Facile Synthesis of (S,S)‐1,2‐Diacylamides and (S,S)‐1,2‐Diamines with C 2‐Symmetry

A series of chiral vicinal tertiary diacylamides with C ₂‐symmetry was synthesized from (S)‐α‐phenylethylamine, different aromatic aldehydes, and oxalyl chloride. The diacylamides obtained were then reduced to afford chiral vicinal diamines with C ₂‐symmetry. We propose that the diacylamides existed in four stable conformational isomers in solution because of the dihedral angle between acylamide bonds.     

Regioselective Endocyclic Oxidation of Enantiopure 3‐Alkylpiperidines: Synthesis of (3S,5S)‐(‐)‐3‐Ethyl‐5‐Methylpiperidine

An efficient regioselective endocyclic oxidation of enantiopure 3‐alkylpiperidines 1(a–c) with bromine in acetic acid to generate the corresponding 5‐alkylpiperidin‐2‐ones 3(a–c) as main product is described. In addition, starting from 3a or 3b, the synthesis of (3S,5S)‐(‐)‐3‐ethyl‐5‐methylpiperidine 6 · HCl was achieved. Finally, the X‐ray single‐crystal analysis of compound 4 is reported.     

Novel Cyanoketene N,S‐Acetals and Pyrazole Derivatives using Potassium 2‐Cyanoethylene‐1‐thiolates

Novel ketene N,S‐acetals 3 were readily prepared by the reaction of cyanoacetamide or cyanothioacetamide with phenylisothiocyanate in the presence of potassium hydroxide, followed by alkylation of the produced salts with methyl iodide. The reaction of compounds 3 with hydrazines afforded different substituted pyrazoles 6.     

Stereoselective Synthesis of (2S, 8S)‐2‐Benzyl Hexahydro‐pyrrodizin‐3‐one Starting from (L)‐Proline Based on Stereoselective Benzylation

Abstract

A pyrrolizidine alkaloid, (2S, 8S)‐2‐benzyl hexahydro‐pyrrodizin‐3‐one, was synthesized from (L)‐proline using diastereoselective benzylation as the key step. The absolute configuration of the target compound was confirmed through 2D H‐H COSY and H‐H NOESY spectra.     

PMA‐SiO2: A Heterogenous Catalyst for O‐, S‐, and N‐Nucleophilic Substitution Reactions of Aryl Propargyl Alcohols

Aryl‐propargylic alcohols undergo O‐, S‐, and N‐nucleophilic substitution reactions in the presence of a catalytic amount of PMA‐SiO₂.     

An Improved Asymmetric Synthesis of Unusual Amino Acid (2S,3S)‐3‐Hydroxyproline

Abstract

An improved three‐steps method for the conversion of N‐benzyl (S)‐3‐hydroxypyrrolidin‐2‐one 6 to (2S,3S)‐3‐hydroxyproline 1 is reported. The key step is the reductive cyanation of 6. The synthesis of 1 constitutes a formal asymmetric synthesis of (2S,3S)‐3‐hydroxyproline betaines 2.     

Synthesis of Novel (3a,S)‐1‐Aryl/aryloxy/alkoxy‐3a,4‐dihydro‐3H‐1λ5‐[1,3,2]oxazaphospholo [3,4‐a] indole‐1‐ones,Thiones, and Selenones

Synthesis of novel (3a,S)‐1‐aryl/aryloxy/alkoxy‐3a,4‐dihydro‐3H‐1λ⁵‐[1,3,2]oxazaphospholo [3,4‐a] indole‐1‐ones, thiones, and selenones was achieved in two steps with high yields from 2,3‐dihydro‐1H‐indol‐2(S)yl methanol (1) and dichlorophenyl phosphine/ethyl dichlorophosphite (2a and b) in the presence of triethylamine in dry THF followed by treatment with hydrogen peroxide, sulfur, and selenium. The compounds 4g–k have been synthesized by the direct cyclocondensation of 1 with different substituted phenyl phosphorodichloridates (2c–e, g) and bis(2‐chloroethyl) phosphoramidic dichloride (2f).     

Synthesis of Urine Drug Metabolites: Glucuronosyl Esters of Carboxymefloquine,Indoprofen, (S)‐Naproxen,and Desmethyl (S)‐Naproxen

Abstract

A general procedure for the synthesis of 1‐O‐acyl‐β‐D‐glucuronic acids using the benzyl 1-O-trichloroacetimidoyl-2,3,4-tri-O-benzyl-D-glucopyranuronate 6 as donor is exemplified by the synthesis of the urine metabolites of (S)‐naproxen, desmethyl (S)‐naproxen, indoprofen, and carboxymefloquine. The key intermediate benzyl 2,3,4‐tri‐O‐benzyl‐D‐glucopyranuronate 5 is easily accessible in four steps (29%) from the peracetylated β-D-glucuronic acid 1.     

