Stereocontrolled Synthesis of syn‐β‐Hydroxy‐α‐Amino Acids by Direct Aldolization of Pseudoephenamine Glycinamide

β‐Hydroxy‐α‐amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β‐hydroxy‐α‐amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one‐flask protocol. Enolization of (R,R)‐ or (S,S)‐pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L ‐ or D ‐threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55–98 %, and are readily transformed into β‐hydroxy‐α‐amino acids by mild hydrolysis or into 2‐amino‐1,3‐diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes.     

Practical Synthesis of anti‐β‐Hydroxy‐α‐Amino Acids by PdII‐Catalyzed Sequential C(sp3)H Functionalization

An improved and practical procedure for the stereoselective synthesis of anti‐β‐hydroxy‐α‐amino acids (anti‐βhAAs), by palladium‐catalyzed sequential C(sp³)?H functionalization directed by 8‐aminoquinoline auxiliary, is described. followed by a previously established monoarylation and/or alkylation of the β‐methyl C(sp³)?H of alanine derivative, β‐acetoxylation of both alkylic and benzylic methylene C(sp³)?H bonds affords various anti‐β‐hydroxy‐α‐amino acid derivatives. As an example, the synthesis of β‐mercapto‐α‐amino acids, which are highly important to the extension of native chemical ligation chemistry beyond cysteine, is described. The synthetic potential of this protocol is further demonstrated by the synthesis of diverse β‐branched α‐amino acids. The observed diastereoselectivities are strongly influenced by electronic effects of aromatic AAs and steric effects of the linear side‐chain AAs, which could be explained by the competition of intramolecular C?OAc bond reductive elimination from Pd^IV intermediates vs. intermolecular attack by an external nucleophile (AcO^?) in an S_N2‐type process.     

Synthesis of Cyclosporine and Analogues: Structural Requirements for Immunosuppressive Activity

Cyclosporine is a new immunosuppressive drug which was first marketed in 1983 under the trade name Sandimmune®. This compound, an innovation in selective immune modulation, was isolated from a fungal culture and characterized as a cyclic undecapeptide containing a novel amino acid together with several N-methylated amino acids. The new amino acid (4R)-4-[(E)-2-butenyl]-4,N-dimethyl-L -threonine (MeBmt) was the only unknown amino acid of cyclosporine and there had previously been no means for its isolation. For this reason and because it seemed possible that MeBmt could play a significant role in determining the pharmacological activity of cyclosporine, its synthesis in enantiomerically pure form was undertaken. The next step was the development of a total synthesis of cycloporine, which appeared attractive, not only for its intrinsic worth, but also as an important tool for investigating the relationships between structure and immunosuppressive activity. Essential for the immunosuppression are the amino acids MeBmt, Abu, Sar, and MeVal in the positions 1, 2, 3 and 11, but probably also still larger parts of the molecule. Such information could be valuable for finding new chemical leads or drugs with a new activity profile.     

Optically active polymers of 3-alkylmalic acids: Contribution of the bioconversion for diversifying the chiral precursors

The need for new optically active monomers and polymers is conducive to the setting up of stereospecific synthesis routes starting from chiral precursors. The biomass can be considered as a major source for extracting such biomolecules aimed at chemoenzymatic transformation and further polymerization. Due to its versatility, ß-methylaspartate ammonia-lyase, from cell-free extracts of Clostridium tetanomorphum, has been used in the bioconversion of alkylfumarates into optically active pure 3-alkylaspartic acids with alkyl=methyl, ethyl, isopropyl. These amino acids have been transformed in several steps into optically active benzyl 3-alkylmalolactonates leading to semi-crystalline polyesters. 3-Methylaspartic acid includes two chiral centers and the racemic compound containing the four stereoisomers can be prepared by a multiple step synthesis. The ability of ß-methylaspartase to catalyse both syn- and anti-elimination of ammonia from natural 3-methylaspartic acid has been expressed to retain one stereoisomer and this bioconversion is a preparative method for obtaining unnatural stereoisomers. Moreover, the catalytic hydrogenolysis of the benzyl α,ß-substituted ß-lactone yields stable 3-alkylmalolactonic acid which can be coupled with functional alcohols and copolymerized. At last the introduction of (2S)-3,3-dimethyl-2-butanol, using Rhodotorula glutinis as microorganism in a biological synthesis step, as chiral ester pendant group, has conducted to optically active polyesters with very high melting transition temperatures. The combination of bioconversion and chemical synthesis is a very useful tool for building hydrolyzable functionalized polyesters required for temporary applications.     

