Polyenolates of Unsaturated Carboxylic Acids in Synthesis. Synthesis of Unsaturated α-Amino Acids and β-Hydrazing Acids

Regioselective reaction of lithium diene-and triene-diolates 1 and 2 with O-diphenylphosphinyl hydroxylamine affords unsaturated α-amino acids 3 and 4. Addition to DEAD leads selectively to γ-hydrazino unsaturated acids 5 and 6.     

A New Asymmetric Synthesis of β-Aminophosphonic Acids

Addition of α-phosphonate carbanions to (S)-sulfinimines 2 gives N-sulfinyl-β-aminophosphonates 3 with a high diastereoselectivity (up to 10:1). The major diastereomer of 3 (R=Ph) was converted into (+)-(R)-β-amino-β-phenylethanephosphonic acid 5.     

Engineered Biocatalytic Synthesis of β-N-Substituted-α-Amino Acids

Non-canonical amino acids (ncAAs) are useful synthons for the development of new medicines, materials, and probes for bioactivity. Recently, enzyme engineering has been leveraged to produce a suite of highly active enzymes for the synthesis of β-substituted amino acids. However, there are few examples of biocatalytic N-substitution reactions to make α,β-diamino acids. In this study, we used directed evolution to engineer the β-subunit of tryptophan synthase, TrpB, for improved activity with diverse amine nucleophiles. Mechanistic analysis shows that high yields are hindered by product re-entry into the catalytic cycle and subsequent decomposition. Additional equivalents of l -serine can inhibit product reentry through kinetic competition, facilitating preparative scale synthesis. We show β-substitution with a dozen aryl amine nucleophiles, including demonstration on a gram scale. These transformations yield an underexplored class of amino acids that can serve as unique building blocks for chemical biology and medicinal chemistry.     

Synthesis and Heterocyclization of β-Aroyl-α-diphenylphosphorylpropionic Acids

It has been established that diphenylphosphine oxide reacts smoothly with -aroylacrylic acids with the formation of -aroyl--diphenylphosphorylpropionic acids, which were cyclized under the action of hydroxylamine, hydrazine hydrate, and phenylhydrazine hydrochloride into phospho derivatives of dihydrooxazinone and tetrahydropyridazinone respectively. It was shown that imidazole may serve as nucleophilic protection for the synthesis of dihydropyridazinone derivatives from -aroylacrylic acids.     

A Novel Synthesis of β-Hydroxy-α-amino Acids

β-hydroxy-α-amino acids constitute an important class of compounds as naturally occurring amino acids and as components of many complex natural products possessing a wide range of biological activities. [1] As a consequence of the essential role played by these amino acids in the biological systems and their utility as synthetic building blocks, a number of useful strategies have been devised for their preparation. [2]     

Synthesis of β-Lactams from Acids and Imines Using Thiocarbonyldiimidazole

Thiocarbonyldiimidazole has been found to be an efficient acid activator for the synthesis of β-lactams by ketene-imine cycloaddition at room temperature. The experimental procedure is simple and results in excellent yields of the products. All products were characterized by spectral data and elemental analyses.     

Synthesis of a new Class of Chiral β—Mercaptoalcohols from Amino Acids

The syntheses of three new optically active β-mercaptoalcohols,(R)-1,1-diphenyl-2-mercapto-3-methyl-1-butanol,(R)-1,1-diphenyl-2-mercapto-4-methyl-1-pentanol,and (R)-1,1-diphenyl-2-mercapto-1-benzenepropanol from the corresponding amino acids are described.The enantiomeric excesses of these β-mercaptoalcohols were determined by ^1H NMR as their (S)-mandeloyl derivatives.     

The Synthesis of Cyclic Amino Acids

Several cyclic amino acids (1-4) were synthesized from glycine. Isocyanate ester was prepared as the key intermediate and reacted with dibromoalkanes to afford the target compounds.     

Synthesis of Amphiphilic Conjugates Based on Silicon-Containing β-Cyclodextrin and Pharmacologically Important Acids

Russian Journal of General Chemistry - Amphiphilic conjugates were obtained containing fragments of pharmacologically important monocarboxylic aromatic acids, which are of interest for biomedical...     

