Nitrite-mediated hydrolysis of epoxides catalyzed by halohydrin dehalogenase from Agrobacterium radiobacter AD1: a new tool for the kinetic resolution of epoxides

Halohydrin dehalogenase obtained from Agrobacterium radiobacter AD1, has been tested for the nitrite-mediated ring opening of epoxides. This reaction mainly leads to the formation of unstable hydroxynitrite ester intermediates, which can be further hydrolyzed to the corresponding diols. This conversion proceeds with high enantioselectivity and high regioselectivity towards styrene oxide derivatives. It has been concluded that halohydrin dehalogenase can serve as an attractive alternative to epoxide hydrolases in the preparation of enantiopure epoxides by kinetic resolution.     

Sulfur-Functionalized Allyl Anions as Synthetic Building-Blocks

Abstract

Ring-opening of epoxides by functionalized allyl anions 1,7,9 is used in the synthesis of furan and pyran derivatives.     

Ring opening in epichlorohydrin and β-methylepichlorohydrin under the action of the [PtCl4]2– anion in aqueous solutions

Oxidative addition of epoxides to [PtCl₄]^2– in aqueous acids affords the platinum(iv) derivatives [PtCl₅(CH₂CR(OH)CH₂Cl)]^2– (R = H (1) and Me (2)). Complex 1 was isolated as a cesium salt and characterized by IR spectroscopy. The complex is stable in acidic media; under basic conditions, the original epoxide and platinum(ii) are recovered. The formation of complex 2 was detected by ¹H NMR spectroscopy.     

“Greener” chemical syntheses using mechanochemical mixing or microwave and ultrasound irradiation

Abstract

Various emerging “greener” strategic pathways, researched primarily in the author's own laboratory, are summarized. They include solvent-free mechanochemical methods that involve the use of hypervalent iodine reagents at room temperature for the synthesis of heterocyclic entities, and useful conversion of ketones into β-keto sulfones and their α-tosyloxy derivatives in high yields. A solvent-free approach that involves microwave (MW) exposure of neat reactants (undiluted) catalyzed by the surfaces of less-expensive and recyclable mineral supports, such as alumina, silica, clay, or “doped” surfaces, is described; it is applicable to a wide range of cleavage, condensation, cyclization, rearrangement, oxidation, and reduction reactions, including rapid one-pot assembly of heterocyclic compounds from in situ generated reactive intermediates. The strategy is adaptable to multi-component reactions, e.g. Ugi and Biginelli reactions, for rapid assembly of a library of compounds. Synthesis of a wide variety of significant precursors and intermediates, namely enones, imines, enamines, nitroalkenes, and oxidized sulfur species, is possible and their value in concise MW synthesis of 2-aroylbenzofurans and thiazole derivatives is illustrated. Ultrasound- and MW-assisted solventless preparation of ionic liquids and their application in alkylation and metal-catalyzed multi-component reactions are described. With a view to consume greenhouse gas, carbon dioxide (CO₂), efficient reaction of epoxides with CO₂ provides ready access to cyclic carbonates using only a catalytic amount of recyclable indium-based ionic liquid. MW heating in aqueous reaction media enables expeditious N-alkylation reactions of amines and hydrazines to afford a series of heterocyclic ring systems, such as N-azacycloalkanes, 4,5-dihydropyrazoles, and pyrazolidines. A general and expeditious MW-enhanced nucleophilic substitution approach uses easily accessible starting materials such as halides or tosylates in reaction with alkali azides, thiocyanates, or sulfinates in the absence of any phase transfer catalyst to produce azides, thiocyanates, and sulfones, respectively, wherein a variety of reactive functional groups are tolerated. A three-component condensation (MCC) approach for the synthesis of useful 2-amino-2-chromenes is described using a recyclable nanosized magnesium oxide catalyst in aqueous poly (ethylene glycol) (PEG) medium at room temperature. A general greener approach to shape-selective generation of nanomaterials is summarized including their potential application as nanocomposites.     

