A linchpin approach to unsaturated fatty acids: 11,12-epoxyeicosatrienoic acid and 11S,12S-dihydroxyeicosatrienoic acid ethyl esters

[Chemical reaction: See text] A "linchpin" coupling strategy is described for the construction of long-chain fatty acid metabolites. This strategy led to a short synthesis of the ethyl esters of both 11,12-epoxyeicosatrienoic acid (EET) and 11S,12S-dihydroxyeicosatrienoic acid (DHET).     

Chemistry of dihydroresorcinol

Summary Hydrolysis of 2-( -cyclohexylideneethyl)dihydroresorcinol (II) gives an unsaturated keto acid (VIII) which is converted by a double cyclization under the influence of polyphosphoric acid to 1-keto-^9,11,13 -octahydrophenanthrene (XV). This series of reactions can be useful for the synthesis of polycyclic compounds related to steroids.     

Synthesis of 1,8-Dioxo-octahydroxanthene Derivatives Catalyzed by p-Dodecylbenezenesulfonic Acid in Water

With the increasing concerns of the environment, more and more chemists are devoted to the research of the "green synthesis" which means that the reagent, solvent and catalyst are environmentally friendly in the organic chemical reactions. The importance of aqueous reaction is now generally recognized, and development of carbon-carbon bond-forming reactions that can be carried out in aqueous media is now one of the most challenging topics in organic synthesis.[1]Herein, we report a clean synthesis of 3,3,6,6-tetramethyl-9-aryl-1,8-dioxo-octahydroxanthene derivatives from aromatic aldehyde and 5,5-dimethyl-1,3-cyclohexadione using p-dodecylbenezenesulfonic acid (DBSA) as the catalyst in water.This method provides several advantages such as high yield, simple work-up procedure and environmental friendliness and water was chosen as a green solvent. All the products were characterized by m.p., 1H NMR, IR and elemental analyses.     

"Molecular chameleons". Design and synthesis of a second series of flexible nucleosides

The second series of flexible shape-modified nucleosides is introduced. The "fleximers" feature the purine ring systems split into their individual imidazole and pyrimidine components. This structural modification serves to introduce flexibility to the nucleoside while still retaining the elements essential for recognition. As a consequence, these structurally innovative nucleosides can more readily adapt to their environment and should find use as bioprobes for investigating enzyme-coenzyme binding sites as well as nucleic acid and protein interactions. Their design and synthesis is described.     

Step‐by‐Step Synthesis of Monodisperse Methacrylamidoalkyl Oligolactates

Summary: This paper describes the facile step‐by‐step synthesis to graft lactic acid or lactoyl lactate onto primary as well as secondary alcohol derivatives of methacrylamides via esterification. Elongation of the chains is achieved by repeating the coupling reactions with either hydroxyl‐protected monolactate or hydroxyl‐protected dilactate, followed by mild deprotection using tetrabutylammonium fluoride. This versatile synthesis route generates, on a multi‐gram scale, monodisperse oligolactates of predetermined lengths with functional end groups. The products can be used, for example, as building blocks for biodegradable polymeric materials.

The synthesis of monodisperse oligo(lactic acids) with methacrylamide end groups and a predefined number of lactic acid units.     

Enantioselective synthesis of d-α-amino amides from aliphatic aldehydes

Peptides consisting of d-amino amides are highly represented among both biologically active natural products and non-natural small molecules used in therapeutic development. Chemical synthesis of d-amino amides most often involves approaches based on enzymatic resolution or fractional recrystallization of their diastereomeric amino acid salt precursors, techniques that produce an equal amount of the l-amino acid. Enantioselective synthesis, however, promises selective and general access to a specific α-amino amide, and may enable efficient peptide synthesis regardless of the availability of the corresponding α-amino acid. This report describes the use of a cinchona alkaloid-catalyzed aza-Henry reaction using bromonitromethane, and the integration of its product with umpolung amide synthesis. The result is a straightforward 3-step protocol beginning from aliphatic aldehydes that provides homologated peptides bearing an aliphatic side chain at the resulting d-α-amino amide.     

Solid-Phase Organic Synthesis of Vinyl-Substituted 1,3,4-Oxadiazoles Using Polymer-Bound α-Selenopropionic Acid

Vinyl-substituted 1,3,4-oxadiazoles can be efficiently synthesized through acylation, cyclocondensation, and oxidation–elimination reaction from polystyrene-supported α-selenopropionic acid and acid hydrazides. This new solid-phase organic synthesis method could provide the target compounds in good yield and purity, with advantages of decreased volatility and simplification of workup procedure.     