Synthesis of 1,2,4‐Triazinediones, 1,2,4,3‐Triazaphospholines,and 1,2,4,3‐Triazaphospholine‐3‐oxide Derivatives

The reaction of N ¹‐tosylamidrazones 1 with oxalyl dichloride, phosphorus trichloride, and phosphoryl chloride leads to 1,2,4‐triazinediones 3 , 1,2,4,3‐triazaphospholines 4 , and 1,2,4,3‐triazaphospholine‐3‐oxides 5 , respectively. The structures of the new products have been established by IR; ¹H, ¹³C, and ³¹P NMR studies; and elemental analysis.     

Novel Synthetic Route of (2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic Acid

(2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic acid, a key intermediate of Fidarestat, was synthesized from natural chiral pool D‐mannitol. Its structure was confirmed by optical analyses, elemental analyses, and IR, ¹H NMR, and ESI‐MS spectra.     

Comparative Analysis of the Properties of Tween‐20, Tween‐60, Tween‐80, Arlacel‐60, and Arlacel‐80

Foamability and foam stability, emulsifying power, surface tension, and interfacial tension were investigated for Tween‐20 (polyoxyethylene sorbitan monolaurate), Tween‐60 (polyoxyethylene sorbitan monostearate), Tween‐80 (polyoxyethylene sorbitan monooleate), Arlacel‐60 (Sorbitan stearate), and Arlacel‐80 (Sorbitan oleate). Among all the surfactants tested for their foaming power and foamabilty, Arlacel‐60 and Arlacel‐80 showed the best results; the foaming power and foamability was found to be 100%. The surfactants having foam stability more than 50% can be considered as metastable and those less than 50% are considered as low‐stability foams. In case of surface tension and interfacial tension property measurements, Arlacel‐80 showed the best results. At 1% surfactant concentration, the surface tension and interfacial tension of Arlacel‐80 was found to be 29.9 dynes/cm and 1.1 dynes/cm at 30°C ambient temperature. Also, Arlacel‐60 was found to exhibit the best emulsifying power among all the surfactants tested. At 30°C, the emulsifying property of Arlacel‐60 was 6 hours.     

Microwave‐Accelerated,Three‐Component,One‐Step Synthesis of 2‐Acylimino‐3‐aryl‐3H‐thiazolines under Solvent‐Free Conditions

2‐Acylimino‐3‐aryl‐3H‐thiazoline derivatives could be generated in excellent yields through three‐component condensations of aroylisothiocyanates, primary amines, and ω‐haloacetophenone under solvent‐free microwave irradiation.     

Synthesis of the Potassium Channel Opener (3S,4R)‐3,4‐Dihydro‐4‐(2,3‐dihydro‐2‐methyl‐3‐oxo‐pyridazin‐6‐Yl)oxy‐3‐hydroxy‐6‐(3‐hydroxyphenyl)sulphonyl‐2,2,3‐trimethyl‐2H‐benzo[b]pyran

The preparation of the potassium channel opener (3S,4R)‐3,4‐dihydro‐4‐(2,3‐dihydro‐2‐methyl‐3‐oxo‐pyridazin‐6‐yl)oxy‐3‐hydroxy‐6‐(3‐hydroxyphenyl)sulphonyl‐2,2,3‐trimethyl‐2H‐benzo[b]pyran (1) as a single enantiomer is reported. Considerable improvements have been implemented with respect to the original synthesis that allow for the preparation of multigram quantities of the final target compound. The optimized synthesis consists of a six‐step linear sequence whose key step is an asymmetric epoxidation protocol through the use of Jacobsen's (S,S)‐(+)‐N,N′‐bis(3,5‐di‐tert‐butylsalicylidene)‐1,2‐cyclohexanediaminomanganese(III) chloride catalyst.     

Synthesis,Structures, and Properties of Novel N‐Aryl‐phenanthren‐o‐iminoquinones

The interaction of 9,10‐phenanthrenquinone with primary amines has been studied. Use of sterically hindered anilines gave the phenanthren‐o‐iminoquinones in good yields. These compounds are structural analogues of o‐benzoquinones. Using single‐electron reduction, o‐iminoquinones may synthesize metal's free‐radical complexes.     

