Glycine anion equivalent

Husson and co-workers (47-50) have made extensive application of their chiral azomethine ylide precursor. The synthon 177, prepared in one step in essentially quantitative yield on a multi-gram scale, had previously been used in a wide range of asymmetric processes as a chiral glycine anion equivalent. However, low-temperature treatment with TMS triflate (yet another example of the use of... 

Casiraghi, G, Rassu, G, Spanu, P, Pinna, L, A-rerr-Butoxycarbonyl-2-(fert-butyldimethyl-silyloxy)pyrrole as a glycine anion equivalent a flexible enantioselective access to polyhydroxy-a-amino acids. Tetrahedron Lett., 35, 2423-2426, 1994. 

In 1978, O Donnell and coworkers developed the benzophenone imines of glycine alkyl esters 4 as glycine anion equivalents, which have been found to be perfed to use in the phase-transfer catalysis [10]. An essential feature of this reaction system lies in the selective mono substitution of the starting Schiff base, the O Donnell substrate 4. This can be possible because of the significant difference in acidity of a-hydrogen between starting substrate 4 p/C,(DMSO) 18.7 (R=Et)] and a-monosubstituted produd S p/C,(DMSO) 22.8 (R=Et, E = Me), 23.2 (R=Et, E = CH2Ph)] [11]. This dramatic acidity difference makes it possible for selective formation of only monoalkylated product without concomitant production of undesired dialkylated produd or racemization. 

Now the terminal OH group can be deprotected, turned into a leaving group 336, and used to alkylate an asymmetric glycine anion equivalent, the heterocycle 337. The azide is then reduced and protected to give 338, a protected version of 330. The yield in the alkylation was 94% and only one diastereoisomer was detected. 

Glycine anion equivalent. After a Lewis acid-catalyzed condensation with an aldehyde at C-5 and functional group protection, the degradation of the pyrrolinone ring unveils a )3-hydroxy-a-amino acid chain. More elaborate systems can be obtained from chiral aldehydes such as glyceraldehyde acetonide. 

By Chain extension. — Addition of the glycine anion equivalent 3 to aldehydo-sugar derivatives such as L-arabmo-2, led to various 2-amino-2-deoxy-aldonic acids, such as 2-amino-2-deoxy-D-g/ycero-L-ga/flcto-heptonic acid 4 which was obtained in 35% overall yield (Scheme 1). ... 

The reaction of cyclic oxonium derivatives of polyhedral boron hydrides with acetamido diethyl-malonate (glycine anion equivalent for amino acid synthesis), a variation of the classical Sdrensen synthesis of amino acids, followed by acidic hydrolysis and decarboxylation was proposed as a route to boron hydride-based aminoacids (Figure 24.10) [31,51]. 

Oxazinones derived from chiral 1,2-amino alcohols and glycine have been demonstrated to function as effective chiral glycine anion equivalents in dia-stereoselective alkylations [20, 21, 57, 58). Williams landmark investigations have established the versatility of this auxiliary, which is conveniently excised by hydrogenolytic cleavage subsequent to the asymmetric step. A particularly noteworthy feature of 54 as an auxiliary is its use in consecutive alkylations to construct a,a-disubstituted amino acids such as 57 (Scheme 10.7) [58]. In the conversion of 54 into 57, both alkylations preferentially occur from the face opposite to the phenyl substituents, thus furnishing the disubstituted amino acid 57 in 93 % yield and > 99 % ee. 

Alkylation of Glycine Anion Equivalents in the Presence of Chiral Phase-Transfer Catalysts... 

Trifluorothreonine is one of the rare fluorinated compounds found in nature (cf. Chapter 4). The best method for the synthesis of fluorothreonines is the acylation of an equivalent of glycinate anion by a fluoroacetic derivative. The four stereoisomers of monofluorothreonine have been prepared. A completely stereoselective chiral approach involves the alkylation of the Seebach imidazolidinone by fluoroacetyl chloride (Figure 5.16). ... 

