The synthesis of 4-(2,6,10-trimethyl-1,3,5,9-undecatetraenyl)benzoic acid based on alkoxy alkene-acetal condensation

4-(2,6,10-Trimethyl-1,3,5,9-undecatetraenyl)benzoic acid (1) was synthesized starting from ethyl 4-formylbenzoate (2) and linalool. The key intermediate, ethyl 4-(2-methyl-3-oxo-1-propenyl)benzoate (5), was obtained by the addition of diethyl acetal (3), prepared from2, to ethyl 1-propenyl ether (EPE) followed by the hydrolysis of the resulting adduct.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 914–915, May, 1993.     

A new polyketide purpurogenic acid: the activated production of polyketides by the diethyl sulphate mutagenesis of marine-derived Penicillium purpurogenum G59

A new polyketide, purpurogenic acid (1), and two known polyketides, (-)-mitorubrin (2) and (-)-mitorubrinol (3), were isolated from a fungal mutant derived from the diethyl sulphate (DES) mutagenesis of marine-derived Penicillium purpurogenum G59. The planar structure of new 1 was elucidated by spectroscopic methods and the absolute configuration was assigned on the basis of [α]_D and CD data. In our preliminary MTT assay, 1 inhibited human cancer K562, HL-60, HeLa and BGC-823 cells with the inhibition rates of 52.7, 78.8, 38.4 and 35.3% at the 100 μg/mL, respectively.     

Application of 1-Azidoalkylphosphonates in the Synthesis of Phosphonodipeptides and Other N-Substituted Aminophosphonates

Efficient synthesis of diethyl 1-(isothiocyano)alkylphosphonates, and N-derivatives of diethyl 1-aminoalkylphosphonates as well as phosphonodipeptides were developed using diethyl 1-azidoalkylphosphonates as starting materials.     

Preparation of Isoquinolin-(2(1H)-yl)but-2-enedioate Derivatives

One-pot, three-component reactions of isoquinoline, dimethyl/diethyl acetylenedicarboxylate, and indole, carbazole, pyrazole, or imidazole gave dimethyl/diethyl 2-(1-(1H-indol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate, dimethyl/diethyl 2-(1-(9H-carbazol-9-yl)isoquinolin-2(1H)-yl)but-2-enedioate, dimethyl 2-(1-(1H-pyrazol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate, or dimethyl 2-(1-(1H-imidazol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate respectively in good to excellent yields.     

New class of diethyl substituted phosphoramidimidates and phosphonimidates: synthesis,spectral characterization and antimicrobial activity

Abstract

A series of new class of diethyl N-2-hydroxyethyl-N'-substituted phosphoramidimidates 6(a–e) and diethyl P-morpholino-N-substituted phosphonimidates 6(f–j) was synthesized. The precursor intermediates, diethyl substituted phosphoramidites 3(a–b) were prepared initially by a reaction of various amines 1(a–b) and diethyl phosphorochloridite (2) and then they were treated by in situ with aromatic/alkyl azides through Staudinger reaction to accomplish title products. Structures of all the synthesized compounds were characterized by spectroscopic data such as IR, NMR (¹H, 13C, ³¹P), mass, and elemental analyses. The synthesized compounds were screened for their in vitro antimicrobial activity to understand their biological potency. The biological screening results disclosed that compounds 6b, 6c, 6e, 6g, 6h and 6j having potent antimicrobial activity against all the tested pathogens.     

PREPARATION OF DIETHYL 1-BROMOALKYLPHOSPHONATES

Abstract

Diethyl 1-bromoalkylphosphonates 1 have been obtained in good to moderate yields by the reaction of diethyl I-hydroxyalkylphosphonates 2 with the triphenylphosphine-carbon tetrabromide system or dibromotriphenylphosphorane.     

SYNTHESE DU FOSTEDIL (4-(2-BENZOTHIAZOLYL) BENZYLPHOSPHONATE DE DIETHYLE) A PARTIR D'IMIDATES N-ACYLES

Fostedil (diethyl 4-(benzothiazol-2-yl) benzylphosphonate) 7 has been synthesized efficiently by treatment of 2-(4-bromomethylphenyl) benzothiazole 6 with triethylphosphite. The latter (6) has been prepared by bromation of benzothiazole 3c. N-acylimidates 1(a–d) react with 2-aminobenzenethiol 2 to lead to the corresponding benzothiazoles 3(a–d) after elimination of primary amide 5. The structure of these products have been unequivocally confirmed by means of IR, ¹H, ¹³C, and ³¹P NMR spectroscopy and mass spectra.     

