Structural Diversity-Oriented Synthesis of Orthogonally Protected Cyclic Amino Acid Derivatives with Multiple Stereogenic Centers

The synthesis of three-dimensional cyclopentane amino acid derivatives with multiple stereocenters and with high regiochemical and diastereochemical diversity has been achieved starting from cyclopentadiene-derived β-aminocyclopentenecarboxylic acid. The small-molecular design was based on stereo- and regiocontrolled functionalization of the starting cyclopentene β-amino acid through stereoselective oxirane formation/regioselective oxirane opening and resulted in regio- and diastereoisomers of novel orthogonally protected aminocyclopentanecarboxylates.     

Synthesis and Reactions of 4-Oxiranylmethylfuro[3,2-b]pyrroles and Their Benzo Derivatives

Methyl 4-oxiranylmethyl-4H-furo[3,2-b]pyrrole-5-carboxylates 2a-c and methyl 1-oxiranylmethyl-1H-benzo[4,5]furo[3,2-b]pyrrole-2-carboxylate (2d) were prepared by reaction of the appropriate starting compounds 1a-d with excess chloromethyloxirane. The compounds 2a-d undergo oxirane ring opening by heterocyclic amines (morpholine, pyrrolidine, piperidine or 4-methylpiperazine) giving N-2-hydroxy-3-heteroaminopropyl-substituted compounds 3a-f or substituted 4,5-dihydrofuro[2',3':4,5]pyrrolo[2,1-c][1,4]oxazin-8-ones 4a-e.     

Amino Acid Based Epoxy-Poly(Ester Amide)s—A New Class of Functional Biodegradable Polymers: Synthesis and Chemical Transformations

A new class of biodegradable functional polymers – epoxy-poly(ester amide)s (EPEAs), was synthesized for the first time on the basis of naturally occurring α-amino acids, fatty diols and cis- and trans-epoxysuccinic acids. The syntheses were conducted via both solution Active Polycondensation and Interfacial Polycondensation using, accordingly, either activated di-p-nitrophenyl esters or dichlorides of cis- and trans-epoxysuccinic acids as bis-electrophilic monomers. Di-p-toluenesulfonic acid salts of bis-(L-phenylalanine)-1,6-hexylene and bis-(L-leucine)-1,6-hexylene diesters were used in both cases as bis-nucleophilic counter-partners. High-molecular-weight polymers (M_w up to 67.000) with desirable material properties were obtained via solution polycondensation using di-p-nitrophenyl-trans-epoxy succinate. The EPEAs were chemically modified further under mild conditions: oxirane groups along the backbone were reacted with both nucleophilic and electrophilic reagents, and also subjected to thermal and chemical curing. The macromolecular transformations of EPEAs substantially broaden material properties and, hence, the potential to apply amino acid-based biodegradable poly(ester amide)s as absorbable drug carriers and surgical devices.     

Glycidyl Esters of Aromatic Acids

Abstract

The reaction of substituted benzoic acids, dicarboxylic acids such as phthalic, terephthalic, and isophthalic acids, and the sodium or potassium salts of these acids with equimolar or excess epichlorohydrin in the presence of benzyltrimethylammonium chloride has been studied using various solvents such as toluene, dioxane, monochlorobenzene, and tetrachloroethylene. Use of the free carboxylic acids gave only fair to low yields of glycidyl esters, while sodium or potassium salts of the carboxylic acids gave excellent yields of materials of high oxirane content. The epoxidation of chlorohydrin esters of these acids by the dehydrochlorination was also studied using various dehydrochlorinating reagents such as NaOH, KOH, Na₂CO₃, and NaAlO₂ in such solvents as water, dichloromethane, dioxane, and monochlorobenzene at various temperatures. Reaction time, reaction temperature, and water content were found to influence the yield of glycidyl esters. It is suggested that the reaction path involves nucleophilic attack upon the terminal position of the epoxide or epichlorohydrin. The resulting alkoxide then reacts further to give either a glycidyl ester or a chlorine-containing by-product, the predominant course depending upon reaction conditions.     

The strategic marriage of method and motif. Total synthesis of varitriol

Detailed in this report are several new efficient synthetic approaches toward the natural product anti cancer agent varitriol, culminating in a concise total synthesis. A common theme for these routes is that they employ a new catalytic stereoselective vinyl oxirane ring expansion reaction, which provides rapid access to the common cis-2,5-tetrahydrofuran core. The combination of careful synthetic design and proper selection of starting materials results in an excellent marriage between this new method (vinyl oxirane ring expansion) and the motif (varitriol).     

