N-Acyl Glycinates

N-Acyl Glycinates, RCONHCH2COO M+ Produced by reaction similar to that of AG above. RCO is usually derived from coconut oil for detergent use. 

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A variant of the Perkin reaction is the Erlenmeyer-Plochl-azlactone synthesis By condensation of an aromatic aldehyde 1 with an N-acyl glycine 5 in the presence of sodium acetate and acetic anhydride, an azlactone 6 is obtained via the following mechanism ... 

Hierbei werden N-Acyl-glycine in Gegenwart von Acetanhydrid und Natriumacetat mit aromatischen Aldehyden zu 4-Alkyliden-5-oxo-4,5-dihydro-l,3-oxazolen (Azlactonen) kondensiert, deren saure und basische Hydrolyse zu a-Oxo-carbonsauren fiihrt (vgl. Bd. VIII, S. 447 Bd. XI/2, 306, 368) ... 

Bradshaw, H.B., Rimmerman, N., Hu, S.S., Burstein, S. and Walker, J.M. (2009) Novel endogenous N-acyl glycines identification and characterization. Vitam. Horm. 81,... 

Similarly, N-acyl glycinates like N-octanoylglycine trifluoroethyl ester [197] and N-octanoyldimethylglycine trifluoroethyl ester [198] have been successfully employed as acyl donors in subtilisin-catalyzed KR of aliphatic and benzylic amines. Based on the opposite selectivity displayed by subtilisin and lipases, in these cases the (S)-amides and (R)-amines were obtained, both with excellent stereodiscrimination values. 

A general synthesis of tryptophan involves condensation of 3-formyl-indole with oxazolinones derived from N-acyl-glycine. Recently, Kirby and Varley 225) have used this method to synthesize tryptophan stereoselectively labelled with tritium and deuterium in the p-methylene group. The synthesis employed is depicted in the following scheme (21) to (24) and (25). The hydrogenation step leading to the racemate... 

Analogous to azloci11i n-mezloci11i n, acylation of the amino group of 2-phenyl glycine containing cephalosporins is consistent with antipseudomonal activity. There are many... 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

The displacement of the chlorine atom in 395 by triphenylphosphine or other phosphorus derivatives leads to the corresponding phosphorylated oxazolones 397 or 398 that have been used to prepare new and interesting substituted vinylphos-phonium salts (Scheme 7.127). Of particular interest is the synthesis of N-acyl-a-(triphenylphosphonio)glycinates as new cationic glycine equivalents. ... 

If the terminal Hmb-substituted amino acid is glycine then the subsequent residue, even if p-branched, may be coupled through its pentafluorophenyl ester or similar. 151 For any other Hmb amino acid the subsequent residue must be coupled as its symmetric anhydride in dichloromethane. The only limitation to the inclusion of Hmb into a sequence is that 3-branched amino acids will not quantitatively N-acylate a terminal Hmb residue, except glycine, on a practical timescale. 

N-Myristoylation is achieved by the covalent attachment of the 14-carbon saturated myristic acid (C14 0) to the N-terminal glycine residue of various proteins with formation of an irreversible amide bond (Table l). 10 This process is cotranslational and is catalyzed by a monomeric enzyme called jV-myri s toy 11ransferase. 24 Several proteins of diverse families, including tyrosine kinases of the Src family, the alanine-rich C kinase substrate (MARKS), the HIV Nef phosphoprotein, and the a-subunit of heterotrimeric G protein, carry a myr-istoylated N-terminal glycine residue which in some cases is in close proximity to a site that can be S-acylated with a fatty acid. Functional studies of these proteins have shown an important structural role for the myristoyl chain not only in terms of enhanced membrane affinity of the proteins, but also of stabilization of their three-dimensional structure in the cytosolic form. Once exposed, the myristoyl chain promotes membrane association of the protein. 5 The myristoyl moiety however, is not sufficiently hydrophobic to anchor the protein to the membrane permanently, 25,26 and in vivo this interaction is further modulated by a variety of switches that operate through covalent or noncovalent modifications of the protein. 4,5,27 In MARKS, for example, multiple phosphorylation of a positively charged domain moves the protein back to the cytosolic compartment due to the mutated electrostatic properties of the protein, a so-called myristoyl-electrostatic switch. 28 ... 

