Hydroxy acid modifying

S)-omino acid modifier (S)- hydroxy acid modifier... 

Based on these preliminary findings, related couplings to pyruvates and iminoacetates were explored as a means of accessing a-hydroxy acids and a-amino acids, respectively. It was found that hydrogenation of 1,3-enynes in the presence of pyruvates using chirally modified cationic rhodium catalysts delivers optically enriched a-hydroxy esters [102]. However, chemical yields were found to improve upon aging of the solvent 1,2-dichloroethane (DCE), which led to the hypothesis that adventitious HC1 may promote re-... 

New modifiers have traditionally been discovered by the trial-and-error method. Many naturally occurring chiral compounds (the chiral pool38) have been screened as possible modifiers. Thus, the hydrogenation product of the synthetic drug vinpocetine was discovered to be a moderately effective modifier of Pt and Pd for the enantioselective hydrogenation of ethyl pyruvate and isophorone.39 Likewise, ephedrine, emetine, strychnine, brucine, sparteine, various amino acids and hydroxy acids, have been identified as chiral modifiers of heterogeneous catalysts.38... 

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... 

G Galaverna, R Corradini, A Dossena, R Marchelli. Histamine-modified cationic /3-cyclodextrins as chiral selectors for the enantiomeric separation of hydroxy acids and carboxylic acids by capillary electrophoresis. Electrophoresis 20 2619-2629, 1999. 

Amino acid-modified furocoumarins were prepared by condensation of the T-hydroxysuccinimide ester of 3-(2,3,5-trimethyl-7-oxofuro[3,2-g]chromen-6-yl)propanoic acid 51 with amino acids <2003JPH177>. Ethyl 3-(7-hydroxy-4-methyl-2-oxo-2/7-3-chromenyl)propanoate 49, prepared in 56% yield by Pechmann condensation of resorcinol and diethyl 2-acetylglutarate in the presence of HCl, was condensed with 3-chlorobutan-2-one in the presence of base to give propanoate 50 (Scheme 4). The MacLeod method was then used to fuse a furan ring to the benzopyran-2-one system. Heating 50 with NaOH solution (1 M) readily cyclized it into the corresponding psoralen furocoumarin 51 with simultaneous hydrolysis of the ester. 

For instance, RNi modified with an optically active amino acid or hydroxy acid hydrogenates methyl acetoacetate (MAA) to produce optically active methyl 3-hydroxybutyrate (MHB) as shown in Fig. 1. 

Raney nickel modified with an amino acid or hydroxy acid can be prepared by a very easy and simple method. Scheme 1 shows the standard procedure for the preparation of modified RNi (MRNi). Raney nickel is prepared from 1.5 g of alloy (Ni/Al = 42/58) by the digestion with 20 ml of 20% aqueous sodium hydroxide at 100°C for 1 hr followed by 15 successive washings with 30-ml portions of water. The RNi thus obtained is modified by soaking for 1 hr with occasional shaking in 100 ml of aqueous modifying... 

The direction of enantio-differentiation (the predominant enantiomer R or S, to be produced) is decided by two factors. One factor is the configuration of the chiral structure, that is, if the catalyst modified with (S)-glutamic acid [(S)-Glu-MRNi] produces (R)-MHB from MAA, then (R)-Glu-MRNi produces (S)-MHB (2). The other factor is the nature of X. That is, when the amino acid or hydroxy acid with the same configuration is used as the modifying reagent, the configurations of the predominant products are enantiomers of each other in most cases. For example, (S)-aspartic acid-MRNi produces (R)-MHB and (S)-malic acid-MRNi produces (S)-MHB (19). 

The degree of EDA is governed by the nature of the substituent (R). The effect of R is observed often in opposite directions between amino acid MRNi and hydroxy acid MRNi. For example, the increase in bulkiness of R increases the EDA of amino acid-MRNi but decreases that of hydroxy acid MRNi as shown in Fig. 3 (77, 72). An increase (decrease) in electron density at the chiral center of the modifying reagent increases (decreases) the EDA of amino acid-MRNi and decreases (increases) the EDA of hydroxy acid-MRNi as shown in Table 111 (52a). 