The effect of terminal epoxy modification on the mesomorphic and thermal stability of biphenyl ester liquid crystals

ABSTRACT

A series of biphenyl ester compounds with alkenyl, alkyl, oxirane, and 1,3-dioxolane as the terminal groups have been synthesised for investigating the mesomorphic and thermal stability. Based on the same carbon skeleton, the allyl-terminated compound V1OLC has no mesophase, while the oxirane-terminated compound POLC not only has wider multiple smectic mesophase compared with the propyl-terminated compound 3OLC but also exhibits the best thermal stability. However, when the terminal groups change from oxirane to 1,3-dioxolane, EOLC shows neither mesophase nor the good thermal stability. In addition, with the extension of the terminal chains, the butyl-terminated compound 4OLC gives the widest smectic mesophase. These imply that the mesomorphic and thermal stability of these biphenyl ester compounds are dependent on the suitable terminal chain lengths and epoxy sizes. Meanwhile, Density Functional Theory (DFT) calculations were conducted to assist in analysing the experimental results.     

An Efficient Synthesis of 4,5-Dihydro-3(2H)-pyridazinone Derivatives

Reaction of hydrazine with 5-(2-aryl-2-oxo-ethan-1-yl)-5-R Meldrum's acids 3 gives 4,6-disubstituted 4,5-dihydropyridazin-3(2H)-ones 4 at room temperature. The method is simple and the yield is good. The production of the starting material 3 also is discussed.     

Synthesis of New Symmetric Disubstituted Dithioether Dithiols

Abstract

The β,β′-dihydroxydithioethers, derived from oxirane, have been converted into dithioethers dithiols in good yields. A colloidal solution of gold nanoparticles (AuNPs) with 5,8-dithiadodecane-3,10-dithiol was prepared and showed a good stability from tight binding offered by the thiol group on the Au surfaces.     

Ribozymomimetic Chemical Synthesis of Peptide Bond Using Phosphorous Acid/Oxirane Mediators

Abstract

A model system is created that mimics natural ribosome as well as the way of ribozyme action. It uses oxirane analogue as condensation reagent and H₃PO₃ as activator for the carboxyl group and as protecting reagent for the NH₂ function. In order to demonstrate the ability of the H₃PO₃/oxirane system to mimic natural peptide bond synthesis on the ribosome as well as to mimic the ribozyme synthesis and hydrolysis of an inter biomonomeric bond, four model compounds containing an amide bond were synthesized using phosphorous acid/oxirane mediators.

GRAPHICAL ABSTRACT     

A Convenient Route to Functionalized Branched-Chain Sugars Via a Tosyl-Epoxide Derivative

Abstract

Starting from methyl 4,6-O-benzylidene-2-deoxy-α-D-ribo-hexopyranoside-3-ulose 1 and proceeding through its corresponding tosyl-epoxide derivative 2, various branched-chain sugars (3-8) were prepared by nucleophilic and reductive ring openings. The presence of the sulfonylated oxirane group was found to be compatible with chemical transformations of the benzylidene acetal group (9-11), allowing facile access to the 6-deoxyhexoses (12-13).     

Chiral spiro-connected 2,3,3-trisubstituted oxiranes New dopants for induced ferroelectric phases

Abstract

The synthesis, phase behaviour and spontaneous polarization of a new class of chiral dopants for induced ferroelectric phases of general structure A and B, possessing a 2,3,3-trisubstituted oxirane ring spiro-connected with four-, five- or six-membered carbocycles are described. In a series of these compounds with the same mesogenic building blocks the one with the five-membered carbocycle exhibits the highest induced spontaneous polarization. Introduction of a carbonyl group adjacent to the oxirane ring leads to an increased induced spontaneous polarization. The sign of the helical twisting power is positive for compounds with a cyclobutane ring and negative for those with a cyclopentane or a cyclohexane ring, although the absolute configuration at the chiral carbon is the same for all compounds.     

A General Way,From L-Ascorbic And D-Isoascorbic Acids,To Homochiral α-Hydroxy, α,β-Dihydroxy And α,β-Epoxy-Aldehydes,Useful Building Blocks For The Synthesis Of Linear Oxygenated Fatty Acids Metabolites

Abstract

Enantiomerically pure α-hydroxy, α,β-dihydroxy and α,β-epoxyaldehydes, useful building blocks for the synthesis of acyclic oxygenated fatty acids metabolites, were synthetized via epoxybutanediol acetonide starting from the commercially available L-ascorbic and D-isoascorbic acids.     

