 1-aminoalkylphosphonic acids are the preferred starting materials for peptide synthesis. 8 In general, 1-aminoalkylphosphonic acids cannot be esterified under conditions that work for amino acids, and protection of the amino group is absolutely essential. Diethyl 1-aminoethylphosphonate [9, Alap(OEt)2] is synthesized from Alap in two steps (Scheme 6). Orthoformates are highly recommended because esterification is almost quantitative. 24 ... 

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. 

Protection of the amino group by acetylation, as in acetanilide, therefore usually permits monosubstitution reactions with appropriate electrophilic reagents to proceed smoothly. Thus with bromine, p-bromoacetanilide is the main product the small quantity of the ortho isomer simultaneously formed can be easily eliminated by recrystallisation (Expt 6.67) hydrolysis of p-bromoacetanilide gives p-bromoaniline. Nitration leads similarly to p-nitroacetanilide which can be hydrolysed to p-nitroaniline (Expt 6.68). 

Following their syntheses of ( )-pancracine and related alkaloids (vide supra), Hoshino et al [106] had described a different approach involving radical cyclisation of an isoquinoline derivative which permitted a rapid assembly of keto-5,11-methanomorphanthridine skeleton. The syntheses of 413, 414 and 415 commenced with the known 4-hydroxy-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoIine (439) (Scheme 62). Subsequent to protection of the amino group as the trifluoroacetyl derivative, the amide alcohol 440 was converted into the amide thioether 441, by reaction with phenylthiol in the presence of zinc iodide. Alkaline hydrolysis of 441,... 

As part of an extensive investigation of syntheses of deaza derivatives of pteroic acid, Rydon s group described the first synthesis of 4-amino-4-deoxy-5,8-dideazapteroic acid (212a) [99, 119]. In their approach (Scheme 3.39), 4-methylanthranilic acid was fused with urea to give (207) from which (208) was obtained in two steps. Attempts to brominate (208) directly were unsatisfactory, necessitating protection of the amino groups by benzoylation giving... 

A photoreactive analogue, 2 -azidoAP (574ee) was prepared as shown in Scheme 3.120 [242], Intermediate (582) was synthesized from 2-nitro-4-amino-benzoic acid by protection of the amino group, reduction, diazotization and peptide coupling. 

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