Aminomalonic acid derivatives

There is no asymmetric carbon atom in aminomalonic acid molecule. When both of the carboxylic acids are substituted by esterification with different alcohols, optical isomers are generated. It is known that aminomalonic acid derivatives readily racemize in solution under ordinary conditions. L-Asp-Ama(OFn)-... 

The decarboxylation of aminomalonic acid derivatives constitutes a classical route to proteinogenic and non-proteinogenic amino acids. In 2003, Brunner et al. [16] explored the potential of the 9-ep/-cinchonine-benzamides previously designed [14], in the decarboxylation of A-acetylaminomalonic acid derivatives 22a-c. Selected examples presented in Scheme 3.8 indicate that a number of 9-epi-cinchonine-benzamides reached acceptable levels of enantioselectivity, up to 71%. hi contrast to 2-cyano-2-aryl propionic acids 14 and 20,9-ept-cinchonine-benzamides 19b, c and f gave rather disappointing results with A-acetylaminomalonic acids... 

The enantioselective decarboxylative protonation of aminomalonic acid derivatives has been also extensively investigated by Rouden et al. [17]. Their first contribution in this area aimed at preparing enantioenriched pipecoUc esters by decarboxylation of A7-acetyl piperidinohemimalonate 24 [17]. Among the different cinchona alkaloids investigated, the best result was obtained by means of 9-ep/-cinchonine-benzamide 19b, previously developed by Brunner [14, 16]. Pipecolic ester 25 was obtained in up to 52% ee when conducting the reaction in THF at room temperature for 24 h. Various bis-cinchona alkaloids such as (DHQDj AQN 26 or (DHQDj Pyr 27 were also evaluated providing modest enantiomeric excesses not exceeding 24% ee. Most of the results outlined in this study were obtained in the presence of a stoichiometric amount of the chiral base. The few attempts to carry out experiments under catalytic conditions seem to... 

Peptides, Kke amino acids, can taste bitter, sweet, salty or indifferent. Most natural and synthetic oligopeptides have a bitter taste (see Section 2.3.3.2). A sweet taste indicates dipeptides derived from L-aspartic acid (2-91) and others derived from its lower homologue L-aminomalonic acid (2-92). is always a hydrogen atom or a methyl group, substituents are alkyls or aryls and substituents are esterified carboxyl groups (usually methyl esters, but some ethyl, propyl, isopropyl and other esters are also sweet). The best... 

Spiro compounds. For example, Gong and coworkers combined 17 and in situ generated azomethine ylides derived from the condensation of aminomalonate 33 and aldehydes 15 to afford spiro[pyrrolidin-3,3 -oxindoles] 34 in good yields and excellent stereoselectivities when the binaphthol phosphoric acid derivative IV was used as catalyst (Scheme 10.8) [16]. 

Similarly, the methiodide was reacted with diethyl (2,2,2-trichloro-ethoxycarbonyl)aminomalonate as a nucleophile to give 118, which was then converted to the amine 119 by deprotection of the 2,2,2-trichloroethoxy-carbonyl group with zinc and potassium dihydrogen phosphate. Dehydrative cyclization of 119 to the azepinoindole 120 was achieved by heating 119 in the presence of a catalytic amount of pyridinium p-toluenesulfonate in dichloromethane. Hydrolysis of 120 with potassium hydroxide in methanol yielded the malonic acid derivative which was then readily decarboxylated on heating in aqueous ethanol to accomplish total syntheses of ( )-cis- and ( )-tranj-clavicipitic acid (84,85) in aratio 3 2 (Scheme 18) (57). 

Derivatives of 2-phenylimidazoles 10, 11 of immunestimulating activities that are obtained by addition of aminomalonic acid amide on hydrochloride iminoester at 0 C, and consequent boiling the mixture in methyl alcohol environment are described in patent [22] ... 

Two approaches to the 2-benzazepine system, in particular the 2-benzazepinone 142, have been reported by Le Diguarher et al. The first started from (acid-catalyzed cyclization to 141 N-alkylation and carbamate deprotection then afforded 142. The second route was based on A-HOC aminomalonate 144 and 2,2 -dibromo-o-xylene, and then steps via 145 and... 