Synthesis and characterization of polymeric triphenyltin and cyclotetrameric tricyclohexyltin 2-(1H-imidazol-1-yl)acetates

The reaction of 2-(1H-imidazol-1-yl)acetic acid with (Ph₃Sn)₂O or Cy₃SnOH (Cy?=?cyclohexyl) yields triphenyltin 2-(1H-imidazol-1-yl)acetate (1) and tricyclohexyltin 2-(1H-imidazol-1-yl)acetate (2), respectively. 2-(1H-imidazol-1-yl)acetates in these two complexes show remarkably different coordination modes. Complex 1 forms a polymeric chain structure through intermolecular Sn–N interactions, while 2 displays a 28-membered macrocyclic tetranuclear structure by the assembly of Sn–N coordination bonds.     

Synthesis and Some Properties of 2-(5-Methyl-2-Phenyl-2H-1,2,3-Diazaphosphol-4-yl)-4H-Benzo[d]-1,3,2-Dioxaphosphorin-4-One

Abstract

2-(5-Methyl-2-phenyl-2Н-1,2,3-diazaphosphol-4-yl)-4H-benzo[d]-1,3,2-dioxaphosphorin-4-one 1 readily reacts with hexafluoroacetone, mesoxalic acid diethyl ester, trifluoropyruvic acid ethyl ester and chloral to give 2-(5-methyl-2-phenyl-2H-1,2,3-dizaphosphole-4-yl)-derivatives of 1,3,2- and 1,4,2-dioxaphosphepines.     

Efficient Synthesis and Practical Resolution of 1-(Naphthalen-1-yl)ethanamine,a Key Intermediate for Cinacalcet

An efficient synthesis of 1-(naphthalen-1-yl)ethanamine ( RS -2) and its practical resolution to optically pure (1R)-(naphthalen-1-yl)ethanamine ( R -(+)-2), a key intermediate in the synthesis of cinacalcet hydrochloride (1), is described. The resolution of RS -2 using R-(?)-mandelic acid as a resolving agent in ethanol was established on an industrial scale to give pure R -(+)-2 with >99.8% ee after liberation of the amine from its mandelate salt. An efficient process for the racemization of undesired isomer S -(?)-2 is also provided to maximize the yield of desired enantiomer.     

Unusual behavior of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one towards some phosphorus reagents: Synthesis of novel diethyl 2-phosphonochromone,diethyl 3-phosphonopyrone and 1,3,2-oxathiaphosphinines

The chemical reactivity of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) towards some phosphorus reagents was studied. The enaminone 1 was cyclized into diethyl 2-phosphonochromone 2 via its treatment with diethyl phosphite in basic medium. However, its reaction with triethoxy phosphonoacetate gave the substituted pyrone phosphonate 3. In addition, two novel examples of 4-(dimethylamino)-6-(2-hydroxyphenyl)-2-sulfido-4H-1,3,2-oxathia-phosphinines 6 and 7 were obtained from treatment of enaminone 1 with O,O-diethyl dithiophosphoric acid and Lawesson’s reagent. When enaminone 1 was also treated with phosphorus decasulfide, it was turned into 4H-thiochromene-4-thione while its treatment with phosphorus tribromide, phosphorus oxychloride, or phenylphosphonic dichloride, 4H-4-oxo-chromene was isolated in all cases. The possible reaction mechanisms of the formation of these products were discussed. The structures of newly isolated products were established by elemental analysis and spectral tools.     

Multicomponent one-pot synthesis of (dihydro-1H-benzo[d]imidazole) phosphonate

Abstract

We present a multicomponent reaction strategy to synthesize a (dihydro-1H-benzo[d]imidazole)phosphonate family of compounds, using benzimidazoles, diethyl chlorophosphate and aliphatic amines as starting reactants. Giving its simplicity, our procedure involves reaction times of only few hours and avoid the usage of any catalyst agent. All the newly synthesized compounds were characterized by Nuclear Magnetic Resonance spectroscopy (¹H, ¹³C and ³¹P) and mass spectrometry by the DART method.     

Reactions of 1,2-ethanedithiol and 2-mercaptoethanol with unsaturated derivatives of four-coordinate phosphorus acids

The reaction of 1,2-ethanedithiol with diethyl vinylphosphonate in the presence of EtONa occurs as the addition of the sulfhydryl group to the β-carbon atom of the substrate to give 1 : 1 and 1 : 2 adducts. The nucleophilic addition of 2-mercaptoethanol at the β position of the multiple bond of diethyl vinyl-, diethyl allenyl-, and diethyl prop-1-ynylphosphonates involves only the sulfhydryl group.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2156–2159, October, 2004.     

