Facile,eco-friendly,one-pot protocol for the synthesis of indole-imidazole derivatives catalyzed by amino acids

An efficient, convenient green approach for the synthesis of indole-based 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles by multicomponent reaction of substituted 2-arylindole-3-carbaldehydes, benzil, substituted anilines, and ammonium acetate using catalytic amino acid (glycine) in ethanol is described. Several amino acids have also been evaluated as organic catalysts for these reactions. The structures of the compounds have been established on the basis of infrared, mass, and ¹H NMR spectral data. The mild reaction conditions, inexpensive/economical reagents, and good yield show the usefulness of this approach.     

A novel multicomponent reaction between amino acids,aromatic aldehydes and p-toluenesulfonylmethyl isocyanide: an efficient and green one-pot synthesis using nanosilica

The novel diastereomeric sulfonylamide derivatives 4a–h were synthesized by multi-component reactions between (l)-α-amino acids, 1, aromatic aldehydes, 2 and p-toluenesulfonylmethyl isocyanide, 3 in water/methanol using nanosilica as a catalyst. The one-pot green reactions were carried out at room temperature with a quantitative yield in water/methanol. The yield of the reactions and products was determined and discussed. The reusablity of the catalyst is discussed.     

A green and convenient protocol for the synthesis of novel pyrazolopyranopyrimidines via a one-pot,four-component reaction in water

Novel tricyclic fused pyrazolopyranopyrimidines containing both biologically active pyranopyrazole and pyranopyrimidine templates are synthesized using a one-pot, four-component reaction involving ethyl acetoacetate, hydrazine hydrate, benzaldehydes, and barbituric acid catalyzed by DABCO in water. Pure target compounds are obtained in very good to excellent yields over short reaction times and with a straightforward work-up procedure.     

Efficient and one-pot synthesis of novel sulfamates from carboxylic acids

Effective synthesis of novel sulfamates from various carboxylic acids has been developed in the presence of chlorosulfonyl isocyanate (CSI) in mild conditions. Several acids, bases and solvents effects were investigated for one-pot synthesis sulfamates as a catalyst. Finally, triflic acid was found to possess efficiently under optimized conditions in acetonitrile. This method is easy, fair price and practical. It can be synthesized on grams and milligrams scale.     

Creating carbon-carbon bonds with samarium diiodide for the synthesis of modified amino acids and peptides

In this perspective, an overview of our experiences on the application of samarium diiodide in organic synthesis for the preparation of amino acid and peptide analogues is presented. Three different carbon-carbon bond forming reactions are discussed, including side chain introductions, gamma-amino acid synthesis and acyl-like radical additions for the construction of C-C mimics of the peptidic bonds.     

Combined application of organozinc chemistry and one-pot hydroboration-Suzuki coupling to the synthesis of amino acids

Hydroboration using 9-BBN-H of the protected enantiomerically pure but-3-enylglycine derivative 11, prepared by copper-catalysed allylation of the serine-derived organozinc reagent 1, followed by Suzuki coupling of the derived borane with a variety of aromatic halides, 2-bromopyridine and 2-bromopropene gives the protected amino acids 14a-l and 15. This method augments our previous methods for the synthesis of phenylalanine homologues.     

Design and synthesis of novel fluoro amino acids: synthons for potent macrocyclic HCV NS3 protease inhibitors

The Hepatitis C Virus (HCV) is a major health hazard and its infection is a leading cause of chronic liver disease world wide. In our efforts toward the discovery of a back up to our first clinical candidate, Boceprevir (SCH 503034), we approached the depeptidization of the molecule through macrocyclization. Herein we report the design and synthesis of fluoro amino acids with desired stereochemistry required for the synthesis of macrocyclic inhibitors with fluorine at various positions of the aliphatic chain. Biological activities of representative examples are also reported.     

A new protocol for the one-pot synthesis of symmetrical biaryls

Biaryls play an important role in modern organic chemistry. Although a large number of protocols for the synthesis of symmetrical and unsymmetrical biaryls already exist, most of them are not generally applicable. In our studies toward the total synthesis of the secalonic acids, we were interested in bis(pinacolato)diboron as a reagent for transforming haloarenes into arylboronic esters. By optimizing the reaction conditions, we were able to obtain biaryls containing various functional groups in good to excellent yields.     

A novel approach to the synthesis of amino acids based on cobalt bis(dicarbollide)

A novel approach to the synthesis of boron-containing amino acids based on ring opening of cyclic oxonium derivatives of polyhedral boron hydrides under the action of the terminal functional groups of natural amino acids was proposed. This approach was successfully implemented for the synthesis of cobalt bis(dicarbollide) — tyrosine conjugate.     