Scalable synthesis of an integrin-binding peptide mimetic for biomedical applications

A scalable, solution-phase synthesis of the selectively protected non-peptide RGD (arginine-glycine-aspartic acid) mimetic 6 is described. This synthesis serves as an alternative to the previously described solid-phase synthesis of this compound, thereby making this important integrin-binding mimetic readily accessible. The free carboxylic acid of 6 was conjugated to a protected diamine, followed by global deprotection to give a derivative 27, suitable for immobilization onto amine-reactive surfaces. The RGD mimetic 28 demonstrated superior biological activity in comparison to a native linear RGD peptide and the semi-synthetic cyclic cRGDfK peptide in a cell attachment inhibition assay.     

A Facile Method for Monoesterification of α, ω-Dicarboxylic Acids: Application to the Synthesis of Traumatic Acid,A Prostaglandin Synthon

During the past decade, methyl 7-(5-oxocyclopentenyl)heptanoate (6) has been frequently used as a key intermediate in prostaglandin synthesis.¹ Although keto ester 6 can be readily obtained by treatment of traumatic acid (5) with polyphosphoric acid followed by esterification with methanolic hydrochloric acid,² this approach is not attractive for large-scale synthesis due to the expense of the latter natural product (5). Recently Salomon and Reuter have reported¹ an alternate route to synthon 6 based on a starting material derived from aleuritic acid, a major component of shellac.     

Microwave-assisted green synthesis of 1, 3-benzodioxole derivatives

Abstract

2-Phenyl-substituted 1,3-benzodioxole derivatives were synthesized by microwave irradiation by reacting catechol with benzoic acid derivatives in the presence of polyphosphoric acid as a catalyst which acts as a solvent and also as a cyclizing agent. This synthesis has various advantages over other catalytic conventional synthesis because it saves time, increases yield, and is a simple, economical, and effective synthesis. Moreover, this is also an excellent green chemistry approach as it does not require additional toxic solvents or harmful chemicals, and overall it reduced energy utilization than the other methods of synthesis.

     

Efficient and direct solid phase synthesis of ketomethylenimino and ketomethylenamino peptides

The aim of this study is the synthesis of pseudopeptides on solid supports, in order to quickly obtain modified peptides. We report a convenient step-by-step synthesis of ketomethylenimino ψ[CO-CHN] and ketomethylenamino ψ[CO-CH₂-NH] peptides. The key is the reaction between the free amino terminus of the supported peptide and a glyoxal-modified amino acid, leading to a ketomethylenimino bond, which can be reduced to a ketomethylenamino bond.     

Tailoring Lewis/Brønsted acid properties of MOF nodes via hydrothermal and solvothermal synthesis: simple approach with exceptional catalytic implications

The Lewis/Brønsted catalytic properties of the Metal–Organic Framework (MOF) nodes can be tuned by simply controlling the solvent employed in the synthetic procedure. In this work, we demonstrate that Hf-MOF-808 can be prepared from a material with a higher amount of Brønsted acid sites, via modulated hydrothermal synthesis, to a material with a higher proportion of unsaturated Hf Lewis acid sites, via modulated solvothermal synthesis. The Lewis/Brønsted acid properties of the resultant metallic clusters have been studied by different characterization techniques, including XAS, FTIR and NMR spectroscopies, combined with a DFT study. The different nature of the Hf-MOF-808 materials allows their application as selective catalysts in different target reactions requiring Lewis, Brønsted or Lewis–Brønsted acid pairs.

The Brønsted/Lewis acid properties of Hf-MOF-808 can be tuned by simply controlling the solvent employed in its synthesis, with direct catalytic implications on the activity and selectivity of organic reactions sensitive to the active site nature.     

Coassembly of amphiphiles with opposite peptide polarities into nanofibers

The design, synthesis, and characterization of "reverse" peptide amphiphiles (PAs) with free N-termini is described. Use of an unnatural amino acid modified with a fatty acid tail allows for the synthesis of this new class of PA molecules. The mixing of these molecules with complementary ones containing a free C-terminus results in coassembled structures, as demonstrated by circular dichroism and NOE/NMR spectroscopy. These assemblies show unusual thermal stability when compared to assemblies composed of only one type of PA molecule. This class of reverse PAs has made it possible to create biologically significant assemblies with free N-terminal peptide sequences, which were previously inaccessible, including those derived from phage display methodologies.     

Microwave-assisted synthesis of new substituted anilides of quinaldic acid

In this study a one step method for the preparation of substituted anilides of quinoline-2-carboxylic acid was developed. This efficient innovative approach is based on the direct reaction of an acid or ester with substituted anilines using microwave irradiation. The optimized method was used for the synthesis of a series of eighteen substituted quinoline-2-carboxanilides. The molecular structure of N-(4-bromophenyl)quinoline-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. It crystallizes in the monoclinic space group with four molecules within the unit cell and the total structure of the compound can be described as "a slightly screwed boat".     

