Acids, A-acylamino

Azlactones (anhydrides of a-acylamino acids) are formed by the condensation of aromatic aldehydes with acyl derivatives of glycine in the presence of acetic anhydride and anhydrous sodium acetate. Thus beiizaldehyde and acetyl-... 

Alkylethers (269), R2 = alkyl, are obtained by the action of phosphorus pentasulfide on alkyl esters of a-acylamino acids (64, 334, 711) by means of the GabriePs synthesis (Section II.4), while aryl ethers (269), = aryl,... 

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

Stannyl esters have been prepared to protect a -COOH group in the presence of an -NH2 group [( -Bu3Sn)20 or -Bu3SnOH, CgH, reflux, 88%]. Stannyl esters of A -acylamino acids are stable to reaction with anhydrous amines and to water and alcohols aqueous amines convert them to ammonium salts. Stannyl esters of amino acids are cleaved in quantitative yield by water or alcohols (PhSK, DMF, 25°, 15 min, 63% yield or HOAc, EtOH, 25°, 30 min, 77% yield). ... 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

Cryoscopic studies have shown that a-acylamino acids undergo... 

The pH-sensitive liposomes consist of mixtures of several saturated egg phosphatidylcholines and several A -acylamino acids. The release of drug is suggested to be a function of acid-base equilibrium effected by the interaction between ionizable amino acids and N-acy-lamino acid headgroups of the liposomes. There appears to be a close relation between Tc and pH effect [72],... 

The two-step activation of oxazolidinones is depicted in Fig. 8.26. Hydrolysis yields an A-(l -hydroxy alkyl) derivative, which breaks down to liberate the peptide or A-acylamino acid (Fig. 8.26, Reactions a and b). Since oxazolidinones are prepared by the condensation of a peptide and an aldehyde (Fig. 8.26, Reaction c), the reverse reaction (i. e., one-step activation) cannot be excluded. Examples of this type of prodrug are provided by a series of oxazolidinones of the general structure 8.190 (R = PhCH20 R = H, Me, i-Pr, or PhCH2 R" = H, Me, or Ph Fig. 8.26) [248]. In phosphate buf-... 

Erlenmeyer synthesis org chem Preparation of cyclic ethers by the condensation of an aldehyde with an a-acylamino acid in the presence of acetic anhydride and sodium acetate. 3r-l3n,mT-3r sin-th3-s3s erucic acid org chem C22H42O2 A monoethenoid acid that is the cis isomer of bras-sidic acid and makes up 40 to 50% of the total fatty acid in rapeseed, wallflower seed, and mustard seed crystallizes as needles from alcohol solution, insoluble in water, soluble in ethanol and methanol. o rus ik as ad erythrite See erythritol. er o.thrTt ... 

In the third transition state (TS3), the neutral catalyst is recovered by transferring the proton back from the catalyst to the substrate. In other words, the (former) azlactone ether oxygen atom deprotonates the tertiary ammonium ion. For proton transfer, again an LBHB is formed (N-0 distance 2.479 A, <(0,H,N)=166.2°). In the product complex, the catayst is neutral and the A-acylamino acid ester is bound in its iminol form to the catalyst (Product(iininol)). Finally, an additional 66.6 kJ moF are gained by the subsequent iminol-amide tautomerization (Product(ainide)) (Fig. 1). 

A-Alkyl- and A-aryl-a-acylamino acids with a mixture of acetic anhydride and perchloric acid form 1,3-oxazolonium perchlorates... 

From Other A-Acylamino Acid Derivatives and Glycine Equivalents.. . 213... 

In addition, the use of an enantioselective or diastereoselective hydrolysis of racemic oxazolones offers another possibility to obtain new synthetic amino acids. Similarly, alcoholysis of 5(4H)-oxazolones gives the corresponding A -acylamino acid esters. 

TABLE 7.34. SYNTHESIS OF UNSATURATED 5(4/f)-OXAZOLONES FROM A-ACYLAMINO ACID DERIVATIVES AND VILSMEIER-HAACK REAGENT... 

