Metal-free and highly regioselective synthesis of N-heteroaryl substituted pyrazoles from α,β-unsaturated N-tosylhydrazones and heteroaryl chlorides

A cascade cyclization/nucleophilic aromatic substitution (S_NAr) reaction of α,β-unsaturated N-tosylhydrazones with N-heteroaryl chlorides was developed for the synthesis of N-heteroaryl pyrazole derivatives. This one-pot reaction provided bi(heteroaryl) derivatives in good to excellent yields and with excellent regioselectivity. The procedure is operationally simple and applicable to large-scale synthesis.     

Sulfuric acid immobilized on silica: an efficient reusable catalyst for the synthesis of O-isopropylidene sugar derivatives

Sulfuric acid immobilized on silica proved to be an efficient catalyst for the synthesis of O-isopropylidene sugar derivatives from reducing sugars. The method is very simple and economic for large-scale synthesis in which the catalyst is recovered and reused several times. Reactions with d-glucose, d-galactose, d-mannose, l-rhamnose, l-arabinose, d-xylose and l-sorbose led to the formation of the corresponding thermodynamically stable di-O- and/or mono-O-isopropylidene derivatives in good to excellent yields.     

N,N-Dichlorobis(2,4,6-trichlorophenyl)urea (CC-2) as a new reagent for the synthesis of pyrimidone and pyrimidine derivatives via Biginelli reaction

A simple and efficient method for the synthesis of 3,4-dihydropyrimidin-2-(1H)one and benzo[4,5]imidazo/thioazo[1,2-a]pyrimidine derivatives has been described using N,N′-dichlorobis(2,4,6-trichlorophenyl)urea (CC-2) as a new reagent. This method is found to be efficient and convenient for the synthesis of pyrimidone and pyrimidine derivatives.     

Extended applications and potential limitations of ring-fused 2,3-oxazolidinone thioglycosides in glycoconjugate synthesis

The utility of ring-fused 2,3-oxazolidinone derivatives of 2-amino-2-deoxy-thioglycosides in the synthesis of glycopeptide intermediates and building blocks for the synthesis of heparan sulfate oligosaccharides is reported. These unique ring-fused monosaccharides afford a novel and efficient route to alpha-O-linked 2-amino-2-deoxy amino acid derivatives and heparan sulfate oligosaccharide intermediates.     

Efficient trans-acetoacylation mediated by ytterbium(III) triflate as a catalyst under solvent-free condition

A simple and efficient trans-acetoacylation method for the synthesis of β-keto ester derivatives has been described using ytterbium(III) triflate as a new catalyst under solvent-free condition. This method was found to be efficient and convenient for the synthesis of a wide variety of β-keto ester derivatives.     

Ligand-free palladium assisted insertion of isocyanides to urea derivatives for cascade synthesis of phenylamino-substituted quinazolinones

Palladium catalyzed cascade coupling of substituted urea derivatives and tert-butyl isocyanide for the efficient synthesis of phenylamino-substituted quinazolinones has been developed in moderate to good yields. This method provides a short and alternative approach for the synthesis of quinazolinones derivatives which are valuable compounds with biological and pharmacological potentials. A plausible mechanistic scheme is proposed.     

An efficient synthesis of dehydroamino acids and dehydropeptides from O-Cbz and O-Eoc derivatives of serine and threonine

A simple and efficient method for the synthesis of dehydroamino acids from serine and threonine is reported. Various O-Cbz and O-Eoc derivatives of serine and threonine are prepared using CbzCl and EocCl, respectively, and are subjected to an anti-selective elimination on treatment with K₂CO₃ in DMF at 65 °C to afford dehydroalanine and dehydroamino butyric acid derivatives, respectively, in excellent yields. The high stability of these carbonate derivatives of serine and threonine allows their use in normal peptide synthesis as protected serine and threonine residues. Peptides synthesized by incorporating O-Cbz or O-Eoc derivatives undergo ready elimination under the reported conditions, to give the corresponding dehydropeptides in excellent yields. The reaction conditions are mild enough not to cause the racemization of other stereogenic centers present in the peptide.     