Stimuli-responsive polypeptide materials prepared by ring-opening polymerization of α-amino acid N-carboxyanhydrides

Design and synthesis of biodegradable stimuli-responsive polypeptides are important areas considering their promising applications in biomedical fields. This article summarizes the most recent progresses in the development of stimuli-responsive polypeptide materials prepared via ring-opening polymerization of α-amino acid N-carboxyanhydrides. We discuss the design, synthesis and structure-property correlation of emerging materials including thermo-responsive, redox-responsive, photo-responsive and biomolecule responsive polypeptides. Considering the unique structural features of amino acids, we try to emphasize that the thermo-responsive properties not only depend on the amino acid structure but also rely on the secondary structures of polypeptides. © 2013 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013     

Visible-Light-Driven Three-Component Reaction of Unactivated Alkenes Enables Access to Monofluoro γ-Amino Acids

A strategy for the synthesis of diverse protected α-monofluoro-γ-amino acid derivatives has been developed. This reaction assembles a simple enamide, quinoxalin-2(1H)-one, and diethyl 2-bromo-2-fluoromalonate through a three-component reaction driven by visible light. The advantages of this protocol include the simplicity of its operation, mild conditions, high functional group tolerance, and applicability to a wide variety of substrates. The synthesis of this fluorine-containing amino acid derivative has significant value for potential applications in medicinal chemistry and chemical biology.     

The ‘Azirine/Oxazolone Method’ on Solid Phase: Introduction of Various α,α‐Disubstituted α‐Amino Acids

Peptides containing various α,α‐disubstituted α‐amino acids, such as α‐aminoisobutyric acid (Aib), 1‐aminocyclopentane‐1‐carboxylic acid, α‐methylphenylalanine, and 3‐amino‐3,4,5,6‐tetrahydro‐2H‐pyran‐3‐carboxylic acid have been synthesized from the N‐ to the C‐terminus by the ‘azirine/oxazolone method’ under solid‐phase conditions. In this convenient method for the synthesis of sterically demanding peptides on solid‐phase, 2H‐azirin‐3‐amines are used to introduce the α,α‐disubstituted α‐amino acids without the need for additional reagents. Furthermore, the synthesis of poly(Aib) sequences has been explored.     

光学活性含硅氨基酸的合成

光学纯的硅取代氨基酸是一类非天然的手性氨基酸合成子，在药物，植物保护 剂和精细化学品的合成具有极为广阔的应用前景，其合成方法包括化学不对称合成 及化学合成外消旋体－生物学拆分两种，综述了该方面的研究进展。     

光学活性双氨基酸的合成

光学活性的双氨基酸作为一类非天然的氨基酸合成子, 在医药、农药和肽类合成中有着重要的作用. 评述了近年来关于光学活性双氨基酸合成的进展.     

Industrial methods for the production of optically active intermediates

Enantiomerically pure amino acids, amino alcohols, amines, alcohols, and epoxides play an increasingly important role as intermediates in the pharmaceutical industry and agrochemistry, where both a high degree of purity and large quantities of the compounds are required. The chemical industry has primarily relied upon established chemical methods for the synthesis of these intermediates, but is now turning more and more to enzymatic and biotechnological fermentation processes. For the industrial implementation of many transformations alternative methods are available. The advantages of the individual methods will be discussed herein and exemplified by syntheses of relevant compounds.     

A first glance into the nutritional properties of the sea cucumber Parastichopus regalis from the Mediterranean Sea (SE Spain)

This work reports for the first time the nutritional profile, including proximate chemical composition, amino acids, fatty acids and minerals of Parastichopus regalis from the Mediterranean Sea (SE Spain). The studied species had a high moisture content, moderate protein and low lipid levels. The most abundant amino acids were glutamic acid, arginine and tyrosine. Polyunsaturated fatty acids, especially arachidonic acid, dominated the fatty acid profile. Iron, sodium, calcium and zinc were the most abundant mine rals. In general, P. regalis has a balanced nutritional quality suitable for human consumption.     