If the starting A -acylamino acid contains a leaving group in the acyl group moiety then hydrolysis of the corresponding oxazolone 445 generates an acrylic acid derivative such as 446. Treatment of 446 with ammonia then produces glycyl-... 

In the heterocyclic series, racemic 3-(fur-2-yl)alanine has been prepared from furfural using this approach. In addition, (3-(pyrid-3-yl)alanine, ° p-(quinol-3-yl)alanine, ° a p-(benzofuranyl)alanine derivative, 2-amino-3-(2,2 -bipyridi-nyl)propanoic acid, and some interesting derivatives of histidines—in particular 1-alkylhistidines with amphiphilic properties have all been synthesized using this methodology. The complete reaction sequence starting from an aldehyde and an A-acylamino acid derivative is shown in Scheme 7.150. 

Reaction of A -acylamino acids with the Vilsmeier-Haack reagent leads to 2-alkyl-4-[(Af,Af-dimethylamino)methylene]-5(47i)-oxazolones 814. The reactivity of these compounds with various nucleophiles has been studied. Primary alkylamines undergo amine exchange with 814 to afford 2-alkyl-4-[(alkylamino)methylene]-5(4/i)-oxazolones 815 (Scheme 7.250). ° ... 

A convenient synthesis of a-acylamino aldehydes (541) has, for example, been developed which is based on the transformation of the a-acylamino acid (540) into its acylimidazolide with carbonyldiimidazole (79CC79). Diisobutylaluminum hydride reduction of the imi-dazolide then affords the aldehyde, generally in high optical purity (equation 6). 

Some reactions of munchnones occur via acylamino ketenes, the covalent valence tautomers of the betaines. The ketenes are intermediates in the thermolysis (see Scheme 22) and in the formation of azetidinones from imines (equation 69) they are thought to be involved in the aminolysis of the mesoionic compounds, which results in amides of a-acylamino acids, and in the formation of the benzodioxin (247) by the combined action of acetic anhydride and tetrachloro-o-benzoquinone on Af-benzoylalanine (equation 70). 

The standard procedure for the preparation of 5(4/J)-oxazolones is dehydration of a-acylamino acids with acetic anhydride (equation 150). Saturated azlactones lacking a substituent at C(4) are rather sensitive and difficult to isolate and in such cases it is... 

The standard method of preparing anhydro-5-hydroxyoxazolium hydroxides (300) is by dehydration of iV-substituted a-acylamino acids, usually with acetic anhydride (equation 154) dicyclohexylcarbodiimide and trifluoroacetic anhydride have also been used. N-Acylglycines (299 R3=H) give rise to unstable mesoionic oxazoles which tend to dimerize (see Section 4.18.3.1.5(0) if such acids are treated with trifluoroacetic anhydride, stable trifluoroacetyl derivatives (300 R3 = CF3CO) are isolated. Numerous unstable betaines (300 R1, R = alkyl or aryl, R -H) have been generated by the action of triethylamine on the corresponding hydroperchlorates, prepared by the method shown in equation (151). 

The phosphaalkyne 403 adds to 3-phenylsydnone regioselectively to give the heterocycle 404 in high yield. Mnchnones (l,3-oxazolium-5-olates), traditionally generated by the cyclodehydration of A-acylamino acids using acetic anhydride or a carbodiimide, also take part in cycloadditions, as exemplified in Scheme 89 <1996JA2574>. The... 

More than 25 years ago Wakamatsu et al. [ 11 a] found that aldehyde 1 could be coupled with carboxamides 32 and carbon monoxide under pressure to give A -acylamino acids 33, a process catalyzed by octacarbonyldicobalt and known as... 

Another route to carboxylic acids from aldehyde products (once again, generally produced via hydroformylation catalysis) was discovered by Wakamatsu and coworkers. They reported the carbonylation of aldehydes and primary organic amides to produce A-acylamino acids (equation 16). The reaction is efficiently catalyzed by HCo(CO)4 at 100 °C and 140 bar of 3 2 H2/CO (hydrogen is needed to help stabilize HCo(CO)4). Yields of over 90% of the appropriate... 

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