Amino acids catalytic asymmetric synthesis

An early success story in the field of catalytic asymmetric synthesis is the Monsanto Process for the commercial synthesis of l-DOPA (4) (see Scheme 1), a rare amino acid that is effective in the treatment of Parkinson s disease.57 The Monsanto Process, the first commercialized catalytic asymmetric synthesis employing a chiral transition metal complex, was introduced by W. S. Knowles and coworkers and has been in operation since 1974. This large-scale process for the synthesis of l-DOPA (4) is based on catalytic asymmetric hydrogenation, and its development can be... 

The use of chiral oxazolines as ligands for catalytic asymmetric synthesis is undoubtedly the most important development in oxazohne chemistry. Compared with other ligands, oxazolines offer the advantage of being easily accessible from chiral amino alcohols that are, in turn, readily available from a chiral pool of amino acids. There have been numerous reports on this exciting use of oxazolines during the last 10 years. Many of the ligands studied to date contain at least two oxazoline units. The synthesis and reactions of bis(oxazohnes) are discussed in detail in Chapter 9 the discussions in this section are limited to mononuclear oxazolines. 

Until 1968, not a single nonenzymic catalytic asymmetric synthesis had been achieved with a yield above 50%. Now, barely 15 years later, no fewer than six types of reactions can be carried out with yields of 75-100% using amino acid catalysts, i.e., catalytic hydrogenation, intramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosilylation, and epoxidations. 

In the preceding Section we considered the catalytic asymmetric synthesis. In this connection the induction of asymmetry by catalytic amounts of chiral information (= amino acids or their derivatives) was treated. The chiral information was transferred into a prochiral substrate. 

Cinchona alkaloids, of course, have occupied the central position in the design of chiral PTCs. By employing a simple chemical transformation of the tertiary amine ofthe natural cinchona alkaloids to the corresponding quaternary ammonium salts, using active halides (e.g., aryl-methyl halides), a basic series of PTCs can be readily prepared. Cinchona alkaloid-derived PTCs have proved their real value in many types of catalytic asymmetric synthesis, including a-alkylation of modified a-amino acids for the synthesis of higher-ordered a-amino acids [2], a-alkylation of... 

Scheme 4.1 Synthesis of a-alkyl-a-amino acids via asymmetric phase-transfer catalytic alkylation ofbenzophenone imine glycine ester (A).

The Stacker reaction has been employed on an industrial scale for the synthesis of racemic a-amino acids, and asymmetric variants are known. However, most of the reported catalytic asymmetric Stacker-type reactions are indirect and utilize preformed imines, usually prepared from aromatic aldehydes [24]. A review highlights the most important developments in this area [25]. Kobayashi and coworkers [26] discovered an efficient and highly enantioselective direct catalytic asymmetric Stacker reaction of aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst prepared from 2 equivalents of Zr(Ot-Bu)4, 2 equivalents of (R)-6,6 -dibromo-1, l -bi-2-naphthol, (R)-6-Br-BINOL], 1 equivalent of (R)-3,3 -dibromo-l,l -bi-2-naphthol, [(R)-3-Br-BINOL, and 3 equivalents of N-methylimida-zole (Scheme 9.17). This protocol is effective for aromatic aldehydes as well as branched and unbranched aliphatic aldehydes. 

North and co-workers required a convenient, catalytic asymmetric synthesis of specifically the (S) -enantiomer of allyHc amines [32]. They prepared a new catalyst, 17, by modifying Tomioka s tridentate amino ether la [19a], but utiHzing only readily available (S)-amino acids. Catalyst 17 was prepared in 45% yield overall from commercially available (S)-proline according to a procedure very similar to that described for the preparation of la (Scheme 10). 

Catalytic, asymmetric synthesis of ihoi-disubstituted amino acids using a chiral... 

CATALYTIC, ASYMMETRIC SYNTHESIS OF o,a-DISUBSTITUTED AMINO ACIDS USING A CHIRAL COPPER-SALEN COMPLEX AS A PHASE TRANSFER CATALYST... 

Heterocycles as ligands in catalytic asymmetric synthesis of a-amino acids 07CRV4584. 

Basu, B. and Frejd, T. (1996) Catalytic asymmetric synthesis of bis-armed aromatic amino acid derivatives. Problems related to the synthesis of enantiomerically pure bis-methyl ester of the (5,5 )-p3nidine-2,6-diyl bis-alanine. Acta. Chem. Scand., 50, 316 22. 