One hydroxy acid containing a phenyl group gave two kinds of MRNi with different directions of EDA by modifying below and above pH 10.5. This phenomenon also indicates the possibility that the EDA of MRNi does... 

Since RNi contains a large amount of aluminum and 2-hydroxy acid is a strong chelating reagent, one difference between RNi and RNiA could be ascribed to their difference in aluminum contents. Table XII (49) shows the correlation between the aluminum content and the EDA of those catalysts modified with tartaric acid. The aluminum content of RNi was decreased by pretreatment with hydroxy acid. Moreover, reduced nickel prepared from NiO (HNi-1) gives an effective modified catalyst and its pretreatment with hydroxyacid does not affect its EDA. 

Sachtler s group (73) and Yasumori (64) studied the IR spectra of silica-supported Ni modified with amino acid and 2-hydroxy acid and the XPS of TA-MRNi. Both authors deduced almost the same model as proposed by Suetaka. Recently Sachtler s group proposed other models as shown in Fig. 22 from results obtained in enantio-differentiating hydrogenations of MAA with nickel catalysts modified with nickel and copper tartrates (74). The nickel tartrate adsorbs at the vacant coordination site of nickel in this model. 

Nickel, cobalt, copper, ruthenium, and copper-ruthenium catalysts modified with optically active amino acid or hydroxy acid have been extensively investigated by Klabunovskii s group since 1964 (82). However, those catalysts have been reported to have lower EDA than that of MRNi. 

Several synthetic applications are given in Scheme 16 (40). The hydrogenation of a /3-keto ester on a 6-100-kg scale is used for the synthesis of tetrahydrolipostatin, a pancreatic lipase inhibitor developed at Hoffmann-LaRoche Company (1c). Tartaric acid is the best chiral modifier a-amino acids or a-hydroxy acids are not satisfactory. The source... 

Some of the versions of the mixed anhydride technique discussed may involve components other than a-hydroxy acids. Therefore, the resultant products cannot be considered as main-chain modified peptidomimetics. However, on many grounds these methods are of general importance in depsipeptide synthesis. For example the classical peptide reagent isobutyl chloroformate appears to be suitable for ester bond formation through the corresponding mixed anhydride with Boc- or Z-protected amino acids and the Thr (3-hydroxy group in the synthesis of a number of natural peptide lactones.145 7 ... 

Modifier structure. Tartaric acid is clearly superior to a-amino acids or other a-hydroxy acids [1,4] (see also Section V). 

We then focused on the synthesis of lipid A analogs which contain 3-hydroxy fatty acids. For this purpose, sufficient amount of (R)-3-hydroxytetradecanoic acid ( ), which is the commonest hydroxy acid in Salmonella lipid A, was first prepared by means of an asymmetric reduction of the corresponding keto ester, i. ., methyl 3-oxotetradecanoate (j ) (7). Catalytic hydrogenation of 21 in the presence of Raney Ni modified with (R, R)-tartaric acid foaBr (8) afforded the crude (R)-ester in 85% enantiomeric excess. After saponification, the resultant acid was purified through its dicyclohexylammonium salt to give the optically and chemically pure (R)-acid In a yield of 61% from... 

The hydroxynitrile lyase (HNL) class of enzymes, also referred to as oxynitrilases, consists of enzymes that catalyze the formation of chiral cyanohydrins by the stereospecific addition of hydrogen cyanide (HCN) to aldehydes and ketones (Scheme 19.36).275 279 These chiral cyanohydrins are versatile synthons, which can be further modified to prepare chiral a-hydroxy acids, a-hydroxy aldehydes and ketones, acyloins, vicinal diols, ethanolamines, and a- and P-amino acids, to name a few.280 Both (R)- and (.S )-selective HNLs have been isolated, usually from plant sources, where their natural substrates play a role in defense mechanisms of the plant through the release of HCN. In addition to there being HNLs with different stereo-preferences, two different classifications have been defined, based on whether the HNL contains a flavin adenine dinucleotide (FAD) co-factor. 

Systematic studies on the enantioselective heterogeneous catalytic hydrogenation of carbonyl compounds were carried out by Izumi using Raney nickel modified with various chiral reagents. Hydroxy acids or amino acids were used for the modification of the nickel catalyst, and (-i-)-tartaric acid (2R,3R)... 

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