Synthesis and Self‐Assembly of Bolaamphiphiles Based on β‐Amino Acids or an Alcohol

The synthesis of bolaamphiphiles from unusual β‐amino acids or an alcohol and C₁₂ or C₂₀ spacers is described. Unusual β‐amino acids such as a sugar amino acid, an AZT‐derived amino acid, a norbornene amino acid, and an AZT‐derived amino alcohol were coupled with spacers under standard conditions to get the novel bolaamphiphiles 5 – 8 (Scheme 1), 12 and 13 (Scheme 2), and 17 and 20 (Scheme 3). Some of these compounds, on precipitation from MeOH/H₂O, self‐assembled into organized molecular structures.     

Microbial production of natural poly amino acid

Three kinds of poly amino acids, poly-γ-glutamic acid, poly(ε-L-lysine) and multi-L-arginyl-poly (L-aspartic acid) can be synthesized by enzymatic process independently from ribosomal protein biosynthesis pathways in microorganism. These biosynthesized polymers have attracted more and more attentions because of their unique properties and various applications. In this review, the current knowledge on the biosynthesis, biodegradations and applications of these three poly amino acids are summarized.     

Synthesis of Functionalized Novel α‐Amino‐β‐alkoxyphosphonates through Regioselective Ring Opening of Aziridine‐2‐phosphonates

Aziridines are highly useful compounds as building blocks for the synthesis of important organic compounds. Amino acid synthesis by aziridine ring opening reaction is a good example to the use of aziridines. Although this reaction is studied by many groups, the synthesis of amino phosphonic acids is less explored. In this study, we have carried out the ring opening reaction of aziridinyl phosphonates with a variety of alcohols including the more functional propargylic and allylic alcohols. These reactions provided functionalized α‐amino‐β‐alkoxyphosphonates in 40–91 % yield.     

Synthesis of Phosphonopeptides Using Pivaloyl Chloride

Abstract

Aminopnospnonic acids can be used as components in the synthesis of peptides resulting in the phosphonopeptides, which are interesting not only from the chemical point of view but also for their promising biological properties. An aminophosphonic acid unit can be attached to the C-terminus of amino acids or peptides by the usual methods of peptide chemistry. However, the specific properties of aminophos-phonates can sometimes lead to complications, for example formation of by products (1). de have tested the method of phospnonopeptide synthesis using pivaloyl chloride. It was found that dialkyl esters of 1-aminoalkylphosphonic acids readily react with mixed anhydrides of N-protected amino acid and pivalic acid to give the fully protected phosphonopeptides with good yields.     

Chromatographic determination of amino acids in foods

Amino acids in foods exist in a free form or bound in peptides, proteins, or nonpeptide bonded polymers. Naturally occurring L-amino acids are required for protein synthesis and are precursors for essential molecules, such as co-enzymes and nucleic acids. Nonprotein amino acids may also occur in animal tissues as metabolic intermediates or have other important functions. The development of bacterially derived food proteins, genetically modified foods, and new methods of food processing; the production of amino acids for food fortification; and the introduction of new plant food sources have meant that protein amino acids and amino acid enantiomers in foods can have both nutritional and safety implications for humans. There is, therefore, a need for the rapid and accurate determination of amino acids in foods. Determination of the total amino acid content of foods requires protein hydrolysis by various means that must take into account variations in stability of individual amino acids and resistance of different peptide bonds to the hydrolysis procedures. Modern methods for separation and quantitation of free amino acids either before or after protein hydrolysis include ion exchange chromatography, high performance liquid chromatography (LC), gas chromatography, and capillary electrophoresis. Chemical derivatization of amino acids may be required to change them into forms amenable to separation by the various chromatographic methods or to create derivatives with properties, such as fluorescence, that improve their detection. Official methods for hydrolysis and analysis of amino acids in foods for nutritional purposes have been established. LC is currently the most widely used analytical technique, although there is a need for collaborative testing of methods available. Newer developments in chromatographic methodology and detector technology have reduced sample and reagent requirements and improved identification, resolution, and sensitivity of amino acid analyses of food samples.     