Reduction of a S-aminoketone resulting from the addition of an equivalent of a glycinate anion on ethyl difluoro- or trifluoroacetate is stereoselective and leads to ethyl di- or trifluorothreoninate threo (syn). Release of the acid, performed by saponification, is accompanied by a partial epimerization into an alio compound. However, the amino acids are obtained in enantiopure forms by using a lipase. . It s important to note that (25, 35)-difluorothreonine exhibits activity toward the growth of leukemia cell hnes comparable to 5-fluorouracil. ... 

Fluoral has been condensed with an equivalent of chiral glycinate anion. The chirality stems from a chiral nickel complex with a chiral Schiff base derived from proline as hgand (Figure 5.17). (25, 35)-Difluorothreonine has thus been obtained with an excellent selectivity (de > 95%). This method also allows preparation of numerous fluoroalkyl and fluoroaryl analogues of threonine. Enantiopure difluorothreonine could also be prepared from ascorbic acid. ... 

The synthesis of tricholomic acid (751), an unusual amino acid isolated from tricholoma muscarium, uses an aldol condensation between 590 and 745 (a glycine acyl anion equivalent) to establish the absolute configuration of the amino functionality early in the synthesis (Scheme 108) [140]. The aldol reaction produces a 3 2 mixture of diastereomers that can be separated as in the form of the corresponding N-Cbz benzyl esters 746 and 747. 

Azomethinium salts are very versatile intermediates since they present an extremely electrophilic carbon for nucleophilic attack. High yields of these salts can be obtained in one step from a-amino acids via their tert-dcsmno derivatives Ethyl N-Benzylidene-glycinate has been used for the synthesis of a-amino acids and as an acyl carbanion equivalent A new reactive formaldehyde anion equivalent is lithium methylthioformaldine, (4,5-dihydro-5-methyl-l,3,5-dithiazin-2-yllithium A convenient synthesis of 2-alkyl- and 2-aryl-l,3-benzo-dithioles, which are precursors of acyl carbanion equivalents, has recently been published . 

Next the product is acylated with bromoacetyl chloride and the glycine equivalent is constructed in place by a Gabriel amine synthesis (phthalamide anion followed by hydrazine) subsequent to which cyclization to benzodiazepine occurs. The synthesis of the tranquilizer quazepam (88) is finished by thioamide conversion with phosphorus pentasulfide. ... 

Selenoprotein A is remarkably heat stable, as seen by the loss of only 20% of activity on boiling at pH 8.0 for lOmin (Thrner and Stadtman 1973). Although selenoprotein A contains one tyrosine and no tryptophan residues, it contains six phenylalanine residues and thus has an unusual absorbance spectrum (Cone et al. 1977). Upon reduction, a unique absorption peak emerges at 238 nm, presumably due to the ionized selenol of selenocysteine, which is not present in the oxidized enzyme. The activity of selenoprotein A was initially measured as its ability to complement fractions B and C for production of acetate from glycine, in the presence of reducing equivalents (e.g., dithiothreitol). Numerous purification schemes were adopted for isolation of selenoprotein A, all of which employed the use of an anion exchange column to exploit the strongly acidic character of the protein. 

The Michael additions of various carbon nucleophiles such as cyanide [15b, 22b], anions generated from nitromethane [27], ferf-butyl acetate [9], malon-ates [27] and O Donnell s glycine equivalent [541, cuprates [9,15b] or Grignard reagents [53] under copper catalysis [55] have also been reported (Scheme 24). 

Moreno-Manas, M., Pleixats, R. and Roglans, A. (1995) Ethyl A-(diphenylmethylene)glycinate as anionic glycine equivalent transition metal mediated preparation of bicyclic and tricyclic a,a-disubstituted a-amino acids and derivatives. Liebigs Arm., 1807-14. 

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