Use of hydrolases for the synthesis of cyclic amino acids

The synthesis of several cyclic amino acids that have all the necessary structural features to make them ideal scaffolds for use in medicinal chemistry is described. A key step in each synthesis is the use of hydrolase enzymes to define a chiral centre. In order to elaborate these building blocks into more complex molecules, crystallization and asymmetric hydrogenation were used to define further stereocentres.     

Efficient copper-catalyzed synthesis of poly-N-heterocycles containing amino acid residues

An efficient copper-catalyzed method has been developed for the synthesis of poly-N-heterocycles containing amino acid residues. The protocol uses readily available 2-halobenzamides containing amino acids and their methyl esters, substituted phenylacetonitriles, and malononitrile as the starting materials and the reactions were performed well under mild conditions. The method should provide a novel and useful strategy for synthesis of N-heterocyclic compounds.     

In vivo incorporation of multiple noncanonical amino acids into proteins

Expansion of the standard genetic code enables the design of recombinant proteins with novel and unusual properties. Traditionally, such proteins have contained only a single type of noncanonical amino acid (NCAA) in their amino acid sequence. However, recently reported initial efforts demonstrate that it is possible with suppression-based methods to translate two chemically distinct NCAAs into a single recombinant protein by combining the suppression of different termination codons and nontriplet coding units (such as quadruplets). The possibility of expanding the code with various NCAAs simultaneously further increases the toolkit for the generation of multifunctionalized proteins.     

A simple protocol for the synthesis of 2-arylbenzoxazoles by oxidation with o-iodoxybenzoic acid (IBX) and its application in the synthesis of arylbenzoxazole-containing amino acids

A simple protocol for the preparation of 2-arylbenzoxazoles has been developed based on the oxidation of phenolic Schiff bases with o-iodoxybenzoic acid (IBX), wherein the oxidant can be recycled. The robustness of this new protocol has been demonstrated in the synthesis of arylbenzoxazole-containing amino acids.     

硫杂杯芳烃冠醚的合成及其与氨基酸配合性能的研究

在普通杯芳烃骨架中引入硫原子可以改善普通杯芳烃的配合性能。文中首先合成了硫杂杯[4]芳烃四酰肼衍生物3,在弱酸的催化下继续与化合物4反应,高产率地合成了同时含酰胺和席夫碱单元的硫杂杯[4]芳烃冠醚衍生物5,新化合物的结构经1H NMR、元素分析、ESI-MS等表征证实。同时探讨了新型硫杂杯[4]芳烃衍生物5与系列-α氨基酸的配合性能。     

A compilation of amino acid analyses of proteins

The amino acid analyses of 186 proteins are given as residues per 1000 residues. Additional information as carbohydrate composition, content of uncomon amino acids, and sources of all proteins are also presented.     

New synthetic routes to the kainoids: a synthesis of kainic acid and its analogues

New approaches to the synthesis of kainic acid and its analogues are presented. Two distinctly different approaches are described; the former utilised an intermolecular nitrile oxide addition to a homochiral substrate to furnish epikainate models and the second utilised amino acid chemistry to secure kainic acid.     

Deamination of the amino acid fragment in imine metallacycles: unexpected synthesis of an NH-aldimine organometallic compound

We report that the action of Lewis bases, such as triphenylphosphine, pyridine, or trimethylamine, on imine metallacycles derived from amino acids leads to the formation of the first organometallic compound of an NH aldimine, a highly reactive organic species, and the corresponding alpha-ketoester, in a deamination reaction that mimics the metabolism of alpha-amino acids. The synthesis of different cyclopalladated compounds by a reaction between palladium acetate and the Schiff bases 2,4,6-Me(3)C(6)H(2)CH=NCH(R(1))COOR(2) (R(1) = CH(2)Ph, R(2) = Et and R(1) = Ph, R(2) = Me) is also reported.     

Proximate composition,amino acid and fatty acid composition of fish maws

Fish maws are commonly recommended and consumed in Asia over many centuries because it is believed to have some traditional medical properties. This study highlights and provides new information on the proximate composition, amino acid and fatty acid composition of fish maws of Cynoscion acoupa, Congresox talabonoides and Sciades proops. The results indicated that fish maws were excellent protein sources and low in fat content. The proteins in fish maws were rich in functional amino acids (FAAs) and the ratio of FAAs and total amino acids in fish maws ranged from 0.68 to 0.69. Among species, croaker C. acoupa contained the most polyunsaturated fatty acids, arachidonic acid, docosahexaenoic acid and eicosapntemacnioc acid, showing the lowest value of index of atherogenicity and index of thrombogenicity, showing the highest value of hypocholesterolemic/hypercholesterolemic ratio, which is the most desirable.     

A generic platform for the immobilisation of engineered biocatalysts

The application of biocatalysis in the pharmaceutical industry is rapidly growing as a result of increased access to enzymes that meet the demands of industrial processes. This expansion of activity has led to a corresponding increase in the demand for immobilised enzymes. EziG? (EnginZyme AB, Sweden) is marketed as a general matrix for enzyme immobilisation on controlled porosity glass. In this work we identified criteria for a “general” enzyme immobilisation technology in the context of the requirements of the pharmaceutical industry. We subsequently evaluated EziG? for generality in a series of case studies for the application of immobilised biocatalysts. In this study we have focussed on the challenges facing both academic and industrial applications such as enzyme stability, multistep reactions and reactions in continuous flow.     

Chiral discrimination by hydrolytic enzymes in the synthesis of optically pure materials

Enantioselection effected by commercially available hydrolytic enzymes reported in recent years from our own laboratory and those published by other groups is described. The discussion is confined to enantioselection in symmetric diols, amino acids and benzopyran derivatives only. The paper describes a variety of substrates accepted by these hydrolytic enzymes to produce compounds in high enantiomeric excess which can be used as chiral building blocks for the synthesis of compounds of pharmaceutical and synthetic interest.     

Improved synthesis of unnatural amino acids for peptide stapling

The procedures for the synthesis of various α-alkenyl and alkyne amino acids were systematically optimized in light of enhancing atom economy, reducing hazardous reagent usage, and simplifying workup. By starting with Boc-Pro-OH and coupling with EDCI/DMAP followed by alkylation, chiral auxiliary was synthesized with high yield and enantioselectivity. For alkylation of the chiral complex, tBuONa was found and proved by quantitative calculation to be superior to tBuOK in generating more nucleophilic enolate salt, thereby can significantly enhance yield under room temperature. Final Fmoc protection was also dramatically facilitated in one-pot sequential manner by adding EDTA-2Na as the nickel chelator. Synthesis of α-bisalkenyl amino acid was also accomplished by achiral complex approach with high yield and efficacy. Accordingly, five most commonly used N-Fmoc protected α-alkenyl and alkynyl amino acids were synthesized and characterized.     

New method for the synthesis of 2-phenylproline and its derivatives

A new method has been developed for the synthesis of 2-phenylproline and its derivatives by intramolecular cyclization of the corresponding derivatives of N-(3-chloro-or 1-oxo-3-chloropropyl)--phenylglycine under phase transfer catalysis conditions.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, 375014 Yerevan, Armenia; e-mail: rafael@msrc.am. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 488–492, April, 2000.