Unexpected photochemical transformation of imidazole derivatives containing the 5-hydroxy-2-methyl-4H-pyran-4-one moiety. Environmentally friendly method for the synthesis of substituted imidazo[1,5-a]pyridine-5,8-diones

An unexpected photochemical transformation of imidazole derivatives containing the 5-hydroxy-2-methyl-4H-pyran-4-one moiety was discovered, which led to the synthesis of previously unknown imidazo[1,5-a]pyridine-5,8-dione derivatives. The structures of imidazole and imidazo[1,5-a]pyridine-5,8-dione derivatives were unambiguously determined by X-ray diffraction analysis.     

Synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via a Pictet-Spengler approach

A protocol for the diastereoselective synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via Pictet-Spengler condensation with L-DOPA or l-DOPA derivatives and 1H-indole-3-carbaldehydes is presented. The protocol is used for the successful synthesis of several tetrahydroisoquinolines as well as diketopiperazine fused analogues.     

Design and synthesis of two triazonine-carbaldehyde derivatives using several chemical tools

Several triazonine-carbaldehyde derivatives have been prepared using different protocols; however, some require special reagents and conditions. The aim of study involved the synthesis of two triazonine-carbaldehyde derivative using testosterone or OTBS-testosterone as chemical tool. Triazonine-carbaldehyde derivatives were prepared by a series of reactions that involve the following: (1) synthesis of two nitrobenzamide derivatives by reaction of testosterone or OTBS-testosterone with p-nitrobenzoyl azide using Copper(II) as catalyst; (2) reaction of the nitrobenzamides with ethylenediamine to form two triazonine derivatives using boric acid as catalyst; (3) preparation of hexynyl-triazonine derivatives by the reaction of two triazonines 6-chlorohex-1-yne in basic medium; (4) reaction of hexynyl-triazonine derivatives with benzaldehyde to form two triazoninol analogs; (5) preparation of triazoninynal derivatives through oxidation of triazoninol analogs with dimethyl sulfoxide; and (6) synthesis of triazonine-carbaldehyde derivatives by the reaction of triazoninynal derivatives with hexyne-1 using Copper(II) as catalyst. The chemical structure of compounds was determined by spectroscopic and spectrometric methods. In conclusion, in this work were prepared two triazoninone derivatives using several chemical techniques, which are simple procedures and easy to handle.     

A new bicyclic proline-mimetic amino acid

A new constrained bicyclic α-amino acid proline-mimetic was developed. The synthesis was achieved starting from derivatives of the chiral pool, thus allowing to prepare analogues of either l- or d-proline by choosing appropriate stereoisomers of serine and α,β-isopropylidene-glycerol derivatives. The scaffolds were prepared as N-Fmoc-amino acid suitable for solid-phase peptide synthesis.     

N-arylation of carbamate-protected glycine derivatives via palladium catalysis

A synthesis of N-aryl and N-heteroaryl amino acid derivatives using palladium catalysis is described. Several carbamate-protected glycine derivatives react with aryl and heteroaryl halides using a palladium/Xantphos catalyst system to access the desired synthons.     

Synthesis of β-nitramino derivatives ofgem-dinitroalkanes

A method for the synthesis of β-nitramino derivatives ofgem-dinitroalkanes by nitration of the products of condensation of sulfamic acid derivatives with the correspondinggem-dinitroalkanes was proposed.     

Improved syntheses of meso-aryl tetrabenzotriazaporphyrins (TBTAPs)

New tetrabenzotriazaporphyrins are reported that are functionalised at the meso-position. The derivatives functionalised with meso-bromophenyl substituents are synthesised using an improved variation on the traditional reaction between phthalonitriles and Grignard reagents. For all other new derivatives, a modern protocol is employed that gives convenient access to these challenging materials by template co-macrocyclisation between phthalonitriles and aryl-aminoisoindoline derivatives like 15. The newly developed procedure allows design and synthesis of elaborate, functional composites and this is demonstrated by synthesis of meso-pyrenylTBTAP 24, a linked double chromophore in which the two complementary units lie perpendicular to each other and therefore have minimal ground state interaction.     

