Chiral reagents amino acids

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)... 

As a part of ongoing efforts to synthesize a potent, orally active anti-platelet agent, xemilofiban 1 [1], development of an efficient chemoenzymatic process for 2, the chiral yS-amino acid ester synthon (Fig. 1) was proposed. The scheme emphasized the creation of the stereogenic center as the key step. In parallel with the enzymatic approach, chemical synthesis of the / -amino acid ester synthon emphasized formation of a chiral imine, nucleophilic addition of the Reformatsky reagent, and oxidative removal of the chiral auxiliary. This chapter describes a selective amida-tion/amide hydrolysis using the enzyme Penicillin G amidohydrolase from E. coli to synthesize (R)- and (S)-enantiomers of ethyl 3-amino-5-(trimethylsilyl)-4-pen-tynoate in an optically pure form. The design of the experimental approach was applied in order to optimize the critical reaction parameters to control the stereoselectivity of the enzyme Penicillin G amidohydrolase. 

Acyl fluorides. Carboxylic acids are readily transformed into acid fluorides by this reagent in the presence of i-Pr2NEt. Weinreb amides can be prepared henceforth. W-Protected chiral a-amino acids are derivatized without racemization. 

This reaction was first reported by Schollkopf in 1979. It is a synthesis of an unnatural nonproteinogenic amino acid from the lithiated enolate equivalent of a simple amino acid (e.g., glycine, alanine and valine), which involves the diastereoselective alkylation of the lithiated bis-lactim ether of an amino acid with an electrophile or an Aldol Reaction or Michael Addition to an o ,jS-unsaturated molecule and subsequent acidic hydrolysis. Therefore, the intermediate of the bis-lactim ether prepared from corresponding amino acids is generally referred to as the Schollkopf bis-lactim ether, " Schollkopf chiral auxiliary, Schollkopf reagent, or Schollkopf bis-lactim ether chiral auxiliary. Likewise, the Schollkopf bis-lactim ether mediated synthesis of chiral nonproteinogenic amino acid is known as the Schollkopf bis-lactim ether method, Schollkopf bis-lactim method, or Schollkopf methodology. In addition, the reaction between a lithiated Schollkopf bis-lactim ether and an electrophile is termed as the Schollkopf alkylation, while the addition of such lithiated intermediate to an Q ,j8-unsaturated compound is referred to as the Schollkopf-type addition. ... 

In addition, Jorgensen et al. have shown that racemic oxazolones were excellent reagents for the synthesis of chiral quaternary amino acids by... 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

The term chiral recognition refers to a process in which some chiral receptor or reagent interacts selectively with one of the enantiomers of a chiral molecule. Very high levels of chiral recognition are cormnon in biological processes. (—)-Nicotine, for example, is much more toxic than (-F)-nicotine, and (-F)-adrenaline is more active than (—)-adrenaline in constricting blood vessels. (—)-Thyroxine, an amino acid of the thyroid gland that speeds up metabolism, is one of the most widely used of all prescription... 

Fig. 7-6). Two unichiral amides which have been known capable of this reaction are 1-phenylethylamine [15] and l-(l-naphthyl)ethylamine [16]. Marfey s reagent [N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide] was introduced as a reagent to deriva-tize amino acids with cyclopentane, tetrahydroisoquinoline or tetraline structures [17]. Simple chiral alcohols such as 2-octanol can also be used to derivatize acids such as 2-chloro-3-phenylmethoxypropionic acid [18]. 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Optically active five- or six-membered cyclic A -acyliminium ions of this type are generated from the a-inethoxy derivatives, easily obtainable through anodic methoxylation of intermediates that are prepared via ex-chiral-pool syntheses from certain natural amino acids. Reaction of 5-substituted five-membered cyclic A -acyliminium ions with various nucleophiles leads to the predominant formation of cw-products with moderate selectivity. The trans-selective reaction with alkyl copper reagents appears to be an exception. 

A simple and rapid method of separating optical isomers of amino acids on a reversed-phase plate, without using impregnated plates or a chiral mobile phase, was described by Nagata et al. [27]. Amino acids were derivatized with /-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA or Marfey s reagent). Each FDAA amino acid can be separated from the others by two-dimensional elution. Separation of L- and D-serine was achieved with 30% of acetonitrile solvent. The enantiomers of threonine, proline, and alanine were separated with 35% of acetonitrile solvent and those of methionine, valine, phenylalanine, and leucine with 40% of acetonitrile solvent. The spots were scraped off the plate after the... 

For a facial selective assembly ofthe stereogenic centers and the introduction of the amino functionality, chiral nitrogen-containing reagents, such as benzyl(2-pheny-lethyl)amine (2-19) and trimethylsilyl RAMP derivative 2-24 were applied. Treatment of diacrylates 2-18, 2-21, and 2-23 with 2-19 and 2-24, respectively, gave the protected amino acids 2-20, 2-22, and 2-25 in good yields as single isomers. 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

Possible racemisation of imines, derivatives of amino acids and R(—)-myrtenal, has been examined by Dufrasne et al.1 After 72 h, no significant effect on chiral purity was observed. For imines being derivatives of chiral primary amines and the a-substituted 8-keto-aldehydes, no evidence of epimerisation has been indicated by the NMR measurements.3 For a series of imines, being derivatives of amino acids or amino acid esters and (R)-BINOL reagents, Chin et al.5 have tested the possibility of epimerization under experiment conditions. It was shown that R S ratio has changed only slightly, and after 24 h, the difference was lower than 10%. 

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