Amino acids N-acylation

The condensation of thioacetic acid with amino acids under drastic conditions provides a useful new synthesis of thiazoles (Scheme 146) (668, 669). Instead of the amino acid, N-acyl (279) or N-thioacylanaino acids (278) are used. 

Glycine conjugation Carboxylic acids Acyl-CoA amino acid N-transferase Glycinamide conjugates... 

The S-CoA derivative then acylates the amino group of the particular amino acid in an analogous way to the acetylation of amine groups described above, yielding a peptide conjugate. This is catalyzed by an amino acid N-acyltransferase, which is located in the mitochondria. Two such enzymes have been purified, each using a different group of CoA derivatives. 

Low molecular mass permeation enhancers include numerous classes of compounds with diverse chemical properties including detergents, surfactants, N-acetylated x-amino acids, N-acetylated non-a-amino acids, fatty acids, medium-chain mono- and diglycerides, acyl carnitine, alkanoyl cholines, Ca2 + chelating agents, zonula occludens toxins and NO donors. 

The principal aminoarylarsinic acids are given in the following scheme, where X is AsO(01I)2. The list only contains acids with free amino-groups, N-acyl and N alkyl derivatives, condensation product-s of these amino-acids being dealt with in separate sections. 

Jursic, B. S., Neumann, D. Preparation of N-acyl derivatives of amino acids from acyl chlorides and amino acids in the presence of cationic surfactants. A variation of the Schotten-Baumann method of benzoylation of amino acids. Synth. Common. 2001, 31, 555-564. 

Conversion of the carboxylic acid to its CoA ester derivative is the rate-limiting step. The enzyme that catalyzes the final reaction, acyl-CoA amino acid N-acyltransferase, is localized in the mitochondria of the kidney and liver. The amino acid substrate selectivity, which varies from species to species, resides in the specific N-acyltransferase that... 

Spectroscopic (NMR, IR) studies show, that protonation (or coordination with Lewis acids) occurs predominantly at the oxygen atom as depicted in Eq. (11-3)5,6). In the absence of other strong bases the positively charged C-atom in the protonated monomer is attacked by the N-atom of another lactam and primary amino- and N-acyl lactam end-groups are formed (11-3) ... 

Goff and Zuckermann [51] reported the synthesis of 2-oxopiperazine 16 by intramolecular Michael addition on the solid phase. The coupling of resin-bound unsaturated dipeptoids with a variety of Fmoc-L-amino acids, N,N -diisopropylcarbodiimide (DIPCDI), and 1-hydroxybenzotriazole (HOBt) affords tripeptoids, which after treatment with 20% piperidine in DMF, were acylated with benzoyl chloride-EtaN in 1,2-dichloroethane. Following treatment with 95% TFA in H2O, a diastereomeric ratio of monoketopiperazines 16 was obtained (Fig. 8). Rather than benzoyl chloride, phenylisocyanate or bromoacetic acid and an amine could be used. 

Regioselective introduction of protecting groups in lysine poses no major problem. The copper(II) complex of the amino acid is acylated and the N -acyl-derivative secured through decomposition of the complex, for instance with H S ... 

Slightly different conditions were chosen by Gamerith, who used TFAA with acetonitrile as a solvent in the ratio of 1 2 and re-examined the optimal acylation conditions. Although most amino acid n-propyl esters were completely acylated in 6 minutes at 30 °C or even room temperature, serine, tyrosine, lysine and tryptophan needed higher temperatures, up to 150 °C, but losses occurred at the higher temperatures. Gamerith concluded that the best compromise for all amino acids was 5 minutes at 150 °C [65, 66]. 

R = CH3 —> Af-methyl tauride N-acyl amino acids Example acyl sarcosinates... 

A2AKK5 Acyl-coenzyme A amino acid N-acyltransferase 1 46,070 8 1.0000 2 2... 

Cottingham, I.R., Austin, A., Sidebottom, C. and Slabas, A.R. (1988) Purified enoyl-[acyl-carrier-protein] reductase from rape seed Brassica napus) contains two closely related polypeptides which differ by a six-amino-acid N-terminal extension. Biochim. Biophys. Acta 954, 201-207. 

The N-terminal amino acid was acylated by a fatty acid molecule. Acid hydrolysis gave a mixture of saturated fatty acids, all with an even number of carbon atoms (C16-C24 major members C20 and C q). Partial hydrolysis gave N-acyl-D-phenylalanine, so the location of the D-amino acid residue became known (77). The hydrophobic character of this peptidolipid is to be noted. 

Hydrolysis permitted isolation and identification of eight amino acids N-methylglycine (sarcosine), three L-amino acids (valine, serine, lysine), two D-amino acids (cysteic acid, serine) as well as D-a//othreonine and L-2,3-diaminopropionic acid. Their configuration was determined by capillary gas chromatography on an optically active phase. No fatty acid was isolated by hydrolysis only methylketones were obtained, showing that the acyl part was derived from P-keto-acids with iso, anteiso and normal chains of length Ci4 C... 

Brzezinska KR, Demlng TJ (2001) Synthesis of ABA triblockcopolymers via acylic diene metathesis polymerization and living polymerization of alpha-amino acid-N-carboxyan-hydrides. Macromolecules 34 4348 354... 

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