Stereoselectivity amino acid ester hydrolysis

This unnatural acid is used as a chiral intermediate for the synthesis of a number of products. Chemical asymmetric synthesis was very difficult and so the stereoselective synthetic properties of enzymes were exploited to carry out a selective reduction reaction. The stereoselective hydrolysis of protein amino acid esters had already been commercialised by Tanabe in Japan using immobilised aminoacylase, and selective reduction reactions using whole yeast cells are already used in a number of processes, such as the selective reduction of the anti-cancer drag Coriolin. 

This section deals mainly with the metalation of lactim ethers and subsequent reaction with electrophiles to generate new C—C bonds at position 3 or 6. Hydrolysis of the products leads to new amino acid esters. The chief attraction of this synthetic route is the high degree of stereoselectivity in the carbon—carbon bond-forming step. It is known as the Schollkopf method for the chiral synthesis of amino acids. 

One reason for an otherwise apparently excessive interest in Co(trien)X2+ systems is the use of ds-Co(OH)(trien)(OH2)2+ in the hydrolysis of amino acid esters, amino acid amides and peptides785 to form cis-px- and cis-/J2-Co(trien)(aa)2+ (aa = amino acid) complexes.16 In principle, a peptide could be degraded in a stepwise manner and each amino acid residue successively characterized. By the introduction of a chiral center into the backbone of the trien moiety, it was hoped to make such reactions stereoselective. Consequently, while fully A-alkylated trien systems have been widely investigated for M11 central ions, the C-alkylated trien systems have been almost exclusively the reserve of the Co111 chemist (Table 11). 

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. 

Enzymes are also often applied in synthesis (Whitesides, 1995), in particular in regio- and stereoselective oxidation, hydrogenation, and chemically difficult hydrolysis reactions. Cross-linked enzyme crystals acquire high stability while preserving their activity in aqueous electrolytes as well as in organic solvents such as toluene or t-butanol. This has been shown for purified ther-molysin, a protease used for peptide synthesis using amino acid esters as NH ... 

Amino-acid esters may be stereoselectively hydrolysed at pH 8 by polymeric catalysts containing amino-acid derivatives chelated to Cu" or Ni" attached to matrices of cross-linked polystyrene or polyacrylamide. Selectivity results from amino-acid ester co-ordination rather than from the affinity of the catalyst for the hydrolysis product. ... 

The hydrolysis of enantiomeric amino-acid ester derivatives catalysed by an optically active bifunctional catalyst containing hydroxamic and imidazole groups shows a pH dependency of stereoselectivity with rate differences between enantiomers of up to 2. ... 

Asymmetric transformations of ot-amino acids promoted by optically active metal complexes have been reported by several groups 269). The control of the stereoselective hydrolysis reactions of racemic esters by chiral micellar compounds prepared from amino acids has been intensively investigated 270). 

The method of Kim et al.[89-93] starts from the synthesis of the three-carbon phosphonium salt according to the modified method of Corey et alJ94,95] The Wittig reaction of the phosphonium salt with a Z-protected a-amino aldehyde using potassium hexamethyldisilazanide provides the ds-alkene without racemization. Efficient hydrolysis of the orthoester without double bond migration is achieved by acidolytic hydrolysis with aqueous hydrochloric acid in tert-butyl alcohol under reflux conditions. Then, an a-amino acid methyl ester is coupled. The desired epoxide product is obtained by treatment with 3-chloroperoxybenzoic acid. The epoxidation reaction is stereoselective and predominantly provides one isomer (R,S S,R = 4-10 1). The trans-epoxide can also be prepared using a trans-alkene-containing peptide. A representative synthetic procedure to obtain the ds-epoxide isostere is detailed below. 

The coordination of optically active amino acids and their methyl esters to nickel(II) complexes of l,2-bis(2-(5)-aminomethyl-l-pyrrolidinyl)ethane (24 R = H) and l,2-bis(2-(S)-N-methyl-aminomethyl-l-pyrrolidinyl)ethane (24 R=Me) has been studied.98 Some amino acidate ions coordinate stereoselectivity, as do their methyl esters, so that base hydrolysis of the esters proceeds stereoselectively. 

Asymmetric 1,3-dipolar cycloaddition of nitrones to ketene acetals is effectively catalyzed by chiral oxazaborolidines derived from N-tosyl-L-a-amino acids to afford 5,5-dialkoxyisoxa-zolidines with high regio- and stereoselectivity [70] (Eq. 8A.46). Hydrolysis of the N-O bond of the resulting chiral adducts under mild conditions yields the corresponding [1-amino esters quantitatively. 