Synthesis of new thioxanthenes by organocatalytic intramolecular Friedel–Crafts reaction

An efficient organocatalytic route has been developed to synthesize novel substituted thioxanthenes (2a–2v) starting from diaryl thioether alcohols (1a–1v) using the intramolecular Friedel–Crafts reaction. The starting materials were obtained in two stages via a coupling reaction followed by the Grignard reaction. In this study, we tried for the first time to use some organic Brønsted acids as organocatalysts (3a–3h) in the intramolecular Friedel–Crafts cyclization reaction of thioether alcohols. The synthesis of original substituted thioxanthenes was achieved within 15?minutes by using N-triflylphosphoramide (3h) with quantitative yields in THF at room temperature.     

SYNTHESIS OF SOME NEW 1,2,4-TRIAZOLO[3,4-b]-THIADIAZOLE DERIVATIVES AS POSSIBLE ANTICANCER AGENTS

3-Substituted-4-amino-5-mercapto-1,2,4-triazoles are versatile synthons for constructing various biologically active heterocycles. Their cyclization with carboxylic acids gives fused five-membered derivatives, whereas with α-bromoketones gives a six-membered heterocycle. In this article we report the synthesis of a series of 1,2,4-triazolo[3,4-b]thiadiazoles 5 starting from 4-amino-3-substituted-5-mercapto-1,2,4-triazoles 3 and fluorobenzoic acids 4 using phosphorous oxychloride as cyclizing agent. Fourteen of the newly synthesized compounds were screened for anticancer properties. Four among them showed in vitro anticancer activity.     

Practical Oxirane Ring Opening with In Situ Prepared LiCN; Synthesis of (2S,3R)-3-(2,4-Difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)-1-butanenitrile

Trisubstituted oxirane 1 was regiospecifically opened with LiCN in situ prepared from acetone cyanohydrin and LiH to provide the corresponding β-hydroxy nitrile 2 in satisfactory yield, enabling us to manufacture a key intermediate for a new antifungal agent on a multi-kg scale. Some applications of this method to the ring opening of other oxiranes and nucleophilic substitution are also described.     

One Pot Synthesis of Some New Heteroylselenoglycolic Acids and Their Biological Activity

Abstract

A convenient one pot three-stage synthesis was used for obtaining new heteroylselenoglycolic and di-heteroylselenoglycolic acids by nucleophilic substitution reaction of the starting compounds pyridineselenol, pyridazineselenol, and quinolineselenol with α-chloro- or α,α-dichloroacetic acids for 1-h stirring. The newly synthesized compounds were screened biologically for anti-microbial and anti-oxidant activities. The structure of all new compounds was confirmed by ¹H NMR, ¹³C NMR, Mass, and IR spectroscopy and elemental analyses.     

An Improved Method for Preparation and Purification of Safrole Oxide

Abstract

A superior method for the preparation of safrole oxide is described using m-chloroperbenzoic acid as the oxidant. Improvements in the purification process are outlined which give the desired oxirane in a high state of purity free of an unidentified pink contaminant obtained as a by-product.     

Synthesis of 1,6-Anhydro-2,3-di-O-farnesyl-5-O-([{phosphonomethyl}phosphinyl]methyl)-α-d-galactofuranose: A Zaragozic Acid-Presqualene Pyrophosphate Hybrid

Abstract

A multi-step synthesis of a new potential inhibitor (i.e., compound 2) of squalene synthase is described, starting from D-galactose. The title compound is a hybrid of presqualene pyrophopshate and the recently discovered zaragozic acids, which are picomolar competitive inhibitors of the enzyme squalene synthase.     

CONTINUOUS OPTICAL RESOLUTION OF (p-IODOPHENYL)GLYCINOL

ABSTRACT

Enantiomeric enrichment of racemic (p-iodophenyl)glycinol was achieved with various optically active organic acids. The scalemic mixtures were further resolved by entrainment with racemic crystals of the starting material. The pure enantiomers were recovered from the mother liquor; the crystalline—almost racemic—base was recycled.     

Stereocontrolled synthesis of 3-amino-2-hydroxyalkyl diphenylphosphine oxides mediated by chiral azetidinium salts and epoxyamines

The stereocontrolled synthesis of amino hydroxyalkyl diphenylphosphine oxides has been achieved starting from (2S,3S)-N,N-dibenzyl-3-hydroxy-2-methylazetidinium bromide or (1R),[1′(S)-(dibenzylamino)ethyl]oxirane. The regioselective ring opening of both heterocyclic systems at the less substituted carbon atom with phosphorus nucleophiles proceeded with full stereochemical integrity.