Die gemeinsame Condensation von Glycin-ethylester, Carbonsaure-ethylester-imiden und Carbonyl-Verbindungen ffihrt zu 4-Alkyliden- bzw. 4-Aralkyliden-5-oxo-4,5-di-hydro-imidazolen, die durch Reduktion und Hydrolyse in N-Acyl-aminosaure-amide, N-Acyl-aminosauren oder in freie a-Aminosauren fibergeffihrt werden kon-nen2 ... 

N-Acyl-aminocarhonsaure-ester allgemeine Vorschrift fiir die Reaktion von N-Acyl-a-brom-glycin-estern mit Organocupraten hoherer Ordnung2 ... 

Durch Ruthenium-katalysierte Oxidation sind neben N-Acyl-N-allyl-aminen (s. Bd. E5, S. 557, 1985) auch Acyl-aryl-amine zu a-Aminosauren oxidierbar, z. B. (5)-2-Deutero-glycin aus N-(a-Deutero-4-methoxy-benzyl)-carbamidsaure-tert.-butylester (1), 54% . Das (R)-2-Deutero-glycin (80%) wird durch Ozonolyse von (/ )-Deutero-(2-furyl)-phthalimido-methan (II) erhalten6 (S. 644). 

Figure 17.19 Rates of hydrolysis of two families of esters by a hydrolase, chymotrypsin. The esters of N-acetyl-L-phenylalanine exhibit very similar rates because the process in each case is limited by the same enzyme deacylation reaction (Zerner et al., 1964). The esters of N-benzoyl glycine exhibit rates varying by more than a factor of 3 because their hydrolyses are mostly limited by the initial enzyme acylation step (Epand and Wilson, 1963).

An example is provided by actin, which contains acetyl-Met-Asp, acetyl-Met-Gln or acetyl-Met-Cys-Asp at the N terminus immediately after synthesis. Then, within 15 min the acetyl-Met is cleaved off, and the next terminal residue is acetylated.548 N-Acylation of nascent peptides by fatty acyl groups can also occur cotranslationally. For example, 14-carbon myristoyl groups are added in amide linkage to the N-terminal glycines of many cellular and virally encoded proteins.535 549 550 This may take place on the ribosomes,551... 

One type of oligoamide that can readily be prepared on supports without the need for any partially protected monomers (which are often tedious and expensive to synthesize) are N-substituted oligoglycines (Figure 16.21). These compounds are prepared by a sequence of acylation of a support-bound amine with bromoacetic acid, displacement of the bromide with a primary aliphatic or aromatic amine, and repeated acylation with bromoacetic acid. Because primary amines are cheap and available in large number, this approach enables the cost-efficient production of large, diverse compound libraries. Alternatively, protected N-substituted glycines can also be prepared in solution and then assembled on insoluble supports (Entry 5, Table 16.2). 

Verbindungen dieses Typs sind auch durch Cyclisierung geeigneter N-Acyl-aminosauren zuganglich. So liefem N-Isonicotinoyl-C-phenylgly-cin 177> und das Azlacton des N-Benzoyl-C-pyridyl-(4)-glycins 173) mit Acetanhydrid die (N-Acetyl-1.4-dihydro-pyridinyliden)-oxazolinone 19 und 20. 

Mazurkiewicz, R. Grymel, M. N-Acyl-a-triphe-nylphosphonioglycinates a novel cationic glycine equivalent and its reactions with heteroatom nucleophiles. Monatsh. Chem. 1999, 130, 597-604. 

Solid-phase synthesis has also been used to make peptoids, some examples of which are shown in Fig. 2.4. Compounds of general structure 2.8, where the amino acid side chain is on the nitrogen, have been prepared either by the corresponding Fmoc-protected N-aUcylated glycines (33) or, in an improved method, via treatment of a resin-bound secondary amine with bromoacetic acid to produce the first peptoid building block, which is then elaborated via iteration of the procedure (34). Other modified P-peptoid structures such as 2.9 with repeating P-amino propionic units have been prepared by acylation of a resin-bound amine with acriloyl chloride followed by Michael addition of a primary amine. The cycle is repeated to build up the polymer... 

Membrane ATPases have also been inhibited by carbodiimides. This reaction is associated with the membrane lipoprotein. Carbodiimide binding proteins have been isolated from bacterial membranes, chloroplasts, animal liver mitochondria, bovine heart mitochondria,molds and yeasts. The site of carbodiimide attack in the protein is probably in the hydrophobic region because only lipophilic carbodiimides are effective inhibitors. The addition of methyl glycinate protects erythrocyte membrane ATPase against carbodiimide inhibition. The inhibition reaction of carbodiimides may involve an O N acyl shift in the initially formed O-acylurea. 

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