New and Efficient Synthesis of 1,3-Dienylphosphonates by Palladium-Catalyzed Substitution of Propargylic Esters to Diethyl Phosphite

An efficient route to the synthesis of 1,3-dienylphosphonates (1) has been developed for the first time by the substitution of propargylic esters (2) to the diethyl phosphite (3) nucleophile in the presence of Pd₂(dba)₃ · CHCl₃ (2 mol %) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4 mol%). Both the alkyl and aryl 1,3-dienylphosphonates can be prepared from this transformation.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Alternatives to N,N‐Diethyl‐2,4‐dimethoxybenzamide as a Precursor for the Synthesis of 6,8‐Dimethoxy‐3‐methyl‐3,4‐dihydro‐1H‐isochromen‐1‐one

Although the amide group of N,N‐diethyl‐2,4‐dimethoxybenzamide facilitates directed ortho‐metallation and subsequent allylation of the aromatic ring, it is not readily hydrolyzed prior to conversion into the title isochromenone. This article describes the use of 1‐(2‐allyl‐4,5‐dimethoxybenzoyl)‐4‐methylpiperazine and N,N‐diethyl‐2‐(2‐hydroxypropyl)‐4,6‐dimethoxybenzamide as alternative substrates for conversion into 6,8‐dimethoxy‐3‐methyl‐3,4‐dihydro‐1H‐isochromen‐1‐one.     

Stereoselective synthesis of the lichen metabolite, (+) montagnetol and its congeners as antimicrobial agents

Abstract

In view of structural diversity, (+) montagnetol, the major metabolite of the fruticose lichen, Roccella montagnei was synthesized along with three of its congeners by employing highly efficient protocols. (+) Montagnetol (2?R, 3S; 11) and (-) montagnetol (2S, 3R; 5) were synthesized in 7 and 9 steps, respectively, from L-ascorbic acid. The two new congeners 3 (2?R, 3R) and 6 (2S, 3S), which differ in configuration at C-2 and C-3 positions of the (+) montagnetol, were synthesized from (?) diethyl D-tartrate and (+) diethyl L-tartrate, respectively. The synthesized compounds were evaluated in vitro for antimicrobial activity against two Gram-positive (S. aureus and E. coli) and two Gram-negative (S. typhi and P. aeruginosa) bacteria and one fungal strain Candida albicans. Interestingly, the congener 3 showed promising anti-bacterial activity (MIC: 0.062?µg/ml) against P. aeruginosa, whereas the congener 6 displayed potent anti-fungal activity (MIC: 0.062?µg/ml) against C. Albicans.     

(Alk-1-ynyl)organylthiocarbenes: generation and reactions with olefins

1-Substituted 1-chloro-3-organylthiopropa-1,2-dienes 1a–f belonging to previously unknown type of allenic compounds were synthesized by chlorination of 1-organylthioalk-1-ynes 3a–f with N-chlorosuccinimide. The reactions of compounds 1a–f with Bu^tOK in hexane at –20 °C are accompanied by -elimination of HCl to give new alk-1-ynyl(organylthio)carbenes 2a–f, which add to olefins to form the corresponding 1-(alk-1-ynyl)-1-organylthiocyclopropanes 5 in yields of up to 60%. The electrophilic properties of carbenes 2 were confirmed experimentally.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2440–2447, November, 2004.     

Diethyl acetonedicarboxylate — a precursor for the synthesis of new substituted 4-aminoquinolines and fused 4-aminopyridines

Summary The reaction of cyclic enaminonitriles1 with diethyl acetonedicarboxylate (2) affords fused 4-amino-3-ethoxycarbonyl-2-ethoxycarbonylmethyl-pyridines4. The course of the reaction and the yield of cyclic products were promoted by tin(IV)chloride. N-substituted diethyl 3-aminoglutaconates3 seem to be intermediates of the cyclization reaction.Dedicated to Prof.Milan Kratochvil on the occasion of his 70th birthday     

Investigation of the Addition of Benzenethiol to p-Chlorophenylphenylacetylene

The addition of benzenethiol to p-chlorophenylphenylacetylene results in the formation of a mixture of two pairs of diastereomeric (E)- and (Z)-1-p-chlorophenyl-2-phenyl-1-phenylthioethylenes (1 and 2) and (E)- and (Z)-1-p-chlorophenyl-2-phenyl-2-phenylthioethylenes (3 and 4). The configurations of these compounds have been established by ¹ H NMR studies, by their preparation from benzyl p-chlorophenyl ketone and p-chloro-benzylphenyl ketone, and by the oxidation of the thioethylenes 1, 2, 3, and 4 to the corresponding sulphonylethylenes 5, 6, 7, and 8, respectively.     

3-Cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines in the synthesis of substituted 3-(aminomethyl)pyridines

The reactions of substituted 3-cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the corresponding 3-aminomethyl derivatives, which were used in the synthesis of the corresponding amides.