Piperidone synthesis using amino acid: A promising scope for green chemistry

Piperidone is a family of organic chemicals characterized by a 6-carbon ring substituted with nitrogen and a double-bonded oxygen atom. Piperidones are named by the location of the nitrogen or amine group on the ring. It differs from piperidine by the presence of oxygen molecule (from ketone). It is used in pharmaceutical companies and chemical manufacturers as intermediates having anti microbial activity. It is usually synthesized using ammonia both in laboratory and industry. In present study, amino acid namely aspartic acid is used instead of ammonia. The amino acid incorporated piperidones is purified and analyzed using NMR spectroscopy. It has antimicrobial activity against Pseudomonas aeruginosa and Salmonella aboni.     

C‐Glycosyl Amino Acids through Hydroboration–Cross‐Coupling of exo‐Glycals and Their Application in Automated Solid‐Phase Synthesis

O‐Glycosylation is one of the most important post‐translational modifications of proteins. The attachment of carbohydrates to the peptide backbone influences the conformation as well as the solubility of the conjugates and can even be essential for binding to specific ligands in cell–cell interactions or for active transport over membranes. This makes glycopeptides an interesting class of compounds for medical applications. To enhance the long‐term availability of these molecules in vivo, the stabilization of the glycosidic bond between the amino acid residue and the carbohydrate is of interest. The described modular approach affords β‐linked C‐glycosyl amino acids by a sequence of Petasis olefination of glyconolactones, stereoselective hydroboration and a mild B‐alkyl‐Suzuki coupling reaction. The coupling products were transformed to C‐glycosyl amino acid building‐blocks suitable for solid‐phase synthesis and successfully incorporated into a partial sequence of the tumor‐associated MUC1‐glycopeptide. The resulting C‐glycopeptides are candidates for the development of long‐term stable mimics of O‐glycopeptide vaccines.     

Applications of Lactic Acid Bacteria and Their Bacteriocins against Food Spoilage Microorganisms and Foodborne Pathogens

Lactic acid bacteria (LAB) are Gram-positive and catalase-negative microorganisms used to produce fermented foods. They appear morphologically as cocci or rods and they do not form spores. LAB used in food fermentation are from the Lactobacillus and Bifidobacterium genera and are useful in controlling spoilage and pathogenic microbes, due to the bacteriocins and acids that they produce. Consequently, LAB and their bacteriocins have emerged as viable alternatives to chemical food preservatives, curtesy of their qualified presumption of safety (QPS) status. There is growing interest regarding updated literature on the applications of LAB and their products in food safety, inhibition of the proliferation of food spoilage microbes and foodborne pathogens, and the mitigation of viral infections associated with food, as well as in the development of creative food packaging materials. Therefore, this review explores empirical studies, documenting applications and the extent to which LAB isolates and their bacteriocins have been used in the food industry against food spoilage microorganisms and foodborne pathogens including viruses; as well as to highlight the prospects of their numerous novel applications as components of hurdle technology to provide safe and quality food products.     

Effective Methods for the Synthesis of N‐Methyl β‐Amino Acids from All Twenty Common α‐Amino Acids Using 1,3‐Oxazolidin‐5‐ones and 1,3‐Oxazinan‐6‐ones

N‐Methyl β‐amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3‐oxazolidin‐5‐ones to synthesise N‐methyl α‐amino acids. Starting from α‐amino acids, two approaches were used to prepare the corresponding N‐methyl β‐amino acids. First, α‐amino acids were converted to N‐methyl α‐amino acids by the so‐called ‘1,3‐oxazolidin‐5‐one strategy’, and these were then homologated by the Arndt–Eistert procedure to afford N‐protected N‐methyl β‐amino acids derived from the 20 common α‐amino acids. These compounds were prepared in yields of 23–57% (relative to N‐methyl α‐amino acid). In a second approach, twelve N‐protected α‐amino acids could be directly homologated by the Arndt–Eistert procedure, and the resulting β‐amino acids were converted to the 1,3‐oxazinan‐6‐ones in 30–45% yield. Finally, reductive cleavage afforded the desired N‐methyl β‐amino acids in 41–63% yield. One sterically congested β‐amino acid, 3‐methyl‐3‐aminobutanoic acid, did give a high yield (95%) of the 1,3‐oxazinan‐6‐one ( 65 ), and subsequent reductive cleavage gave the corresponding AIBN‐derived N‐methyl β‐amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N‐methyl β‐amino acids derived from the 20 proteinogenic α‐amino acids.