Synthesis of α-silylcarboxylic acids

New α-silylacetic acids have been prepared following a general and convenient procedure of a one-pot reaction between trimethylsilylacetate and different chlorosilanes. New derivatives of diphenyl(methyl)silylacetic acid were prepared by a direct alkylation of its dianion with benzyl-, allyl-, and alkyl halides and trimethylchlorogermane to afford new α-silylcarboxylic acids.     

Synthesis of α-monoglycerides of aromatic acids

The synthesis of -monoglycerides of aromatic acids has been performed by the transesterification of the methyl esters of the corresponding acids with glycerol. The structures of the compounds obtained have been confirmed by their IR, UV, and¹H and¹³C NMR spectra.A. B. Bekturov Institute of Chemical Sciences, Academy of Sciences of the Republic of Kazakhstan, Almaty, fax (3272) 61 57 65. Translated from Khimiya Prirodnykh Soedineii, No. 4, pp. 452–457, July–August, 1999.     

Photodecarboxylative additions of N-protected α-amino acids to N-methylphthalimide

Photoreactions involving N,N-dimethylated α-amino acid salts and N-methylphthalimide are dominated by photoreduction and acetone trapping. Only, N-phenyl glycinate underwent photodecarboxylative addition in a moderate yield of 30%. In contrast, N-acylated α-amino acid salts readily gave addition products in fair to high yields of 20-95%. Comparison experiments with N,N-dimethylacetamide and amino-/amido-containing phthalimides revealed the origin of the crucial electron-transfer step and the reactivity order NR₃ »  ? RCONR₂ was established.     

A reasonably stereospecific multistep conversion of Boc-protected α-amino acids to Phth-protected β-amino acids

A method for the synthesis of β³-amino acids starting from α-amino acids is described. This conversion can be effected by an eight-step procedure which involves the transformation of the carboxylic group into an alkyne followed by a selenium-mediated conversion of the carbon-carbon triple bond to a Se-phenyl selenocarboxylate intermediate. The reactive Se-phenyl selenocarboxylate intermediates can be trapped with water, alcohols or the amine of an amino acid derivative to give β³-amino acids, β³-amino esters or mixed peptides, respectively. The whole transformations of the carboxylic group into an alkyne and of the alkyne group into β³-amino acids may not require purification of the intermediate products but a work-up and isolation procedure of crude materials.     

Iron-catalyzed decarbonylation reaction of aliphatic carboxylic acids leading to α-olefins

The catalytic decarbonylation reaction of aliphatic carboxylic acids can be carried out in the presence of an iron complex, and it proceeds smoothly to give α-olefins with high selectivity.     

Synthesis of quaternary α-aminophosphonic acids

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Synthesis of cyclic α-hydrazino acids

Synthesis of five-, six-, seven-, eight-, and nine-membered cyclic α-hydrazino acids from a common starting material ‘diethylmalonate’ with 26, 16, 34, 13.5, and 13.33% overall yields is described. Sequential allylation or homoallylation and electrophilic amination followed by cyclization gave the desired rings. The methyl esters of eight- and nine-membered rings were synthesized by RCM and the corresponding free acids were generated after hydrolysis in the presence of 1 M BBr₃ solution in DCM.     

Chirality measures of α-amino acids

To measure molecular chirality, the molecule is treated as a finite set of points in the Euclidean R(3) space supplemented by k properties, p(1)((i)), p(2)((i)), ..., p(k)((i)) assigned to the ith atom, which constitute a point in the Property P(k) space. Chirality measures are described as the distance between a molecule and its mirror image minimized over all its arbitrary orientation-preserving isometries in the R(3) × P(k) Cartesian product space. Following this formalism, different chirality measures can be estimated by taking into consideration different sets of atomic properties. Here, for α-amino acid zwitterionic structures taken from the Cambridge Structural Database and for all 1684 neutral conformers of 19 biogenic α-amino acid molecules, except glycine and cystine, found at the B3LYP/6-31G** level, chirality measures have been calculated by a CHIMEA program written in this project. It is demonstrated that there is a significant correlation between the measures determined for the α-amino acid zwitterions in crystals and the neutral forms in the gas phase. Performance of the studied chirality measures with changes of the basis set and computation method was also checked. An exemplary quantitative structure–activity relationship (QSAR) application of the chirality measures was presented by an introductory model for the benchmark Cramer data set of steroidal ligands of the sex-hormone binding globulin.     

Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids

An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane–water. The amino moiety must be protonated and located α to a carboxylic acid function in order to undergo initial diazotization and successive hydroxylation, since neither β-amino acids nor acid derivatives such as esters and amides undergo hydroxylations. The method is successfully applied for the synthesis of 18 proteinogenic amino acids.     