Compound (1) and its enantiomer provide a variation on the same theme of stereospecific reductive amination. In this case, reduction of a chiral cyclic hydrazone (derived from an a-keto acid and (1)) with Aluminum Amalgam in wet DME proceeds with high stereoselectivity. Reductive cleavage of the N-N bond and ester hydrolysis complete the procedure, which produces a-amino acids with high optical purity (eq 4). The source of chirality is recovered by conversion of the resulting indoline-2-methanol back into (1). ... 

The current review is of necessity selective. Over the two year period covered, there has been impressive advances in several areas of P(V) chemistry. For example, biological aspects of quinquevalent phosphorus acids chemistry continue to increase in importance. A wide variety of natural and unnatural phosphates including inositols, lipids, some carbohydrates and their phospho-nates, phosphinates and fluorinated analogues has been synthesized. Special attention has been paid to the synthesis of phosphorus analogues of all types of amino acids and some peptides. Numerous investigations of phosphate ester hydrolysis and related reactions continue to be reported. Interest in approaches to easier detoxification of insecticides continues. A number of new and improved stereoselective synthetic procedures have been elaborated. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. 

This effect has been studied in our group by Kenichi Morigaki in his dissertation. He utilized the hydrophobic tripeptide Z-Phe-His-Leu-NHj (Z = carboben-zyloxy). This compound has been shown before in the literature to display catalytic properties towards the hydrolysis of certain esters. The authors were particularly interested in the stereoselectivity of the process of L- towards D-amino acids and less in the enhancement of catalysis operated by the micelles. The substrate chosen was a very lipophylic ester, nitrophenylpalmitate. Morigaki used oleate vesicles, and later POPC liposomes, obtaining qualitatively similar results. ... 

The manufacture of optically active L-a-amino acids from racemic amino acid amides was shown by Mitsubishi Gas Chemical, Japan [117]. In this process different microorganisms were immobilized on polymers made from (meth)acrylic acid esters or urethane acrylates and applied for the stereoselective hydrolysis of racemic amides (Scheme 43). o/L-Leucinamide (rac-136), for example, can be hydrolyzed with Mycoplana bullata cells immobilized on polyethylene glycol dimethacrylate-AT,N -methylenebisacrylamide copolymer at 30 C to produce i-leudne (l-137) over 3,000 h. 

Shiori and co-workers used 5-substituted 4-oxazolecarboxylic acid esters 379 as p-hydroxy-a-amino acid synthons. They described a straightforward synthesis of 379 by acylation of an isocyanoacetic acid ester with an a-alkoxyacid 378 in the presence of diphenylphosphorylazide (DPPA) or diethylphosphoryl cyanide (DPPC) followed by base-catalyzed cyclization (Scheme 1.104). The reaction conditions do not epimerize optically active a-alkoxyacids. Dilute acid hydrolysis of 379 and reaction with (600)2 affords the protected aminotetronic acids 380. Stereoselective hydrogenation of 380 then yields the 1,4-lactones 381, key intermediates in the synthesis of amino sugars. A variety of a-alkoxyacids were studied, and some examples are shown in Table 1.30. 

The unusual chiral (3-methoxy-y-amino acid dolaproine (Dap) is the most complex unit of dolastatin 52, which has a remarkable antineoplastic activity and is now in Phase II human cancer clinical trials. Many synthetic strategies such as aldol condensation and a cobalt-catalyzed Reformatsky reaction have been employed in its synthesis. Almeida and Coelho have demonstrated a stereoselective synthetic method for A-Boc-dolaproine (53) through a sequence of MBH reaction, a diastereoselective double bond hydrogenation and hydrolysis of the ester functional group (Scheme 5.8). ... 

There are numerous examples of enantioselective hydrolyses of the types described in Schemes 3.2 and 3.3, catalysed by lipases and esterases. The selective hydrolysis of amino acid derivatives has been an important part of this field of study. For example, the hydrolase enzyme a-chymotrypsin catalyses the enantioselective hydrolysis of JV-acetyl-DL-phenylalanine methyl ester (5) to give optically pure (L)-acid (6) in 40% yield (Scheme 3.4). The lipase from the fungus Candida cylindracea (ccl) has been shown to hydrolyse octyl 2-chloropropionate (7) with high stereoselectivity on a large scale, giving the (/ )-acid (8) in 46% yield (96% e.e.) and the (S)-ester (45% yield) (Scheme 3.5). 

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