A study of the epoxidation of 6-deoxyhex-5-enopyranosides. 1,5-Dicarbonyl derivatives and novel synthetic routes to D-xylo-hexos-5-ulose and D-lyxo-hexos-5-ulose

The work described deals with the isolation and characterization of epoxides from 6-deoxyhex-5-enopyranosides and preliminary exploration of their synthetic potential. Prolonged epoxidation reaction times led to their hydrolysis in situ and gave novel protected D-hexos-5-ulose derivatives (sugar 1,5-dicarbonyls). Some reactions of the hexos-5-uloses were studied, and in some cases septanoside (seven-membered-ring saccharide) derivatives were isolated. Novel routes to D-xylo-hexos-5-ulose and D-lyxo-hexos-5-ulose, of interest as intermediates in the synthesis and biosynthesis of inositols and aza sugars, are also described. The structures of the epoxides and novel hexos-5-uloses were established by NMR and X-ray crystallographic methods.     

SYNTHESIS OF 1- AND 3-C-(AMINOMETHYL)-1,2,3,4,5-CYCLOHEXANEPENTOLS FROM (+)-epi-QUERCITOL[1]

Oxidation of three di-O-isopropylidene derivatives 2a—4a, newly derived from (+)-epi-quercitol (1), with acetic anhydride in DMSO gave the corresponding ketones 5—7, which underwent aldol-type condensation with nitromethane under basic conditions to give selectively the protected derivatives 8a—10a of C-nitromethyl-1,2,3,4,5-cyclohexanepentols, respectively. On treatment with diazomethane in DMSO, the ketones 6 and 7 gave single spiro epoxides 11 and 12, the structures of which were confirmed by converting them into new C-(azidomethyl)cyclohexanepentols 16 and 17. The nitro compounds were hydrogenated in the presence of Raney nickel to give the amines isolated as the N-acetyl derivatives. Deprotection gave three new 1- and 3-C-aminomethyldeoxyinositols 15c—17c. The aminocyclitols obtained and their N-acetyl derivatives were assayed for inhibitory activity against examples of glycosidases.     

Effect of Temperature on the Cationic Photopolymerization of Epoxides

The effects of temperature on the photoinitiated cationic ring‐opening polymerizations of a number of different epoxide monomers were studied with the aid of a modified optical pyrometer instrument. Depending on the structures of the epoxide monomer, various behaviors were observed. The results were interpreted as due to steric and electronic features inherent in the structures of the monomers that affect the stabilization of the secondary oxonium ions, which are formed as intermediates in these polymerizations. At one extreme, cycloaliphatic epoxides such as cyclohexene oxide give highly reactive oxonium intermediates that exhibit high rates of polymerization even at subambient temperatures. At the other extreme, alkyl glycidyl ethers produce oxonium ion intermediates, which are so stable that they do not spontaneously react to form polymer at room temperature. By manipulation of the structure of the epoxide monomer, novel monomers with tailored reactivities can be prepared.     

Study on the stereochemical control of dihydroxylation of vinyl epoxides and their derivatives

The results obtained from a study on the stereochemical control in the dihydroxylation of the double bond of vinyl epoxides and their derivatives (bromo derivatives, azido derivatives and vinyl aziridines) are presented herein. A significant diastereoselectivity was observed for the bromo derivatives, azido derivatives and N-protected vinyl aziridines, whereas vinyl epoxides and unprotected vinyl aziridines showed no diastereoselectivity. The results obtained are generally consistent with the Kishi model.     

Isolation of the Half-Condensed Pyrazoline Intermediates en Route to N-(1,10-Phenanthroline)-pyrazole Derivatives from the Knorr Reaction

During the synthesis of 2-pyrazole-1,10-phenanthroline derivatives by the Knorr reaction from benzoylacetone and 2-hydrazine-1,10-phenanthroline, three half-condensed intermediates, the 5-hydroxyl pyrazolines (2b–2d), were isolated and characterized by NMR spectroscopy and x-ray diffraction (for 2b and 2d). These pyrazoline intermediates could be readily dehydrated under the catalysis of acetic acid to afford the corresponding pyrazoles with high regioselectivity.     

