Amino acid ester hydrochlorides

N,iV -Sulfinyldiimidazole has also been recommended as a condensing agent for peptide syntheses.[22] In a one-pot reaction the JV-protected amino acid, sulfinyldiimi-dazole, amino acid ester hydrochloride, and triethylamine combine to form the peptide in good yield. Thus, the peptide Z-Asp(OCH2C6H5)-Phe-OCH3 was obtained in 89% yield.[23]... 

Table 14 1 /Is. Dn values of permethylated cyclic oligosaccharide hosts with amino acid ester hydrochloride guests...

Chem Pharm Bull 13 995 (1965) (amino acid ester hydrochloride salts)... 

Recently, the enantiomeric excess of a-amino acid ester hydrochlorides has been determined directly by using FAB (fast atom bombardment) mass spectrometry without chromatographic separation of the enantiomers. ... 

Achiral binuclear reagents have been added to mixtures of a chiral crown ether (74) and chloroform-soluble amino acid ester hydrochlorides to enhance the chiral discrimination in the NMR spectrum. The [Ln(fod)4] preferentially associated with the enantiomer in the bulk solution such that the enantiomer with lower association with 74 showed the larger lanthanide-induced shifts. The system also enhanced the chiral discrimination in acetonitrile-fifs, although [Pr(fod)4] was needed because it causes larger shifts than the... 

A/ -Bis(methylsulfanyl)methylene amino acid esters such as 132 are prepared from the amino acid esters hydrochlorides upon deprotonation with a base by reaction with carbon disulfide and iodomethane (Scheme The corresponding glycine methyl ester is commercially... 

To a soln of amino acid ester hydrochloride (1 mmol) and KOBt (1 mmol) in CH2CI2 (3 mL) was added a soln of Fmoc amino acid chloride (1 mmol) and KOBt (1 mmol) in CH2CI2 (3 mL). The mixture was stirred for 3 h then washed with aq 5% NaHC03, 5% HCl, HjO, sat aq NaCl soln, and dried. The organic layer was concentrated and the residue recrystallized (CHjCyhexane) yields 70-80% (Table... 

Carbodiimides are known to react with primary amines to form guanidines.f In the case of amino acid esters, a subsequent elimination of alcohol is possible with formation of an imino-hydantoin species (Scheme 8). However, these reactions usually require higher temperatures or the occurrence of acid catalysis and therefore can be neglected when unprotonated amino acid derivatives are acylated using carbodiimides. On the other hand, this side reaction becomes more important when protonated amino acids (i.e., amino acid ester hydrochlorides) are coupledf and these byproducts may occur. 

The amino acid (0.05 mol) is heated in ethanol (100 ml) saturated with dry HCl. After removal of the solvent under reduced pressure, the residue of the amino acid ester hydrochloride is dissolved in ice-cold water (100 ml), and 2.3% sodium amalgam (200g) is added slowly with stirring, the pH being... 

Alexander and Busch first described the preparation of complexes of the type cis-[Co(en)2(CH2CHjC02R)Cl]Cl2 (29) by reacting the appropriate amino acid ester hydrochloride with trans-[Co(en)2Cl2]Cl in aqueous solution, the free amino acid ester being generated in situ by the presence of a weakly coordinating base such as McaNH. 

Peptide synthesis. Sheehan and co-workers used this water-soluble reagent for a simplified and rapid synthesis of tetra- and pentapeptides without isolation of intermediates. The reagent (I. I equiv.) is added to a solution of the N-carbobenzoxy-amino acid (I equiv.), the amino acid ester hydrochloride or peptide ester hydrochloride (1 equiv.), and triethylamine (1 equiv.) in methylene chloride. After I hr. at room temperature the solution was washed successively with water (to remove excess reagent and the urea), dilute hydrochloric acid, and sodium bicarbonate solution. The curbobenzoxy group Is removed by hydrogenolysis and the product used directly in the next step. ... 

N-Protection of amino acids.1 The reagent reacts with an amino acid ester hydrochloride, for example that of glycine (4) in chloroform containing triethyl-... 

The reagent (1) also effects synthesis of dipeptides from an N-acylamino acid and an amino acid ester hydrochloride. Yields are in the range of 70-80%. The optical yield in the one case reported was 86%. 

Thioxo-l,3,6-thiadiazocin-5-ones (36) are conveniently prepared from a-amino acid ester hydrochlorides in one pot by sequential treatment with carbon disulfide, followed by 2-bromoethylamine hydrobromide (Scheme 28) <90SC2675>. Starting with L-tyrosine leads to an optically active thia-diazocine indicating that racemization does not occur during the reaction. 

Amides from Carboxylic Acids Peptide Synthesis. Analogous to ester formation, reaction of equimolar amounts of a carboxylic acid and (1) in THF, DMF, or chloroform, followed by addition of an amine, allows amide bond formation. The method has been applied to peptide synthesis (eq 5). One equivalent of (1) is added to a 1M solution of an acylamino acid in THF, followed after 1 h by the desired amino acid or peptide ester. The amino acid ester hydrochloride may be used directly instead of the free amino acid ester. An aqueous solution of the amino acid salt can even be used, but yields are lower. 

The Schiff bases are obtained in situ by mixing sodium salicyaldehyde (10-30% molar excess) with amino acids or amino acid ester hydrochlorides (10-15 fivnol) in methanol. Spectral measurements are carried out 1-4 hr... 

Amino acid ester hydrochlorides were added to cyclo(L-Pro-Sar-Sar)2 In organic solvents. Very little change of the cd spectrum of cyclo(L-Pro-Sar-Sar)2 was observed when an excess amount of DL-vallne ethyl ester hydrochloride was added In dloxane/ethanol(4 5 v/v) mixture. 

A series of various enantiomerically pure amino acid ester isocyanates (for example 452) has been synthesized in yields of 72-95% by carbonylation of the appropriate amino acid ester hydrochlorides (for example 451) with phosgene [311]. The products are based on the amino acids alanine, valine, leucine, isoleucine, phenylalanine, methionine, serine, and glutamic acid. 

An earlier publication [312] described the synthesis of d,l-amino acid ester isocyanates (at that time called dj-carhonyl-amino acid esters) from the corresponding amino acid ester hydrochlorides by carbonylation with phosgene. Ester hydrochlorides of alanine, leucine, phenylalanine 451, aminobutyric add, phenyl glycine, norvaline, norleucine, benzyl cysteine, methionine, aspartic acid, and glutamic acid were used yields of isocyanates were 85-97%. 

The carbonyldiimidazole-based approach has been successfully applied to the synthesis of some more sophisticated urea dipeptides, which represent building blocks for the preparation of inhibitors of HIV-protease. These compounds are simply obtained by sequential addition of GDI and the requisite amino acid ester hydrochloride to the selected amino acid p-toluenesulfonic acid salt 1020 in the presence of triethylamine, DIEA, or N-methylmorpholine (NMM) and avoiding the use of strong bases such as BuLi or lithium diisopropylamide (LDA), which can racemize the stereogenic centers [753],... 

The acetoacetyl derivatives are obtained by the reaction of the amine with diketene . In the case of amino acid ester hydrochlorides the presence of one equivalent of sodium methoxide or of a tertiary base is necessary. The group is removed by applying the conditions of the Knorr synthesis of pyrazol derivatives from various /3-keto esters and their derivatives . The protecting group is removed in acetic acid by using an equimolar amount of phenylhydrazine (reaction 3). 

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