Practical Synthesis of (S)‐(+)‐3‐Octanol by Lipase‐Catalyzed Enantioselective Acetylation

(S)‐(+)‐3‐Octanol (S)‐1 was prepared in high enantiomeric excess through catalyzed acetylation of racemic alcohol 1 by using lipase from Candida antarctica (Chirazyme L‐2) in the presence of vinyl acetate in toluene at 30°C. The pure (S)‐1 was obtained in 73% isolated yield with 62% conversion. Moreover, acetate (R)‐2 was converted to (S)‐1 via mesylation and followed by hydrolysis using sodium bicarbonate solution in 44% yield.     

Simple,Efficient, and Stereoselective Oxidation of Triphenylfurans to cis‐But‐2‐ene‐1,4‐diones

Triphenylfurans are stereoselctively oxidized to cis‐but‐2‐ene‐1,4‐diones, suitable precursors of 3(2H)‐furanones, in very good yields using ammonium nitrate or potassium nitrate in 80% aqueous acetic acid.     

Synthesis of Novel Anellated Pyranosides as Precursors of C‐Nucleoside Analogues Using Isopropyl 6‐O‐Acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose

Abstract

Isopropyl 6‐O‐acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose (3) was converted to the corresponding 3‐[bis(methylthio)methylene] derivative 4 with a push–pull activated C–C double bond. Treatment of 4 with hydrazine and methylhydrazine afforded the pyrano[3,4‐c]pyrazol‐5‐ylmethyl acetates 5a and 5b, respectively. Desulfurization of compound 4 with sodium boron hydride yielded the 3‐[(methylthio)methylene]hexopyranosid‐2‐ulose 7. Compound 7 was reacted with amines to furnish 3‐aminomethylene‐hexopyranosid‐2‐uloses 8, 9. Reaction of 7 with hydrazine hydrate, hydrazines, hydroxylamine, and benzamidine afforded the pyrazolo, isoxazalo, and pyrimido anellated pyranosides (10–13).     

From Tri‐O‐Acetyl‐D‐Glucal to (2R,3R,5R)‐2,3‐Diazido‐5‐Hydroxycyclohexanone Oxime

Abstract

Methyl 3‐azido‐2,3‐dideoxy‐α/β‐D‐arabino‐ and ‐α/β‐D‐ribo‐hexopyranosides were transformed into 6‐iodo analogues via p‐tolylsulfonyl compounds. Elimination of hydrogen iodide from 6‐iodo glycosides provided methyl 4‐O‐acetyl‐3‐azido‐2,3,6‐trideoxy‐α‐ and ‐β‐D‐threo‐hex‐5‐eno‐pyranosides or 3‐azido‐4‐O‐p‐tolylsulfonyl‐2,3,6‐trideoxy‐α‐D‐threo‐ and ‐β‐D‐erythro‐hex‐5‐eno‐pyranosides. Ferrier's carbocyclization of 4‐O‐acetyl‐3‐azido‐2,3,6‐trideoxy‐α‐ and ‐β‐D‐threo‐hex‐5‐eno‐pyranosides gave (2S,3R,5R)‐2‐acetoxy‐3‐azido‐5‐hydroxycyclohexanone, which was converted into oxime. The 2‐OAc group in oxime was substituted by azide ion to yield (2R,3R,5R)‐2,3‐diazido‐5‐hydroxycyclohexanone oxime. The configuration and conformation of all products are widely discussed on the basis of the ¹H and ¹³C NMR.     

Utilization of Maltodextrin‐Based Enantioselective,Potentiometric Membrane Electrodes for the Enantioselective Assay of S‐Flurbiprofen

Abstract

Three enantioselective, potentiometric membrane electrodes (EPMEs) based on carbon paste impregnated with different maltodextrins [dextrose equivalent (DE) (DE 4.0–7.0 (I), 13–17 (II), 16.5–19.5 (III)], were proposed as chiral selectors for the assay of S‐flurbiprofen raw materials and from its pharmaceutical formulation, Froben 100^® tablets. The best response and enantioselectivity were obtained when maltodextrin with lower DE was used for the electrode design. The three EPMEs showed very low detection limits. The surfaces of the electrodes are easily renewable by simply polishing on an alumina paper.     

Iodine‐Mediated Synthesis of 2‐Arylbenzoxazoles, 2‐Arylbenzimidazoles,and 1,3,5‐Trisubstituted Pyrazoles

2‐Arylbenzoxazoles and 2‐arylbenzimidazoles were synthesized by the reaction of aldehydes with 2‐aminophenol and O‐phenylenediamines in the presence of iodine. 1,3,5‐Trisubstituted pyrazoles were synthesized from chalcones and hydrazines in the presence of iodine.