Amino acid monoesters

Substitution in the amino or carboxyl group or in both transforms amino acids into acids, bases or neutral compounds, i. e., the zwitter ion character is lost. The derivatives remain more or less polar, depending on the type of substituent. This must be borne in mind when the solvent is chosen. Substitution products which still possess a free carboxyl and free amino group (e. g., monoacyl derivatives of basic amino acids, monoesters of acidic amino acids or ethers of hydroxy-amino acids) behave chromatographically like free amino acids. 

Protein phosphatases are classified according to their activity toward phospho-amino acids they act on (Fig. 1). Nomenclature is independent of regulation simply because stimuli were unknown. Protein phosphatases hydrolyzing O-phospho-monoesters are currently subdivided into two major classes (i) phosphatases acting on phosphoserine (pSer) and phosphothreonine (pThr), and (ii) the second class... 

Staphylococcal nuclease (SNase) is a single-peptide chain enzyme consisting of 149 amino acid residues. It catalyzes the hydrolysis of both DNA and RNA at the 5 position of the phosphodiester bond, yielding a free 5 -hydroxyl group and a 3 -phosphate monoester... 

A more complex pathway of activation is seen in N-amino acid derivative of phosphoramidic acid diesters of antiviral nucleosides, as exemplified by prodrugs of stavudine (9.79, Fig. 9.14) [153 -155], The activation begins with a carboxylesterase-mediated hydrolysis of the terminal carboxylate. This is followed by a spontaneous nucleophilic cyclization-elimination, which forms a mixed-anhydride pentacycle (9.80, Fig. 9.14). The latter hydrolyzes spontaneously and rapidly to the corresponding phosphoramidic acid monoester (9.81, Fig. 9.14), which can then be processed by phosphodiesterase to the nucleoside 5 -monophosphate, and by possible further hydrolysis to the nucleoside. 

Long N-Acyl g-Amino Acid POE Monoesters (No 5 series)... 

Table 12 shows the chemical shift for the CH-CH part of selected (/ ,/ )-tartaric acid monoesters of amino alcohols, mainly well-known /1-blockers. As can be easily seen, the chemical shifts of the (R)- and (S)-amino alcohol derivatives lie within a narrow range, dependent on the kind of tartaric acid used. Monoesters of a-amino (/f)-alcohols with (R,R)-0,0-diacetyl- or... 

For example, on reaction with (S)-jV-(methylsulfonyl)phenylalanyl chloride, meso-2-cy-clopentene-l,4-diol yields, besides the diester, the two diastereomeric monoesters which are separated chromatographically95. Since the absolute configuration of the amino acid moiety is known, it is (in principle) sufficient to determine the relative configuration at the three stereogenic centers in the monoesters, e.g., by an X-ray analysis (see p 473 for assignment by chemical correlation). 

Protected-amino phosphonic acid monoesters 51 are usually activated by conversion to the phosphonochloridates 52, then coupled with appropriate amine components such as C-protected amino adds or peptides to give phosphonoamidates 53 (Scheme 17). This procedure is in contrast to typical peptide coupling conditions, in which carboxylic acid chlorides are avoided because of their susceptibility to epimerization at the a-carbon. Since enolate-... 

GSH is not transported into cells. For circulating GSH to increase intracellular GSH concentrations, it must first be hydrolyzed to Glu and CysGly, which are subsequently transported into the cell and serve as substrates for GSH synthesis. Thus, GSH administered orally or parenterally, and that produced by the liver and released into the circulation enhance tissue levels of GSH by providing a source of its constituent amino acids. In contrast, GSH monoesters, which are well absorbed after oral administration, as is GSH, are readily transported to cells and then hydrolyzed to GSH and the corresponding alcohol. Thus, higher cellular levels of GSH result from oral administration of GSH monoesters than from oral administration of comparable doses of GSH. 

Figure 7 Preparation of chiral synthon for (3-3-receptor agonist (A) enzymatic resolution of racemic amino acid amide (8) by amidase from M. neoaurum ATCC 25795 (B) enzymatic resolution of racemic amino acid amide (10) by amidase from M. neoaurum ATCC 25795 (C) enzymatic asymmetric hydrolysis of diester (12) to the corresponding (>S)-monoester (13) by pig liver esterase.

The 4-picolyl (Pic) esters were introduced by Young and et al.P and are also used for the side-chain protection of Asp and Glu.P l Synthesis of Boc-Asp(OPic)-OH and Boc-Glu(OPic)-OH is achieved by reaction of the Boc amino acids with 4-pyridyhnethanoFDCC in di-chloromethane and subsequent partial saponification of the diesters with hthium hydroxide to give the (3- and y-monoesters, respectively. 

Many modified Marckwald procedures are available to prepare structurally diverse imidazoles most of them are focused on the preparation of an oe-aminoketone or its equivalents. For example, a regiospecific synthesis of trisubstituted imidazoles has been developed. Thus, treatment of BOC-protected a-amino acids 1265 with malonic monoester leads to a-aminoketones. After removal of the BOC protecting group, the resulted a-aminoketone salt 1266 will condense with isothiocyanates to form thioureas 1267. The intermediates 1285 undergo cyclodehydration under acidic conditions, yielding imidazole-2-thiones 1268 in good yields. Both reductive and oxidative desulfonation have been used to convert the imidazole-2-thiones 1268 into imidazoles (1269 or 1270) (Scheme 321) <2005TL7315>. 

Glycine is the only a amino acid without a chiral centre, but replacing one of the two protons on the central carbon with, say, deuterium creates one the CH2 carbon is prochiral. Similarly, converting malonate derivative into its monoester makes a chiral centre where there was none the central C is prochiral. 

Amino acid analyses of phosvitin preparations also indicated inhomogeneity. It is striking, however, that an equal number of )3-hydroxyamino acids and of phosphorus atoms were found to be present. The phosphorus is alkali-labile at room temperature. Phosvitin is readily dephosphorylated with the aid of an acid phosphatase from citrus fruits (5). Bone phosphatase, on the other hand, does not liberate phosphorus. Moreover, the base binding capacity of this protein indicates that all of the phosphate groups are present in the form of monoesters with two dissociable hydroxyls. 

Tetramic acids are substructures of natural products that show antimicrobial activity. An access to these structures started from Wang resin-bound Fmoc-protected amino acids, which were deprotected and reductively alkylated. These intermediates 111 were transformed into amides, for example with malonic acid monoesters or aryl acetic acids (112 and 114, respectively). Cyclative cleavage was induced with 0.1 M NaOEt at 85 °C and gave substituted tetramic acids 113 and 115 in yields and purities of generally >95% (Scheme 30) [46]. 

Depending on the reaction conditions, a-iminodicarboxylic acid derivatives or 2,6-di-piperazinediones [120] are formed from a-amino acids, oxocompounds and isocyanides. The isomeric 2,4-piperazinediones can thus also be formed by some of the U-4CR of vicinal diamines, isocyanides, oxocompounds and glyoxylic monoesters [121,122],The libraries of highly substituted 2-piperazones were produced by the chemists of Merck Inc. from N-monosubstituted ethylenediamines, carboxylic acids, isocyanides and chloroacetalde-hyde. 

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