Derivatives of heterocyclic α-iminocarboxylic acids. 4. Reduction of N-alkoxycarbonyl derivatives of α-iminocarboxylic acids

When N-methoxycarbonyl and N-benzoxycarbonyl derivatives of methyl esters of aziridine-2-carboxylic acid, L-proline, L-thioproline, and pipecolic acid interact with NaBH₄ in tert-butanol/methanol, the products of reduction of the C-methoxycarbonyl group of the original compounds are accompanied by bicyclic urethanes and oxazolidines. Reduction of N-maleates and N-fumarates of heterocyclic -iminocarboxylic acids leads to the formation of -hydroxymethyl-N-[4-(2-oxo-2,5-dihydrofuryl)] derivatives of pyrrolidine, piperidine, 1,3-thiazolidine, and 1,4-thiazan. In the latter case, 1-aza-2-hydroxymethyl-4-oxo-5-oxa-9-thiabicyclo [5.4.0]undecene-2 is also obtained. The N-maleates and fumarates of aziridine-2-carboxylic acid are reduced anomalously by sodium borohydride, forming 2-hydroxymethyl-2-(-hydroxyethyl)-3-oxa-1-azabicyclo[3.1.0]hexanes.For Communication 3 see [2].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1567–1573, November, 1993.     

Asymmetric Strecker reaction of γ-keto acids. Facile entry to α-substituted and α,γ-disubstituted glutamic acids

The Strecker reaction of γ-keto acid derived sodium salts with (S)-phenylglycinol followed by treatment of the resultant α-amino nitriles with methanolic HCl and heating at 200 °C give bicyclic lactones 11 and 12. Hydrolysis and subsequent debenzylation of 11 and their alkylation products 17 furnish α-substituted and α,γ-disubstituted glutamic acids.     

Novel approach to the synthesis of aliphatic and aromatic α-keto acids

A new practical and efficient synthesis of α-keto acids was accomplished starting from the synthon 1,4-diacetylpiperazine-2,5-dione. The synthesis encompasses both aromatic and aliphatic substrates proving to be versatile and innovative with excellent carbon economy and recycling of the glycine by-product.     

Study of dissociation of α-alkyl-substituted dicarboxylic acids

Dissociation of α-alkyl-substituted dicarboxylic acids low-soluble in water was studied by the method of pH-potentiometry titration. Equilibrium constants of the dissociation at 25°C were determined.     

Derivatives of heterocyclic α-iminocarboxylic acids 3. Synthesis of N-alkoxycarbonyl and N-alkoxycarbonylalkenyl derivatives of α-iminocarboxylic acids

By the interaction of L-proline, L-thioproline, pipecolic acid, tetrahydro-1,4-thiazine-3-carboxylic acid, and diastereomeric esters of tetrahydro-1,4-thiazine-3,5-dicarboxylic acid with methyl chloroformate, methyl propiolate, and acetylenecarboxylic acid, we have obtained N-alkoxycarbonyl and N-alkoxycarbonylalkenyl derivatives of -iminocarboxylic acids. By the reaction of N-methoxycarbonyltetrahydro-1,4-thiazine-3-carboxylic acid with hydrazine hydrate, we have obtained 8-amino-7,9-dioxo-4-thia-1,8-diazabicyclo[4.3.0]nonane.For communication 2, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1561–1566, November, 1993.     

Preparation of α,α-difluoroalkanesulfonic acids

Chlorodifluoromethanesulfonic acid (1) was prepared using a new procedure starting from perchloromercaptan, which is readily obtained from chlorination of CS₂. Modified Swarts reaction transformed N,N-diethyl trichloromethanesulfenamide into N,N-diethyl chlorodifluoromethanesulfenamide, and the latter species was further oxidized and hydrolyzed into chlorodifluoromethanesulfonic acid. The preparations of other two new α,α-difluoroalkanesulfonic acids, phenyl difluoromethanesulfonic acid (2) and 2-phenyl-1,1,2,2,-tetrafluoroethanesulfonic acid (3), are also disclosed. The acids 2 and 3 are stable in the forms of sodium (lithium) salts or in aqueous solutions; however, the pure forms of 2 and 3 can readily undergo defluorinations. 1-3 and their salts have potential applications as superacid catalysts and lithium battery electrolytes.     

Direct synthesis of α-thio aromatic acids from aromatic amino acids

Modified amino acids are useful synthetic components in both chemistry and biology. Here we describe a simple, scalable two-step procedure to generate α-thio aromatic acids from aromatic amino acids with yields of up to 96%. Diazotization and α-lactone mediated bromination efficiently form the α-bromo acid with retention of configuration. Thiol substitution with mild reagents such as sodium hydrosulfide or sodium trithiocarbonate provides the inverted, free α-thio acid. The mildly acidic soft nucleophile can then be utilized in many synthetic applications.     

Highly diastereoselective synthesis of quaternary α-trifluoromethyl α-amino acids by addition of benzylzinc reagents to chiral imines of trifluoropyruvate

An effective and facile method for highly diastereoselective synthesis of quaternary α-trifluoromethyl α-amino acids was developed in good yields with high diastereoselectivity (dr >20:1) via MgCl₂-accelerated addition of benzylzinc reagents (Knochel type organozinc reagents) to (R)-phenylglycinol methyl ether based imines of trifluoropyruvate.