Masked amino acid

The oxazolidine-2,5-dione heterocycle, perhaps better known as the N-carboxyanhydride of an amino acid, has been incorporated employing a modification of chloromethylated poly(styrene) (192) (76USP3985715). The reaction sequence involved utilization of a masked amino acid, ethyl acetamidocyanoacetate (205). The amino acid was liberated in a subsequent hydrolysis/decarboxylation step (Scheme 98). The cyclized, IV-carboxyanhydride-functional resins (206) were reported to be useful in solid phase peptide synthesis and as supports for enzyme immobilization. 

Aliphatic aldehydes typically provide only moderate yields in the Biginelli reaction unless special reaction conditions are employed, such as Lewis-acid catalysts or solvent-free methods, or the aldehydes are used in protected form [96]. The C4-unsubstituted DHPM can be prepared in a similar manner employing suitable formaldehyde synthons [96]. Of particular interest are reactions where the aldehyde component is derived from a carbohydrate. In such transformations, DHPMs having a sugar-like moiety in position 4 (C-nucleoside analogues) are obtained (see Section 4.7) [97-106]. Also of interest is the use of masked amino acids as building blocks [107, 108]. In a few cases, bisaldehydes have been used as synthons in Biginelli reactions [89, 109, 110]. 

The bislactim heterocycle behaves like a masked amino acid moiety and, after (9-acylation, acidic hydrolysis furnishes the A-acyl amino acid ester 644 as a single diastereomer (Scheme 88). The acetyl group migrates from oxygen to nitrogen on distillation of the product. 

Most of the activation methods known from conventional peptide synthesis in solution were explored on polymer concerning their desired reactivity in relation to side reactions, which are particularly unfavorable if the by-products are also bound to the support. Though urethane-masked amino acids generally are shielded from racemization under controlled conditions, this problem limits the use of peptidic building blocks C-terminally activated, since they tend to form the redoubtable oxazolinone intermediate from which the abstraction of a -proton is facilitated (Fig. 40). Recent results indicated a chance to overcome this problem and will be mentioned in the proper section of this chapter. 

As a further consequence of the high reactivity of the excessive 0-acyl isourea in the heterogeneous peptide synthesis mixture, a base-catalyzed intramolecular 0-N-acyl migration takes place, forming the inactive N-acyl dicyclohexylurea. At the same time, this by-product is formed by acylation of already formed still dissolved amounts of dicyclohexylurea, which can be attacked by the symmetric anhydride or the 0-acyl isourea of the carboxylic component as well. Both the N,0-acyl shift and the latter side reaction decrease the total concentration of the activated masked amino acid even N,N -diacyl derivatives of the urea also can be formed as further by-product. Fortunately, all of these acyl urea derivatives are not fixed to the polymer phase and are well soluble in dichloromethane, so that they can be washed out easily from the gel phase after the... 

Figures. The methods for preparation of peptide aldehydes. Methods 1 and 2 prepare an N-terminal aldehyde peptide by oxidation of an N-terminal Ser-peptide or hydrolysis of a dimethoxyacetate-peptide. Methods 3-7 prepare C-terminal aldehyde peptides. Methods 3 and 4 are known as the n + 1 method. The peptide alkyl ester or alkyl thioester is obtained from different types of resins then a masked amino acid glycodiol ester is introduced by enzymatic synthesis (3a, 3b) or by a chemical method (4) finally, the peptide is treated with TFA to give the aldehyde peptide. In methods 5 and 6, aldehyde peptides are obtained from oxidation of a peptide glycol diol ester. In method 7, treatment of an N-protected peptide thioester resin with Pd" and EtjSIH gives the cleaved C-terminal peptide aldehyde.

The Bucherer-Bergs reaction was also employed to install the masked amino acid functionality present in the diester intermediate 45, key for the synthesis of methionine amide 46 (LY2140023) (Scheme 10.12) [42],... 

Compound 71 has a masked amino acid, while 72 already has an amino acid moiety, which makes both of them suitable building blocks for the synthesis of... 

Circular dicliroism has been a useful servant to tire biophysical chemist since it allows tire non-invasive detennination of secondary stmcture (a-helices and P-sheets) in dissolved biopolymers. Due to tire dissymmetry of tliese stmctures (containing chiral centres) tliey are biaxial and show circular birefringence. Circular dicliroism is tlie Kramers-Kronig transfonnation of tlie resulting optical rotatory dispersion. The spectral window useful for distinguishing between a-helices and so on lies in tlie region 200-250 nm and hence is masked by certain salts. The metliod as usually applied is only semi-quantitative, since tlie measured optical rotations also depend on tlie exact amino acid sequence. 

Amino acid anion 1743-1729 Often masked by water deformation band near... 

The phenyl group became a practical protective group for carboxylic acids when Sharpless published a mild, effective one-step method for its conversion to a carboxylic acid. It has recently been used in a synthesis of the amino acid statine, where it served as a masked or carboxylic acid equivalent. ... 

The enantioselective inverse electron-demand 1,3-dipolar cycloaddition reactions of nitrones with alkenes described so far were catalyzed by metal complexes that favor a monodentate coordination of the nitrone, such as boron and aluminum complexes. However, the glyoxylate-derived nitrone 36 favors a bidentate coordination to the catalyst. This nitrone is a very interesting substrate, since the products that are obtained from the reaction with alkenes are masked a-amino acids. One of the characteristics of nitrones such as 36, having an ester moiety in the a position, is the swift E/Z equilibrium at room temperature (Scheme 6.28). In the crystalline form nitrone 36 exists as the pure Z isomer, however, in solution nitrone 36 have been shown to exists as a mixture of the E and Z isomers. This equilibrium could however be shifted to the Z isomer in the presence of a Lewis acid [74]. 

An unusual solvent system was chosen for the intramolecular reductive alkylation of the masked amino ketone (15). The purpose of the strongly acid system was to prevent cyclization of the deblocked amino ketone to 16, further hydrogenation of which gives the unwanted isomer 17 by attack at the convex face. The desired opposite isomer can be obtained by reduction of 16 with UAIH4 (52). 

A-Acido imines (R R"C = N —X=0) like /V-acyl (X = CR) /V-sulfonyl [X = S(R)=0]2-7 or /V-diphenylphosphinoylimines [X = P(C6H5)2]3 are masked inline derivatives of ammonia. Compared to the imines themselves these activated derivatives are better electrophiles showing less tendency to undergo undesired deprotonation rather than addition of organometal-lics1812 The apparent advantages of these compounds have been exploited for asymmetric syntheses of amines, amides, amino acids and /J-lactams1-8 I6. 

In salt substitutes, the metallic or bitter taste of potassium chloride is often masked by other ingredients, such as the amino acid L-lysine, tricalcium phosphate, citric acid, and glutamic acid. 

This fully aromatic amide, based oil the amino acid p-aminobenzoic acid, can be spontaneously synthesized from p-aminobenzoic chloride.7 9 72 To prevent this occurring at an unwanted moment, the amine group is masked by forming the hydrochloric acid salt with hydrochloric acid. 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

The choice of fixation is a matter of experience, since the changes in the antigenicity of the component of interest resulting from the treatment with the fixative cannot be predicted. The epitope (amino acid sequence), against which the antibody was raised, may be hidden (masked), modified or completely lost as a result of an inadequate fixation (Shi et al. 2001). No ideal fixative has been found that can be used universally in immunohistochemistry. The choice of the adequate... 

---