In contrast to phase-transfer catalytic allgrlation, aldol reactions are somewhat less common because it is difficult to control more than one concurrently generated stereocentre, and the retroaldol reaction leads to low chemical yields. In 1991, the first catalytic asymmetric synthesis of P-hydrmg -a-amino acids via aldol condensation under PTC reaction conditions in the presence of catalyst 7a was reported by the Miller group. The moderately optically enriched diastereomeric aldol adducts 77 obtained from heptanal and 5 were derivatised to 78 (Scheme 16.23). °... 

C. Najera, J. M. Sansano, Chem. Rev. 2007, 107, 4584 671. Catalytic asymmetric synthesis of a-amino acids. 

Shao, Chan, and coworkers have developed the first catalytic asymmetric synthesis of chiral p.y-alkynyl a-amino acid derivatives 404 in 61-80% yields and moderate enantioselectivities (66-74%), using ethyl glyoxylate 400, p-anisidine 401, and aliphatic or aromatic alkynes 402 (Scheme 6.60) [126]. This process is catalyzed by a catalyst system between Cu(I) triflate benzene complex and 10mol% of pybox catalyst 403. 

The complexes (72) and (73) are octahedral and, as described in section 6.1.2, can exist in two enantiomeric forms, A and A. In this case, the / -BINAP forms exclusively the R-A diastereomer, and the S-BINAP the S-A. A catalytic quantity (1 mol % or even less) promotes the asymmetric hydrogenation of a wide variety of alkenes bearing nearby polar groups, such as amides, alcohols, esters, etc., which are necessary for high e.e.s. An important application of this is in the synthesis of amino acids by asymmetric reduction of amidoacrylates (74). 

Witayakran S, Ragauskas AJ (2009) Synthetic applications of laccase in green chemistry. Adv Synth Catal 351(9) 1187-1209. doi 10.1002/adsc.200800775 Wolfer J, Bekele T, Abraham CJ, Dogo-Isonagie C, Lectka T (2006) Catalytic, asymmetric synthesis of 1,4-benzoxazinones a remarkably enantioselective route to a-amino acid derivatives fiom o-benzoquinone imides. Angew Chem 45(44) 7398-7400. doi 10.1002/anie. 200602801... 

Han Z, Yamaguchi Y, Kitamura M, Maruoka K. Convenient preparation of highly active phase-transfer catalyst for catalytic asymmetric synthesis of a-alkyl- and a,a-dialkyl-a-amino acids application to the short asymmetric synthesis of BlRT-377. Tetrahedron Lett. 2005 46(49) 8555-8558. 

Ma J-A. Catalytic asymmetric synthesis of a- and (3-amino phosphonic acid derivatives. Chem. Soc. Rev. 2006 35 630-636. 

Nevertheless, if the final racemic end point is to be avoided for very long, this initial evasive mechanism requires supplementation by a corrective mechanism. Krebs (63) and Kisch (60) have confirmed that such a corrective mechanism exists whereby the initial preponderance of one configurational series could be maintained by selective destruction of the unwanted series. They found that oxidative deamination of a-amino acids by a deaminase present in animal liver and kidney tissues is markedly optically selective, the Tinnatirral" d-series being deaminated more rapidly than the natural i-series. This process will continuously correct and regulate the inevitable tendency for at least some of the unwanted antipode to appear in a true catalytic asymmetric synthesis. 

Only a few examples are known in which amino acids are produced by (catalytic) asymmetric synthesis. The asymmetric hydrogenation of dehydroamino acids, previously developed by Monsanto for L-phenylalanine, is today only used for the production of l-DOPA [11]. Many other asymmetric routes for the synthesis of enantiopure amino acids... 

In this chapter we describe the DSM aminoamidase processes in more detail. Three different enzymatic resolution routes have been developed for the preparation of natural and synthetic amino acids using biocatalysts from different origin, i.e.. Pseudomonas pu-tida, Mycobacterium neoaurum, and Ochrobactrum anthropi. Scope and limitations and enzyme characterization of these amidases will be presented together with some specific examples. In addition, the use of some of these amino acids in peptide sjmthesis, catalytic asymmetric synthesis, and further synthetic transformations will be given. 

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