Preparation of amino acids

The derivative of glycine, prepared from benzophenone (cat. BF3 Et20, xylene, reflux, 82% yield), has found considerable use in the preparation of amino acids. It can also be prepared by an exchange reaction with benzophenoneimine (Ph2C=NH, CH2CI2, rt). ... 

The other most important synthetic utility of the Bucherer-Bergs reaction is the preparation of amino acids from the hydrolysis of hydantoins. When carbonyl 1 was symmetrical, the Henze modification gave hydantoin 2, which was then hydrolyzed to the... 

A modified 1,4 diketone 17 was employed for the microwave-assisted preparation of amino acids containing the pyrrole ring (Scheme 6). The products were further employed for the introduction of this original moiety into a peptide sequence [33]. 

Intermolecular N-H insertion of electrophilic carbene complexes has occasionally been used for the preparation of amino acid derivatives and other types of intermediates (Table 4.12) [956,1043,1194-1201]. 

Eberlein, W., Rudolf, K., Dreyer, A., Muller, S.G., Doods, H., Bauer, E. (Boehringer Ingelheim) Preparation of amino-acid derivatives for use as calcitonin gene-related peptide antagonists, DE19911039 (2000). 

Figure 16.27. Preparation of amino acid derived, protected aminosulfonyl chlorides suitable for the solid-phase synthesis of oligosulfonamide peptidomimetics [261-264].

Many of the types of reactions that are useful for the preparation of amino acids have been discussed previously in connection with separate syntheses of carboxylic acids (Chapter 18) and amino compounds (Chapter 23). Examples include the SN2 displacement of halogen from a-halo acids by ammonia,... 

Table 4 Preparation of Amino Acid Dithioesters from N-Protected a-Amino Amides18 ...

Scheme 40 Preparation of amino acid derivatives of phospha sugars 124a-h...

The Michael addition of N-nucleophiles to a./ -unsaturated carbonyl compounds is of obvious synthetic importance, e.g. for the preparation of / -amino acids [50a]. Several metal-containing catalysts have been devised, e.g. the chiral Al-salen... 

A variety of methods have been described in this book for the preparation of amino acids. They range from the use of chiral auxiliaries (Chapter 23), through the use of enzymes (Chapters 3 and... 

The use of phenylglycine amide (3) for the preparation of amino acids is discussed in Chapter 25. 

Laneman, S. A., Froen, D. E., Ager, D. J. The Preparation of Amino Acids via Rh(DIPAMP)-Catalyzed Asymmetric Hydrogenations. In Catalysis of Organic Reactions, Herkes, F. E. Ed., Marcel Dekker New York, 1998, p. 525. 

Rhodium-chiraphos cations also hydrogenate ketone and epoxide functionalities, albeit with low optical yields, and are, therefore, not synthetically useful. While this rhodium system seems somewhat limited to the preparation of amino acids, other rhodium and ruthenium catalyst precursors are currently available which show enhanced activity and selectivity for a much broader group of hydrogenation substrates. 

Reduction of a-nitro-j6-hydroxybutyric acid to D,L-threonine [65] and similar reactions [33,66] have been investigated for the preparation of amino acids. The reduction to amine passes predominantly through the hydroxylamino derivative and only to a smaller degree through the oxime. 

Several hydrolytic enzymes other than esterases have been applied for synthetic purposes. One important subject is the chemoenzymatic preparation of amino acids. An industrial method for the synthesis of unnatural d- or L-amino acids employs the enzymatic hydrolysis of hydantoins, prepared by Bucherer-Bergs condensation using either D- or L-hydantoinase (cf Section 3.2.1.4) [33]. Another efficient method of preparing natural and unnatural amino acids is the two-step synthesis which features a Pd-catalyzed amidocarbonylation (eq. (2) cf Section 2.1.2.4) to afford racemic A-acyl amino acids followed by enantioselective hydrolysis using various acylases [34]. 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

A variety of methods have been described in this book for the preparation of amino acids. They range from the use of chiral auxiliaries (see Chapter 14), to the use of enzymes (see Chapters 13 and 16) and asymmetric hydrogenation (see Chapter 9). to total fermentation (see Chapter 4). The aim of this chapter is to put into perspective the choice of the appropriate method. We have chosen the synthesis of unnatural amino acids for illustration, but the philosophy could be applied to any class of compound. 

Thompson, S.K., Veber, D.F., Tomaszek, T.A., and Tew, D.G., Preparation of amino acid derivatives for treatment of parasitic diseases by inhibition of cysteine proteases of the papain superfamily, Smithkline Beecham, Int. Patent Appl. WO 9953039, 1999 Chem. Abstr, 131, 299694, 1999. 

Fig. 3 Overall sequence for azlactone synthesis, hydrogenation, and hydrolysis for the preparation of amino acids.

The same issue is addressed in Table 8, in which reactions of nonracemic substrates are described. Regioselectivity is under steric control. All four acetates 49-52 provide mainly the ( -enantiomer82-83, probably through a common syn,syrt-n-a] yl complex. In most cases, almost 100% chirality transfer is observed. The a-isocyanocarboxylates (Table 8, entries 9, 10)84 are interesting nucleophiles for the preparation of amino acids easily obtained from the alkylated products after acidic hydrolysis. This sequence constitutes an alternative to the Schiff bases of glycine already discussed (see Table 4). Moreover, radical reduction of the isocyano group with tributylstannane yields the a-unsubstituted carboxylic esters. 

Several recent examples serve to illustrate the potential of allyltributyltin for organic synthesis (Scheme 4). Baldwin and Easton have independently shown that glycine derivatives undergo efficient allylation reactions, providing an avenue for the preparation of non-natural amino acids [8]. Subsequently, addition of glycine-derived radicals to allyltributyltin was shown by Hamon to occur with stereoselectivity if the radical bears an ester chiral auxiliary [9]. An alternative method for the preparation of amino acid derivatives via allylation of carbamoyloxy radicals that are incorporated into an oxazolidin-2-one ring system was reported by Kano... 

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