Amino acids from esters

A polymer-supported sulfonamide, prepared from an amino acid activated ester and a polystyrene-sulfonamide, is stable to acidic hydrolysis (CF3COOH HBr/ HOAc). It is cleaved by the safety-catch method shown below. ... 

The starting point for this amino acid, from which nylon 11 is obtained, is the vegetable product castor oil, composed largely of the triglyceride of ricinoleic acid. This is first subjected to treatment with methanol or ethanol to form the appropriate ricinoleic acid ester. 

A polymer-supported sulfonamide, prepared from an amino acid activated ester... 

A solution of a 2-aminobenzophenone (0.1 mol) and an z-amino acid ethyl ester hydrochloride (0.15 mol) in pyridine (200 mL) was refluxed. During the first 4h, 20-50 mL of liquid was allowed to distill and was replaced by fresh pyridine. Heating was continued for a further 11 h, the mixture was evaporated under reduced pressure and H20 and Et20 were added. In most cases some of the reaction product remained undissolved and was filtered off. The aqueous layer was separated, made alkaline and extracted with Et20. The comhined F.t20 phases were washed with H20. dried and evaporated and the reaction product was separated from unchanged amino ketone by crystallization. 

Polymerization of a stable intermediate prepared from two monomers can produce an alternating copolymer. The amino acid azide hydrobromide method and the amino acid succinimidyl ester hydromide method were applied to prepare ordered copolyamides277) and sequential copolypeptides278-280). 

Anomalous Amino Acids from Aziridine-2-carboxylic Esters. 105... 

FMF Chen, NL Benoiton. Hydrochloride salts of amino acid benzyl esters from />-toluenesulfonates. Int J Pept Prot Res 27, 221, 1986. 

Scheme 6.90 Chiral N-benzoyl-protected a-amino acid allyl esters obtained from 64- and 78-catalyzed asymmetric DKR of racemic azlactones derived from racemic natural nonnatural a-amino acids.

Scheme 6.91 Typical enantioenriched (R)-oxazinones and (S)-configured N-benzoyl-protected 5-amino acid allyl esters obtained from the 78-catalyzed kinetic resolution of racemic oxazinone mixtures subsequent isolation of the ester through (R)-oxazinone hydrolysis.

In a similar study to that outlined by Grigg, Kanemasa et al. (68) has demonstrated the intramolecular cycloaddition of azomethine ylides derived from either amino acids or esters. Treatment of the amino methyl ester 302 with... 

In this section, the synthesis of the first segment, compound 1 in Scheme 2, is presented as an example. Elongation of the segment is performed stepwise from the C-terminal amino acid Pac ester as shown in Scheme 3J5l... 

Research to date focused on isolating insecticidal prototype leads from marine origin has resulted in the report of about 40 active compounds.44 In an attempt to summarize these compounds and their activity margins, they have been categorized into seven classes of chemical structures polyhalogenated monoterpenes, polyhalogenated C15-metabolites, diterpenes, peptides and amino acids, phosphate esters, sulfur-containing derivatives, and macrolides. 

In analogy to proline dipeptides, A1-unprotected 2-carbonylpyrazolidine amino acid dipeptide esters 37 on storage at ambient temperature are prone to conversion into the related triazines 38 that correspond to the aza analogues of piperazine-2,5-diones (Scheme 5). 160 161 An additional side reaction is reported for the 2-azaproline peptides 161 which leads to formation of the cyclic imide 40 from methyl TV -lbenzyloxycarbonylj -carbonylpyra-zolidine glycinate (39) upon treatment with methanolic ammonia (Scheme 6). 

The method of Kim et al.[89-93] starts from the synthesis of the three-carbon phosphonium salt according to the modified method of Corey et alJ94,95] The Wittig reaction of the phosphonium salt with a Z-protected a-amino aldehyde using potassium hexamethyldisilazanide provides the ds-alkene without racemization. Efficient hydrolysis of the orthoester without double bond migration is achieved by acidolytic hydrolysis with aqueous hydrochloric acid in tert-butyl alcohol under reflux conditions. Then, an a-amino acid methyl ester is coupled. The desired epoxide product is obtained by treatment with 3-chloroperoxybenzoic acid. The epoxidation reaction is stereoselective and predominantly provides one isomer (R,S S,R = 4-10 1). The trans-epoxide can also be prepared using a trans-alkene-containing peptide. A representative synthetic procedure to obtain the ds-epoxide isostere is detailed below. 

Figure 11.7 The relationship between the hydrophobicity of the side chain of the amino acid and kcJKM for the hydrolysis of A-acetyl-L-amino acid methyl esters by chymotrypsin. Energies are in kcal/mol. [From V. N. Dorovskaya, S. D. Varfolomeyev,...

Dipeptides with C-terminal 1-aminoalkylphosphonic acids such as L-Ala-L-Alap (8), can be coupled to another amino acid active ester using the same methods used in the synthesis of dipeptides. The dipeptide can be extended from the N-terminal up to hexapeptides. Generally, the yield for each step is >60% J7 ... 

Several other practical syntheses of enantiopure amino acid derivatives have been accomplished recently from substrate 35 (Chart 10.6). The Imperiali group has used two techniques following PTC alkylations that occurred with modest enantioselectivity (50-53% ee). The first involved fractional recrystallization followed by subsequent deprotection/reprotection to give 39 (>99% ee). In the second method, enzymatic hydrolysis of the amino acid methyl ester with alkaline protease and then nitrogen acylation gave 40 (99% ee) [16]. Several other publications that deal with related purification techniques have appeared [17-19]. 

In addition to the mobile phase composition, the effect of other parameters such as temperature, flow rate, pH, and structure of the analytes were also studied, but only a few reports were available in the literature. In 1995, Lin and Maddox [66] studied the effect of temperature on the chiral resolution of amino acids and esters. The temperature was varied from 5°C to 25°C and it was reported that the resolution improved at low temperature. Hyun et al. [48-50,67] carried out the effect of temperature on the chiral resolution of amino alcohols, amines, fluoroquinolones, and other drugs. Again, lowering of temperature resulted in better resolution. The effect of temperature on the chiral resolution of phenylalanine, phenylglycine, and 2-hydroxy-2-(4-hydroxy-phenyl)-ethyl amine is shown in Table 5 [50], which indicates an increase in retention factors at lower temperature, but the best separation occurred at 20°C. These experiments indicated the exothermic nature of chiral resolution on CCE-based CSPs. Lin and Maddox [66] also studied the effect of flow rate on the chiral resolution of... 

A further application of silylated amino acids is the formation of /3-lactams by treating N-TMS-0-amino acid-TMS-esters (497) with Grignard reagents under cycli-zation262 (Scheme 74). From N-TMS-a-phenyl-/ -alanin-TMS-ester (497) via the silylated product (498), 3-phenyl-2-azetidinone (499) can be obtained. 

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