Asymmetric synthesis of amino acids

To some extent, it is a matter of perceived ease of working, or favourable economics, when it comes to choice of method the piperazinedione route can be operated on a scale of several hundreds of grams (Schollkopf et al., 1985). Nonetheless, a major consideration is the stereochemical efficiency that is involved (i.e. the 

Azlactone(3) + H2 + Ru(lll)[chiral phosphine] (catalyst) - L-NH2CHRC02H after hydrolysis 

In the Schollkopf piperazinedione method, namely alkylation of the 2,5-diethoxy compound prepared from L-alanine methyl ester, values greater than 90% are routinely achieved for the alkylation yield and for the diastereoisomeric excess of the product (Allen et al., 1992). Similar results have been reported for the Belokon method and for the Seebach imidazoiidinone method (though there are rather low alkylation yields in some cases). 

General sources of information on general synthetic methods for amino acids (Barrett, 1985) and on asymmetric synthesis (Williams, 1989) are listed in the Foreword. 

Goldberg, I. and Williams, R. A. (1991) Biotechnology of Food Ingredients, Van Nostrand-Reinhold, New York. 

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SCHdLLKOPF Amino acid synthesis Asymmetric synthesis of amino acids from dihydropyraaines... 

The asymmetric synthesis of amino acids via the addition of allyl and 2,3-dimethyl-2-bulenyl organometallics to ( — )-8-phenylmenthyl A-methoxyiminoacetate (14) was examined12. The results show that both allyl- and 2,3-dimethyl-2-butenylzinc bromide provide good stercocontrol. 

Interaction of Ni11 ions with amino acids is also important for asymmetric synthesis of amino acids. A convenient large-scale asymmetric synthesis of enantiometrically pure trans-cinnamyl-glycine and -o-alanine via reaction of cinnamyl halides with Ni11 complexes of a chiral Schiff base of glycine and alanine has been elaborated.1711 Similar procedures have been applied to other amino acids as well.1712... 

Asymmetric synthesis of amino acids.1 These lactones can serve as an optically active form of glycine for synthesis of either D- or L-amino acids. Thus (+ )-1 (or (—)-l) on radical bromination is converted into a single monobromide (2), which can be coupled with nucleophilic organometallic reagents, by either an SN1... 

Gu, R.-L., Lee, I.S. and Sih, C.J., Chemo-enzymatic asymmetric synthesis of amino acids. Enantioselective hydrolyses of 2-phenyl-oxazolin-5-ones. Tetrahedron Lett., 1992, 33, 1953-1956 Crich, J., Brieva, R., Marquart, P., Gu, R.-L., Flemming, S. and Sih, C.J., Enzymic asymmetric synthesis of a-amino acids. Enantioselective cleavage of 4-substituted oxazolin-5-ones and thiazolin-5-ones. J. Org. Chem., 1993, 58, 3252-3258. 

The first 3,6-dialkoxy-2,5-dihydropyrazine used in asymmetric synthesis of amino acids 7 10 was the symmetrical derivative 2, derived from cyclo(L-Ala, L-Ala) (1). This dihydropyrazine can be prepared by direct condensation of the methyl ester of L-alanine and subsequent alkylation with trialkyloxonium tetrafluoroborate7. Although the condensation process results in partial racemization of the alanine moiety, recrystallization yields almost optically pure cyclo(L-Ala, L-Ala) (1). 

U. Schollkopf, Asymmetric Synthesis of Amino-Acids, Chem. Scr. 25, NS 105 (1985). 

When an aldehyde is allowed to react with an optically active amine and hydrocyanic acid, one of the two diastereomeric amino nitriles, (124a) or (124b), may be formed in excess. To prepare the chiral amino acids (125a) or (125b), the nitriles (124a) and (124b), respectively, are hydrolyzed with mineral acids, whereupon R is split off. However, this asymmetric synthesis of amino acids has no industrial significance. 

A group at the Academy of Sciences in Moscow 197) has synthesized chiral threonine. Derivatives of cyclic imino acids form copper complexes with glacine and carbonyl compounds. Hydroxyethylation with acetaldehyde and decomposition of the resulting complexes produced threonine with an optical purity of up to 97-100% and with threo/allo ratios of up to 19 1 197). The chiral reagents could be recovered and re-used without loss of stereoselectivity. The mechanism of this asymmetric synthesis of amino acids via glacine Schiff base/metal complexes was also discussed 197). 

A general approach towards the asymmetric synthesis of amino acid derived 4-alkyl-4-carboxy-2-azetidinones has been described [192], The (+)- or (-)-lO-(N, Af-dicyclohexylsulfamoyl)isobomeol was used as chiral auxiliary in the intramolecular cyclization of /V-(/>methoxybenzyI)-/V-chloroacetyl Phe and Ala derivatives for the stereocontrolled base-catalyzed construction of the (1-lactam ring (Scheme 85). 

Scheme 8.1 Asymmetric synthesis of amino acid derivatives.

For reviews of the asymmetric synthesis of amino acids using quaternary ammonium salts as phase-transfer catalysts, see ... 

As noted in a review, no economical chemical process has emerged for the asymmetric synthesis of amino acids.3 This presumably refers to large-scale production where the research costs associated with the development of a biological approach can be justified. Chemical methods can produce racemic substrates, as illustrated later in this chapter with L-methionine and D-phenylglycine. With methods in place, however, biological methods can be implemented rapidly.4... 

Maerkle W, Liitz S (2008) Electroenzymatic strategies for deracemization, stereoinversion and asymmetric synthesis of amino acids. Electrochim Acta 53 3175-3180... 

Explain how this asymmetric synthesis of amino acids, starting with natural proline, works. Explain the stereoselectivity of each reaction. 

Davis, F. A. Zhou, P. Chen, B.-C. Asymmetric Synthesis of Amino Acid Using Sulfilimines (Thiooxime S-Oxides), Chem. Soc. Rev. 1998,27,13-18. 

Schollkopf-Hartwig bislactim ether reagent for asymmetric synthesis of amino acids by reaction of the metalated reagent with... 

Table 2 Asymmetric Synthesis of Amino Acids by Catalytic Hydrogenation ...

Schdllkopf and cowoikers have pioneered the development of anions of another type of masked carboxylic acid derivative, i.e. bislactim ethers such as (159), derived from (5)-valine and glycine or alanine, for the asymmetric synthesis of amino acids. As shown in Scheme 78, compounds such as... 

Asymmetric synthesis of amino acids.1 Optically active amino acids can be prepared by addition of hydrogen cyanide to SchifT bases prepared from aliphatic aldehydes (representing the R group) and optically active benzylic amines (representing the... 

Asymmetric synthesis of -amino acids was achieved by hydrogenation of secondary enaminoesters of (2) configuration over Pd(OH)2/C, followed by hydrolysis. Interestingly, treatment with sodium cyanoborohydride gave the opposite configuration. 

The addition of allyl and prenyl organometallics (84) to 8-(-)-phenylmenthyl A/-methoxyiminoacetate (83 equation 19) has been examined for the asymmetric synthesis of amino acids. Treatment of (83) with allylboronates and allylzinc bromide affords N-alkoxyamines (85) and (86 Table 19). Both allyl-... 

Enamides can also be used as precursors for the asymmetric synthesis of amino acids via hydroformylation. Thus, asymmetric branched hydroformylation of vinylsuccinimide and vinylphthalimide upon further oxidation leads to, V-protccted amino carboxylic acids such as alanine. Branched products are obtained with high regioselectivities and good to high optical yields of up to 96% (see Table 7)125. 

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