Acylaminomalonic esters and related reagents are widely used for the synthesis of a-amino acids. The method differs from those syntheses already discussed in that the amino group is incorporated into the system from the outset. A popular reagent is diethyl acetamidomalonate (35). The acetamido group can readily be introduced into the reactive methylene position in diethyl malonate by first converting the latter into the hydroxy-imino derivative (33) by reaction with nitrous acid or an alkyl nitrite (cf. Section 4.2.7, p. 413). This derivative is then reduced catalytically to diethyl aminomalonate (34) which is acetylated using acetic anhydride. 

Shaprio described a nonoxidative method for preparing 2-substituted 4-ox-azolecarboxylic acid esters 591 (Scheme 1.161). He prepared the key intermediate, dimethyl amino[(phenylthio)methyl]malonate 588, in three straightforward steps from diethyl aminomalonate hydrochloride. Acylation of 588 gave the A-acyl derivative 589 in excellent yield, which was sequentially chlorinated and cyclized in one pot to afford the 2,4,4,5-tetrasubstituted oxazoline 590. The author noted that anhydrous conditions were required to minimize sulfoxide formation. This was the only product isolated if the chlorination cyclization sequence was carried out in a hydroxylic solvent. 

The first catalytic asymmetric formal [3h-3] cycloaddition of isatin-3-indolyhnethanol derivatives and in situ generated azomethine ylides was recently developed to synthesize structurally diverse spiro[indoline-3,4 -pyridoindoles] 228 bearing one all-carbon quaternary stereogenic center [109]. The reaction takes place with a range of A(-substituted isatin-derived 3-indolylmethanols, aromatic aldehydes 4, and diethyl 2-aminomalonate 221 and is catalyzed with chiral phosphoric acid 227 with the bulky 9-phenanthrenyl group at the 3,3 -positions of the BINOL moiety (Scheme 2.78). 

The first catalytic asymmetric homo-1,3-dipolar cycloadditions have been estatlished via SPINOL-derived chiral phosphoric acid (189)-catalysed reactions of aldehydes (186) and 2-aminomalonates (187). This protocol provided an easy access to synthetically and pharmaceutically important chiral imidazolidines (188) with two stereogenic centers, and four new bonds in a single step (Scheme 50). ... 

A one-pot, three component 1,3-dipolar cycloaddition reaction of aldehydes (289), a-aminomalonate (290), and nitroalkenes (291) has been developed through 3,3 anthiyl substituted hinaphthol derived chiral phosphoric acids (292) (Scheme 78). ... 

The reaction of H"CH0 with Al-acyl protected dialkyl aminomalonates and a-amino-ketones stops at the hydroxymethylation step. This behavior could be exploited for the synthesis of (R,S)-, (R)- and (5)-[3-"C]serine, (/f,5)-[3- C]cysteine and e.p. [1-"C]-chloramphenicol, as illustrated in Figure 5.38. In the [3-"C]serine preparations, saponification and decarboxylation converted the hydroxy["C]methyl derivatives 121 (R = acetyl orp-nitrobenzoyl), generated from H"CH0 and diethyl iV-acylaminomalonate, to racemic Af-acyl[3-"C]serine (122). Optical resolution of 122 with quinine and brucine followed by acid-catalyzed cleavage of the A -acyl groups afforded the enantiomerically pure... 

The phosporic acid (261) catalysed three component reaction involving asymmetric 1,3-dipolar cycloaddition of electron-deficient azomethine ylides (327), aromatic aldehydes (328) and 2-aminomalonates (329) to provide to novel 2,5-dihydropyrrole derivatives (330) with potential bioactivities with enantioselectivities of up to >99% ee (Scheme 86). The Bronsted acids (253) catalysed intermolecular enantioselective alkylation of indoles (332) with cx,p-unsaturated y-lactams (331) thus providing a highly enantioselective method for the synthesis of chiral pyrroli-dinones (333) containing indole moieties, with enantioselectivity (up to 95% ee), has been described by Huang et al. (Scheme 87). " ... 

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