A New Synthesis of β-Phenylethyl Alcohols and Phenyl-Acetic Acids via Hydroboration of Phenylketene Dihalides

The synthesis of phenylethyl alcohols and phenyl-acetic acids have been carried out by various methods. We now report a simple synthesis for these compounds via the unprecedented hydroboration-oxidation reaction on phenylketene dihalides.     

Synthesis of 3-Fluoro-Oxetane δ-Amino Acids

Starting from d-xylose, 2,4-anhydro-5-N-(tert-butoxycarbonyl)amino-5-deoxy-3-fluoro-d-arabinonic acid 11 was synthesized over 10 steps including ring contraction, fluorination, and ester hydrolysis. Bromine oxidation of d-xylose followed by benzylidenation in a one-pot procedure led to a ca. 1:1 mixture of lactone 3 and 2,4;3,5-dibenzylidene xylonic acid (4) as by-product. For the synthesis of the d-xylo derivative 24, the chosen starting material was 1,2-O-isopropylidene-α-d-xylofuranose. A total of 14 steps including epimerization, ring contraction, fluorination, and saponification led to the desired fluoro-oxetane δ-amino acid 24. Hydrolysis of the 3-fluoro-oxetane δ-amino esters 10 and 23 by means of LiOH was successful in agreement with the results previously reported for similar 3-methoxy oxetanes, whereas chemical hydrolysis was not possible for 3-hydroxy derivatives.     

Synthesis of Optical Active 2-Arylpropionic Acids

2-Arylpropionic acid and its derivatives are pharmaceutically and agriculturally useful products1,2, especially, the optical isomer possesses extra higher biological or pharmaceutical activity, for example the antiflammatory agent3 of S-2-(6(-methoxyl- (-naphthyl) propionic acid (Naproxen), the effect of (S)-isomer is 28 times as actives as its R isomer. For the preparation of optically active 2-arylalkanoic acids many different synthetic strategies have been reported, such as, the resolution…     

A Convenient Synthesis of ω-Acetylenic Acids

ω-Acetylenic acids are valuable intermediates in the synthesis of long-chain acids. Their dimagnesium salts may be alkylated with 1-bromo-2-alkynes or 2-alkenes to synthesize many important naturally occurring fatty acids^1–3. Also, internally-monounsaturated acids are prepared by alkylation of ω-acetylenic acid dilithium salts^4,5 or the sodium salts of their N,N-dimethylamides⁶.     

Interaction of Hydroxy Acids with β-Cyclodextrin

The solubility of -cyclodextrin (-CD) was studied in aqueous solutions of various organic acids. The hydroxy acids, especially citric and tartaric acid were found to increase the solubility of -CD, while some other carboxylic acids reduced it. From solubility data the apparent complex association constants were calculated.     

Selection of Amino Acids and the Biomimetic Synthesis of Amido Bond in the Presence of β-CD

A new method was developed to construct a special amido bond in the presence of β-cyclodextrin. This process is similar to peptide synthesis in organisms. NMR experiments were performed to investigate the possible mechanism. This work has potential application in biomimetic peptide synthesis.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Design of Supported Organocatalysts from Carboxylic Acids for the Mannich-Type Synthesis of β-Amino Carbonyl Compounds

New supported acidic organocatalysts were prepared by the impregnation of three carboxylic acids (CF₃COOH, CCl₃COOH, and CH₃COOH) on silica support at room temperature in diethyl ether. The catalysts were characterized by scanning electron microscopy, energy dispersion X-ray analysis (EDX), Brunauer-Emmett-Teller-surface-area-analysis (BET), thermogravitational analysis, Fourier transform infrared, and powder X-ray diffractometry analysis. These solid acids were observed as highly efficient reusable catalysts at room temperature for the selective synthesis of β-amino carbonyl compounds via Mannich-type reactions of acetophenone, arylamine and arylaldehydes using two different conditions in CH₂Cl₂ solution and solvent-free grinding within a short time. The more acidic two catalysts could be recycled for up to five cycles with a small loss in catalytic activity.     

Synthesis of Unsymmetrical β-Arylaminoketones

Azomethines derived from aniline were condensed with acetophenone derivatives to obtain new unsymmetrical -arylaminoketones.     

New Synthesis of β-Iodostyrenes

A general procedure for the synthesis of -iodostyrenes is proposed. Aromatic aldehyde and ketone hydrazones are converted into the corresponding -iodostyrenes by treatment with CHI₃ in the presence of a catalytic amount of CuCl.