From Isocyanides via Four-Component Condensations to Antibiotic Syntheses

The four-component condensation of amines and carbonyl compounds with isocyanides

1 Previously, isocyanides were almost always referred to as isonitriles. However, according to IUPAC Rule C-833.1 only the name “isocyanides” is permissible.

and suitable acid components (water, thiosulfuric acid, hydrogen selenide, hydrogen azide, cyanic acid, thiocyanic acid, carboxylic acids, methyl hydrogen carbonate) to form α-amino acid derivatives was discovered in 1959. This reaction principle shares some features with the Strecker synthesis and the Passerini reaction. The four-component condensation affords easy and effective one-pot synthesis of complex molecules from simple building blocks. Only in recent years, however, have the preparative advantages of the four-component condensation been exploited by numerous authors in the synthesis of diverse natural products and related compounds, although many of the possibilities opened by this principle were recognized more than two decades ago. In this progress report some instructive syntheses of various antibiotics are reviewed. The design of each of these syntheses involves a four-component condensation as key step, by means of which lengthy sequences of reactions are avoided, which otherwise would be required to achieve the synthetic goal.     

Synthesis of N-Fmoc-O- (N'-Boc-N'-methyl)-aminohomoserine,an amino acid for the facile preparation of neoglycopeptides

The synthesis of N-Fmoc-O-(N'-Boc-N'-methyl)-aminohomoserine in 35% overall yield from l-homoserine is described. This amino acid can be efficiently incorporated into peptides using Fmoc-chemistry-based solid-phase peptide synthesis, and the resulting peptides can be chemoselectively glycosylated at the aminooxy side chains to generate neoglycopeptides. The synthesis of this derivative greatly expands the availability of a previously developed neoglycopeptide synthesis strategy.     

Synthesis of phosphinic acids on the basis of hypophosphites: IV. Synthesis of pseudo-γ-glutamylglycine and its enantiomers

A new method for construction of pseudopeptide molecules is proposed, exemplified by the synthesis of [3-amino-3-(hydroxycarbonyl)propyl][2-(hydroxycabonyl)ethyl]phosphinic acid (I) (pseudo--glutamylglycine), starting from ammonium hypophosphite. Enzymatic synthesis using immobilized penicillamidase allowed preparation of the enantiomers of acid I.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 8, 2004, pp. 1273–1278.Original Russian Text Copyright © 2004 by Ragulin.For communication III, see [1].This revised version was published online in April 2005 with a corrected cover date.     

Silica-bonded S-sulfonic acid as a recyclable catalyst for chemoselective synthesis of 1,1-diacetates

A simple and efficient procedure for the preparation of silica-bonded S-sulfonic acid (SBSSA) by reaction of 3-mercaptopropylsilica (MPS) and chlorosulfonic acid in chloroform is described. This solid acid is employed as a recyclable catalyst for the synthesis of 1,1-diacetates from aromatic aldehydes and acetic anhydride under mild and solvent-free conditions at room temperature.     

Regiospecific synthesis of 3-(2,6-dihydroxyphenyl)phthalides: application to the synthesis of isopestacin and cryphonectric acid

DBU catalyzed condensation of phthalaldehydic acids and 1,3-diketones has been developed to be a general method for the synthesis of 3-substituted phthalides. This method, in combination with mercuric acetate mediated oxidative aromatization has been utilized for the regiospecific synthesis of isopestacin (9) and cryphonectric acid (10).     

Amine exchange in formamidines: an experimental and theoretical study

N-H-containing formamidines combine a reasonably strong association to carboxylic acids to form complexes of well-defined geometries with a simultaneous proton-induced electrophilicity enhancement that allows for the exchange of their amine portion. The N=C(H)-NH fragment, therefore, undergoes "imine-like" exchange with N-containing nucleophiles. Because of the prototropic equilibrium, the N=C(H)-NH fragment may behave as a "bisimine" centred on the same carbon, in which both N-containing fragments can be exchanged. Considering the proton-induced sensitisation of both C-N units and the well-defined formamidine-carboxylic acid complex geometry, it should be possible to use carboxylic acids as templates for the synthesis of defined architectures by dynamic amine exchange within formamidines. This study highlights three exchange regimes based on the nature of the incoming amine (aliphatic amines, aromatic amines and alkoxyamines), as well as exchange rules based on the amine leaving groups. Following this analysis, a proof of concept for carboxylic acid templated macrocycle formation through dynamic exchange is provided.