Ultrasound-assisted rapid and efficient one-pot synthesis of furanyl spirooxindolo and spiroquinoxalinopyrrolizidines by 1,3-dipolar cycloaddition: a green protocol

Efficient synthesis of novel spirooxindolo and spiroquinoxalinopyrrolizidine derivatives was expediently accomplished with regioselectivity via one-pot, three-component 1,3-dipolar cycloaddition using ultrasonication. Chalcones derived from both heteroaryl methyl ketones and furfural were used as dipolarophiles in these reactions. The synthesized compounds were analyzed by ¹H and ¹³C nuclear magnetic resonance (NMR), mass spectrometry, and elemental (CHN) analysis. Single-crystal X-ray diffraction studies of one of the compounds (11d) proved the structure and regiochemistry of the cycloaddition. The ultrasound methodology is clearly advantageous, and the desired products were obtained in moderate to good yield in shorter reaction time compared with conventional heating and fusion methods.     

A facile one-pot protocol for the synthesis of tetrazolyl-tetrahydroisoquinolines via novel domino intramolecular cyclization/Ugi-azide sequence

A facile one-pot, four-component domino reaction between 2-(2-bromoethyl)benzaldehyde, isocyanide, amine, and azide for the synthesis of tetrazolyl-tetrahydroisoquinoline derivatives has been developed. The reaction sequence involves intramolecular replacement of halide by iminium nitrogen followed by Ugi-azide reaction. The reaction is catalyst/additive free and takes place under ambient conditions with short reaction times to furnish products in good to excellent yields.     

Design and synthesis of conformationally constrained glycosylated amino acids

To probe the conformational requirements of O-linked glycoproteins for binding to various enzymes and receptors, two conformationally constrained glycosylated amino acids, 2 and 3, were designed. The analogues were found to represent two potential low energy conformations of the parent conjugate, 1, by molecular modeling. A convergent synthesis of both 2 and 3 from D-galactose and L-methionine is presented.     

Sequential Ru-Pd catalysis: a two-catalyst one-pot protocol for the synthesis of N- and O-heterocycles

An atom economic, selective, and highly practical two-metal one-pot synthesis of heterocycles has been developed that efficiently affords enantio- and diastereopure N- and O-heterocyclic products. Furthermore, use of a chiral catalyst in the two-metal procedure allows formation of all possible diastereomers, even those that are traditionally difficult to access via cyclization routes due to thermodynamics. Interestingly, the nature of the enantiodiscriminating event differs between the use of amine versus alcohol nucleophiles. The method also affords heterocyclic products that are synthetically useful intermediates. Through the Z-vinylsilane a variety of stereodefined trisubstituted olefin products can be accessed including several all-carbon motifs. Finally, the utility of these heterocyclic products in total synthesis is demonstrated through concise syntheses of a kainoid intermediate, a constituent of oil of rose, and the ring B portion of bryostatin, a potent chemotherapeutic.     

Sorbent for the separation of enantiomers of amino acids based on silica gel modified with stabilized Au nanoparticles

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A novel direct and one-pot Mannich synthesis of fluorinated β-aminobutanones with sulfamic acid as a green catalyst

A variety of fluorinated β-aminobutanones could be obtained in good to excellent yields at room temperature through the direct and three-component Mannich reactions of unmodified acetone with aldehydes and fluorinated anilines in one-pot procedure. Among the catalysts screened, sulfamic acid was tested to the best in aspect of outstanding stability, inexpensive cost, ready recovery and excellently catalytic activity. All the new compounds were confirmed by IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR and microanalysis.     

Facile one-pot synthesis of tetrahydroisoquinolines from amino acids via hypochlorite-mediated decarboxylation and Pictet–Spengler condensation

A convenient method for oxidative decarboxylation of α-amino acids is presented. The aldehyde products may be isolated or converted to tetrahydroisoquinolines by addition of dopamine via Pictet–Spengler reaction. Racemic products are generated by phosphate buffer >300 mM to maximize regioselectivity. (S)-Enantiomer products are generated by norcoclaurine synthase reaction in maleic acid buffer to minimize chemical background reaction.     

Facile one-pot method for the synthesis of novel glycosylidene-based quinolines

A one-pot approach to the synthesis of novel glycosylidene-based quinolines is described. The reaction involves a Lewis acid catalyzed Povarov addition followed by oxidation of the resulting spiroanellated tetrahydroquinoline intermediates to yield the open-ring glycosylidene-derived quinoline.