An efficient synthesis of β-ketoesters via transesterification and its application in Biginelli reaction under solvent-free,catalyst-free conditions

A simple and efficient transesterification process for the synthesis of β-ketoester derivatives has been achieved by the reaction of methyl β-ketoester with higher alcohols at 110 °C under solvent-free, catalyst-free conditions and its application in synthesis of 3,4-dihydropyrimidin-2(1H)-ones C-5 ester derivatives via Biginelli reaction has been described.     

(Z)-2,2-Dimethyl-5-carboxymethylene-1,3-dioxolan-4-one: a new synthon for the synthesis of α,γ-diketoacid derivatives

The synthesis and reactivity of (Z)-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-one, a new and versatile synthon useful for the synthesis of selectively protected α,γ-diketoacid derivatives, are described. This new, protected form of hydroxyl fumaric acid along with its acid chloride was used to prepare ester, amide, and aryl derivatives. The dioxolane moiety was found to be a convenient functionality that facilitated ready unmasking by straightforward hydrolysis to reveal α,γ-diketoacid derivatives or derivatization to yield ester, amide, and 2,3-pyrrolidinedione derivatives.     

Direct access to 3-substituted 1,4-oxathiepino[5,6-b]pyridine-5-one through one-pot substitution cyclization reaction of 2-mercapto-3-nicotinic acid with α-bromo ketones

A direct, one-pot synthesis route to [1,4]oxathiepino[5,6-b]pyridin-5-one derivatives was optimized by reacting different α-bromo ketones with 2-mercaptonicotinic acid. The advantages of this method include high efficiency, regioselective, and multistep conversion in a single-pot protocol. These types of pyridine annulated[1,4]oxathiepin-5-one derivatives are described here for the first time and seem to be interesting candidates for screening purpose. The presented protocol is suitable for using rare chemicals for synthesis of such derivatives.     

Sulfuric acid immobilized on silica: an efficient reusable catalyst for selective hydrolysis of the terminal O-isopropylidene group of sugar derivatives

Sulfuric acid immobilized on silica proved to be an efficient catalyst for selective hydrolysis of the terminal O-isopropylidene group of sugar derivatives. The method is very simple and economic for large-scale synthesis in which the catalyst is recovered and reused for several runs. Reactions with di-O-isopropylidene derivatives of d-glucose, d-mannose, d-fructose and l-sorbose led to the formation of the corresponding mono-O-isopropylidene derivatives in good to excellent yields.     

Synthesis of N-1 and ribose modified inosine analogues on solid support

Herein, we report the synthesis and the use of new N-1-dinitrophenyl-inosine based solid supports, in which the C-2 of the purine base is strongly activated toward the attack of N-nucleophiles. The synthesized supports, binding the nucleoside by a 5′-O-monomethoxytrityl function, have been used to accomplish the synthesis of a small library of N-1 alkylated inosine and AICAR derivatives. In addition, cleavage of the 2′-3′ ribose bond of N-1 alkylated inosine derivatives anchored to the supports allowed to prepare a new set of N-1 alkylated-2′,3′-secoinosine derivatives in high yields.     

Fmoc-based solid-phase synthesis of adenylylated peptides using diester-type adenylylated amino acid derivatives

Phosphodiester-type adenylylated (AMPylated) Ser, Thr, and Tyr derivatives were developed for Fmoc solid phase peptide synthesis of AMPylated peptides. One-pot/sequential reaction consisting of condensation of an N-nonprotected adenosine derivative and Fmoc-Ser/Thr/Tyr-OAllyl using allyl-N,N-diisopropylchlorophosphoramidite and subsequent oxidation with m-chloroperbenzoic acid gave phosphotriester-type AMPylated Ser/Thr/Tyr derivatives. After Pd(0)-mediated deprotection of allyl groups, the resulting phosphodiester-type AMPylated Ser/Thr/Tyr derivatives were successfully incorporated into peptides by standard Fmoc solid phase peptide synthesis without significant side reactions including dehydroalanine formation.