Butyric 3-amino-, esters

Diacetoxymercuriphenyl-a-amino) butyric ethyl ester, dichloride, dibromide,... 

The first enzymatic reaction investigated in the whole project concerned the introduction of chirality in route B (Fig. 2) by generation of succinic acid mononitrile (R)-12 from its racemic precursor. Since in a broad sense the nitrile ester substrate 10 can be interpreted as an amino acid analogue, proteases recommended themselves as catalysts to be tested. From the literature, 2-substituted succinic and butyric acid esters were known to be resolved by proteases [6, 7]. Proteases are... 

More recently, BackvalFs group reported the DKR of the jS-amino ester, ethyl 3-amino-3-phenylpropanoate, using Candida antarctica lipase A (CAL-A) immobilised in mesocellular foam (GamP-MCF) in combination with the methoxy analogue of Shvo s catalyst at 90°C. It was shown that the use of 2,4-dimethyl-3-pentanol as a hydrogen donor allowed side product formation to be suppressed. Thus, the reaction performed in the presence of trifluoroethyl butyrate as the acyl donor provided the corresponding (5)-amide in 85% yield and 89% ee. 

Asymmetric addition of 4-chlorophenylboronic acid (2u) to a,P-unsaturated y-amino ester (26a), followed by deprotection and ester hydrolysis gave optically active 4-amino-3-(4-chlorophenyl)butyric acid (Baclofen) hydrochloride (Scheme 4.10), which plays an important role in various nervous system functions. The best result was observed with a large excess of organoboronic acids (5.0 equiv to 26a) in a 10 1 dioxane-water mixture containing aqueous cesium carbonate [24]. 

The influence of structural and electronic parameters on the acylation and deacylation rate were separately studied (catalyst-on half cycle vs. catalyst-off half cycle cf. scheme 7.10). Through kinetic H-NMR-studies it was proven that the acylation rate of the dialkyl amino alcohol catalysts and an acyl donor (butyric anhydride) depends on the number of (carbon) spacer atoms between hydroxyl and tertiary amine, the flexibility of the molecule and the presence and position of further heteroatoms. Besides, it could be detected that the methanolysis (off-half cycle) of the formed ]3-amino ester intermediate follows a similar trend as the acylation reaction, but appeared to be rate limiting in this studies setup. The information was used for the selective auto-catalytic acylation and deacylation of complex natural antibiotics. 

Acetoacetic esters react with difluoroamine to give alkyl 3,3-bis(difluoro-amino)butyrates [lOI] (equation 87). 

Chemical Name Prednisolone 21 -[4 -[p-bis(2-chloroethyl)amino] phenyl] butyrate Common Name Prednisolone chlorambucil ester... 

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

Tetracaine Tetracaine, the 2-diethylaminoethyl ester of 4-butylaminobenzoic acid (2.1.6), is also structurally analogous to procaine, in which the amino group of the benzene ring is replaced by a butylamine radical. The methods for its synthesis are the same as the above-mentioned methods for procaine or chloroprocaine, with the exception of using 4-butylaminobenzoic acid in place of 4-aminobenzoic acid. There is also a proposed method of synthesis that comes directly from procaine (2.1.1). It consists on its direct reaction with butyric aldehyde and simultaneous reduction by hydrogen using a palladium on carbon catalyst [6]. 

Carnitine, L-3-hydroxy-4-(trimethylammonium)butyrate, is a water-soluble, tri-methylammonium derivative of y-amino-jS-hydroxybutyric acid, which is formed from trimethyllysine via y-butyrobetaine [40]. About 75% of carnitine is obtained from dietary intake of meat, fish, and dairy products containing proteins with trimethyllysine residues. Under normal conditions, endogenous synthesis from lysine and methionine plays a minor role, but can be stimulated by a diet low in carnitine. Carnitine is not further metabolized and is excreted in urine and bile as free carnitine or as conjugated carnitine esters [1, 41, 42]. Adequate intracellular levels of carnitine are therefore maintained by mechanisms that modulate dietary intake, endogenous synthesis, reabsorption, and cellular uptake. 

Data taken from ref. 22. Rate constants are not listed for amino acid esters such as methyl 4-amino-n-butyrate where lactamization occurs (see ref. 38). b In the case of the cysteine esters, E = SCH2CH(NH2)C02R EH = HSCH2CH(NH2)C02R EH = SCH2CH(NH3)C02R... 

Amino-4-(ethylmercapto)-butyric acid, S-ethyl-L-homocysteine, homocysteine-S-ethyl ester. 

Lipase-catalyzed acylation of one isomer of iV-hydroxymethyl /3-lactam 121 by vinyl butyrate in acetone yielded the ester 122, which afforded 123 after acidic hydrolysis and ion-exchange chromatography (Scheme 7). The unesterified alcohol 124 gave the /3-amino acid 125. Similar reactions yielded 2-aminocyclohex-3-en-l-carboxylic acid and 2-aminocyclohex-4-ene-l-carboxylic acid from l-azabicyclo[4.2.0]oct-3-en-8-one and l-azabicyclo[4.2.0]oct-... 

The hydrogenation of 2,4-diketo acid derivatives to the corresponding 2-hydroxy compounds with cinchona-modified Pt catalysts as depicted in Figure 2.4 can be carried out with chemoselectivities more than 99% and enantioselectivities up to 87% (R) and 68% (S), respectively [30a]. Enrichment to more than 98% ee was possible for several substrates by recrystallization, giving rise to an efficient technical synthesis of (R)-2-hydroxy-4-phenyl butyric acid ethyl ester [30b], a building block for several ACE (angiotensin-converting enzyme) inhibitors, as well as some enantio-merically enriched a-hydroxy and a-amino acid esters (see below) [30c]. 

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