Synthesis and biological evaluation of ( − )-13,14-dihydroxy-8,11,13-podocarpatrien-7-one and derivatives from (+)-manool

13,14-Dihydroxy-8,11,13-podocarpatrien-7-one (1) and a series of ring C aromatic diterpene derivatives were synthesised from (+)-manool (4) and evaluated for their cytotoxic, leishmanicidal and trypanocidal activities. Our results indicated that compound 1 and other podocarpane-type intermediates are cytotoxic. Cleavage of C6–C7 bond of compound 7 improved cytotoxic activity, indicating that, in particular, the 6,7-seco-podocarpane-type compound 20 might serve as a lead compound for further development.     

Triazine‐based Organic Polymer‐catalysed Conversion of Epoxide to Cyclic Carbonate under Ambient CO2 Pressure

In this work we have achieved epoxide to cyclic carbonate conversion using a metal‐free polymeric catalyst under ambient CO₂ pressure (1.02 atm) using a balloon setup. The triazine containing polymer (CYA‐ANIS) was prepared from cyanuric chloride (CYA?Cl) and o‐dianisidine (ANIS) in anhydrous DMF as solvent by refluxing under the N₂ gas environment. The presence of triazine and amine functional groups in the polymer results in the adsorption of CO₂ up to 7 cc/g at 273 K. This inspired us to utilize the polymer for the conversion of a series of functionalised epoxides into their corresponding cyclic carbonates in the presence of tetrabutyl ammonium iodide (TBAI) as co‐catalyst. The product has wide range of applications like solvent in lithium ion battery, precursor for polycarbonate, etc. The catalyst was efficient for the conversion of different mono and di‐epoxides into their corresponding cyclic carbonates under atmospheric pressure in the presence of TBAI as co‐catalyst. The study indicates that epoxide attached with electron withdrawing groups (like, CH₂Cl, glycidyl ether, etc.) displayed better conversion compared to simple alkane chain attached epoxides. This is mainly due to the stabilization of electron rich intermediates produced during the reaction (e. g. epoxide ring opening or CO₂ incorporation into the halo‐alkoxide anion). This catalyst mixture was capable to maintain its reactivity up to five cycles without losing its activity. Post catalytic characterization clearly supports the heterogeneous and recyclable nature of the catalyst.     

Synthesis of Thiazolidine and Thiophene Derivatives for Evaluation as Anticancer Agents

The non-isolated adducts (3a,b) were used as key intermediates to synthesize some novel thiazolidine and thiophene derivatives. Compound (4) exhibited a remarkable antitumor activity against EAC cells compared with the Doxorubicin as a positive control.     

Derivatization-Gas Chromatographic Determination Of Mercaptans

Abstract

After being precipitated as silver mercaptides, mercaptans were converted into their pentafluorobenzyl derivatives in high yields by reaction with sodium sulfide and then with pentafluorobenzyl bromide. The derivatives were analyzed down to sub-ppm levels by gas chromatography with a flame ionization detector. It is possible that the above method is developed for the trace analysis of mercaptans in environmental matrices.     

Synthesis and characterization of some new 1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin

Abstract

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.     

Recent synthetic methodologies for pyridopyrazines: An update

Abstract

Among heterocyclic compounds, pyridopyrazines are the scaffolds that have gained considerable attention on academic and industrial level due to their widespread applications as intermediates in the preparation of advanced and biologically potent pharmaceutical materials. Many pyridopyrazine derivatives are available in market to cure various pharmacological disorders. These candidates can be synthesized via a number of synthetic routes using various reagents like cyclocondensation of diaminopyridines with carbonyl compounds or their derivatives etc. In the present review, we have elaborated all these protocols along with different factors and reaction conditions such as use of metal catalyst, solvent-free and microwave irradiation, one-pot synthesis etc. that have resulted in high regioselectivity and yields. The review focuses on the synthetic methodologies developed in the last decade for different pyridopyrazine derivatives.     

2-(4-β-D-吡喃阿洛糖苷-苯基)-5-取代芳基-1,3,4-噁二唑的合成及镇静活性研究

以豆腐果苷为原料, 与取代苯甲酰肼反应生成中间体4-β-D-吡喃阿洛糖苷-苯甲醛取代苯甲酰腙(2a～2g), 在溴作催化剂的条件下发生关环反应, 合成了一系列豆腐果苷类似物3a～3g. 所有化合物结构经IR, ¹H NMR以及MS谱得以证实. 初步药理实验结果表明, 化合物3a, 3c, 3f与豆腐果苷相比有更好的镇静活性.     

Communication: An Improved Synthesis of Methyl 2,3-Anhydro-α and β-D-Lyxofuranosides

Methyl 2,3-anhydro-α (6) and β (7)-D-lyxofuranosides are important intermediates in the synthesis of C-3 substituted derivatives of D-arabinose which show biological activity as a tumor inhibitor.^1,2 Some syntheses of 6 and 7 are reported but they are either expensive or give poor yields ^3-4 and generally the authors refer to Baker and coll.⁵ who synthesized both α and β epoxides from D-xylose in five steps; yields were 28% and 22% respectively. This synthesis is very well described but reaction times and workups are long and several intermediates are distilled with difficulty under reduced pressure. Unger and coll.⁶, using Baker's method, improved the yield of compound 6 and Martin and coll.⁷ described a three steps synthesis of 6 but the final purification is very difficult and the use of mercuric reagents is not consistent with biological activity; furthermore these two publications concern only α anomer 6.     

New,selectively substituted cyclodextrins as stationary phases for the analysis of chiral constituents of essential oils

New β- and γ-cyclodextrin derivatives, selectively substituted with n-pentyl and methyl groups, e.g. heptakis(2,6-di-O-methyl-3-O-pentyl)-β-cyclodextrin, octakis(2-O-methyl-3,6-di-O-pentyl)-γ-cyclodextrin, and octakis(2,6-di-O-methyl-3-O-pentyl)-γ-cyclodextrin, have been prepared from specifically protected intermediates. The new cyclodextrin derivatives exhibit unique enantioselectivity towards important chiral constituents of essential oils. The enantiomers of lavandulol, α-bisabolol, nerolidol, and other terpenoid alcohols could be resolved and their presence in different essential oils could be proved. Methyl jasmonate and epi-methyl jasmonate could, in addition, be detected in jasmine concrete by two-dimensional gas chromatography. The enantiomers of the macrocyclic ketone muscone have been separated for the first time.     

Gas Chromatographic Analysis of Aminothiol Radioprotective Compounds

Abstract

A gas chromatographic method is described for aminothiols and disulfides. This method is based upon the formation of the trimethysilyl derivatives and their separation by gas chromatography. The kinetics of the derivative formation were investigated. A synthetic method for C4 to C6 aminothiols is given.     

Tautomerism of quinazolin-4-ones with 2,3-annulated hydrogenated 1,3-diazaheterocycles. Synchronous and asynchronous double proton transfer in cyclic hydrogen-bonded associates

It was shown by quantum chemical methods and ¹H NMR spectroscopy that in the series of prototropic tautomeric quinazolin-4-ones with hydrogenated 1,3-diazaheterocycles annulated at positions 2 and 3, namely, imidazole, pyrimidine, or [1,3]diazepine (compounds 1–3, respectively), the 1H-tautomeric form strongly predominates in the gas phase and in solutions regardless of the nature of these cycles. Tautomerization of tricycles 1–3 occurs via the intermolecular mechanism to form as intermediates hydrogen-bonded cyclodimers of these compounds or their cyclosolvates with proton-donor solvents. The key step of the reaction is the intraassociated concerted double proton transfer, which can proceed in nearly synchronous and asynchronous modes. In particular, double proton transfer in cyclodimers of quinazolinones 1–3 is asynchronous and proceeds with the formation of solvate-stabilized polar transition states, which are similar in structure to ionic intermediates of the nonconcerted double proton transfer.